Post-concussion symptoms have long been thought to be more severe and prolonged in people who have pre-existing psychological problems. This has been shown to be the case in the military personnel. A new study confirmed this observation in the first prospective study. Over 2,000 high school and college athletes in Wisconsin were asked to answer 18 questions (Brief Symptom Inventory-18, or BSI-18) and then were followed for three years. The 18 questions, which are listed below, addressed the presence of anxiety, panic attacks, depression, and somatization (excessive bodily sensations). In the ensuing three years, 127 athletes sustained a concussion. The concussion had to be diagnosed by a licensed athletic trainer according to the Department of Defence definition, which includes alteration of mental status with associated headache, nausea, vomiting, balance difficulties, dizziness, cognitive difficulties, and other. These athletes were again evaluated two and six weeks later. Eighty percent of concussed athletes were men. The mean duration of symptoms was five days. Ninety five percent of them recovered completely within a month. High somatization score on the BSI-18 questionnaire predicted prolonged duration of symptoms, while no correlation was found with the years of playing a sport, the type of sport (most played football), number of prior concussions, migraines, ADHD, or the grade point average. Another factor that delayed recovery was the initial symptom severity after the concussion. Most of the concussions were mild with less than 10% of athletes losing consciousness.

An interesting and unexplained fact, not examined in this study, is that milder concussions tend to cause more severe symptoms than severe ones.

This was a very thorough study, but it was relatively small, so it is possible that other pre-concussion factors may also delay recovery. One such factor is pre-existing migraines. I see many patients, adults and children, who suffered from migraines and after a concussion have worsening of their migraines or new daily persistent headaches. If they themselves have never suffered from migraines, often their mother or siblings have a history of migraines, suggesting genetic predisposition to migraines.

Treatment of post-concussion symptoms, include typical therapies employed in migraine sufferers, including aerobic exercise, biofeedback, magnesium supplementation, Botox injections, and a variety of medications.

Brief Symptom Inventory-18

The Somatization dimension
01. Faintness or dizziness
04. Pains in heart or chest
07. Nausea or upset stomach
10. Trouble getting your breath
13. Numbness or tingling in parts of your body
16. Feeling weak in parts of your body
The depression dimension
02. Feeling no interest in things
05. Feeling lonely
08. Feeling blue
11. Feeling of worthlessness
14. Feeling hopeless about the future
17. Thoughts of ending your life
General anxiety
03. Nervousness or shakiness inside
06. Feeling tense or keyed up
15. Feeling so restless you couldn’t sit still
09. Suddenly scared for no reason
12. Spells of terror or panic
18. Feeling fearful

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Intravenous magnesium infusions may not be as safe in pregnant women as it has been always thought. The FDA recently moved intravenous magnesium from category A into category D (see category definitions below). This came about after the FDA reviewed 18 cases of babies who were born with serious problems after their mothers received intravenous infusions of large amounts of magnesium for 5 to 7 days in order to stop premature labor. The FDA strongly discourages this practice and states that “Administration of magnesium sulfate injection to pregnant women longer than 5-7 days may lead to low calcium levels and bone problems in the developing baby or fetus, including thin bones, called osteopenia, and bone breaks, called fractures.”

However, treatment of choice for eclampsia remains intravenous magnesium. Eclampsia, one of the most serious complications of pregnancy can be treated only with high doses of intravenous magnesium. Without intravenous magnesium eclampsia can lead to epileptic seizures, very high blood pressure, kidney failure and death.

The FDA also recommends that “Magnesium sulfate injection should only be used during pregnancy if clearly needed. If the drug is used during pregnancy, the health care professional should inform the patient of potential harm to the fetus.”

We do treat many patients, including pregnant women, with intravenous infusions of magnesium if they are deficient in magnesium and if their migraines respond to such infusions. Typically, these infusions are given monthly and the amount is only 1 gram, while for preterm labor the dose is 4-6 grams to start and then 2-4 grams an hour as needed. This monthly dose of 1 gram is extremely unlikely to cause any adverse effects. We find that migraines triggered by magnesium deficiency do not respond well to any other treatments and considering the risk of drugs, it is much safer to administer 1 gram of magnesium. This amount of magnesium just corrects the deficiency and does not cause very high magnesium levels, which can be detrimental.

Several other drugs routinely used in pregnancy may also not be as safe as we thought. Acetaminophen (Tylenol) has been considered one of the safest choices. However, recent evidence suggests possible link to attention deficit disorder with hyperactivity (ADHD).

Butalbital, which is an ingredient in the popular headache drugs such as Esgic, Fioricet and Fiorinal is associated with an increased risk of congenital heart defects. Fioricet also contains caffeine, which has negative effects on the fetus and which can cause rebound (medication overuse) headaches.

FDA drug categories in pregnancy

Category A
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Example drugs or substances: levothyroxine, folic acid, liothyronine

Category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Example drugs: metformin, hydrochlorothiazide, cyclobenzaprine, amoxicillin, pantoprazole

Category C
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: tramadol, gabapentin, amlodipine, trazodone, prednisone

Category D
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: topiramate (Topamax), divalproex sodium (Depakote), lisinopril, alprazolam, losartan, clonazepam, lorazepam

Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

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Dr. Leo Galland, whom I’ve known professionally for many years, has written (with his son) another outstanding book, The Allergy Solution. Sometimes I see a patient, who in addition to migraine headaches, suffers from a variety of other ailments. These patients usually see an allergist, an ENT doctor, an infectious disease specialist, and several other physicians, all without answers or relief. In most cases, Dr. Galland is the one who can figure out what’s wrong and how to fix it.

Dr. Galland’s new book, which I just read cover-to-cover, presents scientific research that explains hidden causes of unexplained symptoms such as migraines, fatigue, weight gain, chronic pain, poor sleep, allergies, and reflux. The book describes the role of immune function, stress, nutrition, inflammation, environmental health, leaky gut, and the microbiome.

Most importantly, The Allergy Solution gives people practical solutions to relieve their symptoms, which are very often caused by allergies. Dr. Galland convincingly shows that allergies are aggravated by stress, abnormal gut bacteria, specific vitamin and mineral deficiencies, and other factors. He writes about scientific studies that show the effect of meditation on inflammation and how taking probiotics can improve not only your digestive problems but also migraines and many other symptoms. From this book you will learn the role of vitamin D, zinc, magnesium and a variety of other minerals and vitamins in returning you to health. One of the things I learned is that a combination of vitamin B12 and a mineral called molybdenum can reduce the amount of sulfites in your body. Sulfites, which often trigger migraines are used as a preservative and also occur naturally in wine.

To tell you more about what’s in the book, here is a series of questions answered by Dr. Galland:

Q: What have you discovered about the surprising hidden truths behind chronic symptoms?
A: You may not think of yourself as allergic. Your nose may not run, and your skin doesn’t itch. But you have common complaints that just won’t go away.
Do you suffer from:
•Weight gain?
•Depression or anxiety?
•Brain fog?

A hidden allergy is often the culprit. Chronic conditions that were previously diagnosed as autoimmune diseases, psychiatric disorders, or many others, wind up being allergic in origin.

Our search for answers to common mystery conditions, and the source of the allergy epidemic inspired us to write our new book, The Allergy Solution: Unlock the Surprising, Hidden Truth about Why You Are Sick and How to Get Well.

We reveal the proven role of allergy in causing weight gain, fatigue, headache, joint and muscle pain, a range of digestive symptoms from heartburn to diarrhea, mood problems, poor mental focus, and more. A step-by-step method for determining if you have hidden allergies is provided. And if you suffer from classic allergies like rhinitis, eczema or have asthma, our program addresses these issues from a nutritional and lifestyle perspective.

Q: Why are we seeing an epidemic of allergy today?
A: Allergies were once rare. Today they affect over a billion people. Environmental toxicity, depletion of beneficial intestinal bacteria and fast food all contribute to allergies.
Pollen counts are going up and up. A big cause? Air pollution, the kind generated by cars, buses and trucks. Scientists at the US Department of Agriculture investigated how air pollution affects ragweed. They discovered that pollution makes the plants grow twice as large and produce 5 times as much pollen. Many types of pollen, especially ragweed, are actually toxic. They contain an enzyme that damages the lining of your nose and lungs when you breathe them in. This sets the stage for rising allergies.

Driving While Allergic: Dutch scientists tested driving skills in people with allergies and discovered that Pollen exposure impaired the operation of an automobile to the same extent as drinking two cocktails.
Air fresheners increase the risk of allergies and asthma, mostly because of the chemical fragrances they contain, reports a study from the University of California. So what’s alternative? We can’t think of a better way to freshen your air than with ventilation. If the air outside your home is actually worse than the air inside, then try a commercial air purifier.

Cleaning sprays are also hazardous to your health. Using a household cleaning spray just once a week elevates your risk of developing asthma by 30 to 50 per cent, reports a study from Europe. But true clean doesn’t come from a cleaning spray. The Allergy Solution contains a program for freeing your home from these toxins. We call it Mission Detoxable. Step one is easy: ditch the chemical sprays and use water and baking soda for most cleaning jobs. Vinegar in water is great for glass and tile.
Q: How does nutrition impact allergies?
A: Research shows that people with allergies often suffer from nutritional deficiencies and may need nutritional enrichment of protective factors like selenium, magnesium, vitamins C and D, and omega-3 fats. In The Allergy Solution we provide a nutritional approach to overcoming allergy through food and supplements.
All of us need concentrated nutritional support for T-regs, which comes from natural folates found in vegetables such as leafy greens; carotenoids found in orange and yellow vegetables; the bioflavonoids found in things like parsley, strawberries and oolong tea; and detoxifying compounds found in broccoli.

Q: What are the most important nutritional factors for reversing allergy?
A: It is vital that the food you eat supply the nutrients you need to help your body remove toxins and establish healthy immune balance. To accomplish this, we include a simple program in The Allergy Solution called the Power Wash. It’s like hitting the re-set button on your computer. You can get started over a 3-day weekend.
With the Power Wash you eliminate the major problem foods like wheat, dairy, soy, corn, yeast, eggs and you nourish your body with a specially designed combination of vegetables, fruits, spices, herbs, and teas. They’ve been chosen because they support the function of a critical part of your immune system: regulatory T-lymphocytes. We call them T-regs. Their role is to turn off the unwanted immune reactions that create allergies. If you have allergies, you suffer from defective function of T-regs.
Q: How does allergy cause weight gain and prevent weight loss?
A: What happens is a vicious cycle driven by the effects of allergy on your metabolism. Clinical research reveals a strong link between allergy and weight gain. People with allergies are more likely to become overweight. People who are overweight are more likely to develop allergies.
Laboratory research shows that allergic reactions actually make fat cells grow larger and larger. Fat cells create a type of inflammation that unleashes stronger allergic reactions. Balancing immunity is essential for healthy weight loss.

Q: How does your program affect the skin?
A: Your skin is your most visible barrier against a toxic environment and a key target for allergic reactions. Allergy rapidly ages the skin and reversing allergy is essential to restoring its vitality.
The nutrients that nourish your immune cells are also essential for nourishing your skin. In addition, Mission Detoxable helps you decrease the stress placed on your skin by avoiding toxins in your home.

Q: What’s the role of your gut in creating or defending against allergy?
A: Two-thirds of your immune system is located in your intestinal tract. The gut is like a boot camp for training your immune cells. The drill sergeants are the bacteria living in your intestines. Biodiversity of these bacteria is essential for immune health and protects against allergy.
Antibiotics, pesticides, herbicides, disinfectants and the modern diet all destroy this diversity and contribute to the allergy epidemic. Our book contains a program for overcoming allergies by healing your gut. It’s called ARC, for Avoidance, Reflorastation and Cultivation.

Q: How does your book address the environmental challenges facing the world?
A: We wrote The Allergy Solution to change how the world thinks about allergy, health, and our relationship with the environment. We reveal the science that says allergies are not just annoying symptoms to be covered over by medications, and the environment is not just a convenient place to put our car exhaust, toss our garbage, and spray our pesticides. In the chapter “How Did We Get So Sick” we bring to light the astonishing research that connects pollution, global warming and toxins to rising allergies and asthma.

The environment is all around us and within us, inside our digestive tract, respiratory system, and whole body. we have exposed the truth that just as the earth’s environment is out of balance, our bodies have become out of balance. Now the environment we all depend on is threatened as never before.

Q: Can We Be Part of the Solution?
A: Absolutely. A community effort is needed to protect the environment and our health. Let’s all work together to turn around air pollution, giving those with asthma—and those without—a better chance to breathe free? Reductions in air pollution could also curb the rising levels of pollen, helping those with hay fever feel more comfortable. Using fewer toxic chemicals would reduce the burden on the environment.

Allergies are connected to the food we eat, the air we breathe, and the environment we live in. Join us and be part of the solution. Learn more about natural health by joining our community at Follow Dr. Galland on and Twitter (@leogallandmd), and follow Jonathan Galland at and on Twitter @JonathanGalland.

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Sumatriptan (Imitrex) and similar drugs (so called triptans) are “designer” drugs that were specifically developed for the treatment of migraine headaches. They are very effective, but do not help all migraine sufferers. Anti-inflammatory pain killers, such as aspirin and ibuprofen work well for some people and sometimes these drugs are combined with triptans to achieve better relief.

Many migraineurs experience nausea and sometimes vomiting as part of their migraine, which prevents or delays the absorption of medicine, making it ineffective or less effective. To address this problem, two of the triptans, sumatriptan and zolmitriptan (Zomig) are available in a nasal spray form. Sumatriptan can be also self-administered as an injection and recently a skin patch of sumatriptan (Zecuity) became available. An anti-inflammatory pain medicine, ketorolac is also available as a nasal spray, as does a narcotic pain killer, Stadol (butorphanol). While Stadol is addictive and has other serious side effects, intranasal ketorolac (Sprix) is a very good pain medication. Sprix works much better than the ketorolac tablet, but not as well as an injection of ketorolac (Toradol).

Intranasal ketorolac was compared with intranasal sumatriptan in a study that was recently published in the journal Headache. The study showed that ketorolac and sumatriptan nasal sprays were equally effective and both were better than placebo spray. Both drugs caused nasal irritation and unpleasant taste in some patients, but these were not severe.

The main problem with intranasal ketorolac is its cost. On the price of 5 vials of Sprix (with a coupon) is about $1,000. Each vial is good for one day of use; it contains 8 sprays (15 mg each) and the usual dose is one spray into each nostril, repeated every 6 hours as needed. However, there is a way around the cost of this medication. Ten 30 mg vials of generic ketorolac for injections cost $15. You just need to buy a nasal spray bottle, empty the contents of the vial into it and use it as needed.

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The FDA approved Botox injections for the treatment of chronic migraine headaches more than five years ago. I just discovered that in this period of time only 100,000 chronic migraine sufferers received this treatment. According to the Migraine Research Foundation, 14 million Americans suffer from chronic migraines, so less than 1% of them have recieved this potentially life-changing treatment.

There are several possible explanations.
1. Botox is expensive and many insurance companies make it difficult for patients to get it. They require that the patient first try 2 or 3 preventive drugs, such as a blood pressure medicine, (propranolol, atenolol, etc.), an epilepsy drug (gabapentin, Depakote, Topamax), or an antidepressant (amitriptyline, nortriptyline, Cymbalta). Patients also have to have 15 or more headache days (not all of them have to be migraines) in each of the three preceding months. If these requirements are met, the doctor has to submit a request for prior authorization. Once this prior authorization is granted, the insurer will usually send Botox to the doctor’s office. After the procedure is done, the doctor has to submit a bill to get paid for administering Botox. This bill does not always automatically get paid, even if a prior authorization was properly obtained. The insurer can ask for a copy of office notes that show that the procedure was indeed performed. All this obviously serves as a deterrent for many doctors. Some of them find that the amount of paperwork is so great and that the payment is so low and uncertain, that they actually lose money doing it.

2. There are not enough doctors trained in administering Botox. This is becoming less of a problem as more and more neurologists join large groups or hospitals where at least one of the neurologists is trained to give Botox and gets patients referred to him or her. However, doctors in solo practices or small groups without a trained injector can be reluctant to refer their patients out for the fear of losing a patient. They may suggest that this treatment is not really that effective or that it can cause serious side effects.
The majority of doctors who inject Botox are neurologists, but there are only 15,000 neurologists in the US and many specialize in the treatment of strokes, Alzheimer’s, epilepsy, MS, and other conditions. This leaves only a couple of thousand who treat headache patients. Considering that there are 14 million chronic migraine sufferers, primary care doctors will hopefully begin to provide this service.

3. Chronic migraine patients are underdiagnosed. Many patients will tell the doctor that they have 2 migraines a week and will not mention that they also have a mild headache every day. The mild headaches they can live with and sometimes my patients will even call them “normal headaches”, which they don’t think are worth mentioning. Good history taking on the part of the doctor solves this problem. However, once doctors join a large group or a hospital, they are pressured to see more patients in shorter periods of time, making it difficult to obtain a thorough history.

4. Some patients are afraid of Botox because it is a poison. In fact, by weight it is the deadliest poison known to man. However, it is safer than Tylenol (acetaminophen) because it all depends on the amount and too much of almost any drug can kill you. Fifty 500 mg tablets of Tylenol kills most people by causing irreversible liver damage. Hundreds of people die every year because of an accidental Tylenol poisoning, while it is extremely rare for someone to die from Botox. Tens of millions of people have been exposed to Botox since its introduction in 1989. It is mostly young children who have gotten into trouble from Botox because the dose was not properly calculated. Kids get Botox injected into their leg muscles for spasticity due to cerebral palsy, although children with chronic migraines also receive it (the youngest child with chronic migraines I treated with Botox was 8).

In summary, if you have headaches on more than half of the days (not necessarily all migraines) and you’ve tried two or three preventive drugs (and exercise, meditation, magnesium, CoQ10, etc), try to find a doctor who will give you Botox injections. Botox is more effective and safer than preventive medications because it does not affect your liver, kidneys, brain, or any other organ.

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Yoga is the most impactful import from India to the US. Yoga has many documented health benefits, including relief of headaches. I have been practicing Bikram yoga about twice a week for nearly 12 years. About a year ago I started having some neck and left upper back pain. I thought that strengthening neck exercises, meditation, occasional massage, which is what I recommend my patients, would eliminate the pain (I probably should have also gone for physical therapy). The pain was never severe and would temporarily improve with massage, but because it persisted and became annoying, I decided to try chiropractic.

Many doctors’ attitude towards chiropractors is dismissive, disdainful or worse. When I tried to google the number of chiropractic manipulations done in the US, the first item that popped up was Medscape’s Deaths After Chiropractic: A Review of Published Cases (there were 26 cases in that report). I have personally treated an elderly patient who developed a subdural hematoma (bleeding inside the head) after chiropractic manipulation. My usual advice to patients has been to go for physical therapy and massage instead of chiropractic. If a patient really wants to see a chiropractor, I advise asking not have any high velocity adjustments. This adjustment is done by suddenly turning and lifting your head to one side and it is responsible for most of the complications. I also tell patients that a good chiropractor will always give you exercises to do, while those who don’t, just want you to keep coming for adjustments for years. Many people feel immediate relief from chiropractic, but it lasts only a few days and they have to go back for another treatment. In fact, regular stretching done by a chiropractor can loosen the ligaments around the cervical spine and cause habitual subluxation of the joints. Subluxation is a partial joint misalignment, which a chiropractor can fix, but repeated adjustments stretches the ligaments and make it easier for the joint to misalign again.

So, why did I take a chance with my neck if not life? First, I wanted to experience what a chiropractic manipulation is like (I’ve also tried Botox, intravenous magnesium, TMS stimulation, and other treatments I offer my patients). Second, I ran into (or rather gave a TV interview to) Lou Bisogni, a chiropractor who is the chiropractor for the New York Yankees. If Joe Torre, Yogi Berra, Wade Boggs, Derek Jeter, and other top Yankee players (dozens of their signed photos are on the office walls) have been entrusting their bodies to him, then obviously he must be very good.

Because my pain has lasted for almost a year, Bisogni first X-rayed my neck. I was not surprised to see that my C5-6 cervical disc was mildly degenerated and the C5 vertebra slipped slightly forward over the C6. This misalignment was what must have prevented my pain from going away. Treatment of such mild misalignments is what chiropractors are probably best at. I did tell him that I did not want high velocity adjustments and he reassured me that he wasn’t going to do any. Many chiropractors are fully aware of the risks and do avoid this type of adjustment. Instead, Bisogni would first apply TENS (transcutaneous electric nerve stimulation – an old technique often used by physical therapists as well), ultrasound, or massage, followed by a brief and gentle adjustment. The adjustment was so gentle and brief (5 minutes or so) that I was a bit skeptical about its efficacy. But to my surprise, after 5 – 6 sessions my pain dramatically improved. It is not completely gone, so I will go for a few more sessions.

I did cut back on Bikram yoga to once a week (but added some weight training instead) and modified my routine when I do it. It is possible that extreme flexion and extension of my neck, which is part of some yoga positions (rabbit, camel, pranayama breathing), might have caused my neck problem. So, I avoid flexing and extending my neck all the way as far as I can. Many yoga instructors push their students to achieve a full expression of the pose, but if your neck hurts or feels uncomfortable, tell the instructor that you’d rather not take a chance with your neck. You should definitely avoid head stands (unless you can do them without putting any pressure on your head and support yourself on the forearms) and shoulder stands, which put excessive pressure on your cervical spine. Also, the high heat in Bikram studios can be a headache trigger for some migraine sufferers and I usually recommend to my patients doing yoga at room temperature.

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I have not been aware of any research indicating a link between salt intake and migraines. A study just published in the journal Headache by researchers at Stanford and UCLA looked at this possible connection.
This was a national nutritional study that examined sodium intake in people with a history of migraine or severe headaches.

The study included 8819 adults with reliable data on diet and headache history. The researchers classified respondents who reported a history of migraine or severe headaches as having probable history of migraine. They excluded patients with medication overuse headache, that is people who were taking pain medications very frequently. Dietary sodium intake was measured using estimates that have been proven to be reliable in previous studies.

Surprisingly, higher dietary intake of sodium was associated with a lower chance of migraines or severe headaches. This relationship was not affected by age or sex. In women, this inverse relationship was limited to those with lower weight (as measured by body mass index, or BMI), while in men the relationship did not differ by BMI.

This study offered the first scientific evidence of an inverse relationship between migraines and severe headaches and dietary sodium intake.

It is very premature to recommend increased sodium intake to all people who suffer from migraines and severe headaches. However, considering that this is a relatively safe intervention, it may make sense to try increased salt intake. I would suggest adding table salt to a healthy and balanced diet, rather than eating salty foods such as smoked fish, potato chips, processed deli meats, or pickles. These foods contain sulfites, nitrites, and other preservatives which can trigger a migraine attack.

People with high blood pressure and kidney or heart disease need to consult their doctor before increasing their salt intake.

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Caffeine is a well-know trigger of migraine headaches and I regularly write on this topic (my last post on this topic – caffeine causing headaches in adolescents – was three years ago). Caffeine can help migraines and other headaches, but in large amounts it worsens them due to caffeine withdrawal, which can occur in as little as 3 hours after the last cup of coffee. One of my patients was an extreme case. He told me that he figured out that his early morning migraines were due to caffeine withdrawal and he would set his alarm clock for 4 AM, so that he could wake up, drink some coffee and go back to sleep without the fear of a morning headache. A continuous intravenous drip of caffeine would also solve his problem. Most people opt for stopping caffeine, albeit it can be a difficult process. Going cold turkey is often easier than a gradual reduction in caffeine intake. To avoid severe withdrawal, prescription migraine drugs, such as sumatriptan (Imitrex), intravenous magnesium, nerve blocks and other interventions may be necessary in a small percentage of patients.

This post was prompted by a just published study that showed a higher risk of miscarriages in couples where either partner, male or female consumed more than 2 caffeinated beverages prior to conception. Caffeine has been long suspected but not definitively proven to increase the risk of miscarriages in women who drink large amounts of caffeine during pregnancy, but what is surprising is that consumption of caffeine by the male partner also increases the risk.

At the same time, recent studies widely publicized in the press have shown beneficial effects of consuming large amounts of caffeine. Caffeine supposedly lowers the risk of certain cancers, strokes, diabetes, and other conditions. However, if you suffer from headaches, heart burn due to reflux, or are trying to conceive, caffeine should be avoided.

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Ketamine is a sedating agent used to induce anesthesia. It is also a drug of abuse with street names such as “Special K” or “Ket”.

Ketamine has many advantages, which makes it a very popular choice in anesthesia. It works fast, blocks pain, opens the lungs, it is easy on the heart, and has anti-inflammatory properties. It may also have anti-cancer properties. Ketamine is being extensively tested for the treatment of depression that does not respond to medications.

Because ketamine works on a receptor involved in transmitting pain messages in the brain (NMDA receptor), it has been studied in various painful conditions. The amounts being tested for pain are much smaller than those used to induce anesthesia or even those used recreationally.

Even though it is a drug of abuse, it appears to be less addictive than heroine and prescription narcotics.

There are only few small studies and reports about the use of ketamine for migraine headaches. One such report published in the leading neurological journal Neurology describes 18 patients with prolonged migraine auras who were treated with intranasal ketamine spray. The duration of their auras was not shortened by ketamine, but the severity was reduced.

Another study showed that severe disabling aura was relieved in 5 out of 11 patients with hemiplegic migraine.

Several anecdotal reports have touted the benefits of ketamine in chronic migraines, cluster headaches, and chronic paroxysmal hemicrania (a rare type of headache that often responds to indomethacin and at times to Botox). While such anecdotal reports are useful, we need to have controlled trials to make sure that placebo effect is not playing a major role. There is nothing wrong with utilizing the placebo effect, but only if the treatment is completely benign. Unfortunately, ketamine like any other drug can have potentially serious side effects. This is why before treating pain with ketamine intravenously patients must be screened for possible heart disease or psychiatric disorders such as schizophrenia. While intranasal ketamine can be given in an office setting, intravenous administration must be done under close monitoring. Another issue is the cost since insurance companies do not cover this treatment because it is considered experimental.

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Fibromyalgia is a condition comorbid with migraine, which means that migraine sufferers are more likely to have fibromyalgia and those with fibromyalgia are more likely to have migraines (such relationships are not always bidirectional). One common finding in these two conditions is low magnesium level and both condition often improve with magnesium supplementation or magnesium infusions.

A new study by Dr. T. Romano of 60 patients with fibromyalgia showed that those who have low red blood cell (RBC) magnesium levels are likely to have low levels of growth hormone (IGF-1, or insulin-like growth factor 1). RBC magnesium level is a more accurate test than the routine serum magnesium level, which is highly unreliable as most of the body’s magnesium sits inside the cells.

Dr. Romano recommends magnesium supplementation and a referral to an endocrinologist. It is possible that treatment with growth hormone will help those who are deficient, although it is also possible that magnesium supplementation alone (oral or intravenous, if oral is ineffective) could increase the production of growth hormone.

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A patient of mine just emailed me about a recent segment of the TV show, The Doctors, which featured a woman whose severe chronic migraines were cured by nasal surgery. The segment was shot a few weeks after the surgery, so it is not clear how long the relief will last in her case. The surgery involved removing a contact point, which occurs in people with a deviated septum. The septum, which consists of a cartilage in the front and bone in the back, divides the left and the right sides of the nose. If the bony septum is very deviated, which often happens from an injury, it sometimes touches the side of the nose, creating a contact point between the septum and the bony side wall of the nose.
contact point headache
Several small reports by ENT surgeons have described dramatic relief of migraine headaches with the removal of the contact point. If headaches are constant, then the constant pressure of the contact point would explain the pain. However, many of the successfully treated migraine sufferers had intermittent attacks. The theory of how a contact point could cause intermittent migraines is that if something causes swelling of the mucosa (lining) of the nasal cavity, then this swelling increases the pressure at the contact point and triggers a headache. This swelling can be caused by nasal congestion due to allergies, red wine, exercise, and possibly other typical migraine triggers.

This is a good theory, but it is only a theory and the dramatic relief seen after surgery could be all due to the placebo effect. The only way to prove that contact point headaches exist and can be relieved by surgery is by conducting a double-blind study, where half of the patients undergoes surgery and the other half does not. Giving both groups sedation and bringing them to the operating room will blind the patient while the neurologist who evaluates them will also not know who was operated on and who was not, making this a double-blind study. This design is also good only in theory because those who had surgery will have bloody nasal discharge and nasal packing, thus breaking the blind.

However, despite the fact that we will not see any double-blind studies in the near future, there is one way to predict who may respond to contact point surgery. An ENT surgeon can spray a local anesthetic, such as lidocaine, around the contact point during a migraine attack and if pain goes away, then surgery is more likely to help. I would not recommend anyone having surgery without such a test.

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Marijuana has been tried for a variety of medical conditions, including migraines, and in one of my previous post I mentioned dangers of smoking it. Medical marijuana does not have the same dangers since it is not smoked.

A study just published in the journal Pharmacotherapy involved 121 adults with migraine headaches who were treated with medical marijuana. The number of migraine headaches per month decreased from 10.4 to 4.6 with the use of medical marijuana. Most patients used more than one form of marijuana and used it daily for prevention of migraine headache. Positive results were reported by 48 patients (40%), with the most common effects being prevention of migraine headache and the second most common effect, aborted migraine attacks. Inhaled forms of marijuana were commonly used for acute migraine treatment and were reported to abort migraine headache. Side effects were reported in 14 patients (12%); the most common side effects were somnolence (2 patients) and difficulty controlling the effects of marijuana related to timing and intensity of the dose (2 patients), which were experienced only in patients using edible marijuana. Edible marijuana was also reported to cause more side effects compared with other forms. The authors concluded that the frequency of migraine headaches was decreased with medical marijuana use.

New York state just approved medical marijuana for ingestion by mouth or breathing in vapors. Medical marijuana is approved in NY for several medical conditions, including neuropathic pain, but not migraines. However, many migraine sufferers also have severe neuropathic pain over the scalp and neck. This pain is caused by irritation of the trigeminal and/or occipital nerves and manifests itself as burning or sharp and shooting sensation. To be able to prescribe medical marijuana doctors have to take a 4-hour online course. After taking this course, as I’ve discovered, it is not that simple to issue a prescription. It is done through a New York State website and requires a lot of detailed information. The patient also has to register with the State in order to be able to buy medical marijuana from the approved dispensaries. The dispensaries offer ingestible and vaporized forms of marijuana with a certain ratio of cannabidiol (CBD) and tetrahydrocannabinol (THC).

Pure cannabidiol was just shown to reduced seizures by one-third in patients with intractable epilepsy, that is epilepsy that does not respond to usual epilepsy medications. This was the largest trial of its kind conducted by a group of neurologists led by Dr. Orrin Devinsky of NYU School of Medicine. The true efficacy and safety of the drug is now being evaluated in a double-blind trial, currently under way. THC is responsible for the psychoactive effects of the drug, while CBD does not cause such effects. Pure CBD (Epidiolex) is available only for the treatment of two rare conditions of childhood. The same company also makes Sativex, which is a 50-50 mixture of THC and CBD, and is approved in Europe and Canada for treatment of spasms in multiple sclerosis.

It is possible that pure cannabidiol will also be effective for pain and migraines without causing psychotropic side effects which are caused by THC.

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There has been some backlash against meditation with newspapers publishing articles claiming that meditation is overrated. Fortunately, serious scientists continue to publish solid objective data proving that meditation not only relieves pain and headaches and makes you feel better, but in fact changes the structure of your brain. In my recent post I wrote about one such a study published in the Journal of Neuroscience.

A new rigorous scientific study was just published in Biological Psychiatry. It looked at the benefits of mindfulness meditation and how it changes people’s brains and potentially improves the overall health.

The study was conducted at the Health and Human Performance Laboratory at Carnegie Mellon University.

The researchers recruited 35 unemployed men and women who were looking for work and were under significant stress. Half of the people were taught mindfulness meditation at a residential retreat center, while the other half were provided sham mindfulness meditation, which involved relaxation and distraction from worries and stress.

All participants did stretching exercises, but the mindfulness group was asked to pay attention to bodily sensations, including unpleasant ones. The relaxation group was encouraged to talk to each other and ignore their bodily sensations.

After three days, all participants felt refreshed and better able to deal with the stress of unemployment. However, follow-up brain scans showed changes only in those who underwent mindfulness meditation. The scans showed more activity among the portions of their brains that process stress-related reactions and other areas related to focus and calm. By four months after the retreat most people stopped meditating, however the blood of those in mindfulness meditation group had much lower levels of interleukin-6, a marker of harmful inflammation, than blood of those in the relaxation group.

These changes occurred after only 3 days of meditation. It is likely that an ongoing meditation practice will produce stronger positive effects. Personally, I try to meditate 30 minutes on at least 5 days a week and this is what I recommend to my patients. Even 10 or 20 minutes can have an impact on migraine headaches and general well being.

There are several excellent resources for learning meditation. Free podcasts by a psychologist Tara Brach is an excellent resource. My favorite book to learn meditation is Mindfulness in Plain English by B. Gunaratana. And of course, there is an app for that – and

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Prilosec (omeprazole), Nexium, Prevacid, and other similar drugs in the family of proton pump inhibitors (PPIs) can cause headaches directly, but more often by reducing the absorption of vitamins such as B12 and D, and minerals such as magnesium, over a longer period of time. My previous post described a 26,000 patient study that convincingly showed that PPIs cause vitamin B12 deficiency. We also know that older women on PPIs have a higher risk of bone fractures.

A report just published in JAMA Neurology adds another dangerous association. This was also a very large study that involved over 73,000 older people, of whom almost 3,000 were taking PPIs. Those on PPIs had a significantly higher risk of developing dementia. This is possibly due to a direct toxic effect of these drugs, but more likely it is because these drugs cause vitamin and mineral deficiencies.

Three month earlier, the same journal published a study that showed that low vitamin D levels are associated with a significantly higher risk of developing dementia. A very important finding of this study was that even those who had what is considered a normal vitamin D level of between 30 and 50 had an increased risk of dementia, compared with those whose level was above 50. This is not surprising because a study of multiple sclerosis (MS) showed that those with low normal levels had many more attacks of MS than those who had high normal levels. Vitamin D seems to protect from many other diseases and to prolong life.

Many doctors will often tell you that your vitamin D level is normal if it is above 30, but you should ask what your actual level is and try to get it up to at least into 40s or 50s. The upper limit of normal is 100 (level higher than 125 can be harmful). This may require you taking 5,000 or more a day. Our government’s recommended daily requirement of 600 units is insufficient for most people. The same applies to vitamin B12 – many labs will consider a level between 200 to 1,100 to be normal, but in fact it should be at least 400.

If you take PPIs, try to get off them, which is not an easy task. Stopping such drug causes “rebound” increase in acid secretion, which makes symptoms worse than they were before PPI was started. The way to do it is to switch ot Zantac or Pepcid with antacids taken as needed. Then, you try to stop Zantac and keep taking antacids. After a while, with proper diet, you may be able to stop antacids as well.

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Treatment of medical conditions with electricity was first used by the ancient Romans who used electric eels to treat headaches, gout and in obstetrics.

Electric shock therapy for depression was one of the earliest widespread uses of electricity in medicine and it continues to be used successfully, although with some modifications to reduce side effects. Transcutaneous electric nerve stimulation (TENS) has been shown to relieve pain of neuromuscular disorders (back, muscle and joint pains) as well as headaches (see my blog post on Cefaly). While TENS uses alternating current, direct current has also been widely utilized in treating various conditions, including migraines.

Despite billions of dollars spent on research, there has been very little progress in developing more effective therapies for glioblastomas, the most common and the deadliest form of malignant brain tumor. The standard therapy for glioblastoma has consisted of surgery, radiation, and chemotherapy.
In October of last year, the FDA approved the use of the Novocure Tumor Treating Fields system for the treatment of patients with newly diagnosed glioblastoma. This device delivers alternating electric fields through scalp electrodes to the tumor, interrupting cell division. The addition of the electrical stimulation to chemotherapy increased progression-free survival to 7.1 months, compared to 4.2 months in the group who received chemotherapy alone. There was also an increase in overall survival from 16.6 to 19.4 months. Living three months longer does not seem like a lot, but chemotherapy and radiation, which cause severe side effects, are not much more effective. There is hope on the horizon, however. Several companies are developing vaccines to treat glioblastoma. In one small trial half of the patients survived for 5 years. Northwestern Therapeutics is another company with a similar promising approach in using vaccines derived from patients’ own tumor cells to treat their tumor.

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Pituitary gland which is located inside the skull and underneath the brain is responsible for secreting various hormones. Pituitary adenoma is a benign tumor of this gland and it often causes increased release of either prolactin, growth hormone, or cortisol. Very often the tumor does not release any hormones. These tumors are extremely common – a microscopic tumor is found in one out of five adults, but they cause symptoms only in a very small proportion of such people. The symptoms are related to the type of hormone that is being released or are caused by the pressure of a growing tumor on the surrounding brain structures, or both. A very small tumor can be treated with medications, while large ones often require surgery. Small tumors have traditionally not been thought to cause headaches.

A recent study showed that in a minority of patients small tumors do cause severe headaches and if these headaches do not respond to medications, surgery can provide relief. The study was done by a group of Japanese neurosurgeons who reviewed the records of 180 patients who underwent surgery for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. They found nine patients with intractable headaches as the main complaint, associated with a small, but not microscopic pituitary adenoma (average diameter of 15 mm, or 3/5 of an inch). In eight patients the tumor did not secrete any hormones and in one it secreted prolactin.

All nine patients had complete or significant relief of their headache after surgery. The surgeons measured pressure inside the enclosed space called sella, which contains the pituitary gland and discovered that the pressure was significantly higher in patients with headaches than in those without.

In conclusion, while most patients with small tumors do not need surgery, those who have severe headaches that do not respond to medications, Botox injections, and other medical treatments, could find relief from surgery.

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My most commented on blog post (over 150 comments) is on the daily use of triptans. A new report confirms the safety of long-term daily use of sumatriptan injections in cluster patients. Cluster headaches are arguably the most severe type of headaches and the name comes from the fact that they tend to occur in clusters lasting several weeks to several months. However, in some patients headaches become persistent without any remissions and then they are called chronic cluster headaches. The only FDA approved treatment for cluster headaches is injectable sumatriptan (Imitrex). Most patients have one cluster attack in 24 hours, but some have many. A report mentioned in one of my other previous blogs describes a woman (although men are more commonly affected by cluster headaches) who has been injecting sumatriptan daily on average 20 times a day for 15 years.

A recent report by Massimo Leone and Alberto Cecchini is entitled, Long-term use of daily sumatriptan injections in severe drug-resistant chronic cluster headache.

The authors investigated occurrence of serious side effects in patients with chronic cluster headaches who were using sumatriptan injections continuously at least twice daily (the official limit) for at least 2 years. They found fifty three such patients with chronic cluster headaches seen in their clinic between 2003 and 2014. During the 2-year period, all patients were carefully followed with regular visits at their center. Headaches and sumatriptan consumption were recorded in headache diaries. Patients were questioned at each visit about serious side effects and had at least two electrocardiograms. Brain MRI was normal in all patients. None of the patients had a history of stroke, TIA, ischemic heart disease, myocardial infarction, or arrhythmia, or diseases affecting systemic vessels.

In the 2-year study period, no serious side effects were observed and no patients needed to discontinue sumatriptan use. No electrocardiogram abnormalities were found. All patients needed a full dose (6 mg) of sumatriptan injection (prefilled syringes with 4 and 6 mg available). At the end of the study period, 42% noticed some reduction in the efficacy of sumatriptan injections both in terms of time of onset of effect and on pain intensity, but still considered the drug their first choice to treat the attacks.

In the study period, 36 of the 52 patients (69%) used more than 12 mg of sumatriptan in 24 hours (maximum 36 mg in 24 hours) but no increase in number or severity of side effects was observed during the course of the study. Complete loss of efficacy was not reported by any of the patients.

The authors mention that since the launch of sumatriptan injections in 1992 and until 1998, approximately 451 serious cardiac side effects have been reported to occur within 24 hours after administration of sumatriptan injections, tablets or nasal spray, but this is out of more than 236 million migraine attacks and more than 9 million patient exposures between 1992 and 1998. The majority of patients who developed serious cardiac events within 1 to 3 hours of sumatriptan administration had risk factors for coronary artery disease.

The authors concluded that their results showed that long-term daily sumatriptan use in patients free of heart disease did not cause serious side effects and this is in line with observations from previous studies.

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Sumatriptan is now available in a nasal powder form. We already have sumatriptan in a tablet, injection, nasal spray, and a skin patch. I mentioned this product over 5 years ago and finally it was just approved by the FDA. This does not mean it will be available right away as it often takes many months for the company to ramp up production. In some cases, such as with inhaled migraine drug Semprana (formerly called Levadex), it takes years before the manufacturer achieves FDA quality standards of production.

OptiNose is the company that developed Xsail Breath Powered Delivery Device which is used to deliver sumatriptan nasal powder. OptiNose licensed the product to Avanir Pharmaceuticals and they named it Onzetra. Onzetra is a fast-acting dry powder that is delivered into the nasal cavity. The patient exhales into the device, which seals the nasal cavity, and this carries the medication from the device directly into one side of the nose.

Nasal powder should be much more effective and more consistently effective than the nasal spray. The problem with the nasal spray is that the liquid tends to leak out of the nose or into the mouth, while the powder sticks to the nasal mucosa and all of it gets absorbed. And while the nasal spray contains 20 mg of sumatriptan and Onzetra only 11 mg, Onzetra should be more effective. Similarly, only 6 mg of injected sumatriptan is much more effective than 100 mg of sumatriptan in a tablet. But do we need another form of sumatriptan? Actually this may be a very good product for people who have a sudden onset of a severe migraine or those who vomit with their attacks. The injection works well for these patients, but many would rather avoid the pain of a shot. Zecuity, a new transdermal form of sumatriptan would seem to be a good choice, except for the fact that it works much slower than Onzentra.

The approval of Onzetra Xsal was based on the data from Phase 2 and 3 clinical trials, safety data from over 300 patients, and the historical data from various other formulations of sumatriptan, which have been on the market for over 20 years. One of the studies showed a significantly greater proportion of Onzetra Xsail patients reported headache relief at 30 minutes (42% vs. 27%) and at every time point up to 2 hours post-dose vs. placebo patients (68% vs. 45%).

Onzetra Xsail will be supplied as a disposable nosepiece containing a capsule and a reusable device. Each capsule contains 11 mg of sumatriptan and each kit contains 8 doses.


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Headache is usually the main presenting symptom of temporal arteritis (also known as giant cell arteritis, or GCA), which is caused by inflammation of blood vessels. This condition happens almost exclusively in the elderly. It presents with a severe headache, which is often one-sided. Some, but not all patients have swelling and tenderness of their temporal artery at the temple. This is a serious condition because it damages blood vessels and can cause strokes, loss of vision, and other complications. The diagnosis is made by blood tests (C-reactive protein, or CRP and erythrocyte sedimentation rate, or ESR) and temporal artery biopsy. However, even the biopsy sometimes does not show the inflammation. The treatment consists of steroid medications, such as prednisone. Prednisone is usually very effective. Unfortunately, prednisone needs to be taken for years if not for the rest of the person’s life and when it is used for long periods, it has many potentially dangerous side effects.

A recent study published in JAMA Neurology showed that many patients with biopsy-proven giant cell arteritis have an infection with varicella-zoster virus. This virus is also responsible for shingles and chickenpox

The researchers reviewed samples of temporal arteries for the presence of varicella-zoster virus. It was found in 68 of 93 (73%) of temporal arteries of patients with the disease, compared with 11 of 49 (22%) normals.

The authors concluded that in patients with clinically suspected GCA, prevalence of the virus in their temporal arteries is similar independent of whether biopsy results are negative or positive. They also felt that “Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined”, and that “Considering that antiviral medications such as Acyclovir are very safe, it is reasonable to give them to all patients with temporal arteritis.”

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Trigeminal neuralgia is an extremely painful condition which causes jolts of very intense electric-like pains in the face. Fortunately, many trigeminal neuralgia sufferers respond to medications or Botox injections.

Several surgical procedures have also been used to treat this condition. One of these procedures is destruction of the trigeminal ganglion. The most effective treatment involves opening the skull and placing a teflon pad between the trigeminal nerve and the blood vessel which compresses the nerve (this procedure is called microvascular decompression). This pressure on the trigeminal nerve by an artery is the cause of pain in the majority of patients. While surgery can be truly curative, it carries a risk of serious complications and should be done only if medications and Botox injections fail. Ideally, it should be performed by a surgeon who has performed hundreds of these operations.

Besides medications, Botox, and injections to destroy the trigeminal ganglion, stereotactic radiosurgery, or gamma knife, offers another alternative to brain surgery. This treatment appears to be very effective and a new study published in Neurology suggests that this procedure is more effective if it is done early. If gamma knife radiosurgery is done within a year of the onset of pain, patients remained pain free for an average of 68 months, while if it was done more than 3 years after the onset, the relief lasted only 10 months.

Although microvascular decompression is curative, two groups of patients may opt for radiosurgery. One group consists of patients who are poor surgical candidates because they have other medical conditions which may increase the risk of complications or death. Another group include those who are afraid to have open brain surgery and who prefer to have stereotactic radiosurgery.

As a side note I should mention that gamma knife, or stereotactic radiosurgery is the treatment of choice for most cases of acoustic neuroma, a benign tumor of the vestibular nerve, a nerve going from the inner ear to the brain. Open surgery almost always leads to facial paralysis and complete loss of hearing, while gamma knife can shrink the tumor without any damage to healthy tissues.

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The little white spots seen on brain MRI scans have long been thought to be benign. A nagging concern has always persisted since their meaning has remained unclear. A recent study by researchers at several medical centers across the US established that even very small brain lesions seen on MRI scans are associated with an increased risk of stroke and death.

This is a very credible study since it involved 1,900 people, who were followed for 15 years. Previous studies of these white matter lesions (WML), which are also called white matter hyperintensities (WMH) involved fewer people and lasted shorter periods of time (these are my previous 4 posts on this topic).

Migraine sufferers, especially those who have migraines with aura are more likely to have WMLs. One Chinese study showed that female migraine sufferers who were frequently taking (“overusing”) NSAIDs, such as aspirin and ibuprofen actually had fewer WMLs than women who did not overuse these medications. Even though most neurologists and headache specialists believe that NSAIDs worsen headaches and cause medication overuse headaches, this is not supported by rigorous scientific evidence (the same applies to triptan family of drugs, such as sumatriptan). Another interesting and worrying finding is that the brain lesions were often very small, less than 3 mm in diameter, which are often dismissed both by radiologists who may not report them and neurologists, even if they personally review the MRI images.

The risk of stroke and dying from a stroke in people with small lesions was three times greater compared with people with no lesions. People with both very small and larger lesions had seven to eight times higher risk of these poor outcomes.

This discovery may help warn people about the increased risk of stroke and death as early as middle age, long before they show any signs of underlying blood vessel disease. The most important question is what can be done to prevent future strokes.

An older discovery pointing to a potential way to prevent strokes is that people who have migraines with aura are more likely to have a mutation of the MTHFR gene, which leads to an elevated level of homocysteine. High levels of this amino acid is thought to damage the lining of blood vessels. This abnormality can be easily corrected with vitamin B12, folic acid and other B vitamins.

More than 800,000 strokes occur each year in the United States, according to the National Institute of Neurological Disorders and Strokes. Strokes are a leading cause of death in the country and cause more serious long-term disabilities than any other disease. Routine MRI scans should not be performed, even in migraine sufferers, but if an MRI is done and it shows these WMLs, it is important to warn the patient to take preventive measures.

There are several known ways to prevent or reduce the risk of strokes. These include controlling weight, hypertension, cholesterol, diabetes, reducing excessive alcohol intake, stopping smoking, and engaging in regular aerobic exercise.

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Asthma is more common in migraine sufferers and migraine is more common in those who suffer from asthma (the medical term is co-morbid conditions). A new study published in Headache examines a possible connection between asthma and chronic migraine. Migraine is considered chronic if headache occurs on 15 or more days each month.

This co-morbidity between migraine and asthma is thought to be due to the fact that both conditions involve inflammation, disturbance of the autonomic nervous system, and possibly shared genetic and environmental factors. What is not mentioned in the report is the fact that intravenous magnesium can relieve both an acute migraine (in up to 50% of migraine sufferers who are deficient in magnesium) and a severe asthma attack. This suggests another possible explanation for the co-morbidity. Magnesium deficiency may also explain, at least in part, co-morbidity between migraine and fibromyalgia and vascular disorders.

The Headache report was one of many based on the outcomes of the large and long-term American Migraine Prevalence and Prevention study (AMPP). Study participants had to meet criteria for episodic migraine in 2008, complete an asthma questionnaire in 2008, and provide follow-up information in 2009. The researchers counted the number of these patients who developed chronic migraine a year later. The sample for this study included 4446 individuals with episodic migraine in 2008 of whom 17% had asthma. The mean age was 50 and 81% were female. In 2009, of the patients who had episodic migraines and asthma, 5.4% developed chronic migraine, compared to only 2.5% of those without asthma. So, having asthma doubles the risk of episodic migraine becoming chronic within a year. There was also a correlation between the severity of asthma and the risk of developing chronic migraine.

What we don’t know is whether aggressive treatment of asthma and migraines will reduce the risk of chronification of migraines. It is also possible that simple magnesium supplementation may have a protective effect.

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A hole between the left and the right side of the heart has been suspected to be the cause of migraines in some people. However, closing this hole has not produced dramatic improvement in several blinded studies that have been conducted in the past few years.

The hole, called atrial septal defect (ASD) is present in utero but begins to close as soon as the baby is born. In about 1.5% of the population (in twice as many women than men) the hole does not close completely. In most people this hole is small and does not cause any symptoms. However, if it is big, it requires intervention because it can lead to heart failure and strokes. Smaller ASD may not cause any symptoms, but has been suspected to be related to migraine headaches, especially migraines preceded by a visual aura.

The closure of ASD is done by threading up through a vein in the groin an umbrella-like device which is positioned and opened inside the heart to close the hole. A recent study looked at the need for different blood thinners to prevent blood clots from forming in the heart after the procedure. Half of the 171 migraine patients in the study were given aspirin and placebo and the other half aspirin and clopidogrel, another blood thinner. Interestingly, those who were given two blood thinners (aspirin and clopidogrel) had less severe migraine attacks than those on one (aspirin and placebo). This suggests, that the benefit seen in some of the previous ASD closure studies was due to the blood thinner rather than the procedure itself.

A trial currently under way at the Columbia University Medical Center is examining whether a different blood thinner, Brilinta will improve migraines in those with an ASD. If you’d like to consider participating and want to learn more about the study, go to this website.

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Magnesium deficiency is a regular topic on this blog. Up to half of migraine sufferers are deficient in magnesium, but magnesium levels are rarely checked by doctors. Even when magnesium level is checked, it is usually the serum level, which is totally unreliable. The more accurate test is RBC magnesium or red blood cell magnesium because 98% of body’s magnesium resides inside cells or in bones. At the New York Headache Center we often don’t bother checking even the RBC magnesium level, especially if other signs of magnesium deficiency besides migraines are present. These include coldness of hands and feet or just always feeling cold, leg muscle cramps, palpitations, anxiety, brain fog, and in women, premenstrual syndrome or PMS (bloating, breast tenderness, irritability). For these patients we recommend daily magnesium supplementation and sometimes monthly magnesium infusions.

About 20 to 30 million women suffer from moderate or severe PMS, and a recent study published in the American Journal of Epidemiology indicates that having PMS increases the risk for hypertension (high blood pressure) later in life.

This study was done at the University of Massachusetts, Amherst and it involved 1,260 women who suffered from moderate or severe PMS as well as more than 2,400 women with mild or no PMS. Women with moderate or severe PMS were 40 percent more likely to develop high blood pressure than those with mild or no PMS symptoms. The researchers adjusted the risk for other risk for hypertension, such as being overweight, smoking, drinking, inactivity, use of birth control pills, postmenopausal hormone use, and family history of high blood pressure.

The association between moderate or severe PMS and high blood pressure was most pronounced among women younger than 40, who were three times more likely to develop hypertension.

Interestingly, the risk of high blood pressure was not increased in women with moderate or severe PMS who were taking thiamine (vitamin B1) and riboflavin (vitamin B2). Other researchers found that women who consumed high levels of those vitamins were 25 to 35 percent less likely to develop PMS.

Unfortunately, the researchers did not look at magnesium levels or magnesium consumption in these women. A strong association exists between magnesium deficiency and high blood pressure. There is also an association between an increased magnesium (and potassium) intake and reduced risk of strokes. Supplementation with magnesium during pregnancy decreases the risk of hypertension during pregnancy. There is also a strong association between magnesium and depression.

There are literally hundreds of scientific articles on beneficial effects of magnesium, but unfortunately magnesium remains ignored by mainstream physicians. However, consumers are ahead of most doctors and many do take magnesium supplements. This is helped by many print and online articles and many books. Some of these books include Magnificent Magnesium, Magnesium Miracle, Magnesium – The Miraculous Mineral of Calm, and my two books – The Headache Alternative: A Neurologist’s Guide to Drug-Free Relief and What Your Doctor May Not Tell You About Migraines.

Migralex is a product I patented and developed for the treatment of headaches. It contains an extra-strength dose of aspirin and magnesium. Magnesium in Migralex acts as a buffering agent and reduces the risk of stomach irritation by aspirin. Migralex is available at CVS stores,, and

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Meditation is growing in popularity and deservedly so. Several of my previous posts mentioned the benefit of meditation in migraine headaches. Scientists are conducting rigorous studies that repeatedly show the profound effect meditation has on the brain. The most recent study was done at the Wake Forest Baptist Medical Center and it compared the effect of meditation and placebo on pain.

The study was published in the recent issue of the Journal of Neuroscience. It showed that mindfulness meditation not only provided greater pain relief than placebo, but the brain scans could differentiate patterns of brain activity during meditation from that induced by placebo.

The study involved seventy five healthy, pain-free volunteers who were randomly assigned to one of four groups: mindfulness meditation, placebo meditation (“sham” meditation), placebo analgesic cream or control.

Pain was induced by heat applied to the skin. The mindfulness meditation group reported that pain intensity was reduced by 27 percent and the emotional aspect of pain (how unpleasant it was) by 44 percent. In contrast, the placebo cream reduced the sensation of pain by 11 percent and emotional aspect of pain by 13 percent.

Mindfulness meditation reduced pain by activating brain regions associated with the self-control of pain while the placebo cream lowered pain by reducing brain activity in pain-processing areas.

Another brain region, the thalamus, was deactivated during mindfulness meditation, but was activated during all other conditions. This brain region serves as a gateway that determines if sensory information is allowed to reach higher brain centers. By deactivating this area, mindfulness meditation may have caused signals about pain to simply fade away, said Dr. Zeidan, one of the researchers.

Mindfulness meditation also was significantly better at reducing pain intensity and pain unpleasantness than the placebo meditation. The placebo-meditation group had relatively small decreases in pain intensity (9 percent) and pain unpleasantness (24 percent). The study findings suggest that placebo meditation may have reduced pain through a relaxation effect that was associated with slower breathing.

This study is the first to show that mindfulness meditation does not relieve pain the way placebo does. This study confirms previous observations that as little as four 20-minute daily sessions of mindfulness meditation could enhance pain treatment. Another study has shown that an 8-week course of mindfulness meditation not only relieved pain but also made certain parts of the brain cortex measurably thicker.

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Inpatient migraine headache treatment in the US is usually limited to a five-day course of intravenous DHE and other medications. Even such brief admissions are not always approved by the insurance companies. Many patients improve after these admissions, but often only for a short time because besides some reduction in pain intensity, very little else changes in the patient’s life and her brain. It makes sense that longer-term inpatient rehabilitation of chronic migraine and pain patients can lead to a major and lasting improvement, but it is almost unheard of in the US. However, it is available in Germany and other countries.

Last November I lectured at one of the leading German inpatient rehabilitation facilities, the Berolina Klinik. My blog post about the Klinik was read by an Englishman with severe chronic migraines who was recently treated there with a three-week program with excellent results. Here is one of the articles that appeared in German press – Westfalen-Blatt 27.10.15.

And, shockingly to us Americans, the cost of treatment is less than $7,000 for a three-week stay in this top facility. Even with travel costs, it’s a bargain. I have been mentioning Berolina Klinik to my patients, although haven’t had anyone make the trip yet.

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23andMe offers direct-to-consumer genetic testing by analyzing a saliva sample. It provides information on predisposition for more than 90 traits and conditions ranging from acne to Alzheimer’s. Health-related results were suspended by the FDA because of the concern was that consumers may not be able to correctly interpret the health data, particularly regarding conditions such as Alzheimer’s Parkinson’s, various cancers, and other. What is available is genealogical data and information on several conditions which did receive FDA approval. As of June 2015, 23andMe has genotyped over 1,000,000 individuals.

After submitting a saliva sample, consumers are asked to complete a number of surveys about their medical conditions, including migraines, personal habits, and other information. This has led to some important discoveries, which have been published in scientific journals. Here are some results related to migraines.

23andme discovered three genes which make migraines more likely. This discovery is not as important as it seems because these genes increase the risk of migraines by a very small amount and because dozens of other migraine susceptibility genes are being continuously identified.

In 2012 23andme acquired CureTogether, a “health research project that brings patients and researchers together to find cures for chronic conditions”, where some of the following information comes from.

Here is interesting, but also not very surprising information on most commonly reported migraine triggers:

stress (85%)
insufficient sleep (72%)
dehydration (64%)
looking at bright sunlight (61%)
inhaling smoke/strong odors (57%)
staring at a computer screen (56%)
flashing or flickering lights (56%)
weather changes (50%)
low blood sugar (49%)
loud environments (48%)
heat (47%)
caffeine withdrawal (43%)
alcoholic beverages (42%)
large groups of people (28%)
bananas (6%)

More than 65% of migraine sufferers have tried acetaminophen (Tylenol®), but it doesn’t work very well for most people. Over 20% of people have tried an alcoholic beverage, even though it typically makes migraines much worse. In contrast, less than 20% of people have tried wrapping a cold towel around their head, and yet it is one of the more effective treatments listed by migraine sufferers on CureTogether.

Treatments rated as most effective for patients with migraine
1. Dark, quiet room
2. Sleep
3. Eliminate red wine
4. Passage of time
5. Eliminate MSG
6. Avoid smoke
7. Wear sunglasses
8. Intravenous DHE
9. Imitrex injection
10. Ice packs

According to 23andme, “When symptom data and treatment data come together, powerful things happen. Data from nearly 3,500 CureTogether members tell us that those who experience vertigo or dizziness with their migraines are three times more likely (18% vs 6%) to have a negative reaction to Imitrex®, a sumatriptan medication that is often prescribed for migraine sufferers”.

A word of caution about 23andme. I personally submitted my saliva for testing and completed many questionnaires to help with their research. However, some feel that 23andme’s promises of not sharing personal genetic information with anyone else could be undermined in the future, as it happened with Google. Here is an interesting blog post from the Scientific American on this topic entitled, 23andMe Is Terrifying, but Not for the Reasons the FDA Thinks

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Magnesium infusion given before or during surgery reduces the amount of opioid analgesics (narcotics) needed in the 24 hours following surgery. Doctors at the Saint Barnabas Medical Center in Livingston, NJ reviewed 14 of the most rigorous clinical trials which involved 910 patients. Half of those patients were given intravenous magnesium and the other half, placebo. During the first day after surgery there was a significant reduction in the need for morphine by those receiving magnesium compared with placebo.

Another study published in 2013 reviewed 20 clinical trials of magnesium for post-operative pain. These trials included 1,257 patients. This review also concluded that magnesium improved pain and reduced the need for narcotic pain killers.

Prescription narcotics are frequently in the news because of the epidemic of prescription drug abuse. However, the advantages of not using as much of these drugs after surgery are far greater than just a reduction of the risk of addiction. These drugs cause constipation, which is a problem after surgery even without opioid drugs, and it makes recovery more difficult. They can also cause confusion, difficulty breathing, and other side effects.

There are many possible explanations for the pain-relieving effects of magnesium. We know that it regulates the function of several receptors involved in pain, including serotonin and NMDA. It also relaxes muscles, opens constricted blood vessels, and reduces excitability of the brain and the entire nervous system. Both mental and physical stress depletes magnesium and they are very much present with surgery.

Magnesium is a natural pain blocker, which is effective for many patients with migraine and cluster headaches, as well as those with fibromyalgia, back pain, neuropathy, and other types of pain. Here is a recent blog post on magnesium and migraines.

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Sphenopalatine ganglion (SPG) block has been used for the treatment of headaches and other pain conditions for over 100 years. The original method involved placing a long Q-tip-like cotton swab dipped in cocaine through the nose and against the SPG.

SPG is the largest collection of nerve cells outside the brain and it sits in a bony cavity behind the nasal passages. These nerve cells are closely associated with the trigeminal nerve and include sensory nerves, which supply feeling to parts of the head and autonomic nerves, which regulate the function of internal organs, blood vessels, as well as tearing and nasal congestion. Considering that these nerve cells produce such a wide range of effects, it is logical to expect that blocking these nerves might help headaches.

For obvious reasons we no longer apply cocaine, but instead use numbing medicines, such as lidocaine or bupivacaine. A small study suggested that just putting lidocaine drops into the nose can relieve an acute migraine. I’ve prescribed lidocaine drops to some patients with cluster headaches and a small number reported relief. The problem with nasal drops is that we are not sure if lidocaine actually reaches all the way back to numb the SPG even if they are lying down with the head hanging back over the edge of the bed. Using long Q-tips is uncomfortable and in many patients the Q-tip may also not reach the SPG.

To solve the problem, two doctors developed thin intranasal catheters that appear to consistently reach the area of SPG. Dr. Tian Xia’s Tx360 device seems to be more comfortable for patients because his is a thinner and a more flexible catheter. The recommended local anesthetic is bupivacaine (Marcaine), which lasts longer than lidocaine. A small double-blind study of SPG block using Tx360 in chronic migraine patients showed it to be effective. The active group had a reduction of the Headache Impact Test (HIT-6) score, while the placebo group did not. In this study patients were given the SPG block twice a week for 6 weeks. We need larger and longer-term studies in chronic migraine patients before advising such frequent regimen, not in the least because of cost.

SPG block seems to be more appropriate (and this is what we use it for at the NYHC) for patients with an acute migraine that does not respond to oral or injected medications and for those with cluster headaches. Since cluster headaches usually last for a few weeks to a couple of months (unless it is a patient with chronic cluster headaches), it is practical to try SPG blocks on a weekly basis. Theoretically, because there is so much autonomic nervous system involvement in cluster headaches (tearing, nasal congestion, and other), SPG should be particularly effective for cluster headaches.

Another way to affect the SPG is by stimulating it with electrical current, which seems to be effective for chronic cluster headache patients, according to a small study. This method requires surgical implantation of a device into the area of the SPG. See my previous post on this.

Below is an illustration of the SPG and the Tx360 device.

Sphenopalatine ganglion block with  Tx360 device

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Since my early 20s I’ve been getting visual auras without a headache several times a year. I still get them in my late 50’s and they still occur without a headache. In my 40s I started to have migraine headaches without an aura. My migraines are always left-sided and if I don’t treat them, I will develop sensitivity to light and nausea. Luckily, my migraines are not at all disabling because they remain mild for hours, so I have plenty of time to take 100 mg of sumatriptan, which works very well. The tablet works within one to two hours. When I want to have faster relief, I take a 6 mg sumatriptan injection. This usually happens at night when I want to go to sleep and I don’t want to wait for the pill to start working. I can’t fall asleep with a migraine, while for some, sleeps actually relieves the attack.

I am not happy about having migraines, but they do not interfere with my life and give me a better understanding of what my patients are going through. Also, I try to subject myself to treatments I offer my patients. I do not need to take a daily preventive medicine, such as topiramate or propranolol or Botox injections. However, since Botox is very safe, I did inject myself with Botox once to see what it feels like. It was not very painful, but obviously everyone has a different pain threshold (here are video 1 and video 2 of me injecting patients with Botox). I also gave myself an intravenous infusion of magnesium, which did make me feel warm, but had no beneficial effects since I am not one of the 50% of migraine sufferers who are deficient in magnesium.

The next thing I decided to try is a nerve block. Nerve blocks are injections of a local anesthetic, such as lidocaine or bupivicaine to numb the nerves around the scalp (here is a previous blog on nerve blocks). It is somewhat surprising that numbing a superficial nerve under the skin stops a migraine, which we know to originate in the brain. For the same reason a lot of scepticism greeted me at medical meetings over 20 years ago when I gave lectures on Botox for migraines. Now we know that although the migraine process begins in the brain, peripheral nerves send messages back to the brain closing a vicious cycle of brain activating the nerves and nerves feeding back pain messages into the brain. Disrupting this circuit with a peripheral nerve block for short-term relief and with Botox for long-term prevention seems to be very effective. Nerve blocks can be effective when drugs are not or when drugs are contraindicated because of an illness or pregnancy.

Sometimes, blocking the occipital nerve at the back of the head works well, but other patients need nerves blocked in their temples or forehead. Since my migraines are always localized to the left temple, I decided to give myself a block of the temporal branch of the left trigeminal nerve. The nerve block helped one of two times I tried it. Obviously, I do not recommend DIY nerve blocks or teach patients how to do it, but I did encounter one patient who learned how to give himself an occipital nerve block before coming to see me. There might be some exceptions, such as for people living in remote areas and who do not respond to any other treatments, or in not such distant future, for those traveling to Mars.

The next treatment I will try is a sphenopalatine ganglion block. I will describe this treatment in my next post.

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Acupuncture and Alexander technique appear to be equally effective and significantly more effective for the treatment of chronic neck pain than routine care, according to a study by British researchers published in the latest issue of the Annals of Internal Medicine.

The doctors divided 517 patients who suffered from neck pain for at least 6 years into three groups. The first group received an average of 10 50-minute acupuncture treatments, the second had an average of 14 30-minute Alexander technique lessons, and the third group received the usual care. The authors found that acupuncture and Alexander technique both led to a significant reduction in neck pain and associated disability compared with usual care at 12 months.

One possible explanation of such good efficacy beyond the direct effect of the treatments was that patients in the active treatment groups had improved self-efficacy. Self-efficacy is the belief that one’s actions are responsible for successful outcomes and it was measured by a standardized questionnaire.

It is possible that other forms of therapy that enhance self-efficacy, such as tai chi, meditation, and other can also improve long-standing neck pain, as well as headaches. There are many acupuncture studies that show a significant benefit for migraine headaches (here is one described in a previous post), however unlike this neck pain study most of them did not follow patients for such a long period of time. Alexander technique has been also helpful for some of my patients, but again, good studies are lacking.

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Richard Wenzel PharmD of the Diamond Headache Clinic in the latest issue of the leading medical journal, Headache writes about the shocking fact that this country’s pharmaceutical industry cannot reliably supply medications for patients. He also talks about a connected, also undeniable development: “generic drugs currently push the boundaries of affordability”.

Drug shortages involve easily replaceable drugs, but also many life-saving cancer medications. Headache sufferers have not been spared, especially those with severe illness requiring injectable products; droperidol has been unavailable since 2013, various haloperidol and magnesium products are currently on backorder, and the availability of ketorolac, diphenhydramine, and valproic acid has recently been sporadic.

Dr. Wenzel writes that as of July, 2015, the American Society of Health Systems Pharmacists (ASHP) cited 265 active drug shortages. There’s also a “drugs no longer available” list of 57 medications unlikely to ever be commercially manufactured again, including ergotamine.

In the past two years, injections of dihydroergotamine, an irreplaceable migraine drug developed in 1940s, had been unavailable for two periods of lasting several months. The cost of this generic drug skyrocketed from 10 to up to $130 for a single dose.

Scarcities of raw materials, disruptions to manufacturing plants (eg, hurricane damage), insufficient FDA staff to provide prompt approval for production facilities, industry consolidation, and decisions to stop producing a marginally profitable or unprofitable product have all been cited as shortage reasons.

According to the Healthcare Supply Chain Association the costs of 10 drugs widely prescribed among the general public have jumped up to 8000% in as little as one year (2013–2014). For example, a single tablet of an antibiotic doxycycline went from $0.04 to over $3.60 and the new cost of Isuprel, a heart medication went from $180 to $2700 for a single ampule.

The medical community has been trying to address the problem of shortages and high costs through various organizations and the congress, but to no avail. Actually, the government is to blame in some cases. Besides the FDA staff shortages, low payments by the government (and insurers) that do not cover the cost of production is another common reason. When all pharmaceutical companies stop manufacturing a non-profitable or money-losing drug, one company jumps back in and because it is the only one making this medicine, they can charge exorbitant amounts for a generic drug.

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Solar activity is high again – NASA’s Solar Dynamics Observatory reported a flare on October 1. And in the past two weeks we’ve been seeing many more patients whose cluster headaches returned. The last time we had a surge in the number of cluster patients was last October, when solar activity was also high (see this post).

Unfortunately, there is not a lot we can do about the solar activity, but we do have many treatment options for cluster headaches. These include intravenous magnesium (40% of cluster headache sufferers are deficient), occipital nerve blocks, steroids, daily prevention with verapamil, Botox injections, oxygen inhallation, nasal spray of zolmitriptan (Zomig NS), and sumatriptan (Imitrex) injections. For most cluster patients one more often several of these treatments provide good relief. If these are ineffective, we also use drugs such as lithium, topiramate, and even an herbal supplement, Boswellia.

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A report describing delivery of magnesium through the skin for the treatment of fibromyalgia has just appeared in the Journal of Integrative Medicine. The title of the report is, Effects of transdermal magnesium chloride on quality of life for patients with fibromyalgia: a feasibility study. It was conducted by doctors at the Mayo Clinic, which carries a certain amount of legitimacy. However, close reading of this report shows shockingly poor quality of this study.

It is true that magnesium deficiency has been found in patients with fibromyalgia (especially if levels other than serum or plasma are measured, i.e. ionized or RBC) Fibromyalgia is a syndrome of unknown cause, which is characterized by chronic pain, fatigue, depression, and sleep disturbances. Some studies have found that the lower the level of magnesium, the more symptoms patients were having. There is an association between fibromyalgia and migraine headaches and those of our patients who have both conditions often report relief of both migraines and fibromyalgia with oral magnesium supplementation or intravenous infusions.

Several companies promote products that promise to deliver magnesium into the body through the skin. The oldest one is Epsom salts, which is magnesium sulfate. Taking a warm bath with Epsom salts surely feels relaxing, but there is no evidence that magnesium penetrates through the skin.

The Mayo clinic study enrolled forty postmenopausal female patients with the diagnosis of fibromyalgia. Each was given a spray bottle containing a 31% solution of magnesium chloride (and “a proprietary blend of trace elements”) and asked to apply 4 sprays per limb twice daily for 4 weeks. They were also asked to complete various questionnaires. Only twenty-four patients completed the study, with 4 dropping out because of skin irritation. At week 2 and week 4 most were significantly improved.
The authors concluded that their study “suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia”. This was a very small and unblinded study with many dropouts, which means that no conclusions can be made. It is very surprising why the authors did not measure magnesium levels before and after the treatment, which would make the study much more valuable.

The company that sponsored the study has a product they’d like to sell to the unsuspecting public and it will certainly use this “study” and the Mayo Clinic name to sell their miracle spray. The Mayo Clinic is a highly respected institution and I hope they will not allow its name to be associated with such poor quality marketing studies.

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Zecuity, a skin patch containing a migraine drug sumatriptan was approved by the FDA almost two years ago, but it became available (by prescription) only last month (see my previous post about Zecuity). The product is not available in retail pharmacies, only from a specialty pharmacy. The doctor who prescribes the patch will usually provide information on where to get it. Otherwise, go to, where you can find a section entitled Migraine Support Solutions. At this site you can verify that your insurance covers this product, get it shipped to you, and then get information on how to apply the patch. A discount coupon is also available on the site and it promises that the copay will be as low as $15. That is a good thing, because it looks like (on each patch costs $300. Yes, not $30, but $300 a piece, or $1,200 for a box of 4. I don’t think too many people will be buying this patch if their insurance does not cover it.

So, who is the best candidate for Zecuity? Half of migraine sufferers experience nausea and/or vomiting with their attacks. This makes the absorption of oral drugs, such as triptans (Imitrex, Maxalt, Zomig, etc) so slow as to make them ineffective. In such patients we try to bypass the stomach, which until now was possible to do with a nasal spray, suppository, or an injection. Sumatriptan (Imitrex) is available in the US in tablets, nasal spray and self-administered injections. Nasal spray of sumatriptan is not very effective, but injections work better than tablets. Relief from an injection can occur in as quickly as 10 minutes, but injections can cause more side effects, which are mostly unpleasant rather than dangerous. Obviously, most people would rather not get a shot. One form of injectable sumatriptan delivers the medicine through the skin without a needle (Sumavel), but not without pain see this post.

One other triptan, zolmitriptan (Zomig) is available in a nasal spray and it is more effective than sumatriptan nasal spray, but it is not available in a generic form, making it less accessible because of the high cost and restricted insurance coverage.

The perfect patient for Zecuity is someone who experiences nausea and/or vomiting with their migraine attacks and who does not respond to tablets and has side effects from or aversion to injections. Zecuity provides good relief for such patients with the main side effect being skin irritation from the patch. The patch is fairly large, the size of a palm. It uses a miniature battery to generate an electric current, which helps drive the medicine through the skin. Iontopheresis is the name of this process. Iontopheresis has been known for decades, but Zecuity is the first product approved by the FDA to utilize this technology.

Disclosure – Teva Pharmaceuticals, manufacturer of Zecuity pays me to give lectures about Zecuity to doctors.

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Epilepsy and migraines share many features and those with epilepsy have a higher risk of developing migraines, while those with migraines are more likely to develop epilepsy. Anti-epilepsy drugs are commonly used for the preventive treatment of migraines.

A study just published in Neurology by Hong Kong researchers investigated the effectiveness of mindfulness-based therapy and social support in patients with drug-resistant epilepsy.

It was a blinded and randomized trial. Sixty patients with drug-resistant epilepsy were randomly allocated to mindfulness therapy or social support (30 per group). Each group received 4 biweekly intervention sessions. They measured quality of life, as well as seizure frequency, mood symptoms, and neurocognitive functions.

Following intervention, both the mindfulness and social support groups had an improved quality of life, but significantly more patients in the mindfulness group had a clinically important improvement. Significantly greater reduction in depressive and anxiety symptoms, seizure frequency, and improvement in delayed memory was observed in the mindfulness group compared with the social support group.

The authors concluded that even short-term mindfulness therapy in patients with drug-resistant epilepsy provides significant benefits.

It is surprising that even seizure frequency was reduced, although stress and lack of sleep can definitely increase seizure frequency. The study did not evaluate the quality or duration of sleep, but mindfulness meditation is know to improve sleep. It also improves migraine headaches (see my previous post).

To start meditating you can download a very popular app, Headspace or read a book by BH Gunaratana, Mindfulness in Plain English or download free podcasts at

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About 12% of the population suffers from migraines. In addition to high rates of migraine-related disability, migraineurs are at a higher risk than the general population of additional disability related to depression, anxiety, irritable bowel syndrome, fibromyalgia, and other conditions.

Fibromyalgia is a disorder of the central nervous system with increased brain excitability. It often manifests itself not only with muscle pains, but also fatigue, memory problems, and sleep and mood disturbances. Various studies estimate that anywhere from 2% to 8% of the general adult population suffers from fibromyalgia. Just like with migraine, women are more often affected than men. The likelihood of coexisting fibromyalgia increases with increasing frequency and severity of migraine attacks.

Both migraine and fibromyalgia have been individually linked with increased risk of suicide. However, it is not clear that the risk is more than additive.

A study just published in Neurology, reports that patients with migraine and coexisting fibromyalgia have a higher risk of suicidal ideation and suicide attempts compared with migraine patients without fibromyalgia.

The study looked at 1,318 patients who attended a headache clinic. Of these patients, 133 or 10% were found to also have fibromyalgia. Patients with both conditions had more frequent, more severe, and longer-lasting migraine attacks as well as higher use of abortive medications.

Compared with migraine patients who did not have fibromyalgia, those with fibromyalgia were more likely to report suicidal ideation (58% vs 24%) and suicide attempts (18% vs 6%).

This report suggests that migraine and fibromyalgia may magnify the risk of suicide compared with the risk of the individual conditions. However, because this data comes from a specialty headache clinic, many patients were severely affected by their migraines, with more than 35% having chronic migraine. It is likely that the results would be less dramatic among migraine sufferers in the general population. Almost half of the estimated 35 million migraine sufferers in the US do not consult a physician. Most of them suffer from milder migraines than those who do consult a doctor.

This study suggests that patients with migraine should be evaluated for other chronic pain conditions and for their mental health well-being. In particular, patients with chronic migraine should be screened for other painful conditions and mental illness. And patients with fibromyalgia should also be evaluated for migraine and potential suicide ideation. Patients often do not appear depressed, but simple questions can detect depression, which can lead to effective treatment. Our initial evaluation at the New York Headache Center includes two questions which are highly indicative of depression: 1. Have you been bothered a lot in the last month by feeling sad, down, or depressed? 2. Have you been bothered a lot in the last month by a loss of interest or pleasure in your daily activities?

Antidepressants have been proven to be effective for the prevention of migraines even in the absence of depression and are the best choice for people suffering from both conditions. Prozac, Lexapro and other SSRI antidepressants do not help migraines or pain, but SNRIs such as Effexor, Cymbalta, and Savella or tricyclics such as Elavil, Pamelor, and Vivactil do relieve pain and depression.

Magnesium deficiency is common in both migraines and fibromyalgia and we recommend an oral supplement to all patients. Some patients do not absorb magnesium and respond very well to monthly intravenous infusions of magnesium. Both their migraines improve as do fibromyalgia symptoms.

One interesting difference between migraines and fibromyalgia is the response to Botox. Botox is proven to be highly effective for the prevention of migraines and it works very well to relax spastic muscles. However, Botox appears to be ineffective for the treatment of muscle spasm in fibromyalgia. It is possibly explained by the fact that Botox interferes with the function of acetylcholine, a neurotransmitter involved in contracting healthy muscles. In fibromyalgia, studies suggests a deficit in acetylcholine, so further blocking it would be ineffective or even make the muscle pain worse (which I’ve seen in a few patients).

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Narcotic (opioid) drugs are still widely prescribed by doctors in offices and emergency rooms. They are not only potentially addictive, but also are not effective for the treatment of migraine headaches. The guidelines of the American Academy of Neurology call for avoidance of opioids for migraine and headache.

Doctors at the Cleveland Clinic developed a detailed, step-by-step algorithm that has dramatically reduced the use of narcotics for migraine management in the emergency room and prescribing of them upon discharge.

In the three months before the algorithm was implemented 66% of migraine patients had received narcotics in the ER and 44% had discharge prescriptions for these medications. After algorithm implementation, the rates were 19% and 5%, respectively.

The results of this study were presented at the 2015 annual meeting of the American Headache Society.

The first step of the algorithm involves using a three-question screener for diagnosing migraine. The questions elicited the presence of nausea, sensitivity to light and inability to function normally. If two of these three symptoms were present, migraine diagnosis was made, provided no other serious condition was causing the headache. Doctors then evaluated for potential drug-seeking behavior and repeated ER visits without appropriate follow-up with the patient’s primary care provider.

The first step was intravenous or intramuscular injection of a nonsteroidal anti-inflammatory pain medicine ketorolac (Toradol) plus a nausea drug, metoclopramide (Reglan) plus an anti-histamine, diphenhydramine (Benadryl). If the patient did not experience at least 50% pain relief, step 2 was a steroid medication, dexamethasone (Decadron) plus valproate sodium (Depacon) plus magnesium sulfate. Step 3 used in patients who didn’t experience at least 50% pain relief was a subcutaneous injection of sumatriptan, which was repeated in one hour if the headache did not resolve. If the patient failed sumatriptan in the past, dihydroergotamine (DHE-45) was given with a nausea drug prochlorperazine (Compazine), metoclopramide (Reglan) or ondansetron (Zofran).

If patients do not respond to the third step, they are considered for hospital admission and admission did increase from 8% to 25%.

It is a very good algorithm and if you suffer from severe migraines that at times land you in an ER, I would keep this list of injectable drugs, so that you can ask for them. However, I would ask for intravenous magnesium to be given first since it has a 50% chance of helping without side effects, which can occur with every other drug. I would also use sumatriptan after magnesium since it is very effective and is the only migraine-specific drug available in an injection. Studies suggest that diphenhydramine (Benadryl) and valproex sodium (Depacon) are not very effective, so I would avoid those if you have a choice.

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MRI scans of migraine sufferers are almost always normal. Occasionally we see white spots on the MRI, which can be also found in people with high blood pressure, dementia, and sometimes in perfectly healthy people (see my previous post on this).

However, Mayo Clinic neurologists, led by Dr. Todd Schwedt reported being able to diagnose chronic migraines on the MRI scan. The accuracy of the diagnosis of those who had 15 or more headache days each month was fairly high – 84%. Patients with this frequency of attacks are considered to be suffering from chronic migraines. However, they could diagnose only 67% of those with episodic migraines (less than 15 headache days each month). The researchers used sophisticated software (FreeSurfer) that measured the surface area, thickness, and volume of 68 various brain regions and discovered that changes in 6 of these regions were predictive of migraine diagnosis. These 6 regions participate in pain processing in the brain and include the temporal lobe, superior temporal lobe, anterior cingulate cortex, entorhinal cortex, medial orbital frontal gyrus, and the pars triangularis. The software used in the study is freely available, but using it is time consuming and it is utilized only by researchers and not by any hospital or private MRI facilities.

Their findings confirmed what until now was an arbitrary decision by headache experts to divide migraines into episodic and chronic ones with a 15 day cutoff. Ahother study by Dr. Richard Lipton and his colleagues at the Montefiore headache clinic has found that those who have 10 or more headache days each month have many similar features compared to those who have less than 10.

This is not a purely academic question. Insurance companies will pay for Botox only if a patient has 15 or more headache days each month because this type of patients was used in clinical trials of Botox. However in practice we also see very good response to Botox in patients who have fewer than 15 days.

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Propranolol was first introduced as a blood pressure drug 50 years ago and about 40 years ago it was discovered to be effective for the prevention of migraines. This is quite a remarkable drug because it is also used for rapid heart beat, heart attacks, tremor, and performance anxiety. Public speakers, musicians, and others take a small dose before performances and the drug reduces the physical stress responses such as sweating, tremulousness, weakness, and other. Blinded studies showed that musicians perform better when given a beta blocker compared to musicians who are given a placebo pill.

Since the introduction of propranolol, another two dozen beta blockers have been developed. The newer, so called selective beta blockers (they attach to only one type of stress receptor) tend to have fewer side effects than propranolol and other non-selective beta blockers. Selective beta blockers can be given to patients with well-controlled asthma, while non-selective ones can cause an asthma attack.

Recent studies have shown that chronic stress promotes the growth and spread of cancers. Researchers at MD Anderson Cancer Center decided to review the records of 1,425 patients who were treated for ovarian cancer at four hospitals between 2000 and 2010. Of these, 268 had been treated with a beta blocker while receiving chemotherapy for their ovarian cancer. The average survival of those who were on a beta blocker was 48 months compared to 42 months for those who were not. A more dramatic difference was found between those who were taking a non-selective beta blocker (propranolol in almost all cases): they lived 95 months – twice as long as women not on a beta blocker.

Considering these findings, if I decide to prescribe a beta blocker, I may start prescribing propranolol as the first-line drug for the prevention of migraines. And only if the patient has side effects, will I switch them to a selective beta blocker, such as atenolol or nebivolol (Bystolic). Common side effects of beta blockers are fatigue and dizziness from a drop in blood pressure and difficulty exercising because the heart rate cannot increase high enough to provide for the increase in demand for oxygen. Because regular aerobic exercise is my first recommendation for the prevention of migraines, I tend to reserve beta blockers for patients whose blood pressure is high or at the high end of normal range, whose pulse is fast, and for those who fail other preventive drugs and Botox (however, most insurers approve Botox for chronic migraines only if the patient fails 2 or 3 preventive drugs, including a beta blocker).

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New onset of headaches is always worrisome, but even more so in a pregnant woman. Neurologists at the Montefiore Headache clinic in the Bronx conducted a 5-year retrospective study of pregnant women who presented with an acute headache, were hospitalized, and received a neurologic consultation. The study was published in Neurology.

The researchers identified 140 women with a mean age of 29 years. About 56% of these women presented in the third trimester. Primary headaches was present in 65% and secondary (due to an underlying disease) was found in 35% of women. The most common primary headache disorder was migraine and it was found in 91%, while the most common secondary headache disorder present in 51% was high blood pressure.

Primary headaches included migraine without aura, seen in 37%, migraine with aura, in 24%, chronic migraine, in 6%, episodic tension-type headache, in 3%, chronic tension-type headache, in 1%, and primary stabbing headache, in 2% (this adds up to more than 65% because some had more than one type of headaches). Besides hypertensive disorders such as preeclampsia and eclampsia (18%), secondary headache diagnoses included pituitary adenoma or apoplexy in 4%, infections in 2%, stroke in 3%. Pregnant women with secondary headaches were less likely to have had headaches in the past (37% in secondary vs 13% in primary) and were more likely to have seizures (12% vs 0%), elevated blood pressure (55% vs 9%), fever (8% vs 0%), and an abnormal neurologic examination (35% vs 17%). Psychiatric comorbidity (presence of depression, anxiety, bipolar, etc) and phonophobia (sensitivity to light) were less likely with secondary headache.

The authors concluded that among pregnant women receiving inpatient neurologic consultation, more than one-third have secondary headache. Doctors should be particularly vigilant in the absence of a headache history and if seizures, hypertension, or fever are present. On the other hand, specific headache features such as location of the pain, throbbing character, sensitivity to light and noise are less helpful in distinguish primary vs secondary headaches. The neurologists who conducted this review recommend low thresholds for neuroimaging (CT or MRI scan) and monitoring for preeclampsia and eclampsia. Preeclampsia and eclampsia are complications of pregnancy with elevated blood pressure, sometimes seizures, and kidney problems, which can be life-threatening and which are treated with intravenous infusions of magnesium.

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Migraine with aura is believed to increase the risk of strokes and possibly heart attacks, although the risk estimates vary from study to study.

A recent study demonstrated no increase in the risk of strokes in people who suffered from migraine with and without aura, unless they were active smokers. The findings were published last month in the journal Neurology. Among the 1292 participants with an average age of 68 years there were 262 with migraine. There was no relationship between migraine (with or without aura) and stroke or heart attacks during the 11 year follow up period. However, among the 198 current smokers, there was a 3-fold increased risk for stroke.

The lack of relationship between migraine with aura and stroke seen in previous studies is probably due to a relatively small sample size.

I personally have seen two young women with migraine with aura who suffered a stroke. Both of them were smokers and were taking oral contraceptives. Estrogen contraceptives (even newer ones with lower estrogen content) further increase the risk of strokes in women who have migraine with aura. Progesterone-only pill does not increase the risk of strokes. Some women with severe endometriosis, heavy menstrual blood loss, and severe PMS sometimes have to accept a slight increase in the risk of strokes and take an estrogen-based contraceptive. However, if they smoke, they must stop smoking and also try to reduce other risk factors for strokes, if they are present. These include keeping hypertension and diabetes under control, lower high cholesterol, maintain normal weight and exercise regularly.

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Fluctuations in the female hormone estrogen have been proven to be involved in triggering menstrual and perimenopausal migraine headaches. Testosterone levels have been reported to be low in men and women with cluster headaches. Testosterone replacement therapy seems to help these patients, when other standard treatments for cluster headaches do not.

A study presented at the recent annual meeting of the American Headache Society reported on testosterone levels in men with chronic migraine headaches. A significant percentage of men with chronic migraines also have low testosterone levels. This study did not look at the effect of testosterone replacement therapy, but it is possible that it may help chronic migraine sufferers as it does those with cluster headaches. It seems prudent to check testosterone level in men with chronic migraine headaches who do not respond to standard approaches such as medications, Botox injections, magnesium, and other treatments. And if the level is low, replacement therapy should be tried.

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Ayurvedic medicine has many healthy aspects. However, a recent story on NPR described the risks involved with the traditional Ayurvedic medicines from India. A very high percentage of Ayurvedic supplements in the category called bhasmas sold in the US contains large amounts of lead and other toxic elements. There is a lot more to Ayurvedic medicine than these supplements, so it is important to separate dangerous parts from things like healthy diet, yoga, and other.

Unfortunately, the US government does not regulate supplements, so there is always a question of safety of these products, especially those made outside the US. The one exception is products made in Germany, where supplements are as strictly regulated as drugs (please note that Petadolex, a butterbur product is made in Germany, but is not allowed for sale there). Many patients ask me about not only Indian but also Chinese herbal medicines, which are often combined with acupuncture and other treatment methods. As a rule, I recommend avoiding products made in China or India, where quality controls are very poor. Instead, you should buy products made by major US manufacturers, although they do not make many traditional Chinese and Indian products. However, you cannot always count on products sold in major US store chains either – recently, herbal products sold at Walgreens, WalMart, Target and GNC were found to have no active ingredients. Thankfully, there were no toxic ingredients in those products.

The largest mass poisoning with a Chinese herbal dietary weight loss product occurred in Europe where 18 patients developed kidney failure and urinary cancer.

In summary, no matter how promising a Chinese or an Indian herbal product may sound, it is not worth the risk.

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Ehlers-Danlos syndrome is a group of inherited disorders that are notable for excessive joint mobility with some people also having lax or stretchy skin, at times heart problems, and other symptoms. Headaches appear to be also very common.

We see Ehlers-Danlos syndrome in many of our migraine patients and most of our headache specialist colleagues also notice this association. However, there are very few studies that confirm this observation. One such study was recently presented at the annual scientific meeting of the American Headache Society in Washington, DC. The research was performed at a cardiology clinic in Texas. They looked at the records of 139 patients who were referred to this clinic in a period of one year. Of these 139 patients with Ehlers-Danlos syndrome, 90% were women and the average age was 32. Out of 139 patients, 70% suffered from headaches – 32% had tension-type, 26% had migraines, 9% had chronic migraines and 2% had sinus headaches. These numbers are much higher than what is seen in the general population, confirming clinical observations by headache specialists.

One form of Ehlers-Danlos syndrome affects not only joints and ligaments, but also the heart. So, when see a migraine patients who also appears to have Ehlers-Danlos syndrome, we also ask about symptoms related to the heart and if they are present refer such patients to a cardiologist.

Another presentation at the same meeting described a 23-year-old woman with Ehlers-Danlos syndrome who suddenly developed headaches that would worsen on standing up and improve on lying down. This is typical of headaches due to low cerebrospinal fluid (CSF) pressure, which was confirmed by a spinal tap. The most common causes of low CSF pressure are a leak caused by a spinal tap done to diagnose a neurological disease or caused by a complication of epidural anesthesia. Spontaneous unprovoked leaks have also been reported. In this patient with Ehlers-Danlos syndrome the leak probably occurred because of the lax ligaments that surround the spinal canal and contain the CSF. The report describes the most accurate test to document such leaks, which is an MRI myelogram.

The treatment of CSF leaks begins with a blood patch procedure, but if it is ineffective, surgery is sometimes done to repair the leak. A recent report suggested that Botox could be effective for low spinal fluid pressure headaches.

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I recently gave Botox injections to my oldest patient – an 96-year-old man who is otherwise in excellent mental and physical health has been suffering from daily severe cervicogenic (neck-related) headaches for many years. He had tried pain killers, nerve blocks, radiofrequency ablation (destruction) of nerves in his neck, all with no relief. A month after being treated with Botox he reported having almost no headaches. I have also given Botox to a number of patients with chronic migraines in their 70s and 80s.

At the last scientific meeting of the American Headache Society Cleveland Clinic neurologists presented a report entitled, Safety and Efficacy of OnabotulinumtoxinA (Botox) for Chronic Migraines in the Elderly. They described 28 patients who were older than 65, had an average age of 73 and who were treated with Botox injections for their chronic migraine headaches. They compared the safety and efficacy of Botox injections in this group with that of 700 patients aged 18 to 65 who participated in PREEMPT II study of Botox for chronic migraine (one of the two studies that led to the FDA approval of Botox for chronic migraines, in which we also participated). There was no significant difference in side effects between the younger and the older groups, except for a slightly higher incidence of neck pain after the injections in the elderly. The improvement was also comparable – after Botox the elderly had 11 fewer headache days a month compared with 9 fewer days in the younger group.

In conclusion, while many migraine medications are more likely to cause side effects in the elderly, this is not the case with Botox. Also, Botox appears to be as effective in the elderly with chronic migraines as in younger patients.

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Looking for health advice is one of the most common reason people search the web. Many websites provide health information and some even offer self-diagnosis using a symptom checker. After entering all of the symptoms the website suggests a possible diagnosis and advises to take some home remedies or see a doctor. A study recently mentioned on this blog showed that Wikipedia had errors in 9 out of 10 articles on different medical conditions.

Another recent study by Harvard researchers examined the accuracy of the sites that offer self-diagnosis. Not surprisingly, this study also found that the online programs are often wrong. The results were published in the British Medical Journal.

The lead author Ateev Mehrotra, commented that “These tools may be useful in patients who are trying to decide whether they should get to a doctor quickly, but in many cases, users should be cautious and not take the information they receive from online symptom checkers as gospel.”

Some of these symptom checkers were developed by prestigious institutions, including Harvard and other medical schools, major hospital groups, insurance companies, and some government agencies (including the United Kingdom’s National Health Service).

The researchers presented 45 hypothetical cases (including headaches) to test 23 different symptom checkers. Only 34% listed the correct diagnosis first and the correct diagnosis was in the top three possibilities in 51% of cases.

Dr. Mehrotra said that “It’s not nearly as important for a patient with fever, headache, stiff neck, and confusion to know whether they have meningitis or encephalitis as it is for them to know that they should get to an ER quickly.”

Of the 23 symptom checkers 58% provided correct advice and in more serious conditions, it correctly recommended emergency room visit in 80 percent of cases.

To complicate matters, the checkers with the most accurate diagnoses (Isabel, iTriage, Mayo Clinic, and Symcat) were not the ones that were best at recommending the appropriate level of care (, Steps2Care, and Symptify).

The researchers compared the online symptom checkers with a live telephone triage nurse offered by many insurance companies. The accuracy of live nurses is between 61% and 69%, so these are more accurate accurate, but also leave a lot of room for improvement. Hopefully, these online programs will continue to evolve, but at this point, you should not rely on them.

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The Food and Drug Administration (FDA) has just released a new strengthened warning about NSAIDs. Prescription and over-the-counter NSAIDs (ibuprofen, naproxen, nabumetone, diclofenac, and other) are widely used for the treatment of pain including different types of headaches. They are fairly safe, especially in young healthy people who take NSAIDs for an occasional headache. However, the risk of strokes and heart attacks and heart failure is higher in older people, especially those with risk factors such as smoking, diabetes, hypertension, high cholesterol, and other. These risks are present with all NSAIDs, except for aspirin, which in fact can sometimes lower these risks. So, when in doubt, take aspirin, which is the main ingredient of my product, Migralex. Migralex is fast acting and is less likely to upset your stomach because of the buffering effect of magnesium. You can buy Migralex on,, and CVS stores.

Here is the full text of FDA’s announcement:

Safety Announcement
The U.S. Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on our comprehensive review of new safety information, we are requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. We will also request updates to the OTC non-aspirin NSAID Drug Facts labels.
Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

NSAIDs are widely used to treat pain and fever from many different long- and short-term medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs are available by prescription and OTC. Examples of NSAIDs include ibuprofen, naproxen, diclofenac, and celecoxib (see Table 1 for a list of NSAIDs).

The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, we have reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies,1 a large combined analysis of clinical trials,2 and other scientific publications.1 These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

Based on our review and the advisory committees’ recommendations, the prescription NSAID labels will be revised to reflect the following information:

The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
We will request similar updates to the existing heart attack and stroke risk information in the Drug Facts labels of OTC non-aspirin NSAIDs.
In addition, the format and language contained throughout the labels of prescription NSAIDs will be updated to reflect the newest information available about the NSAID class.

Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken.

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Hopefully, your doctor has given you many treatment options, so that you can manage even the most severe attacks at home (including Compazine or Phenergan anti-nausea suppositories for when you are very nauseated or vomit and Imitrex or sumatriptan injection pen for severe pain). However, many people end up in an ER, where they are usually given an injection or intravenous medications. Unfortunately, there is no standard protocol for the best way to treat an acute migraine that does not respond to oral medications. Ideally, the first step should be an infusion of magnesium, which can provide fast relief for up to 50% of patients. Some ER doctors give an injection of sumatriptan or a non-narcotic pain killer ketorolac (Toradol). Others will give a nausea drug which can also help pain such as metoclopramide (Reglan) or prochlorperazine (Compazine). An allergy medicine, diphenhydramine (Benadryl) is also a popular choice.

A study by Dr. Benjamin Friedman and his colleagues at the Albert Einstein COllege of Medicine in the Bronx compared the efficacy of intravenous Reglan combined with Benadryl and Reglan without Benadryl. This was a double-blind study, meaning that neither the doctor giving the medicine nor the patient knew what was being given. They recruited 208 patients, which is a high enough number to produce reliable results. And the results showed that Reglan without Benadryl provided as much relief as with Benadryl.

Benadryl is not a dangerous drug, but can make you drowsy, so if you can, ask the doctor not to give it to you. It is not easy to tell a doctor what to do, especially during a severe migraine attack. But if doctor is agreeable, ask for intravenous magnesium followed by either sumatriptan or ketorolac injection as well as metoclopramide for nausea.

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For years researchers have tried to find ways to block various chemicals (neurotransmitters) released during a migraine attack, including serotonin, CGRP, nitric oxide, substance P, glutamate, and other. Triptans (such as IMitrex or sumatriptan), the first “designer” drugs for migraine, which were developed over 20 years ago, bind to a very specific subtype of serotonin receptor and are very effective in stopping a migraine attack.

A very promising new type of migraine medications is being developed by at least four different companies – Alder, Amgen, Eli Lily, and Teva. These drugs are monoclonal antibodies against the CGRP molecule or the CGRP receptor. CGRP (calcitonin gene-related peptide) is widely distributed in the body and is involved in regulating blood vessel opening and in the function of the nervous system. All four companies developing these drugs recently presented the results of their phase II clinical trials and the data looks very promising. The antibody tightly binds to its target (CGRP molecule or receptor) with the effect lasting a month, or in case of the Alder drug, up to 6 months. The Alder drug is given every six months intravenously, while the other three, are given every month by an injection into the muscle.

All four drugs appear to be very effective in preventing migraine attacks when compared to a placebo injection. And fortunately, at least so far, they all look very safe. However, in phase II trials only a couple of hundred patients are treated and we need to await the results of the larger and more definitive phase III trials to confirm the safety and efficacy of this new group of medications. This means that the earliest we will see these drugs approved by the FDA is in about 3 years.

It is possible that these drugs will be effective not only for the prevention of migraines, but also for stopping an acute migraine attack.

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An opening between the left and the right side of the heart, called patent foramen ovale (PFO), is found in 25% of the general population. It has been found to be more common in people who suffer from migraines. A large PFOs can cause shortness of breath, heart failure, and strokes and they are usually closed surgically. Several companies developed a device to close this opening without open heart surgery, but rather by inserting an umbrella-like device through a vein in the groin.

The manufacturers of these devices have conducted clinical trials in the hope of preventing migraines by closing the PFO. The results so far have been mixed with some studies showing improvement in migraines and some showing no benefit. A study just presented at the annual meeting of the American Headache Society by Dr. Andrew Charles of UCLA and his colleagues reported on one such trial. This study was blinded, with 107 patients having a sham procedure (the catheter was inserted into the groin vein, but the PFO was not closed) and 123 having their PFO closed. Overall, there was a significant reduction in headache days in the closure group (-3.4 days) compared with the sham group (-2.0 days), however there was no difference in the primary efficacy endpoint of the number of patients with 50% or more reduction in migraine attacks.

A subset of patients did particularly well compared to the sham group – patients who had migraine aura with the majority of their migraine attacks. A significant reduction in migraine days was present in half of patients with aura compared with a quarter in the control group. About 11% (8 out of 74 patients) of those who had migraine with aura had complete elimination of migraine attacks, while this happened to only 1.5% (1 out of 68 patients) in the sham group with auras.

This study suggests that patients who have auras with the majority of their migraine attacks and whose migraines are difficult to control should undergo an echocardiogram to test for the possible presence of a PFO. If PFO is present, it may be reasonable to consider seeing an interventional cardiologist to close the PFO. This is a relatively safe procedure if done by an experienced doctor and that is a very important if. Pick a doctor who has done a hundred or more of these procedures.

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Several presentations at the annual meeting of the American Headache Society held in Washington DC last weekend discussed the treatment of post-concussion symptoms in children (everything below also applies to adults). Among many topics, the speakers addressed the question of aerobic exercise after the concussion. Most experts agree that starting physical exercise too early can worsen the symptoms and delay recovery. At the same time, because aerobic exercise has so many benefits for the brain, it is prudent to begin aerobic exercise 2 to 4 weeks after the concussion. The child should begin exercising for short periods of time and at low intensity. Exercise should be stopped as soon as symptoms, such as headache or dizziness worsen. Brisk walking could be the first activity to be tried. The ideal duration is about 30 minutes and when this goal is achieved, the intensity of exercise can be gradually increased.

As far as the very common cognitive problems after a concussion, the experts also agreed that complete cognitive rest is not helpful. Just like with physical exercise, it is best to begin mild activities, such as reading for pleasure, and then slowly increase the load, as tolerated.

Several scientific presentations reported that the most common type of headaches that occurs after a concussion is migraine. When these post-concussion migraines last for more than 3 months and occur on more than 15 days each month, they are considered to be chronic migraines.

The treatment of post-concussion chronic migraines is the same as the treatment of chronic migraines that occur without a concussion. These treatments may include cognitive behavioral therapy, biofeedback, magnesium and other supplements (magnesium deficiency is found in up to 50% of migraine sufferers and magnesium is depleted by trauma), various preventive medications, and Botox injections.

Although the FDA has not yet approved Botox injections for the treatment of chronic migraines in children, Botox is safer than most drugs. We know about the safety of Botox in children because it has been widely used even in very young children who suffer from cerebral palsy and are unable to walk unless their stiff leg muscles are relaxed by Botox. Botox was approved by the FDA 26 years ago and some kids have been getting injections for over 20 years and so far there have been no long-term side effects observed.

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Zolmitriptan is one of seven triptans available in the US and it comes in tablets (Zomig), orally disintegrating tablets, that is tablets that melt in your mouth (Zomig ZMT), and nasal spray (Zomig NS). The nasal spray was just approved for children 12 and older. It is available in 2.5 mg and 5 mg strength and the 2.5 mg is the starting dose, but kids are allowed to take 5 mg dose up to twice a day.

My previous post mentioned the approval of Treximet, a combination of sumatriptan (Imitrex) and naproxen (Aleve) in adolescents. However, Zomig is the only triptan in a nasal spray form (the second triptan available in a nasal spray is sumatriptan or Imitrex) approved in the US for children. The advantages of this form of drug delivery is that it tends to have faster onset of action and it can be taken when severe nausea or vomiting precludes the use of oral medications. Sumatriptan nasal spray is approved in kids in Europe, so there is no reason not to use it as well, however Zomig spray seems to be better than Imitrex spray. The amount of fluid in a single dose of Zomig is less than that in Imitrex and the spray droplets are of smaller size, leading to better retention of fluid in nasal passages and better absorption. Also, many patients complain of a very unpleasant taste with Imitrex spray, although this can be avoided by sucking on a hard candy while spraying. This will carry the saliva out of the mouth down the throat and the drug will not reach the mouth. When using nasal sprays it is important not to sniff them up your nose because this will carry the medicine into the throat rather than having it stay in the nose where it gets absorbed faster.

Since we are on the topic of nasal sprays, I should mention three other nasal sprays that can be used to treat headaches. Migranal nasal spray contains dihydroergotamine, which is one of the strongest injectable migraine medications. However it is a lot less effective in a nasal spray form. Sprix is a nasal spray of ketorolac (Toradol), a nonsteroidal anti-inflammatory drug, which is also much stronger when injected. It is also available in a tablet, but the tablet is not any stronger than aspirin or ibuprofen. The third nasal spray is Stadol NS and it contains butorphanol, a strong narcotic pain killer. It should be avoided because it is very addictive.

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A combination pill containing 10 mg of sumatriptan with 60 mg of naproxen sodium was just approved by the FDA for children aged 12 to 17. This combination in a higher dose (85 mg of sumatriptan and 500 mg of naproxen) has been available for adults for the past 7 years. This recent FDA approval allows children to take up to one adult strength tablet a day. It is good to have a smaller size tablet for kids. However, there is a big issue of cost. We don’t yet know what the pediatric strength tablet will cost, but a single tablet of the adult strength Treximet is $75. Yes, $75 for one tablet, even with a coupon you can get at and $80 or more without a coupon. Very few insurance companies will pay for Treximet because you can get a generic tablet of sumatriptan (Imitrex), 100 mg for $1.50 and a tablet of naproxen, 500 mg for 7 cents. So, make-your-own Treximet will cost you $1.57. A very rare patient will tell me that they get better relief from the branded pill, which is possible because of the inactive ingredients, speed of onset and occasionally poor quality generics (I wrote about this problem in a previous post). However, such patients are very few.

Besides Treximet, we have two other triptans approved for migraines in children. Rizatriptan (Maxalt, Maxalt MLT) is approved by the FDA for children and adolescents 6 to 17 years of age and it is available in a generic form. Almotriptan (Axert) is approved in adolescents, 12 – 17 years of age, but it is available only as a branded drug ($40 a pill). In the UK, 10 mg sumatriptan nasal spray (Imitrex in the US, Imigran in the UK) was approved for adolescents, ages 12-17, who suffer from migraine and cluster headaches. In the US, we have only 5 and 20 mg nasal sprays of sumatriptan, and both are available in a generic form. Sumatriptan and zolmitriptan (Zomig, Zomig ZMT – orally disintegrating tablet, Zomig NS – nasal spray) were also tested in kids. The reason these two drugs were not approved is because the placebo response in kids tends to be very high and the active treatment was not distinguishable from placebo. This is mostly because headaches in children tend to be shorter in duration and the headache goes away on their own in a couple of hours, making it difficult to separate the active drug from placebo. However, they are probably as effective and as safe as the triptans approved in pediatric patients.

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Transcranial magnetic stimulation (TMS) was approved by the FDA at the end of 2013 (see my earlier post) but it has not yet become available. This approval was for the treatment of acute migraine.

A new study just presented at the International Headache Congress suggests that TMS could be effective for the preventive treatment of migraines with medication overuse headache.

The study included only 28 patients and it was not a blinded study. However, these patients were severely affected and failed several other treatments. They were instructed to use the TMS device twice a day every day with an additional treatment at the time of a headache. Treatment lasted for at least 3 months, with an option to continue for another 3 months.

Of the 28 patients, 24 (86%) reported a reduction in their days of acute medication use per month, while 2 patients reported an increase in acute medication use. Nineteen patients (68%) experienced fewer migraine days per month, and 7 of the 19 had a 50% or greater reduction in migraine days. The number of patients with pain severity rated as excruciating or severe dropped from 19 at baseline to 3 at 3 months (84% reduction). Headache attack duration decreased in 15 patients, remained unchanged in 9, and increased in 4. The disability score (HIT-6) was severe at the beginning of the study in 26 of 28 participants. After 3 months, only 18 had severe disability.

The benefit was seen in patients who had migraines with and without aura.

After 3 months, five patients stopped using TMS because it was ineffective or inconvenient. Four were lost to follow-up. Of the remaining 19, 16 reported reduced days of acute medication use at 6 months, compared with baseline. Disability scores in the 19 patients who used TMS for 6 months were comparable to their scores at 3 months, suggesting that there was no additional benefit from longer-term use, but the benefit was maintained.

No side effects were reported, confirming the safety of TMS. Now we just have to wait for the company (eNeura) to release this product on the market.

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We are again in a cluster season. We do not see any cluster headache patients for months and then dozens come in within weeks. It is not allergies, barometric pressure or any other earth phenomena that trigger cluster headaches in so many people at once. It has been speculated that solar activity may be the trigger and I just checked the NASAs Solar Dynamics Observatory website and found that the sun has “active regions galore”. I wrote about solar activity as a possible culprit last October when we had another wave of cluster patients. Unfortunately, there is not much we can do about the sun, but we do have many effective treatments for cluster headaches, including intravenous magnesium, occipital nerve blocks, oxygen, injectable sumatriptan, verapamil, and for chronic cluster headaches, Botox injection.

A recent study by British neurologists in the journal Headache described the severe impact of cluster headaches on quality of life and neuro-psychological symptoms. The researchers found that cluster headache patients had normal intelligence and executive functions, but had worse working memory, disturbance of mood, and poorer quality of life compared with healthy controls. Similar findings have been found in patients with other chronic pain conditions as well. It is most likely that cognitive impairment and mood changes can be reversed with effective treatment of pain.

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Another supplement to consider for the preventive treatment of migraine headaches is diamine oxidase (DAO). It is an enzyme that breaks down histamine.

Histamine is released during an allergic reaction and is present in many foods. It is one of the neurotransmitters that is involved in the process of migraine. A quarter of the population has insufficient amounts of DAO, which leads to inefficient metabolism of histamine. The largest amounts of DAO in the body are found in the intestines and the kidneys.

A group of Spanish neurologists published a study that showed that of 137 patients with migraines, 119 (87%) showed impaired activity of the enzyme.

The normal enzyme activity is a score of at least 80 histamine-degrading units [HDU]/mL. In a survey which was conducted in 2006 and again in 2012, migraine symptom scores correlated with enzyme activity. Symptom scores rose progressively as enzyme activity dropped below 80 HDU/mL, with scores almost twice as high in the 30-40 HDU/mL range compared with enzyme activity >80 HDU/mL.

Dr. Izquierdo and his colleagues in Barcelona conducted a double-blind, placebo-controlled trial of DAO oral supplementation, for the prevention of migraines in patients with DAO activity less than 80 HDU/mL.

Participants were men or women age 18 to 60 years old with an attack within the previous 6 months. Most of the patients were women, with only 8 men in each group.

The supplement contained 4.2 mg of DAO which participants took with a glass of water before breakfast, lunch, and dinner. The supplement was associated with a similar reduction in the mean number of attacks per month in the placebo and DAO groups, but the group that took DAO used significantly fewer triptan drugs (such as sumatriptan, Imitrex). These results are not overwhelming, but they possibly hide the fact that some of these patients had a very good response while others had none, which averaged out to a modest benefit. Considering that this a very benign supplement with no potential for serious side effects (unlike prescription drugs), it may be worth trying.

Histamine intolerance is defined by an imbalance of histamine and the histamine degrading enzyme diamine oxidase (DAO), which is mainly produced in the small intestine. Excessive amounts of histamine in the body can cause not only migraine and other types of headaches, but also diarrhea, nasal congestion, asthma, rashes, and other symptoms. People who are prone to severe allergic reactions with anaphylactic shock often have lower DAO activity. Diamine oxidase activity can be measured in blood, but the test is expensive and not very reliable. Instead of doing this test, try a low histamine diet or taking a DAO supplement. This is particularly worthwhile for people who in addition to migraines suffer from colitis (such as Crohn’s), allergic conditions, asthma, and celiac disease.

Here is an informative post on this topic on The Daily Headache blog.

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Tension headaches can be prevented, or at least made milder by strength training, according to a new Danish study just published in the journal of the International Headache Society, Cephalalgia.

Tension-type headache is the most common type of headaches and it is usually accompanied by increased muscle tenderness.

The researchers compared muscle strength in neck and shoulder muscles in 60 patients with tension-type headaches and 30 healthy controls, using rigorous strength measurement techniques. Patients were included if they had tension-type headaches on more than 8 days per month and had no more than 3 migraines a month. Compared to controls headache patients had significantly weaker muscle strength in neck extension, which helps keep the head straight. Headache patients also showed a tendency toward significantly lower muscle strength in shoulder muscles. Among the 60 headache patients, 25 had frequent headaches and 35 had chronic tension-type headaches (defined as occurring on 15 or more days each month).

The use of computers, laptops, tablets, and smart phones has increased in recent years and this may increase the time people are sitting with a forward leaning head posture, which contributes to neck muscle weakness.

Neck pain and tenderness is a common symptom in both tension-type and migraine headache sufferers.

This is not the first study to show that muscle strength and weakness were associated with tension-type headaches, but it is still not clear whether the muscle weakness is the cause or the effect of headaches. Neck and shoulder strengthening exercises have been shown to reduce neck pain in previous studies and in my experience strengthening neck muscles will often relieve not only tension-type headaches, but also migraines. So it is most likely that there is not a clear cause-and-effect relationship, but a vicious cycle of neck pain causing headaches and headaches causing worsening of neck pain and neck muscle weakness.

Physical therapy can help, but the mainstay of treatment is strengthening neck exercises. Here is a YouTube video showing how to do them. The exercise takes less than a minute, but needs to be repeated many times throughout the day (10 or more). Many people have difficulty remembering to do them, so using your cell phone alarm can help. Other treatment measures include being aware of your posture when sitting in front of a computer or when using your smart phone, wearing a head set if you spend long periods of time on the phone, doing yoga or other upper body exercises, in addition to the isometrics.

Sometimes pain medications or muscle relaxants are necessary, while for very severe pain, nerve blocks and trigger point injections can help. Persistent neck pain can respond to Botox injections. When treating chronic migraines with Botox, the standard protocol includes injections of neck and shoulder/upper back muscles. Here is a video of a typical Botox treatment procedure for chronic migraines.

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While Botox (OnabotulinumtoxinA) has been shown to be effective in treating chronic migraines, its exact mechanism of action is not clear. Initially, we thought that it works by relaxing muscles in the forehead, temples and the back of the head and neck. However, this is not likely for several reasons. One reason is that some people have pain at the top of their heads, where there are no muscle, and injecting those areas leads relief of pain. Another reason is that Botox seems to be effective in relieving different nerve pains, such as that of shingles (post-herpetic neuralgia), trigeminal neuralgia, and other.

Botox blocks the release of acetylcholine, a neurotrasmitter that is normally released into the space between the nerve ending and the muscle (synapse), making the muscle contract. We also know that Botox blocks the release of other neurotransmitters, which may be responsible for its pain-relieving properties. One of these chemical messengers is CGRP (calcitonin gene-related peptide).

A study just published in the journal Pain by Spanish researchers showed that CGRP level is increased in blood of patients with chronic migraine even when they are not having a migraine attack. CGRP levels were determined in 83 patients with chronic migraines (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 units of Botox. CGRP levels after Botox treatment were significantly lower as compared with CGRP levels obtained before Botox treatment. Pretreatment CGRP levels in responders were significantly higher than those seen in nonresponders. One month after treatment, the CGRP levels did not change in nonresponders, but significantly decreased in responders. Demographic factors, clinical features, and comorbidities (co-existing medical conditions) were not different in responders as compared with those of nonresponders. The authors concluded that “These results confirmed that CGRP levels can be of help in predicting the response to Botox and suggest that the mechanism of action of Botox in chronic migraine is the reversal of sensitization as a result of the inhibition of CGRP release.”

Unfortunately, the test to measure CGRP levels is not yet available outside research laboratories and because this was a small study we do not know how accurate this test will be. It has to tells us with greater than 90% which migraine sufferer will respond. If it is less than 90% accurate, we’d be denying over 10% of patients a very effective and often life-altering treatment. Some studies also suggested that we can predict who will respond and who will not by the description of pain. That is, if the pain is squeezing, crushing from outside in, or involves the eye, then the chances of response are better than if the pain is exploding, or from inside out. The accuracy of this predictor is less than 70%, so it should not be used to screen for potential non-responders.

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A topical cream seems to be effective in treating migraine headaches. Achelios Therapeutics announced results from a Phase IIa placebo-controlled clinical trial in moderate and severe migraine sufferers treated with Topofen, the company’s proprietary topical anti-migraine therapy. This is a well-known non-steroidal anti-inflammatory drug (NSAID) ketoprofen, which is applied to the face and seems to provide relief for patients suffering from acute migraine.

The results of the clinical trial were presented at the American Academy of Neurology annual meeting in Washington, D.C. Surprisingly, this study showed that it may be possible to relieve severe migraine with a topical application to facial nerve endings. Topical application avoids potentially serious side effects of NSAIDs, such as stomach bleeding and ulcers. The randomized, crossover, double-blind, placebo-controlled study involved only 48 adults with a history of episodic migraine with and without aura. Of the severe migraine patients, 77 percent experienced relief of pain and migraine-associated symptoms and 45 percent had sustained pain relief from two to 24 hours compared to 15 percent on placebo. Also, 50 percent of patients who treated their severe pain with Topofen were pain free at 24 hours compared to 25 percent of placebo-treated patients. Some patients experienced application-site irritation, which was mild or moderate in severity. That was the only reported side effect, which resolved quickly.

Such a small study does not prove that this treatment is in fact effective. A typical drug trial required for an FDA approval usually involves hundreds of patients. However, you do not need to wait for this cream to appear on the market because there are creams containing an NSAID already available by prescription (Voltaren Gel) and over-the-counter (Aspercreme). It is possible that the cream tested in the study may be better because it is a different NSAID, but Voltaren Gel is already approved and you can ask your doctor for a prescription. It is possible that insurance companies will not pay for it since it is not approved for migraines. A tube of Voltaren Gel will cost you about $55 (go to to get the lowest price).

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The FDA-approved protocol for Botox injections for chronic migraines calls for 31 injections with 155 units of Botox. This is the protocol we teach young doctors and new injectors.

However, just like with any other medication, doctors are allowed to go “off label”, meaning that we can inject Botox for headache types and pain conditions other than chronic migraine (in which case insurance will usually not pay) and we can also adjust the number of injection sites and the total dose of Botox when treating patients with chronic migraines. I have a fair number of patients who need up to 200 units and on a very rare occasion even 300. The maximum dose allowed during a single treatment is 400 units, which is usually needed when injecting large muscles in arms and legs, like in cerebral palsy or spasticity due to strokes.

This YouTube video shows injections for chronic migraines with additional injections into the masseter muscles (at the corner of the jaw) to treat TMJ syndrome, which is also called temporomandibular disorder. Injections of the temporalis muscles in the temples, which are also involved in chewing and which are always injected for chronic migraines, also helps relieve TMJ syndrome.

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Low vitamin D level predicts larger stroke size and poor outcome, according to a new study by University of Massachusetts researchers. They examined data on 96 consecutive patients with stroke and found a strong inverse correlation between the level of vitamin D and the size of the stroke. This is not surprising since vitamin D seems to be very important for the normal functioning of the nervous system. In a previous post I mentioned a study that showed an inverse correlation between vitamin D level and relapses of multiple sclerosis. Such correlation has been also found with migraine headaches and other major diseases.

Yes, all these studies are correlational and do not prove that taking vitamin D will prevent any of these conditions. But there is no evidence at all that taking vitamin D to maintain your blood level in the normal range has any side effects.

The stroke study was done only in caucasian patients and we know that blacks may need lower levels of vitamin D than caucasians, at least as measured by the standard blood test. This test is not very reliable since it measures the total level of vitamin D, while only the free portion of it is biologically active. To be safe, try to aim to have vitamin D level at least in the middle of normal range, which is from 30 to 100. Many people take the recommended 400 unit dose of vitamin D, but still have low levels in their blood. It is important to check your vitamin D level even if you are taking a supplement. Some patients require 2,000 and even 5,000 units daily to get their blood level to the middle of normal range.

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Topiramate (Topamax) is a drug used for the prevention of migraine headaches (and epilepsy) in adults and last year it was also approved for adolescent migraine sufferers. This drug is notorious for causing cognitive side effects, kidney stones,osteoporosis, overheating, and many other side effects. It is contraindicated (just like another migraine drug, Depakote) in pregnancy because of the risk of birth defects.

A new report published in the journal Pediatrics documents an increased risk of eating disorders in adolescents who take Topamax. This report describes 7 female teenagers who developed an eating disorder or whose eating disorder got worse on topiramate.

Considering that we have many other effective preventive drugs for migraine headaches, topiramate should be used only when several other treatments fail.

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Chronic migraine sufferers appear to be more likely to have dryness of their eyes, according to a study by ophthalmologists at the University of Utah, which was published in the journal Headache. The researchers used sophisticated techniques to measure tear production, corneal sensitivity, dry eye questionnaire, and other tests. The results of these tests were compared in migraine sufferers and healthy control subjects.

A total of 19 chronic migraine patients and 30 control participants completed the study. The nerve fiber density was significantly lower in the corneas of migraine patients compared with controls. All migraine sufferers had symptoms consistent with a diagnosis of dry eye syndrome. The researchers plan to continue studying the interrelationships between migraine, corneal nerve architecture, and dry eye.

Similar findings in patients with episodic migraine were published by a group of Turkish doctors in the journal Cornea in 2012.

Migraine sufferers and their doctors should be aware of this correlation since irritation caused by dry eyes could potentially trigger a migraine. It is possible that some migraines can be prevented by using over-the-counter and prescription eye drops or, in severe cases, eye inserts (Lacrisert). High doses of omega-3 fatty acids have been reported to help dry eyes and omega-3 fatty acids have also been reported to relieve migraines.

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Cluster headaches cause more severe pain than any other type of headaches. Some patients even call them suicide headaches because they provoke thoughts of suicide. The name comes from the fact that they occur in clusters – every day for a couple of months and then they go away for a year or longer. In those with chronic cluster headaches they never go away. The headaches are brief – anywhere from 30 minutes to 3 hours. They are always one-sided, with pain usually around the eye, and are accompanied by tearing, nasal congestion, and sometimes restlessness. More men than women suffer from them.

Treatment of cluster headaches can be very effective. A 10-day course of prednisone or an occipital nerve block can abort the entire cluster. We also have preventive drugs, such as a blood pressure medicine, verapamil (used in high doses), epilepsy drugs, and lithium. These are taken daily to prevent headaches. To treat individual attacks, inhalation of 100% oxygen under high flow, zolmitriptan nasal spray (Zomig NS), and sumatriptan (Imitrex) injections can be true life savers.

Some of the alternative therapies that have been reported to help include melatonin, intranasal capsaicin (hot pepper extract), and an herbal product, Boswellia (Nature’s Way is a good brand for herbals).

Unfortunately, there are some cluster headache sufferers who do not respond to any of these treatments. We even treated some patients with intravenous histamine, which requires hospital admission and two of my patients were implanted with a vagus nerve stimulator (with good relief).

Some cluster patients have been found to have low testosterone levels and treating them with testosterone seems to help.

This testosterone connection led to trials of a fertility drug, clomiphene citrate (Clomid). Clomiphene enhances testosterone production and binds to hypothalamic estrogen receptors, which is why it was considered as a treatment for cluster headaches. A second case of successful treatment of cluster headaches with Clomid has just appeared in the journal Headache. This was a case of a 65-year-old man with a 17-year history of chronic cluster headaches who did not respond or had significant side effects to many cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization.

The patient experienced 3-5 headaches per day. On Clomid (100 mg/day) he became 100% pain-free and remained so for three and half years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years, but then his headaches returned. Clomiphene was restarted, and he became pain-free once again.

Clomid should be considered when the usual preventive drugs for cluster headaches are ineffective.

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Chronic fatigue syndrome sufferers have endured years of neglect and sometimes ridicule. The condition has even been called “yuppie flu”. Informal surveys indicate that half of the doctors do not believe that this is a true physical disease. This is despite the fact that 1 to 2 million Americans have been diagnosed with this condition. In a previous post I mentioned that patients with chronic fatigue are much more likely to suffer from migraines – they occur in 84% of patients. Tension-type headaches were found in 81% and only 4% had no headaches at all.

There is an overwhelming amount of evidence that chronic fatigue syndrome is a physical condition and one of the names that has been used by doctors is Myalgic Encephalomyelitis. The Institute of Medicine recently issued a report, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, which proposes a new name – Systemic Exertion Intolerance Disease, or SEID. The name indicates that the main characteristic of the disease is the fact that exertion of any kind – physical, cognitive, or emotional – can affect many different body organs and impair normal functioning and reduce quality of life. The report also states that to make this diagnosis, the symptoms have to be chronic, frequent and moderate or severe in intensity. The experts suggest that patients could be diagnosed with both SEID and Lyme disease, fibromyalgia, or another disease that causes fatigue. Currently, if a patient suffers from Lyme disease or another fatiguing condition, chronic fatigue is not added as a separate disease. The report also noted that the prognosis is not very good – many people continue to suffer from SEID for many years.

Fibromyalgia, another condition which was thought to be purely psychological, now has three medications approved to treat it (Lyrica, Cymbalta, and Savella), which has led more doctors treat it as a real disease. Unfortunately, there are no drugs approved for chronic fatigue or SEID.

Here are the specific diagnostic criteria for SEID established by the Institute of Medicine:
– Reduction or impairment in the ability to carry out normal daily activities, accompanied by profound fatigue
– Post-exertional malaise
– Unrefreshing sleep
In addition, diagnosis requires one of the following symptoms:
– Cognitive impairment
– Orthostatic intolerance (difficulty standing up and being in an upright position).

I would add that to make this diagnosis, other known potential causes of fatigue should be ruled out. These include thyroid disease, anemia, chronic infections (Lyme and other), vitamin B12 and other deficiencies. As mentioned in a previous post, the test for vitamin B12 is not very accurate. Many laboratories list normal levels being between 200 and 1,000. However, many patients with levels below 400, and some even with levels above 400 still have a deficiency. If a deficiency is strongly suspected, additional tests are needed – homocysteine and methylmalonic acid levels.

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Narcotics are not only ineffective for the treatment of headaches, but they can also make headaches worse and transform an episodic migraine into chronic. A study mentioned in a previous post showed that more than half of migraine sufferers who went to an ER were given a narcotic.

A new study recently published in the journal of the International Headache Society, Cephalalgia showed that if patients presenting with a headache to an ER are treated with an injection of opiates (narcotics) they will stay in the hospital longer than if no narcotics are given. This treatment also leads to an increased risk of return visits to the emergency department within seven days.

The study was conducted by two neurologists, Dr. McCarthy at Puget Sound VA Healthcare System in Seattle and Dr. Cowan at Stanford University in California. They examined charts of 574 people and discovered that 23% received a narcotic when they were seen at an emergency department. Only 53% were given an injection of a drug recommended by a published consensus of headache experts. These include sumatriptan (Imitrex, the only injectable triptan), prochlorperazine (Compazine), metoclopramide (Reglan), chlorpromazine (Thorazine), ketorolac (Toradol), aspirin, acetaminophen, and dihydroergotamine. The remaining 24% were given an injection of another non-narcotic drug.

Patients who were given opiates were 4 times more likely to have a long stay, compared with patients given first-line recommended medications. 69 participants had at least one readmission for headache, of whom 20 returned to the emergency department within seven days. Interestingly, patients who had a CAT or an MRI scan of the brain had a significantly higher rate of early return visits, compared with those who did not have neuroimaging. Approximately 8% of people given opiates had early return visits, compared with 3% of patients given first-line recommended drugs.

Dr. McCarthy was quoted saying that “Opiates have shown less headache pain reduction, higher rates of headache recurrence, and increased sedation, compared with first-line recommended specific headache medications”. He added that regardless of whether the acute headache was diagnosed as a migraine or a tension-type headache, it is likely to respond to most non-narcotic injectable treatments.

An editorial accompanying this article concluded that “The most important intervention emergency physicians can deliver for their headache patients is to connect them with outpatient physicians savvy about headache management, who will then provide these headache patients with appropriate acute therapeutics, initiate preventive therapy, and counsel their patients against receiving opioids in the emergency department”.

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The existence of gluten sensitivity has been long denied by the mainstream medical establishment. A study described in a previous post over two years ago documented higher incidence of migraine headaches in people with gluten sensitivity than in those with celiac disease (56% vs 30%). Celiac disease, which is a severe autoimmune disease caused by wheat allergy, affects about 3 million Americans, but the estimates of gluten sensitivity run as high as 18 million. Billions of dollars of gluten-free products are sold in the US and they can be found in almost every grocery store.

A recent study by the National Institutes of Health led by Dr. Sabatino examined 59 patients who did not have celiac disease, but believed gluten-containing food was causing them intestinal and other symptoms. Every day for one week these people were randomly given capsules containing 5 grams of gluten or a placebo of rice starch. After only one week, those who were taking the gluten pills reported a significant difference in symptoms compared to those who took non-gluten placebo pills. In addition to intestinal pains, they felt abdominal bloating, a foggy mind, depression, and canker sores. Clearly, they didn’t know if they were taking the gluten pill or the placebo, but their symptoms were very revealing and proved the existence of gluten sensitivity.

The bottom line is, if you have stomach pains, bloating, foggy mind, depression, headaches, malaise, and other symptoms, it may be worth going on a gluten-free diet for a couple of weeks to see if your symptoms improve. Unfortunately, we do not have any tests to document this condition, so this is the only way to find out if you have gluten sensitivity.

We do have tests for celiac disease – this condition can be detected by a blood test and an intestinal biopsy done through an endoscopy. However, despite the availability of these tests, even this severe form of gluten sensitivity is diagnosed in only one out of six Americans who suffer from it. And the number of cases of celiac, just like with non-celiac gluten sensitivity, are going up. The incidence of celiac is now five times higher than 50 years ago.

Stomach pains and bloating are the most common symptoms of celiac, but a recent review in JAMA Pediatrics, lists other symptoms, including persistent or intermittent constipation, vomiting, poor appetite, weight loss or growth delay in children, fatigue, anemia, dental problems, canker sores, arthritis and joint pains, bone loss and fractures, short stature, delayed puberty, unexplained infertility and miscarriage, recurring headaches, loss of feeling in hands and feet, poor coordination and unsteadiness, epileptic seizures, depression, hallucinations, anxiety and panic attacks. Many of these symptoms are the result of poor absorption of vitamins and minerals, including magnesium, vitamin D, vitamin B12, and other because of the damaged intestinal lining.

Those with celiac disease are more sensitive to even minute amounts of gluten than people with non-celiac gluten sensitivity.

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Doctors in St. Louis, MO examined how well headaches are treated in children. There has been little research about how well doctors in the US care for children and teens with migraine and if the treatment is consistent with evidence-based guidelines. They also assessed how often opioids (narcotics) are prescribed for children with migraines. The study used Electronic Health Record data to look at how almost 40,000 children and teens with migraine who presented to primary care providers, specialty care, or Emergency Room or Urgent Care (ER/UC) across four states in metropolitan and non-metropolitan areas were treated from 2009-2014.

The results showed that among children and teens presenting for care for migraine or likely migraine, nearly half (46%) were not prescribed or recommended any medication. Only one in six (16%) were prescribed or recommended an evidence-based medication. Among those who received medication, nearly one in six (16%) were prescribed an opiod (narcotic), and these numbers are even higher among teens 15-17.

The findings also revealed that the odds of getting an evidence-based medication were significantly higher if migraine was diagnosed, and the odds of getting any medication (evidence-based or not) were higher in non-metropolitan areas. Children and teens treated in a specialty care setting or the ER/UC were twice as likely to be prescribed an opioid than if treated in primary care.

The authors concluded that “Too many children who present for migraine or likely migraine are not getting any medication for their pain. Too few are receiving care consistent with evidence-based guidelines. And far too many are being prescribed an opiod. Five out of six children and teens are receiving suboptimal migraine care. A significant need exists to increase doctor awareness of the benefits of optimal migraine care and the potential dangers of prescribing opioids for children and teens with migraine.”

Guidelines issued by many medical organizations call for the use of ibuprofen as the first line treatment, however most children with severe migraines need to take a triptan. Triptans include sumatriptan (Imitrex), rizatriptan (Maxalt), zolmitriptan (Zomig), and four other similar drugs. Rizatriptan has been shown to be effective in children as young as 6, while other triptans have been approved for children older than 12. It is very likely that, just like in adults, some children respond better to one triptan and several triptans may need to be tried to find the best one. Just because the FDA approved one triptan for children above the age of 6 and another above the age of 12, it does not mean that there is a significant difference among the seven available triptans. These are safe drugs that have been in use for over 20 years and several of them are available in Europe without a prescription.

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Several million Americans suffer from chronic migraines, headaches that occur on at least half of the days and often daily.

A new study suggests one of the way to prevent this disabling disease. In the American Migraine Prevalence and Prevention Study, people with episodic migraines (those occurring on less than half of the day each month) completed the Migraine Treatment Optimization Questionnaire and provided outcome data in 2006 and in 2007. They were asked four questions about the efficacy of their acute migraine therapies and the responses were divided into: very poor, poor, moderate, and maximum treatment efficacy.

Among 5,681 study participants with episodic migraine in 2006, 3.1% progressed to chronic migraine in 2007. Only 1.9% of the group with maximum treatment efficacy developed chronic migraine. Rates of new-onset chronic migraine increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. The very poor treatment efficacy group had a more than 2-fold increased risk of new-onset chronic migraine compared to the maximum treatment efficacy group.

The authors concluded that inadequate acute treatment efficacy was associated with an increased risk of new-onset chronic migraine over the course of 1 year. They speculated that improving acute treatment outcomes might prevent chronic migraine. However, they also said that reverse causality cannot be excluded, meaning that it is possible that those who would go on to develop chronic migraine had poor response to acute treatment because their headaches were worse and that they would develop chronic migraine regardless of how well their acute treatment worked. However, it makes a lot of sense to assume that effective treatment of individual attacks may prevent headaches from becoming chronic, especially because we know that each migraine attack leaves the brain more excitable for weeks and this makes the next attack more likely.

Effective treatment of acute attacks usually involves the use of triptans, (drugs like sumatriptan, or Imitrex, eletriptan, or Relpax, rizatriptan or Maxalt, and other), although NSAIDs, such as aspirin, iboprofen and other can also help, both alone or in a combination with a triptan. Medications that should not be used are drugs such as Fioricet or Fiorinal (butalbital, caffeine, and acetaminophen / aspirin), codeine, Percocet (oxycodone / acetaminophen), Vicodin (hydrocodone / acetaminophen). These drugs are not only ineffective, but can make it more likely that episodic migraines will turn into chronic. This also applies to other caffeine-containing drugs (Excedrin and other) and even dietary caffeine.

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The new dietary guidelines issued by a government advisory committee have many positive changes from the old guidelines. These include a focus on food rather than nutrients. For example, there is no proposed limit on the intake of cholesterol and eating eggs is encouraged. There is an emphasis on eating less meat and more fruits and vegetables and on limiting sugar intake. All these recommendations apply to headache sufferers as well.

However, the guidelines are advising people to increase their consumption of coffee. They suggest that 3 to 5 cups a day can be part of a healthy diet because there is evidence that coffee may reduce risk of type 2 diabetes and heart disease (and possibly Parkinson’s disease). This is because coffee contains flavonoid compounds that have health benefits. However, coffee and caffeine in general are proven to cause worsening of headaches. As little as 2-3 cups a day can worsen headaches by causing caffeine withdrawal. Flavonoids are present in many fruits and vegetables, so it is not necessary to drink coffee to benefit from these compounds. If you are prone to having headaches it is better to limit your caffeine intake to one cup of coffee a day.

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The Journal of Nutrition just published a study that suggests life-extending benefits of taking vitamin and mineral supplements. Multivitamin with minerals products are the most commonly used supplements in the United States, followed by multivitamin products without minerals. While prior studies did not show an effect of such supplements in preventing deaths from cardiovascular disease, however, no previous trial looked for potential benefits just in women.

This new study examined the effect of a multivitamin with or without minerals on 8678 men and women. An adjustment was made for many potential confounders, that is factors that could have influenced the results, including age, race, education, weight (body mass index), alcohol, aspirin use, serum lipids (cholesterol, etc), blood pressure, and blood glucose.

The researchers observed no significant association between mortality due to cardiovascular disease in users of supplements compared with nonusers. However, when users were classified by the reported length of time products were used, a significant association was found with the use of multivitamins with minerals if they were taken for more than three years, compared with nonusers. This finding applied only to women and only to multivitamin products that also included minerals.

Magnesium is one of the minerals which is always included in combination vitamin products. Many studies have shown a beneficial effect of magnesium on cardiovascular and other causes of death in both women and men. And, of course, taking magnesium prevents migraine headaches since magnesium deficiency is found in up to 50% of migraine sufferers.

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Eating more salt leads to more headaches, according to a study published in BMJ Open last December. In a multicentre feeding study with three 30-day periods, 390 participants were randomised to the DASH (a healthy diet that was expected to lower blood pressure) or control (regular, not very healthy) diet. On their assigned diet (DASH and regular), participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. The occurrence and severity of headache were recorded at the end of each feeding period. The researchers did not attempt to determine which type of headaches people were suffering from, but it is safe to assume that the majority suffered from tension-type and migraine headaches. The average age was 48 and 57% were women.

The occurrence of headaches was similar in DASH versus control, at high, intermediate and low sodium levels. By contrast, there was a lower risk of headache on the low, compared with high sodium level, both on the control and DASH diets. Obviously, there are many reasons to eat a healthy diet, but prevention of headaches is not one of them.

Interestingly, there was no correlation between elevated blood pressure and headaches.

The authors concluded that reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. This study showed that reducing dietary sodium intake offers a new approach to preventing headaches.

P.S. DASH stands for Dietary Approaches to Stop Hypertension, diet rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat.

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Epilepsy drugs Depakote and Topamax are two of only four drugs approved by the FDA for the prevention of episodic migraines (the other two are blood pressure medications in the beta blocker family, propranolol and timolol, while Botox is the only drug approved for the preventive treatment of chronic migraines). However, these two drugs are contraindicated in pregnancy. Considering that the majority of migraine sufferers are young women, this is a topic that needs to be revisited regularly, especially when additional data appears.

A new study just published in the journal Neurology followed children in the British National Health Service whose mothers suffered from epilepsy and who were taking Depakote (valproate) or Tegretol (Carbamazepine) or Lamictal (lamotrigine). Only Depakote caused a significant drop in IQ in children whose mother was taking more than 800 mg of Depakote a day. Children whose mother took less than 800 mg (the usual dose for migraines is 500 mg, but sometimes 1,000 mg is needed) did not have a lower IQ, but had impaired verbal abilities and a 6-fold increase in needing educational intervention.

Unfortunately, Tegretol and Lamictal are not effective for the prevention of migraine headaches, while Topamax which is effective, can cause birth defects. Neurontin (gabapentin) is a relatively benign medication, which is safe in pregnancy and it is somewhat effective in the prevention of migraines, including chronic migraines.

Ideally, all drugs should be avoided in pregnancy. We usually advise non-drug approaches, including regular sleep, healthy diet, exercise, biofeedback or meditation, and magnesium supplementation. If this is insufficient, we usually recommend Botox if migraines remain frequent (they often improve in pregnancy). Botox is not approved for use in pregnant women, but considering that it acts locally on nerve endings with very little of it getting into the blood stream, it is most likely safer than any drug that is ingested.

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I recommend several supplements to my headache patients. However, the supplement industry is not regulated by the FDA and a few days ago another scandal has erupted. The attorney general of New York ordered Walgreens, WalMart, Target and GNC to stop selling their store brand herbal supplements. His investigation revealed that most of the supplements contained no active ingredients. In case of WalMart, only 4% of their herbal products contained an active ingredient. The tests involved Gingko biloba, St. John’s Wort, Ginseng, Garlic, Echinacea, Saw Palmetto, and Valerian root.

Of the herbal supplements for headaches, I recommend Boswellia and Feverfew made by a high quality manufacturer, Nature’s Way. I do not recommend butterbur, even though I participated in a large study that showed its efficacy in preventing migraine headaches. Butterbur contains several toxic chemicals, which can cause liver damage and other serious problems. Petadolex brand of butterbur claims to be free of these toxic ingredients, but the product is not allowed to be sold in Germany where it is manufactured. Here is my previous post on Petadolex.

Non-herbal supplements such as CoQ10 could also present a problem. For years, I have been recommending WalMart’s brand because it was much less expensive than any other brand and because I assumed that such a large company will have strict quality controls. Now I am thinking that it is possible that the price is so low because there is not much CoQ10 in it. CoQ10 by Nature’s Way costs more than twice as much as WalMart’s ($75 vs $30 for a month supply of 300 mg a day), but it may be worth it.

My most recommended supplement for migraines is magnesium and it is much less likely to present a problem because it is very inexpensive. Most of the cost is in manufacturing, bottling, shipping, etc. and not in the active ingredient.

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An email I just received, which is attached at the end of this post, prompted me to write again about magnesium. In my opinion, every migraine sufferer should try taking magnesium. It’s been 20 years since we published our first study of magnesium, in which we showed that during an attack, half of migraine sufferers have a magnesium deficiency. In that study, patients who were deficient had a dramatic relief of their acute migraine with an intravenous infusion of magnesium. Subsequent studies by other researchers have shown that oral magnesium supplementation can also help. The results of those studies were not as dramatic because many people do not absorb magnesium taken by mouth and in one large study the type of magnesium that was used caused diarrhea in almost half of the patients. The magnesium salts that are better absorbed include magnesium glycinate, gluconate, aspartate (these are so called chelated forms), but some people do well with magnesium oxide, citrate, or chloride. The recommended daily dose of magnesium for a healthy adult is 400 mg a day, but some people need a higher dose. However, higher doses can cause diarrhea, while in others, even a high dose does not get absorbed. In these cases, monthly intravenous injections can be very effective. To establish who is deficient, a special blood test can help. The regular blood test is called serum magnesium level, but it is highly unreliable. A better test is RBC magnesium, but even with this test, if the value is normal, but is at the bottom of normal range, a deficiency is likely to be present. In many people there is no need for a test because they have multiple symptoms of magnesium deficiency. These symptoms include coldness of extremities, leg or foot cramps, PMS in women, “brain fog”, difficulty breathing, insomnia, and palpitations.

Here is the email I just received:

Dr. Mauskop,

I am a 76 year old male; serious headaches began at 8 years of age.
Full migraines started at 18 years of age, with aura, intense pain on one side, violent vomiting.
Sought treatment at UCLA, Thomas Jefferson University, London, Singapore. Had brain scans, biofeedback, full allergy testing, beta blockers. Started on Imigran/Imitrex in 1993 in Singapore, worked well, but did not stop pain completely. Still took a day to recover.
Nothing stopped the 2 to 4 episodes per week.
Two months ago, I read about magnesium deficiency. (Not recommended by any doctor before.)
Took 600 mg capsule per day for three days. No migraine.
Had a bit of diarrhea – checked on internet, saw it was the dose of magnesium.
Dropped intake to 340 mg per day.
Miracle: No migraine in two months.
Thank you for your research and service.
I had an annual physical in December, and mentioned to my doctor – an internist – what I had recently read about magnesium. He had not heard about it; checked on the internet while I was there; and said “interesting”. So, the word is certainly not out.


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Many medical and pain conditions, including migraines, are more likely to occur in people who were abused in childhood. A new study by Richard Lipton and his colleagues compared the risk of developing migraines with the risk of developing episodic tension-type headache in people who experienced emotional abuse, emotional neglect, or sexual abuse. Episodic tension-type headaches are relatively mild and are experienced by most people from a variety of triggers, such as stress, sleep deprivation, hunger, and acute medical illness. Migraines, on the other hand, are much more severe and often cause inability to function and interfere with the quality of life.

Incidence of history of abuse was compared in 8,305 migraine sufferers and 1,429 people who had tension-type headaches. Emotional neglect and sexual abuse was more common in those with migraines but with these two types of abuse the development of migraine was linked to the development of anxiety and depression. Only those with emotional abuse had an increased risk of having migraines even without having anxiety and depression. All three forms of maltreatment were also associated with an increase in migraine headache frequency, but only when anxiety and depression was also present. This study also showed that having two or three forms of abuse was more likely to cause migraines than if only one type of abuse was reported.

Previous studies have also shown a correlation between the number of maltreatment types and pain conditions. These pain conditions include fibromyalgia, irritable bowel syndrome, interstitial cystitis, and temporo-mandibular joint disorder. Exposure to abuse or a traumatic event is thought to lead to a persistent increased excitability of the nervous system, which in turn makes one more predisposed to various pain conditions.

The importance of Lipton’s study is in reminding doctors who treat pain conditions to ask about maltreatment in childhood and about other traumatic events. Post-traumatic stress disorder is common in abuse victims and it needs to be recognized and addressed when treating migraines and pain. Psychological approaches, such as biofeedback and cognitive-behavioral therapy should always be included in the treatment of chronic pain and headaches, but it is particularly necessary in people with a history of abuse or emotional trauma.


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A study by Australian doctors led by Dr. Lyn Griffiths confirmed a previous observation that higher dietary intake of
folic acid leads to lower frequency of migraine headaches. A 2009 study by Spanish doctors showed that patients with migraine with aura are more likely to have high homocysteine levels in their blood, a condition that can be corrected by taking folic acid and other B vitamins.

The authors of this new study have shown before that folic acid, vitamin B6, and B12 supplementation reduces migraine symptoms in patients with a certain genetic mutation (MTHFR gene), which leads to high homocysteine levels. However, the influence of dietary folate intake on migraine has been unclear. The aim of their current study was to analyze the association of dietary folate intake with migraine frequency, severity, and disability.

They studied 141 adult caucasian women with migraine with aura who had the MTHFR gene C677T variant. Dietary folate information was collected from all participants. Folate consumption was compared with migraine frequency, severity, and disability.

A significant correlation was observed between dietary folate consumption and migraine frequency. The conclusion of this study was that folate intake may influence migraine frequency in female sufferers with migraine with aura.

Good dietary sources of folic acid include spinach, lettuce, avocado, and other vegetables. If you suffer from migraine with aura you may want to ask your doctor to check your homocysteine level, as well as levels of folic acid and vitamin B12. Vitamin B12 level is not a reliable test because it can be normal even when a person is deficient and that is why it is important to check homocysteine level as well.

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Vitamin D deficiency has received wide attention and many doctors now check for this deficiency during routine check-ups. I’ve posted about the importance of vitamin D in migraine headaches and for general health. Vitamin D deficiency seems to increase the risk of cancer, other serious diseases and death.

However, just like with vitamin B12 and magnesium, the regular blood test for vitamin D can be misleading. It appears that while blacks have lower levels of vitamin D than whites, they have healthier bones. A study by R. Thadhani of Massachusetts General Hospital explained this paradox. It appears that some of vitamin D circulates in the blood in a free form, while the rest is bound to protein. Only the free form is active, but the blood test measures only the total amount of vitamin D. Blacks appear to have much less of the protein-bound vitamin D, so the amount of the active form can be higher in blacks even if the overall amount of vitamin D is lower. These researchers are developing a more sensitive test for vitamin D levels.

To be on the safe side, most people should aim to have their vitamin D level at least in the middle of normal range. The normal range is 30 to 100 and some studies (for example, in multiple sclerosis) suggest that the higher the level (within the normal range), the better. So, I would recommend getting your level up into the 40s and 50s. Many multivitamins, calcium with vitamin D products, and plain vitamin D supplements have only 200 or 400 units of vitamin D (it is usually listed as vitamin D3). I have seen many patients who need to take 2,000 or even 5,000 units daily to have a good level in the blood. In severe deficiency that does not respond to even these amounts, I prescribe 50,000 units of vitamin D weekly, which is available only by prescription. Unfortunately, unlike with magnesium or vitamin B12, vitamin D is not available in an injection.

The bottom line is that if you are taking a supplement, it does not necessarily mean you have enough of vitamin D in your blood and you should have the test repeated.

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While being overweight doese not cause migraines, in those who do suffer with migraines there is an inverse relationship between person’s weight and the frequency and severity of migraine headaches. Weight loss, including that due to weight loss (bariatric) surgery, has been reported to reduce the frequency of migraine headaches and migraine-related disability. Obesity is also associated with headaches due to increased intracranial pressure (also called pseudotumor cerebri) and losing weight improves such headaches as well.

However, while bariatric surgery may improve migraines, in a small number of people it can cause a different type of headaches. This rare type of headache is caused by a spontaneous leak of cerebro-spinal fluid (CSF), the fluid which surrounds the brain and the spinal cord. Such leaks are common after a spinal tap or can be a complication of epidural anesthesia. Loss of CSF can cause severe headaches, which are strictly positional. They are severe in the upright position, sitting or standing, but quickly improve upon lying down.

A study of 338 patients who underwent bariatric surgery at the Cedars-Sinai Medical Center in Los Angeles detected 11 patients who developed a spontaneous CSF leak with severe headaches. Headaches started anywhere within three months and 20 years after surgery. Clearly, headaches starting 20 years later are not likely to be related to surgery, which suggests that this link between bariatric surgery and headaches is far from proven. Of these 11 patients, 9 improved with treatment. The typical treatment for a CSF leak is a “blood patch” procedure, which involves taking blood from the patient’s vein and injecting it into the area of the leak. When blood clots, it usually seals the leak and the headache improves within hours.

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Vertigo and dizziness are more common in migraine sufferers than in people without migraines. A patient I am treating for migraines emailed me a few days ago complaining of vertigo. Dizziness is a term which can mean unsteadiness, lightheadedness, or vertigo. Vertigo is a sensation of spinning, which is most often caused by a disturbance of the inner ear. One type of vertigo is called benign positional vertigo (BPV). BPV usually causes very severe vertigo. One patients told me that while lying on the floor he felt as if he was falling off the floor. BPV is caused by a loose crystal in the inner ear. As the name implies, this type of vertigo occurs only when turning to one side, but not the other. If turning in bed to the right causes vertigo, then the problem is in the right inner ear. A simple (Epley) maneuver can quickly cure this problem by stopping this loose crystal from rolling around and causing havoc. I emailed my patient a link to a YouTube video showing how to do the Epley maneuver and half an hour later she emailed back saying that the vertigo was gone. Sometimes this maneuver needs to be repeated a few times before vertigo completely disappears. Here is the link to the Epley maneuver

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A report by Taiwanese doctors just published in the journal Neurology suggests that having migraine headaches may double the risk of Bell’s palsy.

Several medical conditions, such as asthma, anxiety, depression, irritable bowel syndrome, epilepsy, and other occur with higher frequency in migraineurs, but until now, no one suspected an association between migraines and Bell’s palsy.

The researchers compared two groups of 136,704 people aged 18 years and older – one group with migraine and the other without. They followed these two groups for an average of 3 years.

During that time, 671 people in the migraine group and 365 of the non-migraine group developed Bell’s palsy.

This association persisted even after other factors such as sex, high blood pressure, and diabetes were taken into account.

The authors speculated that the inflammation and the blood vessel problems seen in both conditions may explain this association.

This study appears to be of purely academic interest since we do not know how to prevent Bell’s palsy. However, I decided to write about it because a couple of my colleagues (one in our office and at least one other on a doctors’ discussion board) reported seeing Bell’s palsy soon after administering Botox injections for chronic migraines. This report by Taiwanese doctors suggests that Bell’s palsy might have been not due to Botox, but rather a coincidence since Bell’s palsy is more common in migraine sufferers.

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Trigeminal neuralgia is a very painful and debilitating condition (Here is a review article I wrote for physicians). Fortunately, it is relatively infrequent – affecting 0.3% of the population, compared to 12% afflicted by migraines. This explains relative paucity of studies of this condition. A group of neurologists at the Danish Headache Center studied 158 consecutive patients with trigeminal neuralgia (TN) seen at their center over a period of one year. They published their findings in the journal Headache.

Average age of onset of pain was 53 years. TN was more common in women than men (60% vs 40%) and more common on the right side (56%). When only one of the three branches of the trigeminal nerve were affected, the first and the second were involved in 69% of cases and the third branch (lower third of the face) alone was involved in only 7% of sufferers.

The pain of trigeminal neuralgia is described the same way by almost all sufferers – it feels like a strong electric shock. It can be triggered by chewing, brushing teeth, speaking, air movement from wind or air conditioner, and at times it occurs without any provoking factor. In this study, half of the patients reported having a more persistent but milder pain in addition to the typical stabbing, electric-like pain. One fifth of patients reported to have some tearing on the side of pain and in 17% there was some loss of sensation over the area of pain.

Treatment of TN usually begins with epilepsy drugs,such as carbamazepine (Tegretol) or oxcarbazepine (Trileptal). Although 89% of patient in this study reported some improvement, only 56% of them were taking these medications because in others they caused unacceptable side effects. Other drugs that can be helpful for TN include baclofen (a muscle relaxant) and Botox injections. I’ve treated a handful of patients with TN with Botox
and about half of them responded. Botox is injected into the area of pain, which tends to be small and only a very small amount of Botox needs to be injected. Injections of Botox are safer than any oral medication, but depending on the area injected, they can cause cosmetic side effects – asymmetric appearance of the face. Botox is approved by the FDA for chronic migraines but not TN, which means that insurance companies are not likely to pay for it. However, only about one tenth of the amount of Botox used for migraine is needed to treat TN, the cost is much lower.

The authors plan to provide additional information about this group of patients in future publications.

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Cost is the only major issue with Botox injections, which is the only FDA-approved treatment for chronic migraines and which is now covered by almost all insurance companies. It is very safe and highly effective, relieving headaches in 70% of migraine sufferers. A study just published in the journal Headache suggests that Botox may be not only clinically effective, but also cost-effective.

Researchers from the Renown Neurosciences Institute in Reno, Nevada analyzed data from 230 chronic migraine sufferers who did not respond to two or more prophylactic drugs and were given Botox injections. Botox was given twice, three months apart. Compared with the 6 months before Botox, there were 55% fewer emergency room visits, 59% fewer urgent care visits, and 57% fewer admissions to the hospital. In those 6 months the savings amounted to half of the cost of Botox treatments. Considering that improvement tends to get more pronounced with each subsequent Botox treatment, it is very likely that the costs savings would grow with additional treatments.

Obviously, besides saving money, Botox provides a significant improvement in the quality of people’s lives, which is much harder to measure. At our Center we give Botox to more than a quarter of our patients and see a dramatic improvement in the majority. Botox is not only much more effective for chronic migraines, but it is also much safer than any oral medication.

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Cyclic vomiting syndrome (CVS) is usually seen in children. The attacks of vomiting often stop as the child gets older, but then they usually go on to develop migraine headaches. A recent report in Headache describes three adults with CVS. The article also mentions a previous report which described another 17 adults with this syndrome.

CVS typically consists of recurrent stereotypical attacks of incapacitating nausea and vomiting, separated by symptom-free periods. Supporting evidence that helps diagnose this condition include personal or family history of migraine and other symptoms, such as headaches, motion sickness, and sensitivity to light.

Just like in children, CVS in adults is a diagnosis of exclusion, meaning that other causes of vomiting must be considered and ruled out. I mentioned in a previous post that one out of three children with CVS turned out to have another medical problem rather than migraine.

CVS in adults seems to respond well to an injection of sumatriptan (Imitrex). This allows for a quick relief of symptoms and makes this debilitating condition very manageable. Besides Imitrex injections, Zomig (zolmitriptan) nasal spray can sometimes be effective as well.

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Placebo effect is a well-documented phenomenon, which is particularly pronounced when treating migraine headaches. Intravenous (IV) infusion of saline water is a placebo commonly used in studies where placebo is compared to a medication also given IV.

It is baffling why a group of Canadian physicians decided to test the effect of (IV) fluids on migraines in children and adolescents seen in an emergency room (the study was just published in Headache). They compared a group of children who were told that they will get only IV fluids with another group who was told that they might also get a medication with the IV fluids. The second group actually watched a nurse add something to the bag of IV fluid, but the children were not told that it was just more of the saline water. The researchers thought that the expectation of getting a medicine will help relieve their migraine headache. In fact neither group, the one who received IV fluids without expecting any medicine and the group who thought that they may be getting medicine had much relief. Strangely, the doctors concluded that additional studies using larger volumes of IV fluids are warranted. As if there is a chance that giving more fluids will stop a severe migraine. Sadly, intravenous fluids are often used in emergency rooms as a treatment for migraines in adults and children and we did not need this study to show that it is an ineffective approach. Doing more such studies seems unethical. Imagine a parent getting up in the middle of the night, taking a sick child to an emergency room where the child receives only intravenous fluids and is sent home with the child still in pain.

Emergency rooms, even in the medical mecca of New York City, are notorious for using ineffective treatments for migraine headaches. If not intravenous fluids, patients often get narcotic (opioid) pain killers, tranquilizers, or antihistamines, such as Benadryl. Some patients are just given a tablet of ibuprofen and are sent home after waiting for hours to be seen and treated. Here is a previous post on what to ask for if you end up in an emergency room with a severe migraine. Obviously, some doctors will not comply with your request, but it is worth asking.

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Considering that meditation can literally change your brain, it is not at all surprising that it can also prevent migraine headaches. A study by doctors at Wake Forest School of Medicine and Harvard Medical School published in the journal Headache confirmed that meditation can prevent migraine headaches.

I’ve written before about studies showing that meditation reduces negative perception of pain and that even three daily 20-minute meditation sessions reduce pain.

Stress is one of the most common triggers for migraine headaches. Many studies of various mind/body interventions have been shown to be helpful for migraine. The researchers in the latest study used a standardized 8-week mindfulness-based stress reduction program that teaches mindfulness meditation and yoga. This approach has been shown to be effective for chronic pain syndromes, but this was the first time it was tested for migraines.

The study included 9 adults who received their usual care and 10 who were enrolled in the meditation program. The program consisted of 8 weekly 2-hour sessions, plus one mindfulness retreat day (6 hours) led by a trained instructor.

All 10 patients completed the program. The program participants had on average 1.4 fewer migraines per month. The reduction ranged from 3.5 to 1.0 migraines, while in the control group the improvement ranged from 1.2 to 0 migraines per month. Headaches were less severe and shorter in those who meditated compared to those who did not. Disability also improved (measured by Migraine Disability Assessment and Headache Impact Test-6) in the active group, compared to controls.

The authors concluded that mindfulness-based stress reduction is safe and feasible for adults with migraines. Although the study included a small number of patients this intervention had a beneficial effect on headache duration, disability, self-efficacy, and mindfulness. The authors feel that there is a clear need for studies with larger numbers of patients. I, on the other hand, feel that every patient with migraines should try meditation even before larger studies are completed. If meditation can increase the thickness of your brain and prevent age-related brain atrophy, it is very likely to have many other health benefits, including prevention of migraine headaches.

How do you start meditating? Meditation classes are widely available and you can start by reading a book or taking an on-line course. I can recommend a book by BH Gunaratana, Mindfulness in Plain English and a website,, but there are many other good resources available.

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Germany was just voted world’s favorite country, according to a report in the USA Today. It also may be the most advanced country in the area of medical rehabilitation. I just came back from Germany where I was invited to give lectures at two prominent clinics. Doctors from both institutions had visited our New York Headache Center to learn about our approach to the treatment of migraines and to learn Botox injection techniques.

My first stop was at the Berolina Klinik, a 280-bed rehabilitation hospital located 80 miles west of Hanover. This hospital provides rehabilitation for a variety of conditions, including orthopedic problems, depression, and chronic headaches. Patients are admitted for a period of 4 to 5 weeks. Treatments available at this institution include physical therapy, biofeedback, individual and group psychotherapy, art therapy, and other. All patient rooms are private. There is a 25-meter (82 feet) swimming pool, gym, inviting dining rooms (with excellent food – I sampled it), green lawns with reclining chairs, and all of it immaculately clean and well-maintained. Staying in such a facility for 4 to 5 weeks is a luxury not available to most Americans. The hospital welcomes patients from abroad and the cost is surprisingly low – about $9,000 for a month of stay, which is less than a third of the cost in the US. They will even pick you up at the Frankfurt airport (third busiest in Europe), which is only 3 hours’ drive. Most of the German patients treated at the Berolina Klinik are covered by insurance, mostly by the German pension fund. The pension fund annually evaluates every facility using strict outcome measures, including the percentage of patients employed two years after being treated at a rehabilitation facility. Berolina Klinik consistently rates among the top German rehabilitation clinics. Dr. Zoltan Medgyessy is the main headache specialist at the clinic and is considered to be one of the leading headache experts in Germany.

The second stop was in Kiel at one of the best German headache and pain clinics, Schmerzklinik Kiel, which is directed by Dr. Hartmut Göbel. This clinic is also an in-patient facility (unlike in the US, where the word clinic implies an office setting). Approximately 70% of patients treated at the Schmerzklinik suffer from headaches and 30% from chronic pain. The clinic is housed in a beautiful building located on the Kiel fjord. Dr. Göbel is one of the top headache researchers and he and I have collaborated on the study of butterbur for the treatment of migraines, which was published in 2004. On this trip I had the honor of speaking in Dr. Göbel’s Master Class – an annual training course for German headache specialists. While I would refer patients who need longer-term rehabilitation (or detox from opioid and other headache drugs) to the Berolina Klinik, Schmerzklinik is where I refer European patients with complicated headache problems and those needing shorter hospital stays.

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A new report by Drs. Gfrerer, Maman and their colleagues at the Massachusetts General Hospital in Boston entitled Non-Endoscopic Deactivation of Nerve Triggers in Migraine Headache Patients: Surgical Technique and Outcomes was recently published in the journal Plastic & Reconstructive Surgery. Surgery for refractory migraine headaches was developed by Dr. Bahman Guyuron and others and was reported to benefit between 68 and 95% patients. This surgery involves cutting or freeing up nerves in the scalp that appear to be responsible for triggering migraines. Some surgeons use a laparascopic technique, which involves making only a few small incisions while others do this surgery through conventional incisions. The authors of this new study argue that endoscopic techniques may not be appropriate in many cases since some surgeons have little experience or limited access to the endoscope and in some patients this technique is not practical because the nerves could run in an unusual pattern, which would make them hard to find through a small incision.

This study involved 43 consecutive procedures in 35 patients. All patients completed questionnaires before and 12 months after surgery. The overall positive response rate was 91%. Total elimination of migraine headaches was reported in 51%, greater than 80% resolution of symptoms in 21%, and 28% had resolution between 50-80%. No improvement was reported after 9% of procedures. There were no major adverse events.

The authors concluded that non-endoscopic surgery was safe and effective treatment in select migraine headache patients.

Most headache experts agree that until proven effective in large controlled studies, surgery should be done only as a part of such a large controlled trial. Just like with previous studies of surgery for migraines, this was a small and not a rigorously controlled trial. Placebo response to surgical procedures is usually very high, however it is rarely 90% and the effect rarely lasts 12 months, as it did in this study. Considering these facts, as well as that this study was done at a reputable institution and that this group consisted of refractory patients (those who did not respond to conventional therapy, including Botox), surgery may in fact offer some real benefits to a small group of patients. We need larger and better controlled trials to figure out if that is indeed the case and what type of patients are the best candidates for surgery.

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Fish oil, or rather omega-3 fatty acids, seem to reduce the risk of Lou Gehrig disease or ALS (amyotrophic lateral sclerosis). An article in JAMA Neurology by Dr. Fitzgerald and her colleagues analyzed 1,002,082 participants in 5 different large-scale studies. A total of 995 ALS cases were documented. A greater omega-3 intake was associated with a reduced risk for ALS. Consumption of both linolenic acid and marine (fish oil-derived) omega-3s contributed to this inverse association. The researchers concluded that consumption of foods high in omega-3s may help prevent or delay the onset of ALS.

Omega-3s may also relieve migraine headaches, help cope better with stress, prevent damage to nerve endings by chemotherapy, prevent mental decline, and provide other benefits.

I usually recommend (and take it myself) Omax3 brand, which is very pure and concentrated.

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Cluster headaches usually occur once or twice a year for a period lasting from a few weeks to a few months. During those periods, they occur daily or more than once a day. Interestingly, these episodes of cluster headaches tend to occur at the same time of year in many patients, but not always at the same time of year. Looking at our data, we have found that in some years many cluster patients developed their attacks in August, another year, in November, and this year, it has been September – October. This year, we are also seeing many patients whose cluster headaches are not responding to usual treatments.

It does not appear that barometric pressure or allergies are responsible for triggering cluster headaches. One unsubstantiated theory is that the solar activity is responsible for bringing on cluster headaches. This report in the Wall Street Journal indicates that we are currently going through a period of an unusually intense solar activity. Perhaps this is why some of our cluster patients are having unusually severe headaches.

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The first time I heard of the potential benefit of stem cells for migraine headaches was last year from one of my patients. This 55-year-old woman had been having some improvement from intravenous magnesium and nerve blocks, while Botox was ineffective. However, she reported a dramatic improvement in her headaches after receiving an intravenous infusion of stem cells in Panama. The stem cells were obtained from a donated umbilical cord.

Stem cell research has been controversial because most of the early research used stem cells obtained from an aborted fetus. Since then, stem cells have been obtained from the bone marrow, umbilical cord, placenta, and artificial fertilization. Another rich source of stem cells is body’s fat tissue. Most of the stem cell procedures are not yet approved in the US. The main concern is that when you obtain stem cells from another person’s umbilical cord or placenta, there is a risk of transmitting an infection. There are relatively few stem cells in the bone marrow, placenta or the umbilical cord, which means that after isolating them, they need to be grown in a petri dish. This process involves adding various chemicals, which may not be safe, according to the FDA.

A group of doctors in Australia recently reported relief of migraines using stem cells from patients’ own fat. These doctors did not grow these cells, but infused them intravenously right after separating them from fat. The infused cells were not only stem cells, but so called stromal vascular fraction, which also includes cells that surround blood vessels. These four patients were given stem cell treatment for osteoarthritis and not migraines, but they noticed that their migraines and tension-type headaches improved.

Four women with long histories of chronic migraine or chronic tension-type headaches were given an infusion of cells isolated from fat, which was obtained by liposuction. Two of the four patients, aged 40 and 36 years, stopped having migraines after 1 month, for a period of 12 to 18 months. The third patient, aged 43 years, had a significant decrease in the frequency and severity of migraines with only seven migraines over 18 months. The fourth patient, aged 44 years, obtained a temporary decrease for a period of a month and was retreated 18 months later and was still free of migraines at the time the report was submitted one month later.

This case series is the first published evidence of the possible efficacy of stromal vascular fraction in the treatment of migraine and tension-type headaches.

It is not very surprising that stem cells can improve migraine headaches because stem cells are tested as a treatment for a variety of inflammatory diseases, such as multiple sclerosis, arthritis, and colitis. Inflammation is proven to be present during a migraine attack and this inflammation may attract stem cells. Many experts believe that stem cells may work for MS or other neurological disorders not by becoming brain cells, but by stimulating body’s own repair mechanisms.

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Beta blockers (Inderal or propranolol and similar drugs) are used for the preventive treatment of migraine headaches. Over the years, a few patients have told me that they take a beta blocker only when they have an attack of migraine with very good results. A report published in Missouri Medicine describes seven patients whose acute migraine headache went away with eye drops containing a beta blocker. These eye drops are used for the treatment of glaucoma. The authors argue that having medicine go into the eye allows it to get absorbed quickly into the blood stream. This is certainly true, but my first thought was that there is too little medicine in eye drops to produce an effect outside the eye. However, beta blocker eye drops can worsen asthma, lower the blood pressure and slow the heart rate, suggesting that the amount of medicine in eye drops is sufficient to cause effects beyond the eye. Oral beta blockers used daily for the preventive treatment of migraines are also contraindicated in those medical conditions. Considering that eye drops are probably safer than many oral medications used to treat an acute migraine attack and that they most likely work faster, this treatment is worth trying.

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Parkinson’s disease (PD), parkinsonian symptoms, and restless leg syndrome (RLS) are more common in people who in middle age suffered from migraines with aura. Those suffering from migraine without aura in their midlife had increased risk of having symptoms of Parkinson’s and RLS, but not PD. These are the findings of a large study of residents of Reykjavik, Iceland who were born between 1907 and 1935. These residents had been followed since 1967. Headaches were classified based on symptoms assessed in middle age. From 2002 to 2006, 5,764 participants were reexamined to assess symptoms of parkinsonism, diagnosis of PD, family history of PD, and RLS.

People who suffered from migraines, particularly migraine with aura, were in later life more likely than others to report parkinsonian symptoms and diagnosed to have PD. Women with migraine with aura were more likely than others to have a parent or sibling with PD. Late-life RLS was increased in those with headaches generally.

The authors concluded that there may be a common vulnerability to, or consequences of, migraine and multiple indicators of parkinsonism.

There are no proven ways to prevent PD, but eating more fruits and vegetables, high-fiber foods, fish, and omega-3 rich oils (or taking an omega-3 supplement, such as Omax3) and avoiding red meat and dairy may have some protective effect against PD.

Intensive research into the causes and treatment of Parkinson’s disease, supported by Michael J. Fox and Sergey Brin of Google among others, should lead to true breakthroughs in the next few years.

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Stabbing headaches can be a sign of acute multiple sclerosis, according to a report by German doctors in the journal Headache. Stabbing headache is a rare type of headache, although patients with migraines often report having occasional “ice pick” headaches. Some call these headaches “jabs and jolts”. In some people, stabbing headaches can be quite disabling. The pain lasts only a couple of seconds but can occur up to 100 times a day. Treatment usually involves indomethacin or another non-steroidal anti-inflammatory medication in the aspirin family (including our own Migralex). However, in this case where stabbing headaches were associated with MS, treating MS relieved headaches as well.

In a prior report in Clinical Neurology and Neurosurgery Italian physicians also found that of 26 patients with stabbing headaches they had seen over 10 years, more than half had autoimmune disorders, including multiple sclerosis, Sjögren’s disease, lupus, Behçet’s disease, autoimmune vasculitis, and antiphospholipid antibody syndrome. The authors speculated that stabbing headache may develop as a result of inflammation in the brain with loss of myelin around the nerve fibers, which is seen with MS and other auto-immune disorders.

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Peripheral nerve blocks can be very effective in stopping a severe migraine attack. We utilize them when a patient does not respond to oral or injected medications or when medications are contraindicated because of a coexisting disease or pregnancy.

Dr. Jessica Ailani and her colleagues at the Georgetown University in Washington, D.C. presented their experience with nerve blocks at the last annual meeting of the American Headache Society in Los Angeles. The study included 164 patients. Most patients received occipital and trigeminal nerve blocks using lidocaine or a similar local anesthetic.

Most patients were satisfied with the results, which lasted from several days up to 2 weeks. Only a small number of participants experienced side effects such as soreness at the site of injections, nausea and vomiting, and head and neck pain.

Dr. Ailani noted that more than 71% of patients rated their pain as 4 to 8 out of 10 before treatment with a nerve block. After a nerve block, nearly half (47.2%) said the pain had reduced to 1 out of 10.

“This is a very well-tolerated procedure and patients are very satisfied with the procedure,” said Dr. Ailani.

Nerve blocks can help keeps headache sufferers out of the emergency room and provide an alternative to systemic drugs, that is drugs that are injected or ingested. Systemic drugs affect the entire body while nerve blocks exert only local effects (unless one is allergic to local anesthetics).

Dr. Robert Kaniecki, a headache specialist in Pittsburgh uses nerve blocks for the prevention of chronic migraine headaches. He administers them into the same areas where Botox is injected. He finds that for some of his patients nerve blocks given every 12 weeks can be as effective as Botox. It is possible that such patients have milder migraines since the effect of nerve blocks lasts a very short time (lidocaine leaves the body after 4 hours or so) compared with the effect of Botox which lasts 3 months. Unlike Botox injections, nerve blocks have not been subjected to a rigorous scientific study comparing them to placebo (saline) injections.

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Frequent attacks of migraine are best treated with preventive measures. Several categories of medications have been shown to be effective for the prevention of migraine headaches. These include Botox injections (for chronic migraine), epilepsy drugs (gabapentin, topiramate, divalproex), blood pressure medications (propranolol, atenolol, lisinopril, losartan, and other), as well antidepressants.

Antidepressants, like most other preventive drugs, were discovered to be effective for pain and headaches by accident. We have good scientific proof that you do not need to be depressed to obtain pain and headache relief from these drugs. The effect on pain and on anxiety or depression are independent of each other. However, many patients who have pain and headaches have higher rates of depression and anxiety and these drugs can relieve both conditions.

The oldest category of antidepressants are tricyclic antidepressants. Elavil or amitriptyline was introduced in the US in 1961. Amitriptyline has been extensively tested for a variety of painful conditions, including low back pain, neuropathy pain, migraines, and other. The main side effects of amitriptyline are dry mouth, drowsiness, constipation, and sometimes, weight gain. Other drugs in the family of tricyclic antidepressants often have fewer side effects. Many doctors always begin with nortriptyline or Pamelor, which is a derivative of amitriptyline and may have fewer side effects. Amitriptyline is broken down in the body into nortriptyline, which is less sedating. We also prescribe other tricyclics, desipramine (Norpramine), doxepin (Sinequan), and protriptyline (Vivactil), which also tend to have fewer side effects. When a patient has insomnia and is not prone to gaining wait, amitriptyline may be the better choice since it will also improve sleep.

The starting dose of amitriptyline, nortriptyline, doxepin, and desipramine is 10 or 25 mg taken at night. Then, if this starting dose is ineffective, the dose is gradually increased to 50 mg, then 75, and sometimes higher. Besides being very effective, tricyclics have another advantage – there is a blood test to measure how much of the medicine is absorbed and is circulating in the body. When a patient takes more than 75 – 100 mg without obtaining relief, we do a blood test to see if the blood level is low and we need to increase the dose or if the level is high and the drug is just ineffective. With protriptyline, the least sedating drug, the starting dose is 10 mg and the highest dose is around 30 mg. Treatment of pain and migraines usually requires a much lower dose of a tricyclic than for depression. All of the tricyclics are available in a generic form and are inexpensive.

Another category of antidepressants that relieve pain and headaches is serotonin and norepinephrine reuptake inhibitors, or SNRIs. Some of the SNRIs are FDA-approved for various painful conditions, such as neuropathy, shingles, fibromyalgia, and back pains. Most popular SNRIs are Effexor (venlafaxine), which is available in a generic form, Cymbalta (duloxetine), Pristiq (desvenlafaxine), Savella (milnacipran), and Fetzima (levomilnacipran). These drugs have fewer side effects than tricyclics, although they are sometimes difficult to stop because they can cause heightened anxiety and other withdrawal symptoms.

Nardil (phenelzine) is an antidepressant in the family of MAO inhibitors and it has also been used for the preventive treatment of migraine headaches. However, this drug has many potential serious drug-drug and drug–food interactions and most doctors avoid this medicine. Other MAOI drugs are Parnate (tranylcypromine), Emsam patch (selegiline) and other.

SSRIs are the most popular drugs for the treatment of anxiety and depression, but they are ineffective for the treatment of pain, migraines, and other headaches. These drugs include Prozac (fluoxetine), Paxil (paroxetine), Lexapro (escitalopram), Zoloft (sertraline) and other. They are very popular because they have fewer side effects than other antidepressants, although they probably cause higher rates of sexual dysfunction.

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Severe persistent migraines can affect emotional, interpersonal, social, and work-related functioning. It is difficult to learn how to cope with pain and improve your functioning on your own. Cognitive-behavioral therapy (CBT) has been proven to improve lives of people with pain, including migraine headaches and not only in adults, but also in children. One major problem with CBT is that it is not readily available in many areas and when available, it is expensive.

I’ve written about two online programs for CBT, which offer help to patients with anxiety and depression. Another online service offers free resources that have been shown to improve coping with pain, to decrease anxiety and depression, and to provide other benefits. The site offers help to patients with migraine, as well as cancer pain, back and arthritis pain, and neuropathic pain. The migraine section has five modules: communication skills, emotional coping, self-management skills, knowledge base, and medication safety.

I do have a problem with their medication safety section in that it does not mention caffeine and caffeine-containing drugs when describing rebound, or medication overuse headaches. These drugs include Excedrin, Anacin, Fiorinal, Fioricet, Esgic, and other. At the same time, they list aspirin, which actually may prevent medication overuse headaches and triptans, which rarely cause such headaches (one of my most popular posts is devoted to daily intake of triptans, which is not something I encourage, but which is the only solution for some patients).

But overall, this is a very useful resource for headache sufferers. To take full advantage of this site you need to go through multiple modules, preferably on a regular basis, say twice a week. It is also useful to keep going back to the old material since it is not easy to change faulty thought processes. The site has enough material to keep you engaged for many sessions. And if you do visit the site regularly you will find that your headaches may become more manageable and that they may have less of an impact on your life.

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Expiration date on medications does not indicate that the medication is no longer effective or safe after that date. Having had extensive experience with the production and testing of Migralex, I can reassure you that medications remain safe and effective for years after the expiration date. An article just published in the Wall Street Journal’s “Burning Question” column addresses this issue.

The FDA has conducted a study for the Department of Defense testing 122 different drugs. The conclusion of the study was that 88% of the drugs remain effective for an average of 5 and 1/2 years after the expiration date. The main problem with expired drugs is not that they become dangerous to use, but that their efficacy slowly declines. A doctor quoted in the WSJ article says that there have been no reported cases of toxicity from expired medications. But a decline in efficacy could be a problem with life-saving drugs, such as nitroglycerin for heart, EpiPen for allergies, or insulin for diabetes.

It is very important to store the medications in a dry cool place, rather than in a medicine cabinet in the bathroom, which periodically gets hot and humid. Also, do not leave drugs in a car during the summer – the temperature in a locked car left in the sun can rise to 130 degrees and higher.

I usually advise not to use drugs beyond two years of the expiration date even if they were kept in a dry and cool place. Before using an expired drug inspect the tablet to make sure it hasn’t turned colors, smells bad, or became brittle and crumbling. Obviously, if it is an inexpensive generic drug, get a fresh bottle. However, with expensive drugs, such as some triptans (Relpax, Frova, Axert) and injections of Imitrex (sumatriptan) considerable amounts of money can be safely saved. A common scenario is a patient with cluster headaches who has a bout every couple of years and has only expired injections of Imitrex. It usually takes at least a few days to be seen by a doctor and to get a new prescription, while the attacks of cluster headaches can be devastatingly severe. Again, the worst that can happen is that the injection will be less effective, but usually it will still provide some relief.

There is a difference in how long expired drugs remain effective depending on the formulation. For example, tablets are the most stable, while creams and liquid drugs, such as drops, are least likely to last past the expiration date.

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A report from the Cleveland Clinic and Case Western Reserve describes 22 patients with new daily persistent headaches (NDPH) who were treated with Botox injections.

NDPH is a condition in which the headache begins suddenly without an obvious trigger and persists continuously without a break. Because NDPH is relatively uncommon, there have been no large studies of this condition. Patients with NDPH usually do not exhibit symptoms of migraine, such as throbbing pain, nausea, sensitivity to light, noise or physical activity. Because of its sudden onset, we suspect that these headaches may be the result of a viral or another type of infection. There are no treatments that consistently relieve these headaches, but we usually try all of the drugs and approaches we use in migraines.

A group of doctors from Cleveland, Ohio discovered that while Botox seems to help, only 32% of patients with NDPH showed improvement, confirming the refractory nature of this type of headaches. Twenty one of the 22 patients underwent more than one treatment with Botox and most were given a standard migraine treatment protocol with 155 units injected into 31 sites. The improvement was modest but it did result in headache-free days, which were not observed prior to this treatment. The disability improved slightly and when the improvement did occur, it lasted about 8 weeks. Some of our chronic migraine patients also require Botox injections every 8 to 10 weeks, instead of the usual 12. Considering that we do not have any better treatments, Botox should be offered to patients with NDPH.

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A new combination of two old drugs seems to provide relief for some trigeminal neuralgia (TN) sufferers. The first line drugs for TN are epilepsy drugs, carbamazepine (Tegretol) or oxcarbazepine (Trileptal). A presentation at the last annual scientific meeting of the American Headache Society by Saudi physicians described successful use of another epilepsy/pain drug, pregabaline (Lyrica) with an antidepressant/pain drug duloxetine (Cymbalta). Both Lyrica and Cymbalta are approved by the FDA for the treatment of some pain conditions, although not TN. The doctors compared Lyrica alone with Lyrica and Cymbalta in combination in 200 patients. The combination resulted in an 80% reduction of pain, which was observed within 10 days, while Lyrica alone produced a 60% reduction that started within 20 days. The dose of Lyrica was 150 mg twice a day (after a one week build up from 75 mg twice a day) and the dose of Cymbalta was 60 mg a day.

Since both Cymbalta and Lyrica have pain relieving properties, this appears to be a rational combination of medications to use in TN and possibly other painful conditions, including various types of headaches. However, as a general rule, we try to use a single drug whenever possible to reduce the potential for side effects. TN is such a severe and debilitating condition, that it may be justified to use a combination early, especially if the first line drugs, such as oxcarbazepine fail.

In my previous posts I have described the use of intravenous medications, Botox and other invasive treatments for TN.

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Post-concussion syndrome, which often includes headaches, can persist for many months especially after a minor injury (yes, mild injury is more likely to cause post-concussion syndrome than a severe one).
However, little is known about prognosis after the injury. The symptoms fall into three categories – cognitive (such as memory, concentration difficulties), somatic (headaches, dizziness, etc), and emotional (irritability, anxiety, depression). A study by French physicians recently published in JAMA Psychiatry, also took into account the fact that injuries are often sustained during psychologically distressing events (car accidents, assaults, falls) and looked for symptoms of post-traumatic stress disorder (PTSD) in those patients.

The authors conducted a study of patients seen at an emergency department for a mild head injury. They checked on these patients for persistent symptoms three months after the concussion. The study included 534 patients with head injury and 827 control patients with non-head injuries.

The study showed that three months after the injury, 21.2 percent of head-injured and 16.3 percent of nonhead-injured patients had post-concussion syndrome, while 8.8 percent of head-injured patients met the criteria for PTSD compared with only 2.2 percent of control patients.

Their conclusion was that it is important to differentiate post-concussion syndrome from PTSD because it has important consequences, in terms of treatment, insurance resource allocation and advice provided to patients and their families. They also stressed the importance of considering PTSD in all patients with mild traumatic brain injury who suffer persistent symptoms.

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Botox is FDA-approved only for chronic migraine headaches, however, it is being used “off-label” for other types of headaches as well. We find that frequent episodic migraines, cluster headaches, numular, and cervicogenic (neck-related) headaches improve with Botox. In our practice, post-traumatic headaches also seem to respond to Botox.

A report by neurologists from Stony Brook University describes five patients suffering from post-traumatic headaches, who responded to Botox. These patients sustained a traumatic brain injury and had suffered from post-traumatic headaches for years, despite trials of various prophylactic medications. After treatment with Botox, all of their five patients had greater than 50% improvement of their disability as measured by the MIDAS (MIgraine Disability Assessment Scale) questionnaire.

This is not a surprising observation because in many patients with a traumatic brain injury headaches have migraine features, suggesting similar underlying mechanisms. People with a family history of migraines who sustain a head injury seem to be more likely to develop post-traumatic headaches than those without such family history, which also suggests a link with migraines. Some patients with post-traumatic headaches and especially those with overt whiplash injury (almost all head injuries, to a varying degree, involve a whiplash neck injury) may respond to Botox because Botox relaxes tight muscles. We no longer think that this is the reason Botox helps migraines because there is evidence that in migraines Botox works by blocking sensory nerve endings rather than by relaxing muscles.

Because of the cost, insurance companies are often unwilling to pay for Botox to treat anything but chronic migraines. However, headaches that begin after a head injury and are accompanied by some migraine features can be correctly classified as post-traumatic chronic migraines, thus avoiding difficulties with the insurance companies.

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Acetaminophen is what most obstetricians recommend pregnant women take for their headaches. However, it is not very effective for migraine headaches and it is not as safe as we thought (see my recent post). Fioricet is another drug favored by some obstetrician and it is also not very effective and not very safe.

Sumatriptan (Imitrex) was introduced 20 years ago and the manufacturer has maintained a registry of women who took the drug while pregnant. The final results of this registry were just published in the journal Headache. The registry included 626 women who were exposed to sumatriptan during their pregnancies. They also followed women who took two other migraine drugs, naratriptan (Amerge) and a combination of sumatriptan with naproxen (Treximet). However, there were too few women in those groups to make any conclusions about the drugs’ safety.

As far as sumatriptan, the risk of major birth defects was not increased. The authors also reviewed several other large studies which assessed the risk of taking migraine medications during pregnancy. One of the studies were from the Swedish Medical Birth Register, which included 2257 births following first trimester sumatriptan exposure. No risk was found in this study either.

In summary, pregnant women suffering from severe migraines should be prescribed sumatriptan. Most women respond to an oral form (tablet), but those with very severe attacks should be offered an injection.

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Skipping meals, for some people, is a sure way to get a migraine headache. Even those who do not suffer from migraines can get a headache from not eating breakfast and lunch. However, fasting has remained popular for the treatment of various conditions. Migraine sufferers who suspect that some foods may be triggering their headaches are sometime advised to try an elimination diet. This diet often begins with a fast and then one type of food is introduced at a time to see if it triggers a negative reaction. Anecdotal reports describe relief of migraine headaches with fasting for periods of up to five days. Some programs recommend five-day fasts twice a year, while others are advocating five days each month. A 5:2 diet involves eating a normal amount of calories for five days and the following two days eating 1/4 of that amount. The problem is that some people will have worsening of their headaches in the first day or two. However, most patient reports that after having headaches for a day or two the head becomes very clear.

It is not clear if fasting helps various medical conditions, if indeed it does, which remains an open question. One potential mechanism may involve stem cells. Recent studies suggest that fasting causes proliferation of stem cells. The study was published in the journal Cell Stem Cell. The research was done in mice and showed that prolonged fasting protects against immune system damage and induce immune system regeneration. The researchers speculated that fasting induces stem cells from a dormant state to a state of proliferation.

One of the authors of the study said that “We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system. When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged. What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. ”

Fasting and induction of stem cells seems to reduce an enzyme which has been linked to aging, tumor progression and cancer. Fasting also protected against toxicity in a small human trial where patients fasted for 72 hours prior to chemotherapy.

“Chemotherapy causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy.”

So, how long do you need to fast to induce your stem cells and to get beneficial results? Some advocate suggest one or two days a week. Others promote twice yearly five-day fasts. The bottom line, we have no research on this topic.

Fasting may help protect against brain disease. Researchers at the National Institute on Aging have found evidence that fasting for one or two days a week can prevent the effects of Alzheimer and Parkinson’s disease. Research also found that cutting the daily intake to 500 calories a day for two days out of the seven can show clear beneficial effects for the brain. It is possible that fasting helps by inducing proliferation of stem cells in the brain.

Fasting cuts your risk of heart disease and diabetes:
Regularly going a day without food reduces your risk of heart disease and diabetes. Studies show that fasting releases a significant surge in human growth hormone, which is associated with speeding up metabolism and burning off fat. Shedding fat is known to cut the risk of heart disease and diabetes. Doctors are even starting to consider fasting as a treatment.

3. Fasting effectively treats cancer in human cells:
A study from the journal of aging found that cancer patients who included fasting into their therapy perceived fewer side effects from chemotherapy. All tests conducted so far show that fasting improves survival, slow tumor growth and limit the spread of tumors. The National Institute on Aging has also studied one type of breast cancer in detail to further understand the effects of fasting on cancer. As a result of fasting, the cancer cells tried to make new proteins and took other steps to keep growing and dividing. As a result of these steps, which in turn led to a number of other steps, damaging free radical molecules were created which broke down the cancer cells own DNA and caused their destruction! It’s cellular suicide, the cancer cell is trying to replace all of the stuff missing in the bloodstream that it needs to survive after a period of fasting, but can’t. In turn, it tries to create them and this leads to its own destruction.

This post contains direct quotes from

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Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain. However, Botox is an expensive and somewhat unpleasant treatment. Even though Botox helps a high percentage of patients (about 70%) it would be useful if we could predict who is going to respond and who is not.

One of the predictors seems to be the directionality of pain. That is, if patients with migraine who have constricting (imploding) pain or pain localized to the eye seem to respond better than those who have pain that seems to be pushing from inside out (exploding). This is not a very reliable predictor because some people have difficulty categorizing their pain in that way and because even if they do describe it clearly one way or another, this predictor is far from 100% accurate.

In a study just published in the journal Headache a group of Spanish neurologists claim that they have found a predictor with 95% accuracy. They measured blood levels of calcitonin gene-related peptide (CGRP) and found that those with levels of CGRP above a certain number were 28 times more likely to respond to Botox than those with levels below that level.

CGRP has been shown to be very involved in the process of migraine and several drugs and antibodies which block the CGRP receptor appear to be very promising (see my recent blog post on such antibodies). So, it is not very surprising that this correlation between the response to Botox and blood level of CGRP was found. However, this finding needs to be confirmed in a larger group of patients (this study involved 81 patients) and this test needs to become available commercially since now it can be done only in research laboratories.

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Besides many other mental and physical problems, bullying in school causes headaches. This is the conclusion of a group of psychologists at the University of Padua in Italy who published their findings in the last issue of the journal Headache. They looked at 20 published studies on bullying, which included 173,775 children, and found that 14 of these studies recorded the presence of headaches. While 19% of kids who were not bullied suffered from headaches, this number was 33% in those who were. There was no difference in the incidence of headaches between kids in Europe compared to other countries.

This study confirms what has been reported for health problems in bullied kids in general. It is well known that psychological stress causes physical symptoms. Social pain is a term that psychologists use to describe the effect of peer rejection, ostracism, or loss. Recent studies have shown that physical and social pain share many physiological mechanisms in the brain. The authors also speculate that lack of coping skills, low self-esteem or lack of assertiveness may lead to more psychological and physical problems. They also call on pediatricians, school nurses and others to become more aware of the physical symptoms, such as headache, as a manifestation of bullying.

I have seen a number of children with severe persistent headaches, which required home schooling. In some of these kids bullying was a definite contributing factor, although many children are reluctant to admit this even to their parents.

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The introduction of Levadex has been delayed again, this time for a year. It seems like deja vu all over again – I wrote the same thing on this blog in April of last year. Levadex, which the manufacturer (Allergan) just renamed as Semprana, is an inhaler containing DHE. DHE, or dihydroergotamine is one of the most effective injectable drugs for migraine. It should be even better in an inhaled form because it works faster and causes much less nausea than the injection. The FDA is again delaying the launch because of manufacturing problems. Apparently, the particle size of the drug when it comes out of the inhaler is not uniform enough. Many patients are unhappy, but I am sure that the Allergan is very unhappy too since they spent almost a billion dollars to acquire this drug from a small company that developed it.

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Migraine aura precedes the headache in about 20% of patients. The most common type of aura is visual. It consists of flashing lights, sparkles, partial loss of vision, and other visual distortions, which can move across the visual field. Typical duration of the aura is 20 to 60 minutes and it can occur without a headache. Many people get frightened when experiencing an aura for the first time. Thoughts of a brain tumor spring to their minds. Although auras rarely indicate a serious problem, an MRI scan is usually indicated when an aura occurs for the first time.

MRI scans are considered to be safe in pregnancy, but the current guidelines of the FDA require labeling of the MRI devices to indicate that the safety of MRI with respect to the fetus “has not been established”. Not surprisingly, most expecting mothers instinctively try to avoid any testing. So, what to do if a pregnant woman develops an aura? A study by headache specialists at the Montefiore Headache Center in the Bronx suggests that this is not an uncommon occurrence. Of 121 pregnant women presenting with an acute headache, 76 had migraines and a third of these had an aura for the first time in their lives. Two thirds of auras occurred in the third trimester. This report should be reassuring and may help avoid unnecessary MRI scans. However, MRI may still be needed if there are other signs of a more serious neurological problem on examination or by history.

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“Visual snow” is a continuous TV-static-like visual disturbance experienced by some people who suffer from migraines and by some without migraines. A group of British doctors examined 120 patients with persistent “visual snow” and found that 70 of them also suffered from migraines. Of these 70, 37 had migraine with aura and 33 had migraine without aura. Many of these patient had other visual complaints: some had a trailing after-image when shifting their gaze, saw sparkles, were always sensitive to light, and had poor night vision. Fifty two of them also complained of noise in their ears (tinnitus).

Seventeen of these patients underwent PET scans of their brain, which were compared to PET scans of 17 normal control subjects. Those with “visual snow” had increase brain activity in two parts of the brain, indicating that this is not a psychological or an eye problem, but a brain disorder.

Unfortunately, the authors did not provide any ideas as to how to treat these patients. However, the fact that some areas of the brain were overactive, suggests that using epilepsy drugs, which suppress excessive brain cell activation and are proven to help migraines, may help. These drugs include gabapentin (Neurontin), topiramate (Topamax), and divalproate (Depakote). Before using drugs though, I would suggest trying magnesium orally or intravenously because magnesium also reduces excitability of the nervous system and because half of migraine sufferers have low magnesium levels. See an article on magnesium and migraines here.

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The benign nature of white matter lesions (WML) on MRI scans of patients with migraine was noted in a post last year. While they appear to be benign, they are disconcerting nevertheless. It is possible that we haven’t yet discovered the negative effects they may have.

A study by Chinese researchers published in the Journal of Neurology reported on MRI scans in 141 people, including 45 healthy controls without migraines, 38 chronic migraine sufferers who were not overusing acute migraine medications and 58 patients with chronic migraines who were overusing these medications. They found that women, but not men, who were not overusing acute medications had more WML compared with controls and those who were overusing medications. As reported by other researchers, the number of WML increased with age. Interestingly, most patients who overused medications were taking non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen and naproxen. The authors concluded that taking NSAIDs may have a preventive effect on the development of WMLs, possibly because of their anti-inflammatory properties. Previous studies have shown that aspirin does not even cause medication overuse headaches, unlike drugs with caffeine (Excedrin, Fiorinal, Fioricet), opioid analgesics (Vicodin, Percocet, codeine, etc), and to a lesser extent NSAIDs.

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Idiopathic intracranial hypertension is also called pseudotumor cerebri because just like with a brain tumor, the
pressure is increased inside the skull. This condition usually presents with a headache and sometimes with visual symptoms. Increased intracranial pressure is not only a very painful condition, but also, if left untreated, can cause loss of vision and strokes.

An observational study just published in JAMA Neurology reports on 165 patients with pseudotumor seen by a group of neurologists and ophthalmologists across the country. The mean age of these patients was 29 and only 4 were men. The vast majority of them were obese with an average body mass index of 40, while normal is below 25. Headache was present in 84% of patients and 68% reported transient loss of vision. Half of them had back pains and pulse-like noise in the ears (pulsatile tinnitus) was reported by 52%. Visual loss was found in 32% and it was usually loss of the peripheral vision with an enlarged blind spot in the middle.

The authors concluded that pseudotumor cerebri mostly occurs in young obese women. The importance of this report is in reminding physicians to consider this diagnosis in young obese women with headaches. The diagnosis is confirmed by performing a lumbar puncture (spinal tap), which is the only way to measure intracranial pressure. An MRI scan is also always done (before the spinal tap), to make sure that it is not a real tumor that is causing increased pressure and to visualize ventricles (fluid-filled spaces) inside the brain. These ventricles are usually small in patients with pseudotumor. Performing the lumbar puncture involves draining of the cerebrospinal fluid, which can immediately relieve the headache and also improve vision. Some patients require regular spinal taps or placement of a draining shunt (usually from one of the brain’s ventricle or spinal canal to the abdominal cavity).

However, many patients respond to medications, such as acetazolamide (Diamox) or topiramate (Topamax). Weight loss is the most effective, albeit difficult treatment. The same group of physicians reported that acetazolamide combined with weight loss was somewhat more effective than weight loss alone. Only rarely, when vision is acutely threatened, a surgical procedure to relieve pressure inside the optic nerve is performed by an ophthalmologist (the procedure is called optic nerve sheath fenestration).

In summary, increased intracranial pressure is often mistaken for chronic migraine and should be considered in every young female obese headache sufferer.

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Don’t use Wikipedia for medical information and tell your doctor not to either. It is the most popular reference site not only for the lay public, but also for doctors – anywhere from 47% to 70% of physicians and medical students admit to using it as a reference.

A study just published in a medical journal shows that Wikipedia very often offers erroneous information.The researchers looked at articles on 10 common conditions: coronary artery disease, lung cancer, major depression, concussion, osteoarthritis, chronic obstructive lung disease, hypertension,diabetes, back pain, and hyperlipidemia.

Articles on each condition were evaluated independently by two physicians to make sure that the evaluations were not biased and were consistent between two doctors. The information on Wikipedia was compared to the up-to-date information on these diseases published in scientific medical journals. Shockingly, only information on concussion was accurate, while information on the other nine conditions contained serious errors. This study did not include migraines or other headaches, but it is very likely that at least some information on these conditions are also incorrect.

Tell your doctor about this study, just to make sure that he or she knows about it. For consumers, the best sources of information are,, and

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Cluster headache patients have been coming to our office in increasing numbers in the past few weeks. We seem to be in a cluster season – many patients with cluster headaches come within the same month or two and then, for several months we see very few cluster patients. Many cluster headache sufferers ask about the efficacy of LSD, hallucinogenic mushrooms and seeds.

The use of hallucinogens for cluster headaches was first reported by a Scottish man in 1998. He started using LSD for recreation and for the first time in many years had a year without cluster headaches. The first report in scientific literature appeared in 2006 in the journal Neurology. Dr. Sewell and his colleagues surveyed 53 cluster headache sufferers, of whom 21 had chronic cluster headaches. Half of those who tried LSD reported complete relief.

Researchers are trying to study a version of LSD (brominated LSD) that does not cause hallucinations. This form of LSD was reported in the journal Cephalalgia to stop cluster attacks in all five patients it was given to. It is not clear if any additional studies are underway, but one American doctor, John Halpern is trying to bring this product to the market in the US.

Trying to obtain LSD or hallucinogenic mushrooms carries legal risks, including incarceration. According to Dr. McGeeney, who is an Assistant Professor at Boston University School of Medicine, it is legal to buy, cultivate, and sell seeds of certain hallucinogenic plants, such as Rivea Corymbosa, Hawaiian baby woodrose, and certain strains of morning glory seeds. However, it is not legal to ingest them.

The bottom line is that I urge my patients not to try hallucinogens because their safety has not been established. This is especially true for illicit products, which may contain additional toxic substances.

Fortunately, we do not need to resort to these agent because we have such a variety of safer and legal products. These include preventive medications, such as verapamil in high doses, topiramate, lithium, and for chronic cluster headaches, Botox injections. None of these drugs are approved by the FDA and are not likely to be approved because this is a relatively rare condition, which makes performing large studies very difficult. The only FDA-approved drug for cluster headaches is an abortive drug, injectable sumatriptan (Imitrex).

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Two new migraine drugs are about to be released on the market. They were mentioned in this blog in their earlier stages of development. Another two drugs are more interesting, but are several years away from becoming available (if at all).

Zecuity is a patch that delivers sumatriptan (active ingredient in Imitrex) through the skin. The patch contains a small battery and the electric current it generates helps the medicine penetrate through the skin. The patch is particularly useful when migraine is accompanied by nausea and vomiting. The main side effect of the patch, compared to the tablet, is that it causes irritation of the skin in one third of patients. This product was already approved by the FDA and will be soon available in pharmacies from its manufacturer, Teva Pharmaceuticals.

Levadex is a drug inhaled into the lungs using a device similar to those used for asthma drugs. It contains dihydroergotamine – a very old and very effective injectable drug. Dihydroergotamine does not work well in a nasal spray (Migranal) or when taken by mouth. Levadex causes less side effects, such as nausea, than the injection of this drug. The main target population for this drug is also migraine sufferers who experience nausea and vomiting and for whom tablets do not work. Because it works very fast it may be also very effective for those whose headache starts and escalates to a severe intensity very quickly, which includes not only migraine, but also cluster headache sufferers. Levadex is manufactured by Allergan, the company that also makes Botox. It should be available in the next few months.

Lasmitidan is a new drug being developed by CoLucid. It is in phase III trials, which is the final phase, which if successful, can lead to the FDA approval. Lasmitidan is a new type of drug – it targets a specific serotonin receptor subtype – 1F, while triptans (sumatriptan, rizatriptan, and other) target 1B and 1D serotonin receptors. It may have the advantage of not constricting arteries at all and may be allowed in patients with coronary artery disease. Triptans are contraidicated in such patients.

Merck is developing a drug, which does not have a name yet, only a number – MK-1602. It is a CGRP receptor antagonist – a blocker of a neurotransmitter in the brain that is involved in migraine origination. It is in phase II trials. MK-1602 also has the advantage of not constricting arteries. At least two other companies are developing CGRP antibodies (different from CGRP antagonists) and they were mentioned in a recent post here.

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The versatility of botulinum toxin continues to amaze. The use of botulinum toxin (Botox) for the treatment of migraine headaches (pioneered at the New York Headache Center) is becoming widespread in the US. The original FDA-approved indications for botulinum toxin was a rare eye condition, blepharospasm as well as strabismus. The number of indications (not all of them yet FDA-approved) for botulinum toxin has increased very quickly – from cosmetic use for wrinkles to gastrointestinal disorders (narrowing of the esophagus, rectal fissures), excessive sweating, muscle spasticity of cerebral palsy and following a stroke, neuropathic pain (neuropathy, trigeminal neuralgia, shingles), spastic bladder (which causes frequent urination), and other.

Injecting botulinum toxin into the fat pads around the heart after coronary bypass surgery seems to reduce the incidence of atrial fibrillation, an irregular hear beat. This is the conclusion of a randomized and blinded study of 60 patients, half of whom were injected with saline water and the other half with botulinum toxin (not Botox, but one of the other 3 botulinum toxin products, Xeomin).

Patients who received injections of botulinum toxin instead of saline water had a significantly lower rate of irregular heart beats in the first 30 days (30% versus 7%), according to Evgeny Pokushalov, MD, PhD, of the State Research Institute of Circulation Pathology in Novosibirsk, Russia. Injections of botulinum toxin around the heart did not cause any complications or side effects. These irregularities of heart rhythm can be dangerous and if these findings are confirmed, botulinum toxin injections may become standard during coronary bypass surgery. If these injections are indeed effective they would also save money by reducing the duration of hospital stay and preventing the need for additional treatments of irregular heart beat.

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Triptans, such as Imitrex or sumatriptan and similar drugs are “designer” drugs which were developed to specifically treat migraine headaches. They are highly effective and, after more than 20 years on the market, proven safe. Four out of the seven drugs in this category (Imitrex, Maxalt, Zomig, Amerge) are available in a generic form, which significantly lowers their cost, which was one of the obstacles for their widespread use. So, it would appear that now there is no reason for doctors not to prescribe triptans to migraine sufferers.

In 1998, emergency department doctors gave more than half of the patients suffering from migraine headaches opioids (narcotics) to relieve pain and, according to a new study, 12 years later, this hasn’t changed.

Despite the fact that triptans are widely considered to be the best drugs for acute migraine, the use of these drugs in the emergency department has remained at 10%, according to a study led by Benjamin Friedman, an emergency medicine doctor at the Montefiore Medical Center in the Bronx.

In 1998, about 51% of patients presenting with migraine at the emergency department were treated with an injection of a narcotic and in 2010, narcotics were given to 53% of the patients.

Other than narcotics (opioids) emergency department doctors often give injections of an NSAID (non-steroidal anti-inflammatory drug) Toradol (ketorolac) or a nausea drug, such as Reglan (metoclopramide). These two drugs are more effective (especially if given together) and have fewer potential side effects than narcotics. They also do not cause addiction and rebound (medication overuse) headaches, which narcotics do.

Dr. Friedman and his colleagues looked at the national data for 2010 and found that there were 1.2 million visits to the emergency departments for the treatment of migraine. Migraine was the 5th most common reason people come to the emergency room.

They also discovered that people who were given a triptan in the emergency department had an average length of stay in the ER of 90 minutes, while those given Dilaudid (hydromorphone) – the most popular narcotic, stayed in the ER for an average of 178 minutes.

Opioids should be used only occasionally – when triptans, ketorolac, and metoclopramide are ineffective or are contraindicated. This should be the case in maybe 5% of these patients, according to Dr. Friedman

One possible reason why ER doctors do not follow recommended treatments and use narcotics instead, is that they do not recognize a severe headache as migraine and misdiagnose it as sinus, tension-type or just as a “severe headache”. Many doctors still believe that migraine has to be a one-sided headache, or a visual aura must precede a migraine, or that the pain has to be throbbing. It is well established that none of these features are required for the diagnosis of migraine.

Another possible reason for the widespread use of opioid drugs in the ER is that doctors are very accustomed to using them, while triptans may be unfamiliar and require thinking about potential contraindications, what dose to give, what side effects to expect, etc.

In summary, if you or someone you know has to go to an ER with a severe migraine, ask for injectable sumatriptan (which you should have at home to avoid such visits to the ER) or ketorolac.

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Antibodies blocking a specific neurotransmitter involved in migraines appear to relieve migraine headaches. Two studies presented at the annual meeting of the American Academy of Neurology reported on the use of antibodies to CGRP (calcitonin gene-related peptide) for the treatment of migraine headaches. These were relatively small, but highly scientific (randomized, double-blind, and placebo-controlled) studies. The studies was conducted in patients with frequent migraines.

The two studies used two different antibodies developed by different companies. The results of the trials suggest that this approach is both effective and safe in preventing migraine, at least according to these preliminary studies.

If these antibodies are proven to be indeed safe and effective, they will be the first specific migraine therapy since the introduction of triptans over 20 years ago. Triptans (sumatriptan and other) are abortive drugs, meaning that abort a migraine attack, while CGRP antibodies are used for the preventive (prophylactic) treatment. While Botox was approved three years ago for the preventive treatment of chronic migraines it was not specifically developed for the treatment of migraines. Instead, Botox was found to have this effect accidentally.

One phase II proof-of-concept trial enrolled 218 people with 4 to 14 migraine headache days per month and randomly assigned them to get the antibody or a placebo. The study medication was given every 2 weeks by subcutaneous injection. Active treatment resulted in reduction of an average of 4.2 migraine days per month in the third month for those on the active drug and a drop of 3.0 days for those on placebo.

The side effects were similar between the groups and most were mild and resolved on their own.

In the other study the antibody was given intravenously at the start of the trial, with an hour-long infusion, but was not repeated. This study enrolled 163 patients, with 82 assigned to the drug and 81 to placebo. The average change from baseline in migraine days per month was a decline of 5.6 for the active treatment compared with a drop of 4.6 for placebo patients. Side effects in this study were also mild and occurred with the same frequency in the active and placebo groups.

While the difference between the active treatment and placebo does not seem to be significant, it was statistically significant and it is possible that some patients will respond very well while others not at all.

The next step is much larger phase III studies, which typically involve over 1,000 patients for each compound. If phase III studies also show safety and efficacy of these antibodies, then the FDA might approve them. This means that the earliest one or both of these drugs will become available is about 3 years.

The companies that sponsored these studies were Arteaus and Alder Biopharmaceuticals.

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Epidural steroid injections are popular for persistent neck and back pains. Patients with migraine and other headaches often have neck pain as well and if they happen to visit an anesthesiologist/pain specialist instead of a neurologist, there is a good chance they will be offered a cervical epidural steroid injection. If you or someone you know are offered such injections, just say no.

Despite the widespread use of this procedure, there is no good scientific evidence that these injections help. Not only they probably do not help, they can cause serious side effects. The US Food and Drug Administration (FDA) is warning that injection of corticosteroids into the epidural space of the spine may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death.

The FDA is requiring the addition of a warning to the drug labels of injectable corticosteroids to describe these risks.

The FDA said that “Injectable corticosteroids are commonly used to reduce swelling or inflammation. Injecting corticosteroids into the epidural space of the spine has been a widespread practice for many decades; however, the effectiveness and safety of the drugs for this use have not been established, and the FDA has not approved corticosteroids for such use.”

The FDA reviewed cases of serious neurological adverse events associated with epidural corticosteroid injections. Serious adverse events included death, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke, seizures, nerve injury, and brain edema.

Some doctors perform these injections under X-ray guidance, but even then serious neurological complications can occur. X-ray guidance also exposes patients to harmful radiation and increases the cost of the procedure, which is significant even without the X-ray.

This FDA warning is unrelated to a recent disastrous contamination of corticosteroids used for epidural injections. This contamination occurred at a compounding pharmacy in Massachusetts and resulted in 749 patients contracting fungal meningitis with 61 patients dying from it. This is another reason to avoid epidurals.

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Stress is considered to be one of the main migraine triggers. However, a study just published in the journal Neurology suggests that it is the period after stress when people are more likely to develop a migraine.

A group of doctors at the Montefiore Hospital in the Bronx led by Dr. Richard Lipton enrolled 22 participants, of whom 17 completed their diaries. These migraine sufferers made 2,011 diary entries including 110 migraine attacks eligible for statistical analysis. Level of stress was not generally associated with migraine occurrence. However, decline in stress from one evening diary to the next was associated with an increased chance of migraine over the subsequent 6 to 18 hours. The authors concluded that the reduction in stress from one day to the next is associated with migraine onset the next day. They said that “The decline in stress may be a warning sign for an impending migraine attack and may create opportunities for preemptive drug or behavioral interventions.”

What they meant is that people could try meditation and other relaxation techniques or, if that is ineffective, they could take a medication ahead of time. Taking medication before headache starts is often more effective and requires milder and fewer drugs than if a migraine is already in full bloom.

Many migraine sufferers know that changes in sleep, meal intake, weather, and stress can trigger an attack. So, it is important to keep your life stable as much as possible. Biofeedback, meditation and other relaxation techniques, as well as regular aerobic exercise, magnesium and other supplements, all could improve the resistance against migraine attacks.

The accompanying editorial in Neurology mentioned that migraine is the single biggest source of neurologic disability in the world and any practical finding that helps people avoid migraines can have a major impact on lives of millions of people.

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An oral tablet is the most convenient way to take medicine. However, many migraine sufferers wake up with a headache that is in full bloom and severe nausea or vomiting makes it difficult to take oral medications. Others find that tablets are ineffective or take too long to work.

Sumatriptan (Imitrex), the miracle migraine drug which has changed lives of millions of migraine and cluster headache sufferers, was first released in an injection. The injection is still available and is the most effective way to stop a migraine. The injection comes in a variety of pre-filled syringes and cartridges, which are very easy to self-inject. The problem with injections is that some people don’t like the idea of injecting themselves, which is surprising, considering how much pain and suffering they endure from migraine. Another problem is the cost – even in a generic form a shot costs $35 (see for cheapest prices). The biggest reason why injections are underutilized is that doctors fail to offer this option to patients, many of whom would be happy to use it.

Nasal sprays offer a middle ground option – not as fast or effective as an injection, but faster and sometimes more effective than a tablet. There are several medications available in a nasal spray. The same triptan medication, sumatriptan comes in a nasal spray. However, another triptan, zolmitriptan (Zomig NS) in my experience is more effective. The disadvantage of Zomig is that it is very expensive if not covered by insurance (over $200 a spray) because it is not available in a generic form.

Another nasal spray approved for migraine headaches is Migranal. It contains dihydroergotamine, which is one of the strongest injectable migraine drugs. However, it is much less effective in a nasal spray form. It is also very expensive – $200 a dose. Dihydroergotamine is about to be released in an inhaler. It will be called Levadex and will deliver the medicine into the lungs. Its efficacy should be as good as that of an injection, but with fewer side effects. Hopefully, it will not be more expensive than the generic sumatriptan injection. Otherwise, just like with Migranal, insurance companies will not cover it.

Sprix is a nasal spray containing ketorolac. In a tablet form (Toradol) ketorolac is no more effective than aspirin and is more irritating to the stomach. But it is a very effective drug for migraines when it is injected and to a lesser extent, when sprayed into the nose. It is very popular as an injection in the ERs and at our New York Headache Center. Sprix can sometimes irritate the nasal passages. It costs about $35 a dose.

Stadol (butorphanol) is a narcotic (opioid) pain killer, which costs about $30 a dose in a generic form. It does relieve pain well and is approved for migraine headaches. However, just like other narcotics, it is potentially addictive. Also, many migraine sufferers find that narcotics do not help their migraine and often makes them feel sicker. It also costs over $30 a dose.

There are several over-the-counter nasal sprays containing hot pepper extract, capsaicin. There is no good scientific evidence that these capsaicin products sprayed into the nose relieve migraines or cluster headaches. On the other hand, besides burning and irritation of the nasal passages, they have few side effects and are inexpensive.

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Sleep deprivation is a very common trigger of migraine and tension-type headaches. Scientists have always wondered about the purpose of sleep. We know that sleep helps strengthen our memories. New research suggests that sleep is also needed for other housekeeping chores, such as cleaning junk out of our brains. Literally, the brain rids itself of damaged proteins during sleep. It appears that poor sleep quality leads to accumulation of these proteins, which can lead to a higher risk of Alzheimer’s disease.

Another recent study showed that people with insomnia tended to have smaller brain volume in certain regions of the brain, particularly frontal lobes.

Other research showed that a variety of psychiatric illnesses also lead to a reduced brain volume. The frontal lobes are necessary for planning our actions, mood, and affect.

Veterans with post-traumatic stress disorder (PTSD) frequently complain about sleep difficulties and have documented high rates of sleep disorders

In the latest study, the researchers scanned the brains of 144 veterans using magnetic resonance imaging (MRI).

The participants with poor sleep quality had less frontal lobe gray matter than vets who reported sleeping well.

These veteran had other psychological disorders, in addition to the sleep disorder. Half of them abused alcohol, 40 percent had depression and 18 percent had PTSD.

The connection between sleep disorders and the brain volume was not affected by psychiatric medications.

The researchers speculated that these findings are not necessarily limited to veterans. However, they were careful to stress that their findings do not prove that there is a cause and effect relationship between sleep quality and brain volume. It is possible that something else is causing both sleep problems and shrinkage of the brain or that shrinking of the brain causes sleep disturbances and not the other way around.

What is indisputable is that we all need good night’s sleep to function normally, avoid headaches, accidents, and be happy. Most people need 7 hours of sleep, but there are some who need only 5 or 6 and others, 8 to 9 hours. A very small percentage of people function perfectly well with 3 or 4 hours of sleep. On the other hand, some people do not feel rested no matter how long they sleep. Those usually suffer from a sleep disorder, such as sleep apnea, restless leg syndrome, narcolepsy, and other. The diagnosis is made through a sleep study. Treating the underlying sleep disorder often leads to a dramatic improvement in the quality of life, including an improvement in migraine and tension-type headaches.

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There is no debate about the fact that there is an epidemic of vitamin D deficiency in the United States – it affects about two thirds of the population. However, it is bewildering why scientists are still debating if people should be taking vitamin D supplements. You would think that this is a pretty obvious, common sense conclusion. But common sense is far from common, especially in academia (and obviously not just in medicine – it is much worse in the “soft” social sciences).

Two major studies published in the highly respected British Medical Journal reviewed studies that involved data on more than a million people. Both studies showed that vitamin D provided significant benefits. Vitamin D appears to protect against major diseases. Adults with lower levels of vitamin D had a 35% increased risk of dying from heart disease,14% greater risk of dying from cancer, and a higher risk of dying from any cause. Taking vitamin D reduced the risk of dying from all causes by 11%. The authors estimate that 13% of all deaths in the US are due to low vitamin D levels. This is an astonishing discovery, on the par with the discovery that aspirin dramatically reduces the risk of different types of cancer.

So, a reasonable person would expect the medical community to begin recommending vitamin D supplementation, at least for those with low levels. But here is what one of the authors said:: “Based on what we found, we cannot recommend widespread supplementation”. He called for more clinical trials to prove beyond any doubt that taking vitamin D is a good idea. These trials usually cost many millions of dollars and take many years to complete. How much does it cost to take 2,000 units of vitamin D3 daily? One dollar a month. And what are the potential side effects of taking 2,000 units of vitamin D? None.

The bottom line is, if your vitamin D level is below 40, take 2,000 units a day. Some people may need higher doses if their levels remain low, which is not unusual. The normal range is considered to be between 30 and 100, but there are studies indicating that you are safer with a higher level. One such study showed that attacks of multiple sclerosis are less likely if you have high normal rather than low normal levels. We do not know if taking vitamin D prevents migraines and other types of headaches (such a study does need to be done), but we do recommend to everyone whose vitamin D level is low to get it up to normal range.

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A good predictor of response to Botox injections in chronic migraine patients has been found by Spanish researchers.

While Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain, it does not help everyone. Approximately 30% of patients with chronic migraine headaches do not respond to Botox. We usually try at least two sets of injections three months apart before considering the patient to be a non-responder. Considering that Botox is an expensive treatment, it would be very useful to know beforehand which patients will respond and which will not. Besides the cost, it would also save patients time, during which they could be trying other treatments.

Some studies show that having a constricting headache or pain in the eye is usually a positive predictor of response to Botox. On the other hand, exploding headache (that is when the pain is felt pushing from the inside out), is less likely to respond to Botox injections. However, these are very subjective descriptions and predictions based on them are not that reliable.

A new study by Spanish researchers just published in the journal Headache reported that the levels of CGRP (calcitonin gene-related peptide) and VIP (vasoactive intestinal peptide) in patients’ blood are good predictors of response to Botox in chronic migraine sufferers. These two chemicals, which circulate in the blood and perform various important functions in the brain have long been the subject of scientific research. Actually, we think that Botox works by blocking the release of CGRP from the peripheral nerve endings. Dr. Julio Pascual and his colleagues measured the levels of these two chemicals in chronic migraine patients before they were treated with Botox. Botox was administered according to the standard protocol every 12 weeks for at least two treatment cycles. A patient was considered a moderate responder when both: 1) moderate-severe headache episodes were reduced by between 33 and 66%; and 2) subjective benefit on a visual scale from 0 to 100 was recorded by the patient of between 33-66%. Patients were considered to be excellent responders when both items improved by more than 66%. Those without improvement of at least one-third in the two items were considered as nonresponders.

The study involved 81 patients with chronic migraine and 33 healthy controls. CGRP and VIP levels were significantly increased in the chronic migraine population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. The probability of being a responder to Botox was 28 times higher in patients with a CGRP level above the threshold.

The measurement of CGRP and VIP is done only by research institutions and is not yet offered by commercial laboratories. However, considering how much money can be saved by not giving Botox to those who are unlikely to respond, these tests should become widely available once these findings are confirmed by other researchers.

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Yesterday, the FDA approved the first preventive (prophylactic) treatment for migraines in adolescents – kids between the ages of 12 and 17. Topamax (topiramate) was first approved by the FDA in 1996 to prevent seizures. It was approved for migraine prevention in adults in 2004.
As the FDA stated in its announcement, “Migraine headaches can impact school performance, social interactions, and family life. Adding dosing and safety information for the adolescent age group to the drug’s prescribing information will help to inform health care professionals and patients in making treatment choices.”
The announcement also stated that “About 12 percent of the U.S. population experiences migraine headaches. Migraine headaches are characterized by episodes of throbbing and pulsating pain in the head, and may occur several times per month. Other common symptoms include increased sensitivity to light, noise, and odors, as well as nausea and vomiting. Many patients experience their first migraine attack before reaching adulthood, and migraine can be just as disabling in teens as it is in adults.

The safety and effectiveness of Topamax in preventing migraine headaches in adolescents ages 12 to 17 was established in a clinical trial that enrolled 103 participants. Those treated with Topamax experienced a decrease in the frequency of migraine of approximately 72 percent compared to 44 percent in participants that took an inactive drug (placebo).

The most common adverse reactions with the approved dose of Topamax (100 milligrams) were paresthesia (a burning or prickling sensation felt in the hands, arms, legs, or feet), upper respiratory infection, anorexia (loss of appetite), and abdominal pain.

Topamax increases the risk of the development of cleft lip and/or cleft palate (oral clefts) in infants born to women who take the drug during pregnancy. The benefits and risks of Topamax should be carefully weighed before using it in women of childbearing age. If the decision is made to use the medication by a woman of childbearing age, effective birth control should be used.”

It is a little surprising that the FDA based its approval on such as small study – 103 patients. I should add that topiramate can also cause cognitive side effects, such as memory and word retrieval problems in a significant percentage of children and adults. Approximately 20% of adults taking topiramate for more than a year or two develop kidney stones. This most likely can also happen in children. As you can tell from this and my previous posts, I am not a big fan of Topamax. In kids particularly we begin with life style and dietary changes, biofeedback, magnesium, CoQ10 and other supplements and even Botox injections, which are very safe, before resorting to prophylactic drugs such as topiramate.
Julie Mauskop
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The beneficial effect of Botox on mood has been reported for years. I mentioned this in one of my blog posts in 2011. Now, a new and highly scientific study (double-blind, placebo-controlled) which is about to be published in the Journal of Psychiatric Research confirms that Botox relieves depression. The study is described in today’s New York Times.

I have also heard from many of my own patients who receive Botox for chronic migraines that their mood improves, although in their case it could be to a great extent because their headaches improve.

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A severe migraine attack can sometimes land you in an emergency room. With its bright lights, noise, and long waits, it is the last place you want to be in. To add insult to the injury, some doctors will think that you are looking for narcotic drugs and treat you with suspicion, while others will offer ibuprofen tablets. It is hard to think clearly when you are in the throes of a migraine, so you need to be prepared and have a list of treatments you may want to ask for, just in case the ER doctor is not good at treating migraines.

If you are vomiting, first ask for intravenous hydration and insist on having at least 1 gram of magnesium added to the intravenous fluids. Everyone with severe migraines should have sumatriptan (Imitrex) injection at home since it often eliminates the need to go to an ER in the first place. If you haven’t taken a shot at home, ask for one in the ER. The next best drug is a non-narcotic pain medicine, ketorolac (Toradol) and if you are nauseous, metoclopramide (Reglan). Do not let the doctor start your treatment with divalproex sodium (Depakene, drug similar to an oral drug for migraine prophylaxis, Depakote) or opioid (narcotic drugs) such as demerol, morphine, hydromorphone and other.

This post was prompted by an article just published in the journal Neurology by emergency room doctors at the Montefiore Hospital in the Bronx. It was a double-blind trial which compared intravenous infusion of 1,000 mg of sodium valproate with 10 mg metoclopramide, and with 30 mg ketorolac. They looked at relief of headache by 1 hour, measured on a verbal 0 to 10 scale. They also recorded how many patients needed another rescue medication and how many had sustained headache freedom.

Three hundred thirty patients were enrolled in the study. Those on divalproex improved by a mean of 2.8 points, those receiving IV metoclopramide improved by 4.7 points, and those receiving IV ketorolac improved by 3.9 points. 69% of those given valproate required rescue medication, compared with 33% of metoclopramide patients and 52% of those assigned to ketorolac. Sustained headache freedom was achieved in 4% of those randomized to valproate, 11% of metoclopramide patients, and 16% receiving ketorolac. In the metoclopramide arm, 6% of patients reported feeling “very restless”, which can be a very unpleasant side effect of this drug.

The authors concluded that the valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide was somewhat better than ketorolac but it also had more side effects.

To summarize, ask the doctor to start with hydration and magnesium, then sumatriptan injection, followed by metoclopramide and ketorolac, if needed. If the above treatments do not help, we also give dexamethasone (Decadron, a steroid medication) and DHE-45 (dihydroergotamine). All these medications can be administered in the office and we always tell our patients not to go to an ER and to come into the office if the attack occurs during our office hours.

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Cefaly, a TENS unit specifically developed for the treatment of migraine headaches, was cleared for sale in the US. It was available last year for a short time on, but because it was not yet approved, it was taken off the market. I mentioned in my previous post that TENS units have been in use for muscle and nerve pain for decades. TENS has good proof of efficacy in musculo-skeletal pain, but studies in migraines have been relatively small. Even Cefaly was tested in only 67 migraine patients. So, while it is not definitely proven effective, TENS is safe and is worth a try if usual treatments do not help. Cefaly is easy to use but it is expected to cost around $300. The old-fashioned TENS units are not as convenient to use, but sell for as little as $50. Both Cefaly and regular TENS units require doctor’s prescription, although many websites sell TENS units without one. These devices are usually powered by a 9 volt battery and, unless you have a pacemaker or another electrical device in your body, the risk of side effects is low.

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Imbalance of many hormones produced by our endocrine system can lead to headaches. Here is a brief summary of the hormones linked to headaches.

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Trigeminal neuralgia (TN) is an excruciatingly painful disorder which affects about one in a thousand people. Patients describe the pain of TN as an electric shock going through the face. Eating and talking often triggers the pain, so some patients become malnourished and depressed. The pain is brief, but can be so frequent and severe that it causes severe disability, weight loss, severe anxiety, and depression. The good news is that most people can obtain relief by taking drugs, such as Tegretol (carbamazepine), Trileptal (oxcarbazepine), Dilantin (phenytoin), or Lioresal (baclofen). I have successfully treated several patients who did not respond to these medications with Botox injections.

Patients who do not respond to medications or Botox injections have several surgical options available. According to a new Dutch “Nationwide study of three invasive treatments for trigeminal neuralgia” published in journal Pain shows that every year about 1% of those suffering from TN undergo surgery. Of the three most common types of surgery, percutaneous radiofrequency thermocoagulation (PRT) is by far most popular – in a three year period in Holland, 672 patients underwent PRT, 87 underwent microvascular decompression (MVD), and 39 underwent partial sensory rhizotomy (PSR). The latter two procedures a performed by neurosurgeons (MVD requires opening of the skull), while PRT is usually done by anesthesiologists (a probe is inserted through the cheek to the nerve ganglion under X-ray guidance). MVD was most effective, but caused more complications than PRT, although fewer than with PSR. More patients having PRT had to have a repeat procedure, but it was still safer than the other two. Very often the physician under-treats during the first treatment of PRT in order to avoid complications. Overall, the best initial procedure for those suffering with TN is PRT and if repeated PRTs fail, MVD can often cure this condition.

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Tylenol (acetaminophen, or in Europe it is called paracetamol) is the go-to drug for pain, headaches, and fever during pregnancy. A new study just published in the journal JAMA Pediatrics indicates that this drug may not be as safe as previously thought.

Animal research has long suggested that acetaminophen is a so called hormone disruptor, a substance that changes the normal balance of hormones. It is a well-established fact that an abnormal hormonal exposures in pregnancy may influence fetal brain development.

Danish researchers decided to evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD) in children. They studied 64,322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.

The doctors used parental reports of behavioral problems in children 7 years of age using a specific questionnaire, retrieved diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry, and identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry.

More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at about 1.3 times higher risk for receiving a hospital diagnosis of ADHD, use of ADHD medications, or having ADHD-like behaviors at age 7 years. Stronger associations were observed with use in more than 1 trimester during pregnancy and with higher frequency of intake of acetaminophen.

The researchers concluded that maternal acetaminophen use during pregnancy is associated with a higher risk for ADHD-like behaviors in children.

This presents a difficult problem in treating headaches and pain in pregnant women. Aspirin and other non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen can cause other problems in pregnancy and are particularly dangerous in the third trimester. In women with migraines, acetaminophen tends to be ineffective anyway, so these women should be given migraine-specific drugs, such as triptans (Imitrex or sumatriptan, Maxalt or rizatriptan, and other). They are much more effective than acetaminophen and the woman may need to take much less of these drugs than of acetaminophen. Triptans are also in category C in pregnancy, which means that we do not know how safe they are. Imitrex was introduced more than 20 years ago and we do not that it does not have any major risks for the fetus, but that does not mean that more subtle problems, such as ADHD are also not more common. Another headache drug that should be avoided in pregnancy is Fioricet. It is popular with some obstetricians because it has been on the market for 40 years. However, it contains not only acetaminophen, but also caffeine, which can make headaches worse, as well as a barbiturate drug butalbital, which can also have deleterious effect on the fetal brain.

Fortunately, two out of three women stop having migraines during pregnancy, especially in the second and third trimester. If they continue having headaches, treatment is directed at prevention. Regular aerobic exercise, getting enough sleep, regular meals, good hydration, avoiding caffeine, learning biofeedback, meditation or another form of relaxation, magnesium supplementation, are all safe and can be very effective. Acute treatments that do not involve drugs are often not very practical for a busy person. However, if the headache prevents normal functioning anyway, taking a hot bath with an ice pack on the head at the same time can help some women. Taking a nap, getting a massage, aromatherapy with peppermint and lavender essential oils are good options. For nausea, ginger and Sea Bands are sometimes very effective.

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One of my patients I saw last week developed osteoporosis while taking Topamax (topiramate). Topiramate is known to cause osteoporosis by causing loss of calcium through the kidneys. While osteoporosis is not common, we don’t know if it is really that rare. A side effect that was thought to be rare (less than 1%, according to the manufacturer) when the drug was launched, is kidney stones. Now we know that close to 20% of people taking topiramate for a long time, develop kidney stones. Both kidney stones and osteoporosis occur through similar mechanisms, so it is possible that osteoporosis is also much more common than doctors think.

This patient had no other side effects and topiramate was very effective in controlling her migraines. Since osteoporosis is a very serious and potentially dangerous condition, she will have to stop taking topiramate. However, she does have other options because she has never tried Botox injections and several other drugs for the prevention of migraines.

Another very serious side effect that is not obvious to women taking Topamax, is the potential for serious problems in the fetus. The FDA designates topiramate as belonging to category D: “Pregnancy Category D drugs are those with positive evidence of human fetal risk based on human data, but still may be used in pregnant women in certain situations when its benefits are thought to outweigh potential risks”. Drugs in category B are considered to be safe in pregnancy, while category C means that there is not enough data and category X means it is absolutely contraindicated in pregnancy.

Topamax (topiramate) is one of the more popular drugs for the prevention of migraines (as well as treatment of epilepsy). It works only in half of the patients, while for the other half it doesn’t work or causes unacceptable side effects. The reason for its popularity is that unlike many other medications which can cause weight gain, this one often causes weight loss.

In addition to the side effects that occur over time, there are many that happen quickly and which are usually, but not always, patients easily linked to the drug: 1) cognitive impairment, such as inability to recall a word, slow thinking, or as some patients tell me, feeling stupid, 2) drowsiness, 3) dizziness, 4) fatigue, 5) blurred vision due to an acute glaucoma, and other.

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Vitamin D has been reported to be low in patients with migraines as well as a host of other medical conditions. The big question is whether this is just a coincidence or a cause-and-effect relationship. In some conditions, such as multiple sclerosis, people with higher vitamin D levels have fewer relapses than those with lower levels, indicating a direct benefit of vitamin D. In other diseases, such as Alzheimer’s, strokes, and migraine this relationship is not clear.

A new study by Iranian doctors published in BioMed Research International shows that vitamin D deficiency is found in about half of 105 migraine patients they tested. However, when they looked at 110 matched controls without migraines, they found that half of them were also deficient. They also found that those with more severe migraines did not have lower levels than those with milder ones. This strongly suggests that vitamin D has no effect on migraine headaches.

So if you suffer from migraines, do not expect vitamin D to improve your headaches. However, if your blood test shows a deficiency, you should definitely take a vitamin D supplement to avoid some known and possibly some yet unknown problems. Taking the daily recommended dose of 600 units may not be sufficient and you may need to recheck your level to make sure that you are absorbing it. Some of my patients have needed as much as 5,000 units daily to get their vitamin D level to normal range.

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Generic drugs provide significant savings and 80% of all prescriptions in the US are filled with generic drugs. Many doctors are skeptical when patients complain that the generic is not as good as the brand. But not all generics are created equal, literally. For example, there are about 10 generic manufacturers of Imitrex (sumatriptan). I’ve had patients tell me that certain generics, particularly the ones made by an Indian company Ranbaxy, are much less effective than the brand or generics made by other manufacturers. This problem is widespread and one of my previous posts described a study of the use of generic Topamax (topiramate) in epilepsy patients (this drug is also approved for the prevention of migraines). Patients on a generic were admitted to the hospital more often, had longer hospital stays, and were three times more likely to sustain head injury or a bone fracture.

Yesterday, The New York Times published an expose on the generic manufacturers in India. Ranbaxy was one of the generic drug makers that was reported to have the most problems. Its plants are being repeatedly shut down by the American FDA, who also imposed a $500 million fine. The article cites understaffed regulatory bodies and corruption as the main reasons for poor quality controls. One survey showed that 12% of medications sold in India contained no active ingredients, including life-saving drugs such as antibiotics and cancer drugs. It is not clear what percentage of drugs entering the US is adulterated. At least in India the FDA is allowed to inspect plants and impose fines. In China, the government has refused to let the FDA expand its monitoring. The article has this ominous ending:
“The United States has become so dependent on Chinese imports, however, that the F.D.A. may not be able to do much about the Chinese refusal. The crucial ingredients for nearly all antibiotics, steroids and many other lifesaving drugs are now made exclusively in China.”

So what can you do to protect yourself? By law, the name of the manufacturer must be printed on the medicine bottle you get from the pharmacy. If you find a generic that works well, try to stick to it. If your pharmacy suddenly changes the generic manufacturer and the drug is not as effective or causes side effects, you may want to ask them to get you the generic that worked. The big chains such as Walgreens and CVS may not be able to do it, but most independent pharmacies have more flexibility. You can also try switching from one chain to another since they often stock generics from different companies.

One more tip is from my recent previous post – check for the lowest prices in your area. Also, it is not unusual for your insurance copay to be higher than the actual cost of medicine. For example, you copay could be $15 or more, while if you buy the same generic drug without insurance, it will cost you $4 or $10. And do not expect the pharmacist to tell you this.

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Children with migraine headaches are usually given acetaminophen (Tylenol) or ibuprofen (Advil). A group of Italian doctors compared responses to these two drugs in kids with migraines who took a daily magnesium supplement to those who did not. Results of their study were published in the latest issue of the journal Headache. One hundred sixty children (80 boys and 80 girls) aged 5-16 years were enrolled and assigned to four groups to receive a treatment with acetaminophen or ibuprofen without or with magnesium. The dose of each drug was adjusted according to the child’s weight. Those children who were in the magnesium arm were given 400 mg of magnesium (the article does not mention which salt of magnesium was given – oxide, glycinate, citrate, or another). Migraine pain severity and monthly frequency were similar in the four groups before the start of the study. Both acetaminophen and ibuprofen produced a significant decrease in pain intensity, but not surprisingly, did not change the frequency of attacks. Magnesium intake induced a significant decrease in pain intensity in both acetaminophen- and ibuprofen-treated children and also significantly reduced the time to pain relief with acetaminophen but not ibuprofen. In both acetaminophen and ibuprofen groups, magnesium supplementation significantly reduced the attack frequency after 3 and 18 months of supplementation.

This study was not the most rigorous because it did not include a placebo group as the authors felt that placing children on a placebo would be unethical. However, it was rigorous in other respects and still provides useful information. The first conclusion is that taking magnesium reduces the frequency of migraines in children. The second is that taking magnesium significantly improves the efficacy of acetaminophen and ibuprofen.

The bottom line is that every child (and adult for that matter) should be taking a magnesium supplement. I have written extensively on the importance of magnesium because our research and that of others, including the above study, has consistently shown the benefits of magnesium. Unfortunately, after dozens of publications, hundreds of lectures, and recommendations from medical societies, many doctors still do not recommend magnesium to their migraine patients. Some are not familiar with the research, others dismiss any supplements out of hand, and yet others do not believe the studies because they think that magnesium is too simple and too cheap to be effective. Most doctors are trained to prescribe drugs and they feel that patients expect prescription drugs, so giving them a supplement will disappoint the patient and will reduce doctor’s standing in patients’ eyes. This is clearly not the case since many people prefer more natural approaches and because recommending a supplement does not mean that a prescription drug cannot be also given. In fact, magnesium improves not only the efficacy of acetaminophen and ibuprofen, but also prescription drugs such as sumatriptan (Imitrex).

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White matter lesions that often seen on MRI scans of adult migraine sufferers were also found in children. A study by Washington University researchers inn St. Louis examined MRI scans of 926 children 2 to 17 years of age (mean age was 12.4 and 60% were girls) who were diagnosed with migraine headaches. They found white matter lesions (WMLs) in about 4% or 39 of these children, which is not much higher than in kids without migraines. Just like in the adults, these WMLs were slightly more common in kids with migraine with aura. None of these lesions were big enough to be called a mini-stroke or an infarct. There was no correlation between the number of lesions and the frequency or the duration of migraines. In conclusion, WMLs in children with migraines do not appear to be caused by migraines and are most likely benign in origin. The origin, however remains unknown, which often causes anxiety in parents of these children.

Unlike in children, adults with migraines and especially those with migraines with aura, are much more likely to have WMLs than adults without migraines. But even in adults, these appear to be benign as I mentioned in my previous post.

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“Daily triptan use for intractable migraine” is the title of a report by Dr. Egilius Spierings published in the latest issue of the journal Headache. This is a controversial topic, which I addressed in a previous post. Dr. Spierings, who is affiliated with both Tufts Medical Center and Harvard Medical School presents a case of a 50-year-old woman who failed trials of multiple preventive medications. This woman responded well to sumatriptan, 100 mg, which she took daily and occasionally twice a day with excellent relief and no side effects. Dr. Spierings discusses the evidence for Medication Overuse Headaches (MOH), which is common with caffeine-containing drugs, butalbital (a barbiturate), and opioid drugs (narcotics). It is less clear whether triptans cause MOH and he mentions that most patients who end up taking a daily triptan do so only after they failed many preventive (prophylactic) drugs and after they discover that they can have a normal life if they take a triptan daily. This applies not only to sumatriptan, but any other similar drug, such as Amerge (naratriptan), Zomig (zolmitriptan), Maxalt (rizatriptan), Relpax (eletriptan), and other. After 20 years of being on the market, we have no evidence that these drugs have any long-term side effects. In Europe several of these drugs are sold without a prescription. The major obstacle to their daily use has been the cost. However, several of these medications are now available in a generic form and a 100 mg sumatriptan tablet costs as little as $1.50.

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Many headache sufferers take over-the-counter medications which can cause upset stomach and heartburn due to reflux. Many will then resort to taking acid lowering drugs. These drugs reduce acidity which also impairs absorption of various vitamins and minerals, including vitamin B12, D, magnesium, and other. Magnesium deficiency is known to worsen migraine and cluster headaches.

The most popular drugs for indigestion, reflux, and stomach ulcers are so called proton-pump inhibitors, or PPIs (Prilosec, Protonix, Nexium, and other), and histamine 2 receptor antagonists (Zantac, Tagamet), and they are available by prescription and over the counter. Over 150 million prescriptions were written for PPIs alone last year.

A new study, published in The Journal of the American Medical Association by Dr. D. Corley and his colleagues shows that people who are taking these medications are more likely than the average person to be vitamin B12 deficient.

The study was performed at Kaiser Permanente. It involved 25,956 adults who were found to have vitamin B12 deficiency between 1997 and 2011, and who were compared with 184,199 patients without B12 deficiency during that period.

Patients who took acid lowering drugs for more than two years were 65 percent more likely to have a vitamin B12 deficiency. Higher doses of PPIs were more strongly associated with the vitamin deficiency, as well.

Twelve percent of patients deficient in vitamin B12 had used PPIs for two years or more, compared with 7.2 percent of control patients. The risk of deficiency was less pronounced among patients using drugs like Zantac and Tagamet long term: 4.2 percent, compared with 3.2 percent of nonusers.

The new study is the largest to date to demonstrate a link between taking acid suppressants and vitamin B12 deficiency across age groups. Earlier small studies focused primarily on the elderly.

The surprise was that the association was strongest in adults younger than age 30, since in the past only elderly were suspected to be at risk.

Vitamin B12 deficiency has been very common even in people not taking PPIs. This is in part due to healthier diets, which are often low in vitamin B12 which is found in high amounts in meat and liver. Vegetarians are particularly at risk.

Vitamin B12 deficiency is a serious condition, which in severe cases can be fatal. It can present with fatigue, memory impairment, tingling, weakness, dizziness, worsening headaches, anemia, and other symptoms.

Dr. Corley and his colleagues do not recommended stopping PPIs or similar drugs in people with clear need for these drugs. However, studies have found that the drugs are often overused or used for longer than necessary. One reason for this is that stopping PPIs often causes “rebound” increase in reflux making people think that they must continue taking these drugs. The way to get off PPIs is to first switch to Zantac and antacids, such as Tums or Mylanta. After a few weeks, stop taking Zantac and continue only antacids. Avoid eating foods that worsen reflux, such as chocolate, alcohol, and other, and you may need the antacids only occasionally.

Besides vitamin B12 deficiency, prolonged use of PPIs leads to other problems, including increased risk of bone fractures, pneumonia, and a serious gastro-ointestinal infection with C. difficile.

To see whether study patients were not just low in vitmain B12 but also had symptoms of deficiency, researchers reviewed the charts of 20 randomly selected PPI-using patients to determine why they had their vitamin B12 levels tested. Twenty five percent of that small sample had also been tested for anemia and 15 percent for memory loss. This indicates that many people with this deficiency have symptoms. However, because the symptoms are vague and not specific for this deficiency, doctors often ignore them and do not order any tests.

To complicate matters, when doctors do test for vitamin B12 deficiency, the test they use is not very accurate. Many laboratories list normal levels being between 200 and 1,000. However, many patients with levels below 400, and some even with levels above 400 still have a deficiency. If a deficiency is strongly suspected, additional tests are needed – homocysteine and methylmalonic acid levels.

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Placebo effect is a curse for medical researchers. Every new treatment has to be shown to be better than placebo and placebo is often very effective. In clinical practice, unlike in research, placebo effect is a good thing, but many doctors fail to maximize its effect. If the doctor emphasizes all of the potential side effects and does not stress positive attributes of a drug, the patient is not likely to respond well. However, if the doctor is enthusiastic about the efficacy of a drug, the results can be dramatically different. Obviously, side effects need to be mentioned as well, but if the drug is really dangerous, it should not be prescribed in the first place.

The importance of placebo effect specifically with migraine drugs was described in a study published in Science Translational Medicine. The findings confirm that patients who receive positive messages about the potential efficacy of their treatment may have better treatment outcomes than patients who receive negative messages.

The study involved 66 migraine sufferers with intermittent attacks. Patients first recorded their baseline pain intensity on a scale from zero (no pain) to ten (maximal pain) for an untreated migraine attack. Then each study participant received a series of six envelopes containing treatment for six subsequent migraine attacks: two of the envelopes were labeled as “placebo”, two as “Maxalt” (rizatriptan, one of the the anti-migraine drugs called triptans) and two as “placebo or Maxalt.” However, for each pair of envelopes with identical labels, one envelope actually contained a placebo pill and the other contained Maxalt.

Patients who had taken Maxalt mislabeled as “placebo” reported roughly 50% less pain relief than those who had taken the Maxalt labeled as “Maxalt.” This suggests that more than half of the drug effect was due to the placebo effect.

The study was conducted by Rami Bursteine, Ted Kaptchuk, and other doctors at Harvard Medical School. Dr. Burstein said that labeling Maxalt as “placebo” likely reduced the effectiveness of Maxalt by giving patients negative expectations about the efficacy of the treatment. Similarly, he says, providing patients with a long list of possible side effects, risks, and adverse events in the context of prescribing a drug in clinical practice could give patients negative expectations, and therefore could potentially reduce drug efficacy, resulting in patients taking more drug.

Strikingly, the study also revealed that placebo treatment mislabeled as Maxalt was just as effective in reducing pain as Maxalt mislabeled as placebo. “No one’s ever seen that before in human history, in my knowledge,” Kaptchuk says, referring to the comparison. “It raises the possibility that the placebo effect can be harnessed directly.”

The improvement in symptoms that occurred in patients who knowingly took the placebo pill may have occurred because people often become conditioned to associate taking a pill with feeling better, although no one can explain why or how the placebo treatment works.

It is considered unethical for doctors to prescribe placebo, but they may want to consider first trying drugs that may not be the most effective, but are significantly safer than the stronger ones. One such example in my own practice pertains to the use of epilepsy drugs. Depakote (divalproex) and Topamax (topiramate) are approved by the FDA for the prevention of migraines, while Neurontin (gabapentin) is not. In fact, Neurontin is less effective, but it has significantly fewer side effects. Also, Neurontin is not dangerous if the patient were to get pregnant, while the other two drugs are.

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Strenuous mental activity seems to delay recovery after a head injury, according to a new study published in Pediatrics .

Doctors have always recommended rest after a head injury, but it has never been clear how much to limit activities, what kind to limit (physical, mental, or both), and for how long.

Dr. William P. Meehan III, director of the Micheli Center for Sports Injury Prevention in Waltham, Massachusetts and his colleagues studied 335 patients (62% were males), aged 8 to 23 who came to a sports concussion clinic within three weeks of their injury between 2009 and 2011. Most of the concussions were sustained while playing ice hockey, football, basketball or soccer. The researchers asked them about their symptoms and how often they were reading, doing homework or playing games at each of their appointments.

Those with minimal cognitive activity were not reading or doing homework, and spent less than 20 minutes on the Internet or playing video games each day. They could have watched TV or movies or listened to music. Those with moderate or significant cognitive activity did some reading and some homework, but less than usual. Others had not limited their cognitive activities at all since their last clinic visit.

On average, patients took 43 days to fully recover from their concussions. Those with more minor concussions tended to get over their symptoms faster. So did those who did less with their brains while recovering.

Results showed that only those engaging in the highest levels of cognitive activity had a substantial increase in their symptom duration, while those at all lower activity levels seemed to recover at about the same pace.

According to Dr. Meehan, “This would suggest that while vigorous cognitive exertion is detrimental to recovery, milder levels of cognitive exertion do not seem to prolong recovery substantially”

In general, Meehan said, doctors recommend almost complete brain rest for three to five days after a concussion, followed by a gradual return to normal activities.

Athletes suspected of having a concussion should be seen by the most immediately available medical personnel, like an athletic trainer or team doctor, he said, with a follow-up visit to their primary care doctor.

I would also emphasize the importance of physical rest and complete avoidance of any activities that could result in another head injury before completely recovering from the first one. Complete recovery means no symptoms at all, including headaches, dizziness, mental fog, fatigue, difficulty concentrating, insomnia, anxiety, depression, and other. Taking a magnesium supplement can also help since animal studies show magnesium depletion following an injury. If rest alone does not lead to a complete recovery, cognitive behavioral therapy, medications (for anxiety, depression, and irritability), and Botox injections (for persistent headaches) are sometimes needed.

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Many people who experience severe headaches are often concerned about having a brain aneurysm. What prompted this post is a patient I just saw who was found to have a small (3 mm) aneurysm on a routine MRI scan as well as a new article just published in The Lancet Neurology.

Considering that over 36 million Americans suffer from migraine headaches, this is by far the most common cause of severe headaches. However, aneurysms are not rare – more than 7 million Americans have them. The vast majority of these people do not know that they have an aneurysm and in 50 to 80 percent they never cause headaches or any other problems. Every year, more than 30,000 people do suffer a rupture of the aneurysm. The rupture of an aneurysm is what causes a very severe headache and about one in seven people with a rupture die before reaching the hospital. In addition to a severe headache, the hemorrhage from a ruptured aneurysm can cause a stiff neck, drowsiness, weakness or numbness on one side, difficulty speaking and other symptoms of a stroke.

Dutch researchers analyzed the available data, trying to find predictors of aneurysm rupture. They discovered that the risk goes up with age, high blood pressure (hypertension), history of a previous brain hemorrhage, aneurysm size, its location and the geographic region. There is nothing one can do about age and other factors, but blood pressure is one factor that can be controlled.

If the aneurysm is less than 5 mm, as in my recent patient, the risk of a rupture is very low. However, if the aneurysm is larger, surgical treatment is usually indicated, especially if other risk factors are present.

It is not clear why, but people living in Finland and Japan are about 3 times more likely to have an aneurysm rupture than those in the rest of Europe and North America.

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Branded triptan medications are extremely expensive with one pill of Relpax or Frova costing $30 – $40. Fortunately, Imitrex, Maxalt, Amerge, and Zomig tablets are available in a generic form. However, even the generic version of Amerge is $3 to $4 a pill, although generic Imitrex and Maxalt can be found for $2. Unfortunately, some patients respond only to Relpax, Frova or Zomig nasal spray, which insurance companies tend not to pay for. Other people need medications that are not available in the US, such as domperidone, an excellent drug for nausea or flunarizine, a calcium channel blocker for the preventive treatment of migraine (not such an excellent drug because of its side effects).

Some patients who need a branded product or one not available in the US buy drugs from online Canadian pharmacies. But how do you know if the pharmacy is legitimate? Some sites that claim being a Canadian pharmacy in fact are not Canadian and the drugs they sell are fakes. One way to find a legitimate Canadian pharmacy is to check if it is certified by the Canadian International Pharmacy Association. You can also check if the pharmacy is certified by the and is listed on their free website.

When buying locally, you can find a pharmacy with the cheapest price for a specific drug by going to But do not assume that if a pharmacy offers the lowest price on one drug, its prices on other drugs will also be the lowest.

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Another large scientific article on the benefits of cognitive behavioral therapy (CBT) was just published in the Journal of the American Medical Association. In this study by doctors at the Cincinnati Children’s Hospital led by Dr. Andrew Hershey, CBT was combined with amitriptyline (an antidepressant used for the treatment of pain and headaches) and compared to headache education plus amitriptyline.

They enrolled 135 children (79% girls) aged 10 to 17 years who were diagnosed with chronic migraine (15 days with headaches per month or more) and who had migraine-related disability. The study was conducted between October 2006 and September 2012. An unusually large number of kids completed the trial – 129 completed 20-week follow-up and 124 completed 12-month follow-up.

The treatment consisted of ten CBT or 10 headache education sessions involving equivalent time and therapists’ attention. Each group received the same dose of amitriptyline per pound of weight.

The main end point was days with headache and the secondary end point was the disability score determined at 20 weeks. Durability was examined over the 12-month follow-up period.

The results at the 20-week end point showed that days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group. The disability score decreased by 53 points for the CBT group vs 39 points for the headache education group. At 12-month follow-up, 86% of the CBT group had a 50% or greater reduction in headache days vs 69% of the headache education group;

The authors concluded that among young persons with chronic migraine, the use of CBT plus amitriptyline resulted in greater reductions in days with headache and migraine-related disability compared with use of headache education plus amitriptyline. These findings support the efficacy of CBT in the treatment of chronic migraine in children and adolescents.

The accompanying editorial strongly endorsed the results of the study, which is only the last one of many studies showing the benefits of CBT with or without biofeedback in treating headaches in children and adults. The editorial also pointed out several obstacles to the implementation of these findings. First, many doctors do not refer their patients for CBT because they are not aware of these studies or, more often lack the time and the training to explain the benefits of CBT without implying that the headache is a purely psychological problem, which obviously it is not. Secondly, even if they do refer for CBT, less than half of children and adults actually pursue this treatment.

Most doctors usually just prescribe amitriptyline or an epilepsy drug used for chronic migraines. In my experience with adolescents, Botox provides excellent relief for chronic migraines in children as well as it does in adults, although Botox is approved by the FDA only for adults. Botox has far fewer side effects than medications and I find that it is well accepted and tolerated by kids as young as 10. However, I always start with dietary changes, sleep hygiene, exercise, supplements such as magnesium and CoQ10 and CBT, biofeedback or meditation. These measures alone are often sufficient to provide significant relief and in many children there is no need for medications or Botox.

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Mindfulness appears to reduce the effect of pain on day-to-day functioning in adolescents, according to a new study published in The Journal of Pain by Canadian researchers. This was a scientifically rigorous study of 198 boys and girls aged 13 to 18 years. The researchers made an effort to recruit some children who meditated and some who did not. They were all subjected to the Child and Adolescent Mindfulness Measure questionnaire and to the Pain Catastrophizing Scale (questions such as “When I have pain I feel I can’t stand it anymore). They were asked about their daily pains, such as headache, stomachache, tooth pain, muscle pain, back pain. They were also subjected to experimental pain, which was produced by submerging their hand into ice cold water. The results showed that mindfulness had a direct effect on pain interference with daily activity and an indirect effect on the experimental pain intensity and tolerance by producing less catastrophizing.

The good news is that mindfulness is something that can be learned by meditation and can be taught as part of a course of cognitive-behavioral therapy. Kids with migraines, headaches, and other pains should be always advised to start with meditation, biofeedback, or cognitive-behavioral therapy.

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Research by Israeli pediatric neurologists confirms the clinical observation that chewing gum can make headaches worse. By chewing gum teenagers and younger children appear to be giving themselves headaches, according to a study published in the journal Pediatric Neurology.

Dr. Watemberg, the lead author said that “Out of our 30 patients, 26 reported significant improvement, and 19 had complete headache resolution. Twenty of the improved patients later agreed to go back to chewing gum, and all of them reported an immediate relapse of symptoms.”

Headaches occur in about 6% of children before puberty and become three times as frequent in girls after puberty. Typical triggers are stress, lack of sleep, dehydration, skipping meals, noise, and menstruation. Teenage girl patients are more likely to chew gum – a finding supported by previous dental studies.

Two previous studies linked gum chewing to headaches. One study suggested that gum chewing causes stress to the temporomandibular joint, or TMJ. The other study blamed aspartame, the artificial sweetener used in most popular chewing gums. Dr. Watemberg favors the TMJ explanation because gum does not contain much aspartame. I suspect that it is not the TMJ joint itself that is responsible for headaches, but tension in masticatory muscles – those we chew with. The main ones are temporalis muscles – the ones over the temples, and masseter – those at the corner of the jaw. I can sometimes tell that those muscles are at least in part responsible for headaches as soon as the patient enters the room because they have a square jaw due to enlarged masseter muscles.

Dr. Watemberg says “Every doctor knows that overuse of the TMJ will cause headaches. I believe this is what’s happening when children and teenagers chew gum excessively.” and that his findings can be put to use immediately. By advising teenagers with chronic headaches to simply stop chewing gum, doctors can provide many of them with prompt relief.

For people with hypertrophied (enlarged due to overuse) muscles stopping chewing gum sometimes is not sufficient or they never chew gum, but develop this condition because they clench and grind their teeth in sleep. These patients often respond well to injections of Botox, which shrinks those muscles and often eliminates headaches and relieves TMJ pain and dysfunction. However, Botox is only approved by the FDA for the treatment of chronic migraine and unless the patient also has this condition as well (which is common), the insurance may not reimburse for Botox injections. Biofeedback is another effective treatment for both TMJ disorder and chronic migraines.

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Transcranial magnetic stimulation (stimulation of the brain with a magnetic field) has been researched for over 30 years. It has been used to study the brain and to treat a variety of conditions, such as depression, Parkinson’s, strokes, pain, and other. The U.S. Food and Drug Administration has “allowed marketing of the Cerena Transcranial Magnetic Stimulator (TMS), the first device to relieve pain caused by migraine headaches that are preceded by an aura: a visual, sensory or motor disturbance immediately preceding the onset of a migraine attack.”

Here is an excerpt from the FDA News Release:

“The Cerena TMS is a prescription device used after the onset of pain associated with migraine headaches preceded by an aura. Using both hands to hold the device against the back of the head, the user presses a button to release a pulse of magnetic energy to stimulate the occipital cortex in the brain, which may stop or lessen the pain associated with migraine headaches preceded by an aura.

The FDA reviewed a randomized control clinical trial of 201 patients who had mostly moderate to strong migraine headaches and who had auras preceding at least 30 percent of their migraines. Of the study subjects, 113 recorded treating a migraine at least once when pain was present. Analysis of these 113 subjects was used to support marketing authorization of the Cerena TMS for the acute treatment of pain associated with migraine headache with aura.

The study showed that nearly 38 percent of subjects who used the Cerena TMS when they had migraine pain were pain-free two hours after using the device compared to about 17 percent of patients in the control group. After 24 hours, nearly 34 percent of the Cerena TMS users were pain-free compared to 10 percent in the control group.”

The study did not show that the Cerena TMS is effective in relieving the associated symptoms of migraine, such as sensitivity to light, sensitivity to sound, and nausea. The device is for use in people 18 years of age and older. The study did not evaluate the device’s performance when treating types of headaches other than migraine headaches preceded by an aura.

Adverse events reported during the study were rare for both the device and the control groups but included single reports of sinusitis, aphasia (inability to speak or understand language) and vertigo (sensation of spinning). Dizziness may be associated with the use of the device.

Patients must not use the Cerena TMS device if they have metals in the head, neck, or upper body that are attracted by a magnet, or if they have an active implanted medical device such as a pacemaker or deep brain stimulator. The Cerena TMS device should not be used in patients with suspected or diagnosed epilepsy or a personal or family history of seizures. The recommended daily usage of the device is not to exceed one treatment in 24 hours.”

After 30 years of research we know that the risks of TMS are minimal, although theoretically, TMS induces an electric current in the brain, similarly to what happens with electric shock therapy, but to a much milder degree. TMS treatment of migraines does not appear to cause memory or any other problems seen with electric shock therapy for depression.

The main problem with this device is that it is bulky and inconvenient to carry around. It will probably will be reserved for people who have severe migraines that do not respond to preventive and abortive medications and Botox injections and cause disability. Considering its inconvenience, cost, and the fact that only 15% to 20% of migraine sufferers have auras (most of whom can be treated with medications or Botox), this device is not likely to be used widely. But for those for whom it works, it could be life changing.

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Botox is the most effective preventive treatment for chronic migraine headaches. It is also the only treatment approved by the FDA for this condition, which affects 3 to 4 million Americans.

Despite the wide use of Botox for cosmetic indications, many people still have unfounded fears of this procedure. Some are afraid of the fact that it is a toxin and indeed, in large amounts it is deadly. However, acetaminophen (Tylenol) kills over 500 people every year, which is significantly more than all the deaths from Botox given to millions of people in over the 25 years that Botox has been on the market. There has been no deaths reported when Botox was used for headaches or cosmetic reasons. Botox is not free of side effects, but they tend to be mild and transient.

Another fear is that the procedure is painful and very unpleasant. I recorded this video of me injecting one of my patients (with her permission) so that you can see what the procedure looks like. It took me 3 minutes and 41 seconds from start to finish and, as you can see, with little discomfort.

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The approval of the lower dose Sumavel device is a good opportunity to again remind migraine sufferers about the benefits of injectable sumatriptan. Many doctors do not even mention to their patients that sumatriptan is available in an injection that is easy to self-administer. Obviously, if a tablet of sumatriptan (Imitrex) or another triptan works quickly and prevents the headache from becoming disabling, there is no need for an injection. However, when the tablet does not work fast or well enough or if nausea makes it difficult to swallow tablets, injection can be a life saver. Injections of sumatriptan are available in a variety of devices. One of them is Sumavel, an injection without a needle. This device propels the medicine through the skin as a very thin jet of fluid. It is perfect for those with needle phobia. It also has the advantage of not having to worry about the proper disposal of needles. Having a choice of a 4 mg or a 6 mg dose allows patients with frequent cluster headaches to take 3 4 mg doses in 24 hours (maximum recommended dose is 12 mg). The 4 mg dose is also useful for people who get side effects from 6 mg, since 4 mg may be sufficiently effective without causing side effects.

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The risk of dying from a variety of causes can be reduced by exercise, according to a new study published in the British Medical Journal. The effect of exercise was as strong as the effect of drugs for the prevention of diabetes, coronary heart disease, rehabilitation of stroke, and treatment of heart failure. The authors reviewed 305 previous trials that involved almost 340,000 people, making their findings very reliable.

Exercise has been also proven to prevent migraine headaches (see my previous post). This finding was based on a review of over 46,000 patient records, also a very large number that suggests a true effect. Most people don’t need these studies to convince them of the benefits – they know that exercise improves their headaches and makes them feel better. The most common problem is lack of time and motivation. However, headaches also cost time and reduce productivity, so exercising 30 minutes four days a week will save time.

Doctor recommendations often do influence their patients’ behavior and doctors need to remember to emphasize to their patients the importance of exercise, both for headaches and other conditions.

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Many migraine sufferers appear to have cold hands and nose, according to a new study by Finnish researchers described in the Wall Street Journal. The study compared 12 women with migraines with 29 healthy controls without migraines. Family history of migraine was present in 85% of those with migraines and 31% of controls. Five migraine sufferers had auras. The average temperature of the nose and hands was 3.6 degrees lower in migraine sufferers and two out of three had temperatures lower than 86 degrees, which is considered the lower end of normal. Only one out of three of those without migraines had temperatures below 85 degrees.

The authors speculate that the disturbance of the autonomic nervous system in migraine sufferers might be responsible for the constriction of blood vessels, which leads to lower temperatures. However, the authors do not mention a much more important cause of coldness of extremities, which is magnesium deficiency. Our research has shown that up to half of migraine patients are deficient in magnesium. One of the main symptoms of magnesium deficiency is coldness of hands and feet or just feeling colder in general than other people in the same environment. Other symptoms of magnesium deficiency are muscle cramps in legs and other places, mental fog, palpitations, PMS in women, difficulty breathing (intravenous magnesium is also given for asthma), and other. Blood test for magnesium is not reliable because the routine test measures so called serum level, while over 98% of magnesium sits inside the cells or bones. So, if someone has symptoms of magnesium deficiency we strongly recommend oral magnesium supplementation or give an intravenous infusion of magnesium. I’ve also seen many migraine sufferers without other symptoms of magnesium deficiency who are in fact deficient and respond to magnesium. This is why I wrote an article for doctors in a scientific journal entitled: Why all patients with severe headaches should be treated with magnesium. This is also why I included magnesium as a buffering agent in Migralex, an over-the-counter headache medicine.

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Dr. Andrew Charles and his associates at UCLA just published a fascinating report on migraine aura in the journal Brain. We still do not understand the brain mechanisms that lead to the phenomenon of migraine aura. The published report characterizes a large number of visual auras recorded by a single individual over nearly two decades. This person made detailed drawings of his visual aura in real time during more than 1000 attacks of migraine aura. His auras were never followed by a headache. The drawings showed the shape and location of the aura wavefront or blackout areas in the visual field with one minute intervals. These drawings were digitized by the researchers to make it easier to analyze them. Consistent patterns of aura initiation, propagation and termination were observed in both right and left visual fields. Most aura attacks started centrally, but some also started in the periphery, which in most people is more common. The auras that started centrally moved down and in first and then up and to the side. The speed of progression of the auras was always the same. The speed was about 2-3 millimeters per minute, which is what has been reported by most other people in the past. Some auras started and then quickly stopped without progressing. In some episodes the visual aura disappeared for several minutes before reappearing in a distant location, suggesting that the aura can be clinically ‘silent’. The authors concluded that these results indicate that there can be multiple distinct sites of aura initiation in a given individual, which has never been established before. They also stated that the visual perception of migraine aura changes depending on the region of the brain’s occipital cortex that is involved. This study is another small contribution to the unraveling of the puzzle that is migraine headache.

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Vitamin D seems to prevent relapses of multiple sclerosis, according to a large study by Dr. Ascherio and his colleagues at the Harvard School of Public Health. My previous posts mentioned that a high proportion of migraine sufferers have low vitamin D levels and that low vitamin D levels have been associated with Alzheimer’s disease, other dementias, and strokes. This latest study of patients with MS indicates that those with higher levels of vitamin D did better than those with lower, even if the lower level was still within normal range. Studies of vitamin D in other conditions also reported similar findings of progressive benefits with increasing levels. Many laboratories consider a level between 30 and 100 to be normal. However, even in the absence of definitive proof of benefit, it is probably prudent to aim for a level of at least 50. Just taking vitamin D, even at doses of 2,000 to 5,000 units a day does not guarantee a good level because many people do not absorb it well. Ideally, you should have your vitamin D level rechecked after taking vitamin D for a few months.

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Three out of four migraine sufferers may have reactive hypoglycemia, which may be contributing to their headaches. Reactive hypoglycemia is the so called sugar crash – a drop in blood glucose level after eating or drinking a large amount of sugar. The body’s reaction to the consumption of sugar is to produce insulin, but in those with reactive hypoglycemia too much insulin is produced and the blood sugar level drops below normal.

A recent study published in Cancer Epidemiology, Biomarkers & Prevention and reported in the NY Times showed that high consumption of sugary drinks significantly raises the risk of endometrial cancer. The researchers at the National Institutes of Health who conducted this large study speculated that the wide fluctuations in sugar levels from very high to very low could play a role in the development of cancer.

Obviously, there are other reasons to avoid sugary drinks, such as to avoid weight gain which leads to more frequent migraine and other health problems, such as diabetes, heart disease, strokes, and other. For that matter it is not just sugary drinks, but sugar in any form. Many of my patients are often surprised that I would even advise against drinking orange juice, eating grapes, melons, or other very sweet fruit. These fruit have some redeeming properties, such as having vitamins and fiber, but they also contain too much sugar and can cause the same problems as refined sugar.

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Thirty-two percent of patients with multiple sclerosis experience both migraine and pain with neuropathic (related to nerve damage) characteristics, according to a report by French researchers led by Xavier Moisse. These two symptoms appear to be caused by different mechanisms.

The authors conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 were complete enough be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics and 46% migraine. MS patients with both migraine and neuropathic pain (32% of the respondents) reported more severe pain and had lower health-related quality of life than MS patients with either migraine or just pain. Migraine was mostly episodic, but in 15% they were chronic, meaning that they occurred on 15 or more days per month. Neuropathic pain was most often located in the extremities, back and head, and was frequently described as tingling and pins-and-needles. The intensity of pain was low to moderate. Nonetheless, patients with pain were more disabled than patients with migraine. Migraine, but not pain, was more common with older age, disease duration, relapsing-remitting course, and interferon-beta treatment.

We do see patients without a history of headaches who develop headaches, including migraines, as a side effect of interferon treatment, both when it is given for MS as well as hepatitis C. These headaches can be managed just like any other migraine or chronic migraine with magnesium, medications, Botox injections, etc., although the response to treatment sometimes is not as good. If a patient with MS has both migraines and pain, we try using medications such as gabapentin or amitriptyline, which can help both conditions.

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Many medical specialty groups of doctors have been coming out with “Choosing Wisely” campaign where they recommend avoiding five things in their field. Headache specialists just came out with their own list of items that offer low-value and can be even harmful. The American Headache Society surveyed its members to develop a candidate list of items of low-value care in headache medicine. Then, a committee reviewed the literature and the available scientific evidence about the candidate items on the list and by consensus came up with a final list of five items. The five recommendations are: (1) don’t perform a brain scan (MRI or CAT) in patients with stable headaches that are typical migraines; (2) don’t perform CAT scan for headache when MRI scan is available, except in emergency settings (MRI is much more informative and does not subject the patient to radiation); (3) don’t recommend surgical procedures for migraine, unless it is a part of a clinical trial (several types of surgery are being promoted with little scientific evidence that they are safe and effective); (4) don’t prescribe opioids (narcotic drugs, such as codeine, Vicodin, Percocet) or butalbital-containing medications (Fioricet, Fiorinal, Esgic) as a first-line treatment for recurrent headache disorders because these drugs are often ineffective, can worsen headaches and can cause addiction; and (5) don’t recommend prolonged or frequent use of over-the-counter pain medications for headache. I would stress that the last item is particularly important in regard to caffeine-containing drugs, such as Excedrin and Anacin, while ibuprofen, naproxen, and acetaminophen are much less likely to cause medication overuse (rebound) headaches. Aspirin sometimes can actually prevent headaches from becoming more frequent or chronic (I admit that as a developer of Migralex I am biased in favor of aspirin, but scientific data supports this).

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More patients with fibromyalgia suffer from migraine headaches than those without this fibromyalgia. Those with fibromyalgia are also more likely to have irritable bowel syndrome, depression, and panic attacks. Fibromyalgia has been a mysterious and an ill-defined condition. However, after years of research specific criteria for the diagnosis were developed and several drugs for fibromyalgia were approved by the FDA (Lyrica, Cymbalta, Savella).

A new study by researchers at the Massachusetts General Hospital suggests that half of the patients with symptoms of fibromyalgia have damaged peripheral nerves, a condition called small-fiber neuropathy. They compared skin biopsies (a test to diagnose the neuropathy) in 25 patients with fibromyalgia and 29 healthy controls. In healthy controls only 17% had neuropathy. This type of neuropathy can also occur in diabetics, but none of the 25 patients in the study had diabetes. Other conditions that can cause small-fiber neuropathy are cancer, autoimmune conditions, various toxins, vitamin B12 deficiency, and genetic disorders, but none of these were present either, except for possibly genetic cause since three patients were related (a mother and two daughters).

The practical importance of this finding is that sometimes neuropathy responds to immune therapies, such as intravenous gamma globulin.

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Migraine headaches can be triggered by exposure to a variety of chemicals, including fumes, MSG, artificial sweeteners and many other. Now, scientists at the university of Kansas Medical Center published a study suggesting that BPA, a ubiquitous toxic chemical found in plastics, canned food, and ATM receipts, may be also involved in triggering migraine attacks. The New York Times columnist, Nicholas Kristof has been publicizing the dangers of BPA (bisphenol A) in many of his articles. BPA was recently banned from baby bottles and cups, but it is still widely used everywhere else and can be found in significant amounts in the bodies of 90% of the US population. It is not surprising that BPA could impact migraines because it can produce hormonal estrogen-like effects. Women are three times more likely to have migraines than men, with estrogen being the likely culprit.

The Kansas researchers hypothesized that BPA exposure exacerbates migraine symptoms through estrogen mechanisms. They studied the effect of BPA on female rats, in which a migraine-like state of increased sensitivity was induced. They studied changes in movement of these rats, light and sound sensitivity, grooming, and startle response. They also measured changes in genes related to estrogen and pain perception. After BPA exposure these rats had significantly increased migraine-like behaviors. They moved less, had an increase in light and sound sensitivity, altered grooming habits, and increased startle responses. BPA exposure also increased expression of estrogen and pain-modulating receptors. These results suggest that BPA may be also a contributing factor to migraines in humans.

This study has many limitations, with the main one being that it was done in rats. However, it is possible that BPA is one of many potential triggers which can make migraine headaches worse. However, there is little doubt that BPA is a chemical that should be avoided regardless of its effect on migraines.

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White matter lesions (WML) are more common in people who suffer from migraine headaches with or without aura and my recent post mentioned yet another study confirming this finding. Researchers from Johns Hopkins School of Medicine just published a study in the journal Neurology which provides further reassurance about the benign nature of these mysterious lesions. They examined over 1,000 migraine sufferers with two MRI scans separated by 8 to 12 years. While those with migraines had a significantly greater risk of having these WML or as these researchers called them white matter hyperintensities (WMH) the number of these lesions did not increase with the passage of time. This study contradicts a larger, so called CAMERA study which showed progression of the number of WMLs in women. That study was done in younger people and the authors speculate that whatever might be causing these WML may be occurring at a younger age when the disease of migraine is most active. It is a well established fact that migraines are most common in 20s, 30s, and 40s but then tend to subside.

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Botox injections are currently approved for the treatment of chronic migraines but not cluster headaches. However, my experience at the New York Headache Center suggests that Botox injections may also help relieve cluster headaches, which some call suicide headaches. We inject Botox for cluster headaches in a similar way we do for chronic migraines, that is the injections are given in the forehead, temple and back of the head and neck. One difference is that since cluster headaches are strictly one-sided we inject only one side with the exception of the forehead because injecting only one side of the forehead will result in a lopsided appearance.

Researchers at the Norwegian University of Science and Technology in Oslo came up with an idea of injecting Botox into the sphenopalatine ganglion. This ganglion is a bundle of nerve cells that sits behind the back of the throat and has been a target for all kinds of procedures to relieve various pain problems. Doctors have attempted numbing those cells with cocaine and lidocaine, destroying it with heat, and stimulating it with electric current in an attempt to relieve not only cluster and migraine headaches but a range of painful conditions, including low back pain. Unfortunately, we do not have any good scientific studies proving that any of these procedures on the sphenopalatine ganglion work for any condition it’s been tried for. We have many so called anecdotal reports describing successful cases, but no large controlled trials have ever been performed.

It is not clear why the Norwegian doctors think that injecting Botox into the ganglion will be effective, beyond the fact that Botox “can stops the flow of impulses along the nerves”. A report in says that “The researchers strongly believe in their treatment method, in part because a new study unrelated to their work has shown an effect by using an electric current to paralyse the nerve bundle.” So far it does not seem that they’ve treated any patients, but did start recruiting patients for a study.

They hope to enroll 30-40 cluster headache patients and then another 80 with migraine headaches. also reports that the treatment uses an MRI of the patient’s head to make certain that the surgeon knows exactly where the nerve bundle is. A navigation tool, composed of three small spheres on the pistol, and a plate with three spheres mounted on the patient’s head, enables the surgeon to find the nerve bundle using the MRI image. “A computer sends light signals to all the spheres to form precise points. We don’t miss, but anyone who wants to participate in the study must accept the risk that it could happen, because this has never been done before. If the Botox hits an area near the nerve bundle, it could cause temporary double vision, or weaken the ability of the patient to chew,” says the lead researcher, Dr. Tronvik.

Until we have some evidence that this treatment works we have to work with the standard approaches to cluster headaches, which include, occipital nerve blocks, oxygen, a course of steroid medications, sumatriptan (imitrex) injections, verapamil, lithium, and other drugs. Two of my patients for whom none of these approaches and Botox injections worked did respond to vagus nerve stimulation, or VNS. This procedure involves wrapping a wire around the vagus nerve in the neck and connecting it to a pacemaker-like device which is implanted under the skin in the upper chest. This is also a totally unproven method with only anecdotal evidence. However, VNS has been approved by the FDA for difficult to treat epilepsy and depression. Considering that antidepressants and epilepsy drugs help migraine and cluster headaches, it is logical to conduct studies of VNS before going for a more invasive procedures.

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The previous post mentioned a study confirming that caffeine makes headaches worse in adults 20 years or older. A study by pediatric neurologists from the Cleveland Clinic, Chad Whyte and David Rothner showed that this is also true in adolescents. They looked at 50 children, who were between 12 and 17 years of age who presented to their headache clinic. The average age was 15 and 64% were girls. The mean consumption of caffeine was 109 mg per day. In kids with chronic migraines the intake was 166 mg, while in the rest it was 65 mg. The most popular form of caffeine was soda drinks. This study further confirms the role of caffeine in causing worsening of headaches and leading to chronic migraines.

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A study of 13,573 people by a Harvard physician Catherine Beuttner examined the role of nutrition in patients with migraines and severe headaches. Among these participants of the National Health and Nutrition Examination Survey who were 20 years old or older, 22% or 2,880 suffered from migraines or severe headaches. A large variety of factors that could influence headaches were examined, including age, sex, race/ethnicity, education, smoking, alcohol intake, physical activity, health status, body mass index, diabetes, and number of prescription medications used. Sophisticated statistical analysis established that carbohydrate intake as a percentage of energy consumption and caffeine use were associated with higher prevalence of migraine and severe headaches. On the other hand, fiber intake appeared to reduce the prevalence of migraines and severe headaches. Dr. Beuttner also discovered that intake of foods rich in folate (folic acid, or vitamin B9), thiamine (vitamin B1), and vitamin C was also associated with lower prevalence of migraines and severe headaches.

This large study confirms some of the previous reports about the role of carbohydrates and caffeine in the development of headaches. According to one small study, three out of four migraine sufferers have reactive hypoglycemia. Reactive hypoglycemia is a condition that causes blood sugar to drop too low after eating a carbohydrate-rich meal. This drop of sugar seems to trigger headaches. Many migraine sufferers figure this out on their own and reduce their carbohydrate intake, but some fail to make this connection. So, if you suffer from severe headaches try eating small frequent meals that are low in carbs.

Caffeine is a well-known and proven trigger of migraine headaches. Caffeine can sometimes cause headaches directly, but more often headaches occur due to caffeine withdrawal. This is why many people wake up in the morning with a headache – they’ve gone all night without caffeine. Since caffeine is a short-acting drug withdrawal can occur throughout the day leading people to consume more and more caffeine. Eventually the headache become constant with some improvement after each dose of caffeine, whether it is from coffee, soda, strong tea or medications, such as Excedrin, Anacin, Fioricet, and Fiorinal. Getting off caffeine is the only way to stop these headaches. It can be done gradually or “cold turkey”. Your doctor can prescribe medications to make this process less painful because headaches will get worse before they get better. These medications may include triptans (Imitrex, Maxalt, and other), Migralex, or naproxen (Aleve). Botox injections can also help. Many of my patients argue that caffeine is not the cause of their headaches since headaches started long before they were consuming any caffeine. It is true that caffeine does not cause headaches, but if you suffer from migraines and other headaches, caffeine can make them worse. And getting off caffeine may not eliminate all headaches, but will make them much more amenable to treatment.

As far as folic acid and vitamin B1, there have been some studies proving that B vitamins (including B12) can prevent migrianes, but fiber and vitamin C have not been reported to help headaches in the past.

In summary, if you suffer from migraines or severe headaches try to keep your carbohydrate intake low, eliminate caffeine, increase your intake of foods rich in fiber, B vitamins, and vitamin C. You may also want to consider taking a supplement of these vitamins, along with B12, magnesium, CoQ10, and possibly some herbal products mentioned earlier in my blog or on our main site,

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Omega-3 and omega-6 fatty acids are needed for our body to produce pain-relieving and pain-enhancing substances. Researchers at the University of North Carolina at Chapel Hill conducted a randomized, single-blinded, parallel-group clinical trial, which was published in the journal Pain, to assess clinical and biochemical effects of changing the dietary intake of omega-3 and omega-6 fatty acids on chronic headaches.

After a 4-week baseline, patients with chronic daily headaches undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high omega-3 plus low omega-6 intervention, or a low omega-6 intervention. Clinical outcomes included the Headache Impact Test, which measures headache-related disability, headache days per month, and headache hours per day. They also measured omega-3 and omega-6 levels in red blood cells. Fifty-six of 67 patients completed the intervention.

The first intervention (increasing omega-3 and lowering omega-6) produced significantly greater improvement in the Headache Impact Test score and the number of headache days per month compared to the second group (lowering omega-6). The first intervention also produced significantly greater reductions in headache hours per day. The authors concluded that dietary intervention increasing omega-3 and reducing omega-6 fatty acids reduced headache pain and improved quality-of-life in chronic headache sufferers.

The omega-3 fatty acids are generally considered good and the omega-6 are considered bad, but it appears that what is more important is the balance between the two types. The known beneficial effects of fish oil include their effect on the heart, brain, peripheral nerves, mood, inflammation, as well as headaches. There is little downside to taking omega-3 supplements, as long as you buy fish oil from a reputable store chain or a well-know brand, which is purified of mercury.

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Vertigo presenting during the peri-menopause can be related to migraine, according to a report by Nashville neurologists led by Dr. Jan Brandes. They collected information on 12 women who presented with a new onset of vertigo during their peri-menopause and who fulfilled the criteria for migrainous vertigo. Only 4 of the 12 were previously diagnosed to have migraine headaches and all of them were treated for at least a year for non-migraine causes of vertigo. Once the diagnosis of migrainous vertigo was made a combination of hormonal and conventional migraine preventive therapy produced a significant improvement in these women. The authors concluded that the appearance of vertigo during the peri-menopause should prompt an evaluation for possible migraine connection and if such connection is found the treatment should include a combination of hormonal and traditional migraine therapies.
Other non-migraine causes of vertigo include inner ear problems, brain disorders, such as strokes and tumors, and neck muscle spasm. The latter usually causes dizziness rather than true vertigo, which is defined as a spinning sensation. Dizziness can also be caused by drop in blood pressure, especially on standing up, peripheral nerve damage (such as in diabetes or vitamin B12 deficiency), eye, and other conditions.

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Dihydroergotamine (DHE-45) is considered to be the most effective injectable migraine drug. In addition to injections, it is been available in a nasal spray form (Migranal), but the nasal spray is much less effective than the injection. Early next year we expect to have an inhaled version of dihydroergotamine, Levadex. Clinical trials indicate that it could work as fast and as well as the injection and may have fewer side effects. Dihydroergotamine constricts blood vessels and just like triptans (Imitrex or sumatriptan and other) is contraindicated in people with cardiovascular disease, such coronary artery disease, heart attacks, and strokes. The perception has always been that dihydroergotamine, because it is a less pure drug than triptans, is a stronger vasoconstricter than triptans. However, a recent study by Dutch researchers suggests that this may not be the case.

This study compared the contractile effects of sumatriptan and DHE in human coronary arteries. The study looked at both large (proximal) and small (distal) coronary arteries. The arteries (removed from the body) were exposed to sumatriptan (Imitrex) and DHE. In larger (proximal) coronary artery segments sumatriptan was a stronger constricter than DHE but the difference was not significantly different. In contrast, in smaller (distal) coronary arteries, the contractile responses to sumatriptan were significantly larger than those to DHE. At clinically relevant concentrations contractions to both sumatriptan and DHE in proximal as well as distal coronary arteries were below 6%. The researchers concluded that coronary artery contractions to DHE in distal coronary artery are smaller than those to sumatriptan, although in the clinical situation both drugs are likely to induce only a slight contraction. So, both drugs are relatively safe and dihydroergotamine may be safer than sumatriptan, although both should not be given to migraine sufferers who also have cardiovascular disease or multiple risk factors, such as hyprtension, diabetes, high cholesterol, smoking, and other.

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Fainting spells (syncope) are more common in people who suffer from migraine headaches. Compared with control subjects, migraineurs have a higher lifetime prevalence of syncope (46 vs 31%), frequent syncope (five or more attacks) (13 vs 5%), and being lightheaded on standing up or on prolonged standing (32 vs 12%).

It appears that syncope is also a more common symptom of migraine than previously suspected, according to a study by Case Western Reserve neurologists.

The study involved 248 patients who had at least 3 episodes of syncope. Of these patients, 127 had a headache at the time of syncope and 121 did not. Syncopal headaches were classified as either syncopal migraine or a non-migraine headache. The syncope groups were then compared to 199 patients with migraine headaches.

Nearly one-third of recurrent syncope patients met criteria for syncopal migraine. This group resembled the migraine headache population more than the syncope population in age, gender, autonomic nervous system testing, and associated medical conditions. The syncopal migraine group also reported a longer duration of syncope and a longer recovery time to normal. Finally, anti-migrainous medications reduced syncope in half in the syncopal migraine patients.

The authors concluded that syncope may have a migrainous basis more commonly than previously suspected.

To reduce your propensity to fainting, try to avoid dehydration, hunger, sleep deprivation, alcohol, and other triggers that you can identify. Cardiovascular conditioning is also likely to help.

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Topamax (topiramate) has been reported to cause inability to sweat which can lead to hyperthermia or overheating. At first, this condition was reported as a rare complication, but a study of 173 children showed that 22 of them or more than 10% developed this side effect. The ability to sweat returns when the drug is stopped. Sweating allows the body to coll off and loss of this mechanism can be dangerous in hot weather or during vigorous exercise. Those who take Topamax should speak to their doctor if they notice reduced sweating.

Topiramate is an effective drug which the FDA approved for the prevention of migraine headaches as well as epilepsy and mood disorders. However, in large clinical trials only half of the patients put on this drug for the treatment of migraines stayed on it. The other half either did not obtain relief of their migraines or developed side effects. One of the most common side effects is impairment of cognitive functions – people can’t remember names, can’t come up with the right words, or as some have told me they feel stupid. Other people become very tired from Topamax because they develop metabolic acidosis – their bodies become too acidic. Long-term side effect of kidney stones was also thought to be rare when the drug was introduced, but subsequent studies showed that up to 20% of patients develop kidney stones.

The full extent of side effects of any new drug does not become apparent until years after its introduction. This does not mean that we can afford to wait for years before trying new drugs since some of the patients who come to our center with migraine headaches do not respond to the available treatments. What we can do is monitor these patients very closely and stop the drug as soon as possible.

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Botox injections is the only FDA-approved treatment for chronic migraine headaches. This is a very effective (works in 70% of chronic migraine patients) and very safe treatment. The only major drawback is its cost. However, there is a great variation in the cost from doctor to doctor and hospital to hospital. This post was prompted by an email I received from a former patient. Here are some excerpts from our exchange (with her permission):

“You’ve been my doctor now for many years, and I was just in your office over the summer for Botox treatment, but I live now in Charlottesville, VA and UVA’s hospital down here charges around $6000 for the same procedure that your office can do for $2250. With my insurance, I’m still responsible for 20% of the bill, and I can’t afford to have the procedure done here in Charlottesville.

They tell me it’s because they’re paying for facilities and staff, but even the drug is more than twice as much…THAT doesn’t make sense at all! This treatment has changed my life quite dramatically for the better. I’m so much healthier, more productive, creative, and all around a better citizen and human being as a result of not having constant headaches.”

Part of my response to her: “I am not surprised about the $6,000 price tag – I recently gave a lecture at Harvard and they also charge $6,000 and so do Mayo and Cleveland Clinics. They all also charge $2,000 for IV magnesium, while we charge $250.”

Our out-of-pocket fee for Botox injections is often only $1,700 and sometimes less, depending on the amount of Botox injected. However, the majority of our patients are covered by insurance and they have to pay only their usual copay. Almost all insurance plans now pay for Botox injections for chronic migraines, although they often require trials of prophylactic medications before they approve Botox.

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Cleveland Clinic doctors established that migraine patients who are educated about sumatriptan (Imitrex) and other triptans tend to do better. It is not a surprising discovery, but it highlights the importance of patient education. The study involved 207 patients at the Cleveland CLinic, Mayo Clinic, Brigham and Women’s Hospital. Here are some important facts that migraine sufferers need to know.

One such fact, taking medicine early, seems obvious, but many patients often wait to take a triptan for a variety of reasons. They often think that it may not be a migraine, but rather a tension headache that will not require a triptan. Others are reluctant to take medication because it might be dangerous, although the most common reason is that patients often don’t get enough medicine from their insurer. These are expensive drugs, even in a generic form. However, it is more expensive to lose a day of work and if the medicine is taken early one tablet may be sufficient, but if taken late, the patient may need 2 or 3 tablets to abort an attack.

Another fact is that you do not need to take an aspirin (or Migralex) or ibuprofen before resorting to a triptan if the headache is very severe. Many people often keep trying an over-the-counter drug first, even if they always end up taking a triptan. It is OK to combine aspirin or ibuprofen with a triptan if a triptan alone is insufficient.

Migraine sufferers should also know that triptans are contraindicated in people with coronary artery disease. If you had a heart attack, suffer from angina or have multiple risk factors (hypertension, diabetes, high cholesterol, smoking, etc).

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Migraine affects people in all socio-economic categories, however it is more likely to occur in poor, according to a report in the latest issue of Neurology. Researchers examined the data from the American Migraine Prevalence and Prevention Study. This study surveyed 132,674 females and 124,665 males 12 years of age and older. The participants were divided into three income groups, income below $22,500, between $22,500 and $60,000 and above $60,000. They found that those with lower income were more likely to develop migraine headaches. This is not a new finding and a possible explanation for this phenomenon is that poor tend to have more physical and psychological stress. However, a new and very interesting finding of this study is that the remission rate was the same in poor and well to do. The authors speculate that this may be because once migraines start only biological and genetic factors influence the timing of remission. We do know that in many women menopause leads to cessation of migraine headaches.

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Performing an MRI scan is unnecessary in the vast majority of migraine sufferers. However, many migraineurs end up having this test because they are concerned about having a brain tumor or another serious condition and because many doctors order MRIs to avoid a possible malpractice suit, however remote the possibility. MRI scan does not involve any radiation, so it is not harmful, but it can cause other problems, besides wasting healthcare dollars. The harm often comes from finding an abnormality on the MRI which is benign, but nevertheless can be very anxiety provoking.

Lesions seen on MRI scans which are benign but very upsetting to patients are arachnoid cysts and venous malformations.

The most common finding though is white matter lesions (WMLs), which doctors sometimes jokingly refer to as UBOs – unidentified bright objects. The origin and the meaning of these spots remains unclear, although the most likely explanation is that these spots are due to ischemia or lack of blood flow. A Dutch study of 295 men and women published in 2004 showed that people who have migraine with aura had a higher risk for silent strokes. As far as WMLs, surprisingly, control subjects, that is people without migraines, had the same high chance of having WMLs as those with migraines – about 38%. However, women with migraine were more likely to have these lesions, regardless whether they had auras or not. A follow-up study published in 2012 reported on 203 of the original 295 patients who underwent another MRI scan 9 years later. This study showed that 3 out of 4 women had progression of these lesions, but they did not have any more strokes. They also did not find an increased risk of dementia in these women.

Another important finding from this long-term study is that migraine sufferers who tend to have syncope attacks (fainting) or near-fainting or feeling lightheaded on standing up or when having blood drawn are more likely to have these WMLs. This suggests that lack of blood flow to the brain may be responsible for WMLs. These findings were presented in a separate article in Neurology.

So, while we still don’t know the cause of WMLs they do appear to be benign and do not lead to other serious problems.

If WMLs are related to strokes as suggested by the fact that drop in blood flow to the brain may predispose one to having WMLs and in a severe form drop of blood flow causes strokes, then possibly approaches that prevent strokes may also prevent WMLs. Even if they are benign, having WMLs is concerning because we may not yet know some of their negative consequences. We know that the risk of strokes can be reduced by avoiding smoking, controlling blood pressure in people with hypertension and blood glucose in diabetics, maintaining normal cholesterol levels, maintaining normal weight, and exercising regularly.

A recent study published in Neurology showed that WMLs are strongly correlated with the frequency of exercise – the more people exercised the less likely they were to have WMLs.

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It is hard to believe the report of a group of Danish doctors who found 28 out of 61 (46%) patients undergoing surgery for a herniated lumbar disc to have a bacterial infection in those discs. Just like the idea that stomach ulcers are caused by bacteria seemed preposterous, so does the finding of bacterial infection in patients with low back pain. However, after 10 years of skepticism and ridicule Helicobacter bacteria was recognized as the cause of many stomach ulcers and the doctors who made this discovery were awarded a Nobel Prize. Another recent surprise discovery is that babies are not born sterile but are inhabited by a variety of bacteria which they obviously must have acquired from their mothers while in the uterus. This was established by examining the stool of newborns immediately after birth.

Of the 23 patients with infections 4 had more than one type of bacteria present. The most common type of infection was with Pseudomonas acnes, which does not require oxygen to grow (so called anaerobic bacterium). Most patients with infections had abnormally looking vertebral bones (bone edema), although these abnormalities were not specific, that is they can be present without an infection as well. About 6% of the general population and 35-40% of those with low back pain have these abnormal findings on an MRI scan.

In the second randomized controlled study by Dr. Albert and her colleagues treated 162 patients who had low back pain for more than 6 months, a disc herniation and bone changes on the MRI scan, but who did not undergo surgery. Half of the patients were treated for 100 days with an antibiotic, amoxicillin clavulanate (Bioclavid) and the other half with placebo. The patients taking antibiotics experienced significant improvement for a year compared with those taking placebo. Improvement included the degree of back pain, sleep quality, and disability. Antibiotic caused only mild gastrointestinal side effects.

It is premature to make any definitive conclusions before larger confirmatory studies are conducted. However, in patients with chronic back (and possibly neck) pain as well as bone edema on the MRI scan treatment with an antibiotic should be considered.

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Migraine aura seems to indicate a different underlying brain condition than that of migraine without aura. We know that the risk of strokes is higher in patients who suffer from migraines with aura. The increase in this risk is very slight, although it is three times higher in women than in men and in women it is magnified by oral contraceptives. The risk is also increased in both men and women by the known risk factors, such as high blood pressure, diabetes, high cholesterol, smoking, and other.

A recent study by Stephanie Nahas and other neurologists at Thomas Jefferson University in Philadelphia discovered that aura carries another risk. A study of 139 patients admitted for stroke evaluation showed that those who had a history of migraine aura had a much larger stroke than those without. This is another reason for people who suffer from migraines with aura (or auras without a migraine) to take all possible measures to reduce their risk of strokes. These might include regular exercise, healthy diet, controlling blood pressure, blood glucose, and cholesterol. Some people could also benefit from a daily dose of aspirin (make sure to check with your doctor first), omega-3 fatty acids, and in people with high homocysteine levels, vitamin B12 and other B vitamins.

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At the New York Headache Center we always try to avoid using medications and use alternative (i.e. non-drug) therapies first. We often succeed, but unfortunately, many of our patients do end up taking some drugs. However, when choosing among many medications, we start with the ones that are least likely to harm. Depakote (sodium valproate) is an effective drug for the treatment of epilepsy, mood disorders, and migraines. While we do prescribe Depakote to our patients, it has never been our first, second, or third choice because we already know that it can cause liver problems and fetal malformations. A recent study published in Neurology adds another reason to avoid this medication.

Patients with intractable epilepsy who were taking Depakote were compared with those who were taking other epilepsy medications and with healthy controls. MRI scans showed that those taking Depakote had thinning of the parietal lobes of the brain, had lower total brain volume, and lower white matter volume. This was a small study, but it was conducted because of previous reports of brain atrophy. Fortunately, those previous reports showed that brain atrophy was reversible when the medication was stopped. If you are taking sodium valproate for migraine headaches or a mood disorder, do not stop taking it without consulting your doctor since stopping it suddenly can worsen your condition and in epilepsy patients, cause seizures. But do discuss alternative options with your doctor, although some people may not be able to stop it if no other drugs provides relief of their symptoms.

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A variety of electrical devices have been tried for the treatment of headaches and have been mentioned in several of my previous blogs. One study showed that passing direct current through the head may help migraines and depression. Another study recently presented at the joint meeting of the International and American Headache Societies showed that passing alternating current, just like done by any TENS (transcutaneous electric nerve stimulation) machine, but using a proprietary device, Fisher Wallace Stimulator, did not provide relief. This study performed by Dr. Tietjen and her colleagues in Ohio was blinded and involved 50 patients. They applied the stimulator for 20 minutes every day for a month with one half receiving stimulation and the other half not. After a month both groups used real stimulation for another month. While this device did not cause any serious side effects, it also did not help. Hopefully, we will soon see results of large studies using direct current stimulation since this method appears to be more promising than alternating current used in TENS devices.

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Fish oil supplements may protect the heart in stressful situations, according to a study conducted in Michigan with 67 healthy volunteers. The researchers, led by Jason Carter, looked at the effect of fish oil on body’s stress response. The volunteers were given either nine grams of fish oil pills or nine grams of olive oil as a placebo, over a two-month period. The heart rate, blood pressure and other parameters were measured before and after the study.

After two months, both groups took a math test, which involved adding and subtracting numbers in their head. Their stress response was measured. Those who took fish oil supplements had a milder response to mental stress, including heart rate and sympathetic nervous system activity, which is part of the “fight or flight” response, compared to those who took olive oil instead.

The author concluded that “these results show that fish oil could have a protective effect on cardiovascular function during mental stress, a finding that adds a piece to the puzzle on why taking fish oil helps the heart stay healthy,”

This study supports the evidence that the omega-3 fatty acids have positive health benefits on the nervous and cardiovascular systems.

The author concluded that “In today’s fast-paced society, stress is as certain as death and taxes,” he added. “Moreover, our eating habits have deteriorated. This study reinforces that fish oils may be beneficial for cardiovascular health, particularly when we are exposed to stressful conditions.”

He also suggested “If you don’t do it already, consider taking fish oil supplementation, or better yet, eat natural foods high in omega-3 fatty acids.” Such foods include Alaska salmon, rainbow trout and sardines.

As far as the effect of omega-3 fatty acids on headaches, there is only one small but blinded study of 15 patients that suggests that they might help prevent migraines. Considering that in addition to counteracting the effect of stress, a major migraine trigger, omega-3 fatty acids reduce inflammation (which is one of the underlying processes during a migraine attack), it is very likely that omega-3 fatty acids may help some migraine sufferers.

Most people do not eat enough fish, so it makes sense to supplement your diet with omega-3 fatty acids. It is important to make sure that the brand you take does not contain mercury and other impurities. One of the brands I came across recently, Omax3 was developed by physicians from Yale university. It is pure and concentrated, meaning that you need to take only 2 capsules a day to get 1,500 mg of omega-3s. Most people who do take a supplement often don’t take enough of it. The study mentioned above used 9 grams of fish oil daily, while the headache study used 15 capsules with each containing 300 mg of omega-3s. To get the same amount from Omax3 you’d have to take 6 instead of 15 capsules.

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Advances in MRI imaging have allowed visualizing the trigeminal nerve and a group of Australian researchers reported on their findings in three conditions which cause facial pain. Trigeminal nerve supplies sensation to the face and facial pain of any kind is also transmitted to the brain through this nerve. Their report, which appeared in The Journal of Pain, suggests that imaging trigeminal nerve may help in making a more accurate diagnosis, which is turn may lead to more appropriate treatment.

Trigeminal neuralgia is an extremely painful condition which is characterized by very brief electric-like pains in the face. The pain is triggered by chewing, talking, brushing teeth, touching a specific spot on the face, and at times occurring without any provocation. This condition usually results from compression of the trigeminal nerve by a blood vessel as it exits the brain stem. Treatment usually involves epilepsy drugs, such as carbamazepine (Tegretol) or oxcarbazepine (Trileptal), Botox injections, nerve destruction (radiofrequency thermocoagulation) or if nothing else works, surgery (microvascular decompression of the trigeminal nerve).

Trigeminal neuropathy also causes pain in the face, but it is less intense, usually continuous and is often burning in character. It can result from an injury to the trigeminal nerve in the periphery rather than near the brain stem. Dental procedures and facial injuries can trigger this pain. This pain tends to respond better to antidepressants, such as amitriptyline (Elavil), nortriptyline (Pamelor), protriptyline (Vivactil), and an epilepsy drug, gabapentin (Neurontin).

Temporomandibular joint disorders can result from arthritic changes in this joint, displacement of the cartilaginous disc inside the joint, or from muscle spasm and inflammation around the joint.

Using special MRI techniques the researchers discovered that patients with trigeminal neuralgia had thinning of the nerve, while those with trigeminal neuropathy had thicker trigeminal nerves than normal controls. Patients with temporomandibular disorders had normal thickness of their trigeminal nerves. This is a very useful finding, particularly when the diagnosis is not clear since some patients may have symptoms of both neuralgia and neuropathy. We often have to try several drugs before finding one that is effective and does not cause side effects, so it would be helpful to know from the start which drugs are more likely to work.

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The manufacturer of Petadolex brand of butterbur sent me an email saying that the FDA conducted an inspection of their manufacturing plant in Germany. However, my concerns about butterbur, which I mentioned in a previous blog post, has not been addressed. Here is my email response to the manufacturer:
“Thank you for this additional information. It is good to see that the FDA conducted a “comprehensive inspection” of the manufacturing facility in Germany. However, my concerns about the safety of Petadolex are not due to possible deficiencies in manufacturing, but are related to the extraction process. As far as I know, this is why German and UK governments still do not allow the sale of Petadolex and this is why I do not recommend Petadolex to my patients. I am also concerned that because Petadolex is fairly expensive, many patients will decide to buy a cheaper brand of butterbur, which can be truly dangerous. Once Petadolex is cleared for sale in Germany I will be happy to resume recommending it to my migraine patients”.

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Bipolar disorder and other psychiatric problems are 2-3 times more common in those who suffer from migraine headaches and migraines are 2-3 times more common in patients with mental illness. Those who suffer from migraines are very familiar with the attitude of doctors, family members and employers who consider migraine to be just another headache, meaning that it is not something that should stop you from doing any activities. Some doctors still blame migraine sufferers for their condition and think that this is a problem of neurotic women. People with mental illness face even more severe discrimination from doctors and everyone else. A very good article on this topic, “When Doctors Discriminate” has appeared in the New York Times this Sunday.

Dr. Robert Shapiro of the University of Vermont recently presented a study which looked at attitudes toward patients with migraine, epilepsy and other conditions. It was an internet-based survey of 705 individuals that examined the levels of stigma by asking following questions:
How comfortable would you be with Jane as a colleague at work?
How likely do you think it is that this would damage Jane’s career?
How comfortable would you be with the idea of inviting Jane to a dinner party?
How likely to you think it would be for Jane’s husband to leave her?
How likely do you think it would be for Jane to get in trouble with the law?

Scoring ranged from 0 to 100. The mean scores were very similar for migraine, panic disorder, and epilepsy and were all significantly greater than for asthma. He concluded that migraine carries as much stigma as epilepsy or panic disorder, although he noted limitations.

Another group of researchers from Philadelphia led by Dr. William Young interviewed 123 patients with episodic migraine, 123 with chronic migraine, and 62 with epilepsy for levels of stigma as perceived by these patients.

Chronic migraine patients had much higher scores on the Stigma Scale for Chronic Illness (SSCI) than the other two groups, but that seemed to be due to chronic migraine patients’ reduced ability to work.

Dr. Young reported that migraine patients reported more “internalized” stigma, that is negative attitudes in themselves or anticipation that others would think negatively of them, and less actual discrimination on the basis of their illness, compared with the epilepsy patients.

These studies and the New York Times article indicate a great need for educating both doctors and the general public about the nature of chronic migraines and mental diseases and for combating the stigma associated with these conditions.

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Surprisingly, Botox appears to relieve hemiplegic migraines, according to a report by two neurologists from the Mayo Clinic.

They describe 5 female patients who suffered from very frequent and severe migraine headaches with four of them having chronic migraines, that is had headaches on 15 or more days each month. The headaches were preceded and/or accompanied by weakness of one side of their body. The weakness lasted only 20 minutes in one patients, but for hours and days in others. All five patients were first treated with prophylactic medications, which either did not help or caused unacceptable side effects. Botox injections were given every 3 months into the usual sites around the scalp, neck and shoulders. A total dose of 150 units was injected. Three of the patients had three sets of injections by the time of this report and they continued to respond well.

Migraine with typical visual auras has been reported to respond well to Botox injections, which is also somewhat surprising since Botox appears to work on the sensory nerves. This effect on sensory nerve endings leads to the relief of pain. It is likely that reducing painful episodes in turn leads to a calming effect on the brain in general and the brain stops generating migraines as well as symptoms associated with migraines.

I have also seen many patients with visual, sensory and motor aura respond well to Botox injections, often when prophylactic drugs had been ineffective.

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Auditory hallucinations can be associated with chronic headaches, according to a report by our own Dr. Sara Crystal and three other neurologists from the Bronx.

These four doctors reported on 7 of their own patients and also described 8 patients previously reported in the medical literature. Half of the patients had migraine with aura. Regarding hallucination content, the most common sound was distinct human voices in 8 patients, followed by hearing crickets in 2, and ringing bells in another 2, general white noise, also in 2, and repetitive beeping in 1. Regarding timing, 12 experienced hallucinations along with the headache while 3 heard sounds prior to attacks. The duration of the auditory hallucinations was less than one hour but occasionally lasted 4-5 hours or for the duration of the headache. Ten patients had either a current or previous psychiatric disorder, mostly depression. Improvement in both headaches and auditory hallucinations occurred both spontaneously and when prophylactic medications were used, which included propranolol, topiramate, and amitriptyline.

In conclusion, auditory hallucinations are uncommon, but do occur before or during migraine attacks. They usually feature the sound of human voices. Because these are unusual manifestations of migraine, doctors should consider other possible causes, such as a brain tumor, epilepsy, or schizophrenia.

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The vascular theory of migraine suggested that changes in the blood vessel size and blood flow were responsible for the development of migraine attacks. This theory went out of fashion and for the past 20 years most headache experts thought that the process of migraine begins in the brain and not blood vessels. A new study by researchers at the University of Pennsylvania seems to again implicate blood vessels as the culprit.

Brain is supplied by four blood vessels that come up from the neck into the brain – two carotid and two vertebral arteries. At the base of the brain they connect with each other making a circle of Willis. Thomas Willis was a 17th century English physician who first described this circle. This circle ensures good blood flow to the brain even if one or even two of the four blood vessels become occluded. Only a third of the population actually has a complete circle connecting all four arteries, while in the rest the circle is incomplete.

This is not a new finding – a group of French physicians reported this discovery in 2009. However, the current study showed that having incomplete circle affected cerebral blood flow and this may be contributing to the process of triggering migraines.

This abnormality appears to be particularly common in those who have migraine with aura. The study looked at 170 people from three groups – a control group with no headaches, a group that had migraine with aura, and a group that had migraine without aura. An incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent).

One of the authors commented that “People with migraine actually have differences in the structure of their blood vessels — this is something you are born with” and, “These differences seem to be associated with changes in blood flow in the brain, and it’s possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches.” A very interesting observation was that “Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located. This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines”. It is also possible that the increased risk of strokes in patients with migraine with aura is due to this anatomical defect.

It is most likely that having an incomplete circle of Willis is only one of many predisposing factors. Unfortunately, we cannot do much about this congenital abnormality, but we do have many ways to prevent migraine headaches even without fixing this problem directly.

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Increased intracranial pressure is an under-diagnosed cause of difficult to treat headaches. Persistent chronic headaches that do not respond to treatment may be due to increased pressure inside the head. These headaches may resemble chronic migraine headaches and many doctors will try treating these patients with preventive medications, such as Neurontin (gabapentin), Topamax (topiramate), amitriptyline (Elavil), or Botox injections. If these approaches do not provide relief, measurement of intracranial pressure should be considered. Most patients who suffer from increased intracranial pressure have swelling of the optic nerves (papilledema), which can be detected by examining the back of the eye, a standard part of a neurological and ophthalmological examination. However, some people with increased pressure do not have papilledema and they are the ones who present a diagnostic challenge. This condition is also called pseudotumor cerebri because tumors also raise intracranial pressure. To measure the pressure a spinal tap (lumbar puncture) is performed. The cerebrospinal fluid circulates around the brain, within its ventricles and around the spinal cord. Putting a needle into the spinal fluid at the lumbar spine level is much safer than anywhere else and gives the reading of the pressure everywhere within this enclosed space, including the brain.

Factors that predispose to increased intracranial pressure include delayed effects of a head trauma, certain medications, excessive amounts of vitamin A, obesity, and other. One of the more recent theories suggests that narrowing of the veins that drain blood from the brain is responsible for this condition. This diagnosis is made by performing an angiogram or a magnetic resonance venogram (MRV, a test done by an MRI machine), tests that show blood vessels.

In addition to headaches, increased pressure can cause nausea, dizziness, pulsating noise in the ears, and blurred vision. If left untreated, the increased pressure can lead to loss of vision.

If no obvious causes are found the condition is called idiopathic intracranial hypertension. Its treatment begins with the attempts to lose weight if the person is overweight. Pregnant women who are more prone to develop this condition often obtain relief after the delivery. Medications that can help include acetazolamide (Diamox) and topiramate (Topamax). If medications are ineffective a neurosurgeon can place a shunt that drains cerebrospinal fluid into the abdomen. This is a relatively simple procedure, but it does carry a risk of infections and other complications. Shunting is reserved for patients who have uncontrollable headaches or are threatened with loss of vision.

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Acute treatment of episodic and chronic migraine headaches in the US leaves a lot to be desired. Results of the American Migraine Prevalence and Prevention Study lead by Dr. Richard Lipton indicates that the acute treatment of migraine headaches in patients with chronic migraines is significantly worse than in patients with episodic migraines. Chronic migraines are defined as those occurring on 15 or more days each month, while patients who have 14 or fewer migraines a month are classified as having episodic migraines.

The researchers developed a specific questionnaire to assess acute treatment of migraine headaches. The questionnaire evaluated the effect of treatment on people’s functioning, how rapid was the relief, relief consistency, recurrence risk, and tolerability or side effects. They examined responses from 8612 persons who met criteria for migraine (chronic migraine = 539; episodic migraine = 8073). The treatment scores were significantly lower for persons with chronic migraine vs episodic migraine. The conclusion was that the questionnaire was a robust tool for measuring treatment optimization and that acute treatment was suboptimal for both episodic and chronic migraines, particularly for chronic migraines, suggesting that there are opportunities for improving care.

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Stimulation of the sphenopalatine ganglion seems to relieve cluster headaches according to a study by European neurologists. The study examined the efficacy of the on-demand sphenopalatine(SPG) stimulation in chronic cluster headache patients. 43 patients in this randomized controlled study were implanted with the ATI Neurostimulator System. Chronic cluster headache is a disabling neurological disorder that often does not respond to medical therapy. A previous study showed that this stimulator was effective for acute cluster headache pain relief and in some patients made their attacks less frequent. These patients also had clinically and statistically significant improvement in quality of life and reduction in headache disability.

The 43 patients in the current study were dissatisfied with their cluster headache treatment and 32 of them completed the one-year study with 23 continuing to use the stimulator beyond one year. At enrollment, 18 (78%) of patients indicated their overall evaluation of the ATI Neurostimulation System for treating their chronic cluster headaches as good or very good. 18 (78%) found SPG stimulation a useful therapy in treating their cluster headaches. 19 (83%) found surgical effects tolerable and the implanted neurostimulator comfortable or did not notice it and 23 (100%) found the stimulation sensation tolerable. 15 (65%) did not have significant side effects after stimulation. 21 (91%) would make the same decision again to treat their CH with the ATI Neurostimulation System, and 22 (96%) would recommend the ATI Neurostimulation System to someone else. 13 (57%) of patients experienced clinically significant improvement in headache disability and quality of life compared to baseline.

These results suggest that SPG stimulation with the ATI Neurostimulator is an effective therapy with sustained benefits and a high level of
patient satisfaction. This is an experimental device and is not available in the US. Even when it becomes available it would be more reasonable to try less invasive, even if not proven treatments, such as Botox injections. My experience treating chronic cluster headaches with Botox is only “anecdotal” (as opposed to that from large clinical trials) and involves a small number of patients, but nevertheless it has been very positive.

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Candesartan (Atacand) is a relatively new blood pressure medication in the family of ACE receptor blockers (ARBs), which is also effective in the preventive treatment of migraine headaches. Another ARB, Benicar, or olmesartan has also been shown to be effective in preventing migraine headaches. Propranolol (Inderal), a beta blocker, is one of the oldest preventive drugs for migraines and many doctors often use it first. A recent study by Norwegian doctors compared candesartan with propranolol and placebo. They conducted a triple-blind, double crossover study, with 72 adult patients with episodic or chronic migraine, recruited in an outpatient clinic and through advertisements. Participants underwent three 12-weeks’ treatment periods on either candesartan (Atacand) 16 mg, propranolol slow release (Inderal LA) 160 mg, or placebo. The primary outcome measure was days with migraine headache in a 4 week period. They also looked at days with headache, hours with headache, proportion of responders (50% reduction of migraine days from baseline), and side effects.

Their analysis showed that candesartan and propranolol were equally effective and both were superior to placebo. Both drugs had more side effects than placebo, but side effects were different. The researchers concluded that candesartan should be included in the arsenal of drugs recommended for migraine prevention. The advantage of ARBs, such as Atacand and Benicar, is that unlike beta blockers they do not slow down the heart rate, which can be a problem during exercise. During exercise heart rate increases to deliver more blood to the muscles and lungs, but propranolol prevents this increase in the heart rate, which makes people feel tired, short of breath and not able to exercise as hard as they’d like. This is a significant problem since I recommend regular aerobic exercise as the first and the most important preventive treatment for migraine (and tension-type) headaches.
Julie Mauskop
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Half of the kids seen by pediatric headache specialists suffer from chronic migraines. Dr. Hershey and his colleagues at the Cincinnati Children’s Hospital presented results of a study that compared cognitive behavioral treatment combined with amitriptyline (an antidepressant used to treat migraine and other pains) with amitriptyline alone in children aged 10 to 17 who suffered from chronic migraines. This was a first randomized clinical trial in childred with chronic migraines. Combined psychological & pharmacological treatment has been reported to be effective in adults and children with chronic pain other than migraine. Psychological intervention was cognitive behavioral therapy (including biofeedback); pharmacological intervention was amitriptyline (goal dose of 1 mg/kg/day). The control group was taught attention control with equal to psychological intervention in terms of contact frequency and face-to-face time, and involved education and support. They enrolled 135 children with mean age of 14 years; 15% minority; 79% female. Mean baseline headache frequency was 21 days and mean baseline disability score was 68 (severe disability grade). There were no differences between groups at baseline.

For the combined group, a greater than 50% headache frequency reduction was seen in 66% at post-treatment (20 weeks later), 86% at 12-month follow-up. And most impressively, 71% no longer had chronic migraines at the end of treatment and 88% were not chronic at 12-month follow-up. The disability score dropped to below 20 (mild to no disability) in 75% at post-treatment and 88% at 12-month follow-up. These results were significantly better than in the control group of children. The authors concluded that the combined psychological and medication treatment in youth with chronic migraine shows clinically significant reductions in headache frequency and migraine-related disability. At 12-month follow-up, almost 9 out of 10 children no longer had chronic migraines and were mild to no disability grade. They also felt that the results of this study should immediately impact practice of headache medicine in children. However, they could be wrong speculating that based on the published studies in adults, cognitive-behavioral therapy with amitriptyline may be better than other medications and Botox injections. In order to prove this, they need to do a study directly comparing Botox injections with cognitive-behavioral therapy and amitriptyline. One other factor that is not mentioned by the authors is that chronic migraines often subside on their own, which was shown in a study of 122 Taiwanese adolescents.

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A non-steroidal anti-inflammatory (NSAID) drug naproxen (Aleve) alone seems to be more effective than naproxen combined with sumatriptan (Treximet), according to a study by Dr. Roger Cady and his colleagues from Missouri, which was presented at the International Headache Congress in Boston.
This was a small study involving 39 patients who suffered with moderate to severe attacks of migraine. The researchers looked at possible effect of acute medications on frequency of headaches. As migraine frequency increases, so too can the risk of medication overuse, which leads to more headaches. On the other hand, frequent administration of acute medications may act both as an acute and prophylactic treatment. The patients in the study were 18 to 65 years of age, with frequent episodic migraine with or without aura, in Stage 2 migraine (3 to 8 headache days per month) or Stage 3 migraine (9 to 14 headache days per month). Patients were asked to treat their migraines with sumatriptan/naproxen (Group A) or naproxen alone (Group B) for 3 months. Patients in Group B had a statistically significant reduction in migraine headache days at month 3 compared to baseline. Group A also had a reduction of migraine headache days but this decrease did not reach statistical significance over baseline. In addition, subjects in Group B had a statistically significant reduction of migraine attacks at all three months of the study compared to baseline. A greater than 50% reduction in the number of migraine days at month 3 occurred in 43% (6/14) of subjects in Group B compared to 17% (3/18) of subjects in Group A. Sumatriptan/naproxen was statistically superior to naproxen at 2 hours in reducing the migraine headache severity. The amount of acute medication used decreased from baseline to months 1-3 for both groups. Both treatments were well tolerated. The authors concluded that naproxen provides headache relief at 2 hours and reduces frequency of headache days and migraine attacks. Despite both groups using similar quantities of naproxen, this was not seen in sumatriptan/naproxen group, but sumatriptan/naproxen is more effective as acute treatment at 2 hours in reducing headache severity but does not significantly reduce attack frequency or the number of headache days.
If confirmed by larger studies, this is a very surprising discovery because there is little evidence indicating that triptans, like sumatriptan in this study, cause increased frequency of migraines due to medication overuse. In fact, this study did not show that sumatriptan did that, but only that naproxen alone was better at preventing migraine headaches. We also know from Dr. Richard Lipton’s large studies that aspirin has a preventive effect and naproxen and other NSAIDs do not, although they do not worsen headaches either. The large and multi-decade Framingham study showed that 81 mg of aspirin taken daily also has small but statistically significant beneficial effect in preventing migraine headaches. As far as acute treatment of migraines, in a review by an independent organization, Cochrane Reviews, the extra strength dose of aspirin (1,000 mg) was shown to be as effective as 100 mg of sumatriptan.

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Nausea of migraines responds to an acupressure device, according to two German doctors who presented their findings last week at the International Headache Congress in Boston. I spoke to one of the authors, Dr. Zoltan Medgyessy about his study. The study included 41 patients, whose average age was 47 years. They had been suffering from migraines for on average 26 years and had experienced an average of 33 migraine
days over the previous three months. The average migraine pain intensity was 7 on a scale from 0 to 10; the average intensity of nausea was 6 on a 1-10 scale. Patients were instructed to use the device (Sea Band) instead of taking nausea medication during their next migraine attack and to complete and return a migraine attack diary. After using the acupressure band, 34 (83%) patients noticed a reduction of nausea and 18 (44%) reported a significant improvement in nausea. The average intensity of nausea after therapy was 3. The relief of nausea was reported after an average of 29 minutes. The average duration of the migraine attacks was 22 hours. The Sea Bands were worn on average for 18 hours. Forty patients (98%) reported that they would use Sea Band during migraine attacks again. The authors concluded that the use of an acupressure band can reduce migraine-related nausea. The advantage of this therapy is that it is drug-free and has no risks
or side-effects such as dizziness, fatigue, or restlessness seen with drugs. Its effect is rapid, and it is easy and it is inexpensive to use (in the US, $6 to $10). To prove that this method works beyond just placebo effect we need a blinded trial comparing anti-nausea medication with Sea Bands. I do recommend Sea Bands or a similar device, Psi Band for my migraine patients. A controlled trial in 60 women showed that Sea Bands relieve morning sickness of pregnancy (nausea and vomiting of pregnancy), which suggests that the relief we see in migraine patients is also real and not just due to placebo.

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Oxygen inhalation is a proven method of treating cluster headaches. The patient usually rents a large oxygen tank and breathes in pure oxygen through a mask whenever he gets an attack (it is usually a he since 5 times as many men suffer from cluster headaches as women). Demand valve oxygen (DVO) is a promising new oxygen delivery system for the acute treatment of cluster headaches, according to a recent report by Dr. Todd Rozen.

DVO delivers oxygen to the user as soon as they inhale from an attached mask and the amount of oxygen is controlled by how fast they are breathing. DVO is capable of delivering much more oxygen than by just breathing it through a regular mask. In the study 3 patients tried both DVO and a regular mask. All patients had chronic cluster headaches. On DVO all 3 subjects became pain free; 2 of 3 became pain free on a regular mask, while the third subject needed 30 minutes to get to mild pain. Patients using DVO became pain free faster than when a regular mask was used. This was a very small sample and bigger studies are needed, but DVO appears to be at least as effective for acute treatment for cluster headaches as inhalation of oxygen through a regular mask.

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Infantile colic seems to be a precursor or an early manifestation of migraine headaches in children. A new European study published in the journal JAMA supports an earlier American study mentioned in one of my previous blogs. This European study involved 208 children who were diagnosed with migraine at emergency departments found that 73% of them had a history of colic in infancy, compared with 27% of a control group of children. History of being colicky was as common in children and teens who suffered from both migraine with and without aura.

This study suggests that many colicky babies whose colic does not respond to any treatment directed at their digestive system may be suffering from migraine headaches. Some of these children may develop cyclic vomiting as they get older and then go on to have typical migraine headaches.

The researchers at two Italian and one French hospital did a second study involving 120 children with tension-type headaches. Only 35% of these children had a history of infantile colic, confirming that it is not any headache, but specifically migraine that is associated with infantile colic. Migraines are very common in children. Before puberty, about 6% of boys and girls suffer from migraines. After puberty, boys remain at 6% and the incidence of migraines goes upt o 18% in girls.

One of the authors of the study suggested that migraine medications might be effective for colicky babies, although this would require a controlled study. Such studies in infants are difficult to perform because of the unknown potential side effects, which understandably will lead to parent anxiety. However, the colic is painful and we know that pain even in infancy leads to harmful changes in brain chemicals and brain structure. A colicky baby also causes high stress for the parents.

In my practice, I’ve encountered many children with episodic and chronic migraines whose parents report infantile colic that gradually transformed into a typical migraine. So, unfortunately, migraine can start even before a child can begin to speak.

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Botox is approved by the FDA for the prophylactic treatment of chronic migraine headaches. Chronic migraine was arbitrarily defined by headache researchers as headache occurring on more than 14 days each month. Epidemiological research by Dr. Richard Lipton and his colleagues at the Albert Einstein School of Medicine suggests that there is no biological difference between frequent migraines that occur on 10 or more days each month and chronic migraines.

They compared clinical features and the incidence of other chronic medical conditions in three groups of patients with migraine: low frequency (0-9 days/month), high frequency (10-14 d/mo) and chronic migraine (15-30 d/mo). The American Migraine Prevalence and Prevention Study is a US-population-based study with 16,573 people with migraine who responded to a 2005 survey. Of these, 10,609 had low frequency, 640 had high frequency and 655 had chronic migraines. Rates of pulmonary and respiratory conditions including asthma, bronchitis, chronic bronchitis, emphysema/COPD, allergies/hay fever, and sinusitis increased across headache frequency groups and were significantly different for chronic migraine vs. low frequency, but not for chronic migraine vs. high frequency. A similar finding was seen for cardiac conditions and strokes. Depression, nervousness or anxiety, bipolar disorder/mania, and chronic pain were also much more common and similar in those with frequent or chronic migraine compared to those with low frequency migraines (around 30% vs 15%-18%).

These findings suggest that patients with frequent migraines resemble those with chronic migraines much more than they do those with low frequency migraines. One practical implication of this research is that Botox is very likely to be as effective for patients with frequent migraines (those with 10-14 headache days a month) as it is for patients with chronic migraines. And indeed, I’ve observed an excellent response in patients with frequent migraines in my almost 20 years of giving Botox injections for headaches. The response for both patients with frequent migraines and chronic migraines is about 70%, which significantly exceeds the efficacy of any prophylactic drug with no potentially serious side effects seen with most drugs.

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Calcium inside the nerve cells (neurons) seems to be crucial in making pain chronic, according to a publication in the journal Neuron by researchers in Heidelberg, Germany. They discovered that in patients with persistent pain, calcium in the spinal cord neurons helps contact other pain-conducting neurons resulting in increased sensitivity to painful stimuli. This may explain how the pain memory is formed.

Chronic pain caused by inflammation, nerve injury, herniated disks, and other causes often leads to a persistent structural change in the nervous system. This pain often persists even after the original cause, such as a herniated disc, is removed. Many chronic pain patients including those with chronic migraine develop allodynia, an increased sensitivity which results in pain from touch and minor pressure. Migraine patients often cannot brush their hair or wear glasses because of such sensitivity. In people with chronic pain, too much calcium inside the neurons that transmit pain makes them react to activation of neurons that normally transmit sensation of touch, heat, and other non-painful sensations. This excess calcium enters the nucleus of the cell where the genetic material is located and it activates certain genes that promote pain. One of the researchers, Prof. Kuner said that “These genes regulated by calcium in the spinal cord are the key to the chronicity of pain, since they can trigger permanent changes.”

Blocking calcium in the cell seems to prevent such increased sensitivity. Mice in which the effect of the calcium in the cell nucleus is blocked did not develop hypersensitivity to painful stimuli or a pain memory despite chronic inflammation.

Interestingly, magnesium is a natural antagonist of calcium and I would speculate that its deficiency may also promote chronic pain.

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Female pelvic/genital pain is more common in women with chronic Headache, according to a study presented by Canadian neurologists.
The study was carried out by researchers and clinicians at the Wasser Pain Management Centre, Mount Sinai Hospital and the Centre for Headache at Womens College Hospital in Toronto, Canada. During the study period, every adult English speaking female patient at the Centre for Headache at WCH was asked if they would consent to complete a specifically devised questionnaire. Of the 72 completed questionnaires, 32 (44%) of patients reported that they had pelvic region or genital pain brought on by sexual activity. Thirteen (18%) admitted to having pelvic pain that prevents them from engaging in sexual activity. 46% of these women had not had treatment, 39% were currently being treated, and 15% said they had received treatment in the past. All but one said that she would be interested in receiving treatment if available. The researchers concluded that it is important to ask women with chronic headache about sexual pain and, if present, be able to offer a management option.

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Leeches are not pleasant to look at, but they have been used for medicinal purposes for hundreds of years. Growing up in the Ukraine in the 1960s I remember (this is hard to forget) seeing big jars with leeches in a corner pharmacy. Patients would bring in a prescription from the doctor for 4 leeches to be applied daily. The leeches would be placed into a small jar and taken home by the patient to treat swelling, high blood pressure and I don’t know what else. Leeches went out of fashion because of the advances in medicine and just because they are just disgusting. They are being used again in the US for removing extra blood around the scars after cosmetic surgery, arthritic pains, shingles, and other conditions.

British writer Emma Parker Bowles was recently in the news writing about how leeches cured her migraines. She decided on this unusual treatment because her headaches were so severe. She says, “the word headache doesn’t even begin to describe them”. She goes on with a vivid description, “Migraines are miserable with bells on – actually, the idea of listening to the sound of a bell with a migraine brings me out in a sweat. When I am suffering with one, I can’t even stand the sound of my sheets rustling. Apart from the intense throbbing, all-encompassing pain in my head, I also feel extremely nauseous and sensitive to light. I feel as if I am a vampire – a small sliver of daylight and POOF: I will spontaneously combust”.

Leeches do not hurt when they are applied because they first release a numbing substance, which along with a blood thinner and other chemicals released by the leech may be responsible for their beneficial effect. They do not have any known serious side effects. Leeches are used once and then destroyed to avoid transmitting diseases, although there is no reason why a person could not reuse them herself or himself. Several companies sell leeches to the public with instructions on how to use them. Although leeches have been used for the treatment of migraines for many years, there have been no good clinical trials or even reports of large series of cases, but someone should definitely undertake this research. Me? I am not sure I am ready.

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Many migraine sufferers suffer from nausea and vomiting and cannot swallow pills or even if they can swallow them, it takes too long for them to work. Injections is one way to overcome this problem, but nasal spray is a much more pleasant alternative. There are several migraine medications available in a nasal spray form, including Zomig (zolmitriptan), Imitrex (sumatriptan), Migranal (dihydroergotamine), Sprix (ketorolac), and Stadol (butorphanol). Unfortunately, they don’t always work or work inconsistently. Having nasal congestion due to allergies, a cold, or migraine itself often makes these medicines ineffective. Stadol is a narcotic, which can be addictive, while Imitrex and Migranal require delivery into the nose a large volume of fluid, which tends to leak out or gets swallowed, thus reducing their efficacy.

Seattle-based Impel Neuropharma has been working for five years to show it can quickly deliver drugs through the nose, directly to the brain, rather than what happens with the currently available sprays – absorption into the blood stream first and then carried to the brain. Impel, a University of Washington spinoff, recently presented a study of seven patients who used the company’s nose-to-brain drug delivery device, which was able to propel a test protein deep into the upper nasal passages and to the brain stem at an “order of magnitude” greater concentration than a conventional nasal spray. Researchers saw it get delivered to the destination within 10 to 20 minutes. Most nasal sprays don’t propel drugs anywhere close to the upper nasal passages, which is the only place in the body where nerve cells (neurons) are possibly accessible to the outside environment. This device delivers a pressurized, rotational flow of aerosol to reach those neurons.

The company stated that a nose-to-brain delivery device could, in theory, get an effective pain reliever to work more quickly for patients in need of something fast, and do it safely by minimizing the amount that gets absorbed into the bloodstream. It also could be convenient for patients, especially when compared with injectable treatment options.

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In my previous post I mentioned a TENS unit spcifically designed for the treatment of migraine headaches. It was available for a short time on, but no longer is. It is sold at COSTCO stores in Canada and in Europe. Howere, regular TENS units can be tried and they are less expensive.

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Trigeminal neuralgia is an extremely painful condition that causes electric-like pain in the face. It is often misdiagnosed as a dental problem, sinus headache or another condition. The pain is very brief, just like an electric shock, but it can occur continuously and is often triggered by brushing teeth, chewing, talking, or even by wind. This is a very treatable condition and it usually responds to anti-epilepsy drugs, Botox injections and, if those fail, surgery. Many patients have periods of sudden worsening of pain and until medications or Botox begin to help they need emergency treatment for pain. Narcotics (opioids) are usually ineffective. Dr. Merritt and Cohen of the Beth Israel Hospital in New York recently described the use of intravenous antiepileptic medications for acute exacerbations of trigeminal neuralgia in the emergency department. They described 21 patients, 15 women and 6 men whose aged ranged from 33-88 and the mean age was 69 (trigeminal neuralgia is more common in the elderly). 19 received intravenous fosphenytoin (Cerebyx, a drug related to an oral drug Dilantin) 2 received levetiracetam (Keppra) with excellent relief. Side effects included double vision, dizziness, sleepiness, and itchiness with fosphenytoin and no side effects were observed in 2 who received levetiracetam. Unfortunately, the most commonly used oral drugs for trigeminal neuralgia, carbamazepine (Tegretol) and oxcarbazepine (Trileptal) are not available in an injectable form. Another epilepsy drug, divalproex sodium (Depakote) can be given intravenously (Depakene) but it does not appear to be very effective for trigeminal neuralgia.

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Zomig (zolmitriptan) is the fourth triptan (out of seven) to become available in a generic form. This spells big relief for migraine sufferers who rely on this drug. Only tablets and orally disintegrating tablets (ZMT) will become available, not the nasal spray. Nasal spray offers faster relief and for some patients it is as fast as sumatriptan injection (Imitrex, Sumavel, Alsuma). It may take another 6 months for the price to drop significantly from the current $30 to $45 a pill because at this point only four companies are coming out with a generic version. There are about 10 manufacturers making generic Imitrex. Generic sumatriptan (Imitrex) is now available for $3 a pill, while the other two generics, Maxalt (rizatriptan) and Amerge (naratriptan) are still more expensive.

One caveat with the generics is that the quality sometimes is not as good as that of the brand. Of approximately 10 generic sumatriptan versions, my patients have found that 2 are very ineffective. One of these two manufacturers which is based in India (Ranbaxy), recently paid $500 million fine to the FDA for improper manufacturing, storing and testing of drugs. Many generic manufacturers are based in India and most of them produce good quality products. One of them is Dr. Reddy’s Laboratories. Of the four generic manufacturers of Zomig two are based in India (Glenmark and Zydus), one in Taiwan (Impax) and one is based in the US (Mylan) but also has many manufacturing plants in India. An Israeli company Teva, the largest manufacturer of generics in the world is known for their high quality products and it also has plants in many countries, including India.

Once you find a product that works, stick with that generic manufacturer even if you have to switch pharmacy chains since the entire chain usually carries the same generic. The law requires that the name of the manufacturer is printed on the medicine bottle your receive from the pharmacy, so it is easy to find out who the manufacturer is.

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Pregnant women are admonished not to take any medications while pregnant. Fortunately, two out of three women stop having migraines during pregnancy, especially during the second and third trimester. Unfortunately, one third of women continue having migraines and in some they get worse. Tylenol (acetaminophen), which is deemed to be the safest pain medicine in pregnancy is also the weakest pain killer and does nothing to relieve the agony of a migraine attack. Many obstetricians say that they are also “comfortable” giving drugs containing butalbital (a barbiturate) and caffeine along with acetaminophen (Fioricet) because these drugs have been around for many years. However, barbiturates are really not good for the developing brain while regular intake of caffeine can cause worsening of migraine headaches. Narcotic (opioid) analgesics are not exactly healthy either. Not taking any medications is also harmful to the mother and the fetus because severe pain causes serious distress to both and vomiting, which often accompanies migraines, can cause dehydration. Not treating migraine attacks may also lead to chronic migraines with pain present continuously. So, what is a pregnant woman to do?
At the recent annual meeting of the American Congress of Obstetricians and Gynecologists several doctors expressed their preference for the use of triptans in pregnant women. Sumatriptan (Imitrex) was first introduced 20 years ago and a registry of women who took sumatriptan during pregnancy suggests that this is a safe drug. Pregnancy registry for rizatriptan (Maxalt), which is the second triptan to come to the market 15 years ago, also suggests that it is a safe drug. Of course, it cannot be said that these drugs are proven to be safe for pregnant women because some yet undetected risk may still be present. However, compared to the alternatives and considering that triptans are much more effective, it is logical to recommend their use in pregnancy.
Besides treating an acute attack with triptans we always recommend preventive measures, such as magnesium supplementation (400 mg, on top of what is in a prenatal vitamin, which is usually only 100 mg), biofeedback, regular sleep, and exercise.
Preventive drugs that can cause major problems in the fetus and are contraindicated in pregnancy include divalproex (Depakote) and topiramate (Topamax). On the other hand, Botox is probably a safe preventive treatment in pregnant women suffering from chronic migraine headaches.

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Botox appears to be effective for the treatment of chronic post-traumatic headaches in service Members with a history of mild traumatic brain injury according to a recent report by Dr. Juanita Yerry and her colleagues at Ft. Bragg, NC. The researchers assessed the safety of onabotulinum toxin type A (Botox) in the preventive care of post traumatic headache. Headache is a common complication of mild traumatic brain injury in active duty service members. Migraine and chronic migraine type are the most common headache types. The approved use of Botox in chronic migraine made the doctors think that Botox might be safe and possibly effective in post-traumatic headaches with features of chronic migraines. They examined records of all patients treated with Botox for post-traumatic headache in the Concussion Care Clinic at Womack Army Medical Center, Ft. Bragg, NC between 2008 and 2012. They recorded patient demographics, prior history of headache, injury type, current headache type, time from injury to first injection, treatment techniques, number of treatments/treatment interval, side effects, reasons for discontinuation and Patient Global Evaluation of Change (PGEC). Out of 67 patients (66 male) who were treated 10% had prior history of headaches. Most common injuries were blast (46.3%), parachute jumps (14.9%) and motor vehicle accidents (11.9%). About 56% reported more than one headache type. Headache types included: chronic migraine (22.4%), episodic migraine (7.5%), chronic tension type (7.5%), hemicrania continua (7.5%), nummular (1.5%); mixed tension/chronic migraine (41.8%), and tension/migraine (7.5%). A very large percentage (75%) had a continuous headache. Reasons for discontinuing Botox treatment included ineffectiveness (44.8%), side effects (2.9%), or reinjury (1.5%). They were not able to follow-up with 22% patients of whom 73.3% reported being “much better”. Overall, 60% were better or much better, 4.5% were worse or much worse, and 33% reported no change. The researchers concluded that Botox appears to be safe and well tolerated in active duty service members treated for post-traumatic headaches.

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