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Migraine

People who have experienced “visual snow” know what it means. Their vision tends to be distorted by white spots that resemble what you see on the television when there is no signal.

At the latest meeting of the International Headache Society, the topic of visual snow was addressed in four presentations. The first presentation by British and Swiss researchers attempted to give a definition, so that this phenomenon can be studied scientifically. They collected data on 636 subjects by using an online survey of patients. 636 is a surprisingly high number because this is thought to be a relatively uncommon symptom. I certainly do not see more than a handful of patients each year. They found this phenomenon to be present with equal frequency in men and women and 39% reported to have it all their lives. The majority (56%) saw black and white static, 44% saw colored spots, while 45% experienced flashing, and 52% described it as transparent. The most common non-visual symptom was tinnitus, or ringing in the ears, which was present in 74%. Only 226 patients gave information on headaches and 83% of them suffered at least one attack of migraine. They concluded that visual snow is an unrecognized symptom, which can be very disabling and which deserves further research.

The second presentation reported on 90 patients of the original 636 who agreed to keep a diary of their symptoms for 30 days. The results showed that the visual snow was least noticeable outdoors, in bright sun. It was most pronounced at night. The amount of distraction that was caused by visual snow was correlated to the size and density of the static.

The third study by German and Swiss doctors showed that visual snow is a phenomenon that is common in migraine sufferers, but it is distinct in its character. They came to this conclusion by testing the excitability of the visual cortex of the brain.

The fourth paper described the effectiveness of various treatments. The data was collected by reviewing questionnaires that were returned by 204 patients. The effect of 112 drugs was reported. Unfortunately, less than half (92) of the responders had any relief from medications. Antidepressants and anti-epilepsy drugs were most commonly used. Only 29% improved from benzodiazepine drugs (Valium or diazepam, Klonopin or clonazepam, and other). Recreational drug use was reported 117 times and in 32% produced worsening and in 61% there was no change.

We clearly do not know how to treat this condition, but if you have it, have your doctor check your RBC magnesium level since magnesium deficiency increases the excitability of the nervous system. I would also check vitamin B12, D, and CoQ10 levels, thyroid function, and routine blood tests, looking for an underlying medical condition (for example, anemia) which can worsen many symptoms. Regular and sufficient amounts of sleep, exercise and meditation can also reduce the excitability of nervous system.

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Curcumin, which is one of the ingredients in turmeric, has long been touted for many of its anti-inflammatory and anti-cancer properties. A study presented at the 2017 Alzheimer’s Association International Conference showed that curcumin improves memory in healthy adults without Alzheimer’s disease.

This double-blind study was performerd by Dr. Gary Small and his colleagues at UCLA and it involved 40 men and women with a mean age of 63. Half of these subjects received 90 mg of Theracurmin brand of cucurmin twice a day, while the other half was given placebo for a period of 18 months. Researchers administered both verbal and visual memory tests and also measured brain deposits of amyloid plaques and tau tangles using special imaging methods (PET scans). These deposits are found in the brains of patients with Alzheimer’s.

The scores for both types of memory improved in the curcumin group, but not in the placebo group. Curcumin also prevented buildup of amyloid plaques and tau tangles in the brains. Daily curcumin also improved attention and mood.

Four patients in the curcumin group and two in the placebo group had stomach pains and nausea. These were the only side effects.

The authors concluded that “This relatively inexpensive and nontoxic treatment may have a potential for not only improving age-related memory decline, but also as a prevention therapy, possibly staving off progression, and eventually future symptoms of Alzheimer’s disease.”

There is less clinical evidence for the use of curcumin for the prevention of migraines. A recent study, published in the journal Immunogenetics, Iranian researchers reported that a combination of omega-3 fatty acids and curcumin reduced the production of TNF. TNF is a protein that is involved in sending messages between cells, which leads to increased excitability of neurons, neuroinflammation, and pain. The study involved 74 patients with migraines, who were divided into 4 groups – placebo, curcuming, omega-3, and combination of omega-3 and curcumin. The combination produced not only a reduction in TNF levels, but also fewer migraine attacks than seen in the other 3 groups.

Curcumin is not very well absorbed and several companies have tried to improve its absorption using various methods. The UCLA study utilized Theracurmin, which is an ingredient in several brands of curcumin. Another type, Longvida also seems to be better absorbed and is also used by several manufacturers.

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Ketamine is a medicine that is sometimes given intravenously for anesthesia. It is a controlled drug because it can induce euphoria and is potentially addictive. In a previous post I mentioned several anecdotal reports about the beneifical effect of ketamine for a prolonged migraine aura, hemiplegic migraine and other types of headaches.

A presentation at the recent annual meeting of the American Society of Anesthesiologists described the results of ketamine infusion on severe migraines in patients admitted to the Thomas Jefferson University Hospital in Philadelphia from 2014 to 2016. 48 of the 61 patients (77%) responded to this treatment, meaning that their pain levels improved by at least 2 points on a 1 to 10 scale. On average, the infusion had to be given for 5 days. Side effects included sedation (51%), blurry vision (38%), nausea or vomiting (38%), hallucinations (28%), vivid dreams (13%), and low blood pressure (5%). The authors described the adverse effects as mild in nature and only 1 patient discontinued treatment. However, having hallucinations, drop in blood pressure or vomiting does no sound like mild side effects to me. On the other hand, these were patients whose migraine did not respond to other treatments and they needed to be hospitalized, so these side effects could in fact be acceptable if the treatment ultimately provides relief.

Review of patient records admitted to the same hospital between 2006 and 2014 showed the mean headache pain rating using a 0-10 pain scale dropped from 7 on admission to 4 on discharge. The majority (55 out of 77, or 71%) of patients responded by the same definition of an at least 2-point improvement in headache pain at discharge. Only a quarter of responders maintained this benefit at their follow-up office visit. The mean length of infusion was also 5 days. And again, most patients tolerated ketamine well with “very few serious side effects”.

Anecdotal evidence also exists for the use of ketamine infusions to treat depression. There are some outpatient clinics that offer ketamine infusions for chronic pain and depression and a few of my patients have gone there, but unfortunately with little success.

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Biome, or the collection of bacteria living in our bodies has been receiving belated and well deserved attention. The discovery that bacteria living in our intestines can cause cerebral cavernous malformations or CCM (see photo) is quite dramatic. But there is no need to panic since this is a rare condition. However, it does indicate that gut bacteria can have a major impact on our brains.

It was a serendipitous discovery by Dr. Mark Kahn, professor of medicine at U. Penn, who studied mice with CCM. He noticed that mutant mice prone to CCM stopped developing holes in their brains after being moved to a new building. The exception was mice who developed an abscess after having their intestines accidentally stuck with a needle during a routine injection. Dr. Kahn and his colleagues identified a specific bacterium, Bacteroides fragilis, which was responsible for the development of brain caverns.

This finding may explain why there is such a wide variety of presentations in people who have the familial form of CCM. Some have no lesions even when they are 70, while others have hundreds of them at age 10. Just like mutant mice, humans seem to need an additional trigger to start developing CCMs. This finding provides a clear path to developing an effective treatment and perhaps, just a simple probiotic could keep such patients healthy.

In fact, a probiotic containing 14 different strains of bacteria (Bio-Kult, made in UK) is effective in preventing migraine headaches, according to a study presented by Iranian doctors at the recent International Headache Congress in Vancouver. Fifty patients were recruited into this study with half taking the probiotic and the other half, placebo. After 8 weeks, patients on the probiotic had fewer days with migraine and the pain was milder when compared to those taking placebo.

The big question is, what other brain disorders are triggered or worsened by our gut bacteria. We have more bacterial cells living in our bodies (about 39 trillion) than we have of our own cells (about 30 trillion) and scientists are finally beginning to study them. I Contain Multitudes: The Microbes Within Us and a Grander View of Life, is a fascinating and well-written book by Ed Yong on this subject.

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Botox is the most effective and the safest preventive treatment for migraine headaches. However, in a very small number of patients, Botox loses its effectiveness over time. This happens for two main reasons – the person develops antibodies as a defense mechanism to block the effect of Botox or headaches change in character and stop responding to Botox.

It is easy to tell these two reasons apart. If Botox fails to stop movement of the forehead muscles and the patient can frown and raise her eyebrows, it is most likely because of antibodies. On a very rare occasion this is due to a defective vial of Botox, so to confirm that antibodies have formed, we give a small test dose amount of Botox into the forehead. If again there is no paralysis, we know that antibodies have developed. This can happen after one or two treatments or after 10, but in my experience over the past 25 years, significantly fewer than 1% of patients develop this problem.

Fortunately, some patients who develop antibodies to Botox, known as type A toxin, may respond to a similar product Myobloc, which is a type B toxin. Myobloc is not approved by the FDA to treat chronic migraine headaches, but it has a similar mechanism of action and has been shown to relieve migraines in several studies. Injections of Myobloc can be a little more painful, it begins to work a little faster than Botox, but the effect may last for a slightly shorter period of time.

An even smaller number of patients have naturally occurring antibodies to Botox, which is most likely due to an exposure to botulinum toxin in food. I’ve encountered 4 or 5 such patients and a couple of them who did go on to try Myobloc, did not respond to it either.

When Botox stops working despite providing good muscle relaxing effect, it could be because the headaches have changed in character, severity or are being caused by a new problem. It could be due a sudden increase in stress level, lack of sleep, hormonal changes, drop in magnesium level due to a gastro-intestinal problem, or another new illness, such as thyroid disease, diabetes, multiple sclerosis, or increased pressure in the brain. Such patients need to be re-evaluated with a neurological examination, blood tests, and usually an MRI scan. One of my patients who was doing well on Botox for several years, did not have any relief from her last regular treatment. Since she had no obvious reasons why her migraines should stop responding to Botox, I ordered an MRI scan. Unfortunately, she turned out to have brain metastases from breast cancer which had not yet been diagnosed.

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Sleep disturbances and fatigue are more common in patients with chronic migraine headaches than in people without migraines. Sometimes it is not clear what came first, migraines or the sleep problem with secondary fatigue.

A multicenter study performed in Australia, South Korea, and the US examined the effect of Botox injections given for chronic migraines on sleep and fatigue. This was a 108-week study of 715 adult patients who received Botox injections every 12 weeks. Their sleep quality was assessed by the Pittsburgh Sleep Quality Index and fatigue was measured by the Fatigue Severity Scale, both standard and proven measures of sleep and fatigue.

The authors presented their findings at the American Headache Society meeting held two months ago in Boston. While sleep quality was poor before injections were started, significant improvement was noted 24 weeks later and the improvement persisted for the rest of the study. The same was true for fatigue. These findings suggest that sleep difficulty and fatigue are more often the result of chronic migraine, rather than the other way around.

This does not mean that sleep issues should not be addressed while chronic migraine is being treated. Patients are advised to adhere to sleep hygiene, which consists of going to sleep and getting up at the same time, not reading or looking at any screens in bed, sleeping in a cool and quiet environment, exercising and eating at least 2 hours before bedtime, and avoiding caffeine after 1 PM. Regular practice of progressive relaxation and meditation can be very effective for sleep, migraines, and stress. Natural supplements for sleep, such as melatonin and valerian root are also worth trying.

As far as fatigue, we always check vitamin B12 levels, along with vitamin D, RBC magnesium, thyroid, and other blood tests.

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Sumatriptan (Imitrex) injection was introduced 25 years ago, but it remains extremely underutilized. Of course, why would you inject yourself if a pill does the job. Unfortunately, for many migraine sufferers sumatriptan and other triptan tablets do not provide complete or fast enough relief. In many patients tablets do not work well because some wake up with a severe migraine, in some it starts very suddenly, and in others it is accompanied by nausea and vomiting. All these conditions require a quickly acting drug that bypasses the stomach. Zolmitriptan (Zomig) and sumatriptan nasal sprays or sumatriptan nasal powder (Onzetra) sometimes work well and quickly enough, but the gold standard in the abortive treatment of migraines (and cluster headaches) is sumatriptan injection.

Sumatriptan injection works within 10-15 minutes and often provides complete relief of the headache and associated symptoms – nausea, sensitivity to light and noise, and other. Because of a sudden surge in the sumatriptan level in the blood, side effects are more common than with tablets. These can include pins-and-needles like sensations, tightness in the neck or chest, or temporary worsening of the headache. These side effects last only 15-20 minutes and do not prevent most patients from using injections.

Sumatriptan injections were originally released only in a 6 mg dose. A few years later, 4 mg dose became available. Last year, a simple-to-use autoinjector with 3 mg of sumatriptan (Zembrace) was approved by the FDA. Studies presented at the recent annual meeting of the American Headache Society in Boston compared the efficacy of 3 mg and 6 mg injections. Surprisingly, they were equally effective and well tolerated. The manufacturer of the 3 mg auto-injector also compared their injection device with two older devices. Findings of this study were not a surprise – Zembrace was easier to use with fewer mistakes and faster preparation and administration. Zembrace requires only two steps – pulling off a cap and pressing the pen-like device against the thigh (and holding it pressed for 10 seconds). Also, of all auto-injectors Zembrace has the thinnest needle.

One potential difficulty is the insurance coverage. Since Zembrace is more expensive, the insurers may offer to pay only for the old type devices with 4 or 6 mg of sumatriptan. The manufacturer does offer discounts and coupons, which you can find online.

The bottom line, if you are not getting good relief of your migraine headaches, ask your doctor about sumatriptan injections. If you have tried injections in the past and did not like the side effects – check if the dose you tried was 6 mg and if yes, you may want to try 3 or 4 mg injections.

Sumatriptan injection is the only FDA-approved treatment for cluster headaches. Cluster headaches are very sudden and brief attacks of excruciating headaches that pills rarely have a chance to control.

Conflict of interest disclosure: last year Zembrace manufacturer paid me to participate in an advisory board meeting.

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It is an established fact that migraine, and especially migraine with aura increases the risk of strokes. The increase in the risk is small, but according to a new study published in the British Medical Journal, it is higher during and after surgery.

The researchers examined records of 124,558 surgical patients at the Massachusetts General and two other hospitals. Among these, 8.2% or 10,179 patients had a history of migraines with 1,278 or 12.6% having migraine with aura. The risk of stroke during or within 30 days after surgery was 1-2 in 1,000 among patients without migraine history, 4 in 1,000 in those who had migraines and 6 in 1,000 in patients who had migraine with aura. So, the absolute risk of a stroke is still very small, but the relative risk is statistically much higher. They also discovered that strokes were more common in patients who during surgery needed medications to increase their blood pressure. Most of the strokes occurred within the first two days after surgery.

We do not know why migraine carries an increased risk for strokes, so the only recommendation the authors offer is for migraine diagnosis to be included in the preoperative risk assessment of patients. I would add that according to another study, taking high doses of magnesium and potassium supplements could possibly reduce this risk. Magnesium alone was shown to reduce the risk of strokes in another review of studies involving 6,477 patients. Our own research and that of others have shown the beneficial effect of magnesium on the prevention of migraines as well. Here is one of a dozen posts on magnesium on this blog that provides dosing recommendations.

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Stem cells hold great promise in the treatment of many conditions, possibly including migraines. In a post from 3 years ago I’ve written about a report from Australia that described 4 patients with refractory chronic headaches who had a very good response from stem cells. They were given stem cells for other conditions and coincidentally their migraines improved.

Since many patients come to our practice after seeing several other neurologists and headache specialists, we often have to resort to new, non-traditional, and unproven treatments. This is how I started using Botox 25 years ago (the FDA approved it for migraines only 6 years ago).

After reading the Australian report I decided to try stem cell treatment in some of my most refractory patients. Only patients who failed to respond to Botox and at least 3 preventive drugs were offered to participate in this pilot study. The only type of stem cells that the FDA allows to be injected are cells taken from patient’s own body without altering them. The richest source of stem cells in our bodies is fat. My colleague, Dr. Kenneth Rothaus who is a plastic surgeon, performed a liposuction to obtained fat tissue, from which we separated active cells.

We enrolled 9 patients and 3 did have significant temporary improvement. The results are obviously not dramatic, but it is possible that in less severely affected patients this treatment could work better. More importantly, using stem cells from an umbilical cord or placenta is more likely to be effective as these are younger and more active stem cells. There are many companies researching these cells for various indications, but not yet migraines. The reason why stem cells should help at least some migraine sufferers is the fact that they have strong anti-inflammatory properties while migraine involves neurogenic inflammation.

The results of our pilot study were just published in Case Reports in Neurology.

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Unfortunately, opioid hydromorphone (Dilaudid) is still administered to 25% of patients with an acute migraine visiting an ER. Benjamin Friedman and his colleagues at the Montefiore Medical Center in the Bronx compared the efficacy of 1 mg of intravenous hydromorphone with an intravenous nausea medicine, prochlorperazine (Compazine), 10 mg plus diphenhydramine (Benadryl), 25 mg.
They presented their findings last month at the annual meeting of the American Headache Society. The study was blinded, but a safety monitoring committee stopped it early because the results were so lopsided. Prochlorperazine with diphenhydramine was twice as effective (60%) as hydromorphone (31%) in stopping a migraine and in preventing it from coming back within 48 hours.
So, if you end up in an ER for your migraine, refuse hydromorphone (Dilaudid), meperidine (Demerol), or any other opioid (narcotic) medication. Here is my old post with drugs other than prochlorperazine that are also effective.

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Many migraine sufferers complain about worsening of their migraines when they travel to high altitudes. But do people who permanently live at high altitudes are more likely to have migraines? A report published in the European Journal of Neurology describes a population-based study done in Nepal in which researchers compared the incidence of migraines in Nepalese living at low and high altitudes. A previous study done in Peru suggested such an association between migraine and living at a high altitude.

2,100 Nepali-speaking adults were recruited into this study. More than half, or 1,100 (52.4%) lived above 1000 meters (3,280 feet) and almost one quarter or 470 (22.4%) lived at 2,000 meters (6,560 feet). The researchers took into account the age and the gender of participants. Migraine prevalence increased from 28% to 46% with altitude between 0 and 2,499 meters and thereafter decreased to 38% at 2,500 meters. The likelihood of having migraines was almost two times greater at all higher altitudes compared with those living below the altitude of 500 meters. In addition, frequency and duration of migraine attacks doubled and pain intensity increased by 50% at higher altitudes.

The authors concluded that “dwelling at high altitudes increases not only migraine prevalence but also the severity of its symptoms”.

Acetazolamide (Diamox) can be an effective drug for the prevention of headaches at high altitudes and with barometric pressure drops. Unfortunately, we do not know if taking this medicine long-term is also effective for the prevention of headaches in people living at high altitudes.

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The most satisfying part of our work is that we can help more than 95% of our patients. However, a small number of headache sufferers defy our best efforts and continue to have severe pain, which ruins their quality of life.

I just returned from my second visit to lecture at the Berolina Klinik, a rehabilitation hospital in Germany. It has an outstanding record in rehabilitating chronic headache and other types of patients. I wrote about this clinic after my first visit in 2014.

A report just published in Headache describes a successful rehabilitation program of chronic headache patients in an outpatient setting at the Cleveland Clinic. Drs. Krause, Stillman and their colleagues report on 379 patients who were admitted to the IMATCH (Interdisciplinary Method for the Assessment and Treatment of Chronic Headache) program.

The program lasts 3 weeks, during which patients come to the clinic for 8 hours 5 days a week. Patients are informed that “the primary purpose of treatment is not to reduce pain, but rather to improve their ability to function during pain”. Despite this warning the average pain on admission was 6.1, while on discharge 3.5 and a year later, 3.3. Functional impairment, anxiety, and depression also improved and stayed improved a year after the treatment.

The program is clearly very effective and has an additional advantage of not requiring expensive hospitalization. Most patients stay at a hotel across the street from the clinic.

Here is an outline of the 3-week program:

Medical treatment:

1. History and initial medication adjustments on admission day.
2. Four days of intravenous therapy. Patients meet with the physician daily during infusions.
3. Two brief individual medical appointments per week during the second and third weeks.
4. All patients are drug tested at admission, and subsequent drug testing may be included if staff have concerns about illicit use.
5. Consultation with outside physicians as appropriate.

Psychological treatment:
1. One individual biofeedback session in each of the second and third weeks.
2. One individual psychotherapy session in each of the second and third weeks.
3. Psycho-educational group sessions spread throughout the three weeks. Topics include avoidance of pain displays, diminishing attention to headaches, cognitive-behavioral therapy for management of mood, activity pacing, time management, theories of pain, sleep hygiene, assertiveness training, relaxation training, self-esteem, management of headache flare-ups, and relapse prevention.
4. In the second and third weeks of treatment, patients’ families are requested to participate in a group family meeting, where the necessity of avoiding reinforcement of headache displays and disability is emphasized.

Nursing treatment:
1. Initial assessment, including current medication intake, document allergies, perform an EKG.
2. Patients receive at least 1-2 individual visits with a registered nurse during the second and third weeks of the program.
3. Nursing groups, including pathophysiology of headaches, proper use of a headache diary to track progress, dietary counseling, the impact of headaches and medications on sexuality, and medical communications. Nurses also train the patients in additional relaxation techniques beyond those covered in the psychology groups, and lead group relaxation practice.

Physical therapy treatment:
1. Physical therapy evaluation on their admission day, with particular attention paid to cranio-cervical dynamics. Data are used to develop an individualized, quota-based exercise plan including strengthening, flexibility, and endurance exercises.
2. Beginning on the day after admission, patients participate in daily group exercise sessions, where they learn and practice individually tailored exercise plans.
3. Twice weekly individual physical therapy sessions.

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The field of marijuana research is starting to take off due to the wider acceptance of medicinal marijuana. The other night I attended a lecture in NYC by the “father of cannabis”, Raphael Mechoulam.

According to Wikipedia, “Dr. Mechoulam is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of THC (?9-tetrahydrocannabinol), the main active ingredient of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.”

Dr. Mechoulam identified THC in 1964 and in his lecture he lamented the paucity of research into the many potential healing properties of cannabis in the past 50 years. He strongly feels that the two main active ingredients in marijuana, THC and CBD should be tested rigorously in large double-blind studies just like any other prescription drug. This will allow doctors to prescribe a proven medicine, rather than rely on anecdotal reports and go through trial and error, as we are doing now. His research suggests that cannabis ingredients could possibly help a wide variety of conditions, from diabetes and cancer to pain and nausea.

Prescribing medical marijuana is at least possible in New York and 20 other states, so that we do not have to wait, possibly up to 10 years, for a cannabis-based drug to be approved by the FDA (one CBD-containing drug might be approved soon for a rare form of epilepsy).

At this time we have to go through trials of various ratios of THC and CBD and various modes of delivery (inhaled, sublingual or oral) to determine the best treatment for each patients. Another obstacle is the fact that no insurance company pays for medical marijuana. After a year of prescribing medical marijuana for patients with migraine and other painful conditions it is clear that it works for a minority of my patients. However, I prescribe it only after more traditional methods fail, so my results may not be as good as if I used medical marijuana earlier. Our standard approach involves lifestyle changes, regular exercise, dietary changes, magnesium, CoQ10, and other supplements, followed by drugs and Botox injections. These are mostly well-studied treatments and with the possible exception of drugs, should precede the use of medical marijuana. Having said that, For a few of my patients medical marijuana dramatically improved their quality of life and I am very glad that we have this treatment option available.

Dr. Rafael Mechoulam and Dr. Alexander Mauskop
May 4, 2017, NYC

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Migraine sufferers are more likely to have insomnia than people without migraines. Depression and anxiety, which are more common in migraineurs can often lead to insomnia as well. Surveys indicate that 38% of migraine sufferers sleep less than 6 hours, compared to 10% of the general population. Insomnia is more common in patients with chronic migraine compared with patients who have episodic migraines. Chronic migraine is defined as having 15 or more headache days each month with a migrainous headache on at least 8 of those days.

Most people are reluctant to start taking sleep medications because of the reasonable fear of becoming dependent on medicine, having somnolence the next day and other short-term and long-term side effects. Fortunately, non-drug therapies can be quite effective. In some, natural remedies, such as magnesium, valerian root and melatonin work well without any side effects. Another approach is cognitive-behavioral. According to a study by psychologists at the University of Mississippi, behavioral treatments can be effective in relieving insomnia and in reducing headaches in people with chronic migraine.

The researchers compared cognitive-behavioral therapy specifically developed for insomnia with sham treatment. Those in the active group were asked to go to sleep at the same time, try to stay in bed for 8 hours, avoid reading, watching TV or using their cell phone in bed, and not to nap. If they could not fall asleep after 30 minutes, they were told to get up and engage in a quiet activity. Some were also subjected to sleep restriction – not being allowed to sleep for more hours than the patients reported getting prior to treatment, in the hope that this will lead to better sleep in the long term. The sham group was instructed to eat some protein in the morning, eat dinner at the same time, keep up with their fluid intake, perform range of movements exercise, and regularly press on an acupuncture point above the elbow.

After two weeks of this intervention headaches improved in the sham group slightly more than the active group, but six weeks later, headache frequency dropped by 49% in the active group and 25% in the sham group. Improvement in insomnia symptoms strongly correlated with the headache frequency. The cognitive-behavioral group had a significant increase in the total sleep time and the quality of sleep.

This was a relatively small study, but there is a large body of evidence that behavioral therapies do relieve insomnia. And it is no surprise that better sleep is associated with fewer headaches since sleep deprivation is a common migraine trigger. Sleep restriction is the only part of this treatment that has contraindications – it should be avoided in patients with bipolar disorder or epilepsy.

Another simple method, which I’ve used over the years whenever I cannot fall asleep, is visualization. You have to use not only visual images, but engage all of your senses. For example, imagine yourself in a place where you tend to feel relaxed (lying on a beach, on a cool lawn, on a float in a pool, etc). See all the details and also hear the sound of the wind or waves, smell the ocean or the grass, feel the touch of the wind or sand. It takes an effort at first, but use the same image every time and after a while, as soon as you go to that place, you fall asleep in minutes. Here I found more detailed instructions for this method.

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I am certain that you will learn a lot of useful information from listening to the top headache experts in the world. The event is free during the week when it is held (April 23 – 29), but afterwards you will have to pay for full access to all interviews. The Migraine World Summit is in its second year and it again assembled excellent speakers to address a wide variety of headache-related topics. Last year I spoke on non-drug therapies and this year the speakers are again addressing not only medications, but many alternative treatments and self-care. In addition to many leading neurologists, the event features Ping Ho, MA, MPH, a UCLA expert on alternative therapies, meteorologist, Michael Steinberg of Accuweather, Vidyamala Burch, a mindfulness expert, an Australian psychologist, Paul Martin, a geneticist, Professor Lyn Griffiths of Queensland UT (the event is organized by an Australian migraine sufferer Carl Cincinnato, so there are many Australians represented), and over 30 other experts.

Here is a blurb from the organizers:

In it’s first year, The Migraine World Summit became the largest ever conference for migraine patients. In 2017, we’re back with 36 brand NEW interviews where you’ll discover even more about…

What are the best treatments for migraine?
What can I do when I’ve already tried everything?
What are the secrets to finding effective natural alternatives?
How can I cope with the anxiety, judgment and social stigma of chronic migraine?
What new treatments are coming that I should be aware of?
What are the most common challenges that could appear?
The 2017 Migraine World Summit is online and free from April 23 – 29, 2017!

Register for FREE now at the following link:

http://www.migraineworldsummit.com?afmc=4b

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Stroke is slightly more common in migraine sufferers. There are two main types of stroke: hemorrhagic, which results from a burst blood vessel in the brain and ischemic, which is due to a blood clot closing off blood supply to a part of the brain. Closure of a blood vessel by a clot can be due to a blood clotting disorder, cholesterol plaque, or dissection of a blood vessel. Dissection is a lengthwise tear in the blood vessel wall.

A study just published by Italian researchers in JAMA Neurology included 2,485 patients aged 18 to 45 years with first-ever acute ischemic stroke. Of these patients 334 or 13% had a dissection and 2151 or 87% had a stroke not caused by dissection. Migraine was more common in the dissection group 31% vs 24% in non-dissection group. These differences are relatively small, but the importance of the study is that it should make doctors consider the possibility of a dissection when a patient with migraines develops a different type of headache or has a new onset of neck pain. If a dissection is suspected, a CT angiogram or an MRA should be done. Luckily, many dissections do not cause strokes and heal on their own. However, we do recommend blood-thinning medications (anticoagulants) for several months after the dissection even in the absence of a stroke.

My previous post described a scientific review on this topic, that showed a two-fold increase in the risk of dissection in migraine sufferers. Another practical aspect of these studies, which is mentioned in that previous post, is that if you suffer from migraines, avoid neck manipulation by chiropractors. If you do see a chiropractor, ask them not to do high velocity manipulations (sudden jerky movements), as I did when I visited a chiropractor.

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Photophobia, or sensitivity to light is one of the most common symptoms that accompany a migraine attack. Many patients remains photophobic even after the headache has resolved. In some, a prolonged exposure to bright light or as little as a momentary reflection of the sun in the window glass or water surface can bring on a severe attack.

It is not unusual for some of my patients to wear sunglasses indoors. Once, when I had a migraine while driving at night I had to put on my sunglasses because the headlights of oncoming cars made the pain worse (luckily, I had a sumatriptan injection with me and as soon as I got off the highway and to a traffic light, I gave myself a shot).

Dr. Kathleen Digre, a professor Neurology and Ophthalmolgy at the University of Utah, whose article on dry eyes and migraines I quoted a couple of years ago, recently stated that staying in the dark may actually make photophobia worse. It may be better to gradually expose yourself to more light when you are not in the middle of an attack.

A small study suggested that people who suffer from photophobia between migraine attacks are more likely to experience anxiety and depression than those without photophobia between attacks and those without migraines. It is not clear if anxiety and depression in these patients is due to more severe migraines.

Treatments for photophobia mentioned by Dr. Digre include botulinum toxin (Botox) injections, nerve blocks, medications such as gabapentin, and a natural supplement, melatonin. I should add that any effective acute and preventive treatment that leads to reduced frequency and duration of the attacks can lead to a reduction in photophobia. Effective treatment is also likely to improve phonophobia (sensitivity to noise) and osmophobia (sensitivity to smells), which are somewhat less common.

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A new electric device is being tested for the treatment of migraine by an Israeli company, Theranica. Transcutaneous electric nerve stimulation (TENS) has been successfully used for the treatment of musculoskeletal disorders for decades. The theory behind it is the so-called gate theory of pain. It is thought that by stimulating larger nerve fibers we can block pain messages sent by smaller pain-sensing nerve fibers.

Cefaly is a TENS device which became available in 2014 and it provides electrical stimulation of the supraorbital nerves in the forehead. Only small studies have been conducted, so it is not clear how well Cefaly relieves migraines. As far as our experience, we at the NY Headache Center usually treat more severely affected patients, so it is possible that the results are better in people with less severe migraines.

The new wireless patch that is being developed by Theranica is applied to the upper arm. The results of the first study of this patch were published in Neurology, the medical journal of the American Academy of Neurology.

The study author, is a well-known neurologist and pain researcher, Dr. David Yarnitsky of Technion Faculty of Medicine in Haifa, Israel. He was quoted saying, “People with migraine are looking for non-drug treatments, and this new device is easy to use, has no side effects and can be conveniently used in work or social settings.”

The patch device is controlled by a smartphone app. It was studied in 71 patients with episodic migraine who had two to eight attacks per month and who were not on any preventive medications for migraines. The device was applied soon after the start of a migraine and kept in place for 20 minutes.

The devices were programmed to randomly give either a very weak stimulation to serve as placebo or different levels of stronger electrical stimulation.

A total of 299 migraine attacks were treated by these 71 patients. Two hours after the start of real treatment, pain was reduced by at least 50% in 64 percent of patients, compared to 26 percent of patients who received the sham stimulation.

Starting treatment early produced better results, which is similar to what we see with all migraine medications as well. None of the participants found the treatment to be painful.

The device is very safe and we hope that the ongoing trial that Theranica is conducting in the US will confirm its efficacy. It is not yet available in this or any other country.

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Estrogen-based oral contraceptives are usually contraindicated for women who have migraines with aura. In the latest issue of the journal Headache, Dr. Anne Calhoun of the Carolina Headache Institute argues that this contraindication is no longer valid.

She analyzes research studies that consistently show that stroke risk is not increased with today’s very low dose combined hormonal contraceptives containing 20-25 µg ethinyl estradiol and that continuous ultra low-dose formulations (10-15 µg) may even reduce the frequency of migraine auras. The past prohibitions were mostly based on the risk associated with contraceptives containing over 30 µg and often 50 µg of estradiol.

We often use continuous contraception (not having a period for 3 to 12 months) in women with menstrually-related migraines, which usually are not accompanied by aura.

There is no doubt that the risk of strokes in women with migraines with aura who take oral contraceptives is significantly increased by smoking and other stroke risk factors, such as hypertension, diabetes, high cholesterol, and other. So, women who have migraine with aura and take estrogen-based contraceptives should not smoke, should exercise regularly, have a healthy diet and have regular check-ups to detect conditions that may augment the risk of strokes. If such risk factors are present, progesterone-only or non-hormonal contraceptives should be used.

Dr. Calhoun also points out other benefits of oral contraceptives, besides the reduction of the chance of undesired pregnancy, relief of painful periods, excessive bleeding, acne, and PMS. These include reduction in death rate from any cause, 80% reduction in the risk of ovarian and endometrial cancers and reduced risk of colorectal cancer. On the other hand, oral contraceptives do increase the risk of breast cancer.

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Italian researchers published a study in the journal Headache that attempted to correlate the attachment style in children with migraines with headache severity and psychological symptoms.

Attachment style typically develops in the first year of life. The premise of the study was derived from the attachment theory which suggests that early interpersonal relationships may determine future psychological problems and painful conditions. Previous studies have shown that people with insecure attachment styles tend to experience more pain than people with secure attachment style.

The study involved 90 children with migraines. The mean age was 12 years and there were 54 girls and 36 boys in the study. The kids were divided into a group with very frequent headaches (1 to 7 a week) and those with infrequent attacks – 3 or fewer per month. They also grouped them into those with severe pain, which interrupted their daily activities and those with mild pain that allowed them to function normally. The children were tested for anxiety, depression, and somatization (tendency to have physical complaints as a manifestation of psychological distress). They were also evaluated for the attachment style and were assigned into “secure,” “avoidant,” “ambivalent,” and “disorganized/confused” groups.

Interestingly, the researchers found a significant relationship between the attachment style and migraine features. Ambivalent attachment was present in 51% of children with high frequency of attacks and in 50% of those with severe pain. Anxiety, depression, and somatization were higher in patients with ambivalent attachment style. They also showed an association between high attack frequency and high anxiety levels in children with ambivalent attachment style.

The authors concluded: “We found that the ambivalent attachment style is associated with more severe migraine and higher psychological symptoms. These results can have therapeutic consequences. Given the high risk of developing severe headache and psychological distress, special attention should be paid to children with migraine showing an ambivalent pattern of attachment style. Indeed, a prophylactic and psychological therapy could often be necessary for these patients.”

People who have an anxious–ambivalent attachment style show a high desire for intimacy but often feel reluctant about becoming close to others and worry that people will not reciprocate their feelings. It is possible to mitigate the negative effects of the ambivalent attachment style even in adulthood. It does require a major effort and help from a psychotherapist.

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Botox is by far the safest and the most effective preventive treatment for chronic and frequent episodic migraine headaches. The only downside is the cost. A 200-unit vial of Botox costs about $1,200. Most insurance companies cover Botox if you have chronic migraines (15 or more headache days each month) and if you’ve tried and failed (it did not help or caused side effects) 2 or 3 preventive medications. The copay for a vial of Botox is often as high as $400 or more. If your insurance does not cover Botox at all, or you have “only” 10 to 14 headache days each month, or you do not want to take daily drugs because of potential side effects, you may have to pay the entire cost. To reduce this cost, you may want to ask the doctor to start with 100 units instead of the standard dose of 155 units. Since the manufacturer makes only 100 and 200 unit vilas, the remaining 45 units are discarded. Some doctors are very accommodating, but I’ve heard of many that will not deviate from the FDA-approved protocol of 155 units injected into 31 spots. I discussed some of this in a recent post.

Another way to avoid excessive costs when paying out of pocket for Botox is to avoid large hospitals. A few years ago, while giving lectures at the Mayo Clinic, Cleveland Clinic, and Beth Israel Hospital in Boston, I discovered that they all charged $6,000 for one Botox treatment. What prompted this post is that I recently saw a patient who had Botox injections at the Cedars-Sinai Hospital in Los Angeles and had to pay $11,000. Every charge for a procedure done in a hospital or even at a doctor practice that is owned by the hospital, includes a hefty “facility fee”. This is why hospitals often buy doctor practices – they can triple the charges and even insurers such as Medicare and Medicaid will pay at an inflated rate.

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Atul Gawande is a surgeon at the Brigham and Women’s Hospital in Boston and a professor at Harvard Medical School. He is also a very talented writer who has written four books and has been writing for the New Yorker since 1998. I had the privilege of meeting him and found him to be very humble and low-key, despite him being a surgeon, MacArthur “genius” award recipient, famous writer, etc. His last book, Being Mortal should be read by everyone who is dealing with elderly parents, grandparents, or friends.

His last article in the New Yorker, The Heroism of Incremental Care describes how headache specialists approach patients with severe and persistent migraine headaches. Fortunately, these are a minority of our patients, but require our unflagging attention and care. Some tell me that they’ve tried “everything” and ask, “please do not abandon me”. My response is to reassure the person that I will never stop trying to help and also that I’ve never seen anyone who has tried everything – we always find medications, supplements, devices, procedures, and other treatments that the patient has not yet tried.

Just like with the man in Gawande’s story, some patients improve very slowly and over a long period of time, so patience and perseverance are essential. I must admit that we cannot be sure if it is our treatment or just the passage of time that leads to improvement. However, it may not matter since our support helps avoid a sense of helplessness and hopelessness that can lead to depression and a decline in the ability to function.

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Severe headache is a common symptom of acute glaucoma. It comes from a sudden increase in the intra-ocular pressure caused by the closure of channels that drain fluid from the eyeball. This headache can be similar to a migraine with nausea and light sensitivity. Acute glaucoma is rarely misdiagnosed as a migraine because typically, there is no history of migraines and the eye often gets red, painful with profuse tearing. Cluster headache is sometimes more similar to acute angle closure glaucoma because it also can cause redness of the eye and tearing.

This post was prompted by patient I just saw. This 52-year-old woman has had right-sided migraines for 10 years and about a year ago was found to have mildly elevated intra-ocular pressure (IOP). She has been under my care for almost a year and after receiving three Botox treatments needed only magnesium infusions every 3 weeks. She was still having 2-3 migraines each month, but they were relieved by sumatriptan with naproxen (Treximet). On a recent visit to her ophthalmologist her IOP was higher than usual and she underwent a laser procedure to improve fluid drainage. She reported that it felt as if a balloon was punctured and pressure came out of her eye. The procedure was first done on her right eye where the pressure was higher. Although it’s been only a couple of weeks since the procedure, she feels much improved, without any migraines and without constant mild pressure in her eye, which she was barely aware of until it was gone. Chances are that she will remain susceptible to migraines as they preceded her glaucoma by many years, but she is very likely to have fewer and milder migraines. She may also need to continue intravenous infusions of magnesium because she has a documented severe magnesium deficiency (her RBC magnesium level was 3.7 with the normal range of 4.2 to 6.8), which did not respond to oral magnesium supplements.

The main point of her story is that migraines of long duration can be made worse by a new trigger, such as slow increase in the eye pressure. It is a general rule we teach our neurology residents – if headaches worsen for no obvious reason, search for possible new causes. Another patient who confirmed this rule was a woman who did very well for several years with Botox injections, but then one treatment provided much less relief. Despite the fact that she had no new symptoms or neurological findings, I obtained an MRI scan. Unfortunately, it showed metastatic brain cancer, which originated from undiagnosed breast cancer. Such cases of worsening headaches without other new symptoms of a serious underlying problem are very rare, but require constant vigilance because the temptation is to attribute worsening of migraines to stress, hormones, weather, and other triggers. On the other hand, this needs to be balanced against getting an MRI scan after each unusually severe attack or an increase in headache frequency.

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Many women are more likely to have migraines around the time of their menstrual period and in some, those migraines can be more severe. Previous studies have determined that women living together often synchronized their menstrual periods. A group of Brazilian researchers decided to compare the frequency of menstrual migraines in women who live together and those who live alone. The results were just published in the journal Headache.

The study looked at female students at a university between the ages of 18 and 30 years, all of whom suffered from migraines. One group of women lived together with two or more other students and the second group lived alone. They were asked to keep a headache diary for three months. The researchers recorded the frequency of headaches, presence of menstrual migraine, intensity of headaches, medications used including contraceptives, and triggering factors such as diet, sleep deprivation, and stress. Half of the women living together had menstrual migraines compared with 17% of women living alone. This finding was not related to the use of a contraceptive, test stress, or sleep deprivation. Women living together also tended to have menstrual cycle at the same time as their roommates.

It was a small study – it had 18 women in each group, so the results are not highly reliable.

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Restless leg syndrome (RLS) has been reported to be more common in patients with migraines. I wrote about this association in a previous post about 4 years ago. Another study, just published in The Journal of Headache and Pain confirms this association.

RLS is a common condition that often goes undiagnosed. This is in part due to the fact that RLS begins in childhood and it often runs in the family, so it is not perceived as an illness.

The new study involved 505 participants receiving outpatient headache treatment. The researchers collected information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were divided into low-frequency (1–8/month), high-frequency (9–14/month), and chronic (>15/month) headache groups.

Analysis revealed that with an increase in migraine frequency the occurrence of RLS also increased, particularly in those who had migraines with auras. Anxiety and sleep disturbance was also associated with RLS.

Sometimes the diagnosis of RLS is very easy to make – a person who constantly shakes his or her foot, usually has it. However, in some people the excessive leg or body movements occur only in sleep, so the diagnosis is less obvious to the doctor, but not to the bed partner who is constantly kicked and woken up by these movements. One of my patients could not sleep in the same bed with his wife, because he would move and kick her all night long. After he started taking ropinirole, one of the medications for RLS, he reported that he was able to sleep in the same bed with his wife for the first time in 20 years. If the diagnosis is in doubt, an overnight sleep study can confirm the diagnosis.

Unfortunately the person with RLS suffers much more than the bed partner. Moving all night means not getting good quality sleep and being tired all day. Treating RLS leads not only to improved sleep, but also to an overall improvement in the quality of life.

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Beta blockers, such as propranolol (Inderal) and timolol (Blocadren) are the oldest drugs for the prevention of migraine headaches. They’ve been used for this indication for the past 50 years. Calcium channel blockers are not as effective and never received FDA approval, but are also used treat migraine headaches. Verapamil is more effective for the prevention of cluster headaches, but is not approved for this indication either. A third category of blood pressure drugs effective for the prevention of migraines are ACE receptor blockers (ARBs) such as candesartan (Atacand) and olmesartan (Benicar) and ACE inhibitors such as losartan (Cozaar).

Main side effects of these drugs tend to be related to lowering of blood pressure and include fatigue and dizziness. This is a major limitation of blood pressure medications when used in migraine sufferers because they tend to be young women with low blood pressure to begin with. Verapamil is also known to cause constipation.

Beta blockers and to a lesser extent calcium channel blockers, have long been reported to cause depression. A new study just published
in the journal Hypertension explored the association between blood pressure drugs and admission to to the hospital for mood disorders (depression and bipolar). The researchers examined a large hospital database of 525,046 patients with follow-up for 5 years. Patients on ACE inhibitors or ARBs had the lowest risk for mood disorder admissions, and compared with this group, those on beta blockers and calcium channel blockers showed higher risk, whereas those on no blood pressure medications and those on diuretics showed no significant difference. The authors concluded that calcium channel blockers and beta blockers may be associated with increased risk of admission for mood disorders, while ACE inhibitors and ARBs blockers may be associated with a decreased risk of mood disorders.

Migraine sufferers are at 2-3 higher risk of mood disorders even if they are not on blood pressure medications and we often see depression and anxiety in many of our patients. This study makes a strong argument for the use of ACE inhibitors and ARBs ahead of other blood pressure medications. Another advantage of these drugs is that they do not slow down the heart rate, which is the case with beta blockers. Slowing of the heart rate often interferes with the ability to exercise and exercise is probably the most effective preventive treatment for migraine headaches.

I should also mention that epilepsy drugs such as topiramate (Topamax) can also cause depression, even with suicidal thoughts. Besides blood pressure and epilepsy drugs, antidepressants is another category of drugs used for the prevention of migraines, but even these medications can sometimes cause or worsen depression. All drugs have other side effects as well and this is why we always advise starting with sleep hygiene, healthy diet, aerobic exercise, meditation, magnesium, and other supplements.

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About 6% of young children suffer from migraine headaches. After puberty, this number triples to 18% in girls and remains at 6% in boys. Several abortive drugs (drugs taken as needed), such as rizatriptan (Maxalt) and zolmitriptan (Zomig) are approved for migraines in children. Only topiramate (Topamax) is approved for children (over the age of 12) for the prevention of migraines. We do use preventive drugs approved for adults in children as well. These are divalproex sodium (Depakote), propranolol (Inderal), and botulinum toxin (Botox). Many other drugs, such as amitriptyline (Elavil), gabapentin (Neurontin), candesartan (Atacand) are used “off label”, meaning that they are not FDA-approved for migraines in adults or children. One of the reasons that more drugs are not approved specifically for children is the difficulty in conducting research in kids. Their are migraines are usually shorter in duration and often stop occurring for long periods of time without treatment.

A large multi-center 24-week study just published in the New England Journal of Medicine examined the efficacy of topiramate, amitriptyline and placebo in children between the ages of 8 and 17. It was a double-blind study with neither the children and their parents nor the doctors being aware of who was getting which drug or placebo. The study showed no statistically significant difference among the three groups. The main outcome measure was a 50% or higher reduction of headache days. Placebo achieved this result in 61% of children, while this number was 52% for those on amitriptyline and 55% on topiramate. Not surprisingly, side effects were much more common in children taking medications than placebo. Fatigue and dry mouth were the most common side effects from amitriptyline, while topiramate caused mostly tingling and weight loss. Serious side effects occurred in four – three kids on amitriptyline had a serious mood disorder and one on topiramate attempted suicide.

This study did not prove that amitriptyline and topiramate are ineffective since they did help half of the children they were given to, however the placebo worked at least as well. These findings are not surprising since placebo has a powerful effect, which is often more pronounced in children and because children’s migraines often stop on their own. Even in adults, placebo effect has often made clinical trials, particularly in migraines, very difficult. It took a couple of attempts to prove that Botox prevents migraines better than placebo, again not because Botox was ineffective, but because placebo also worked well.

The initial approach to treating migraines in children and adults should always involve looking for modifiable triggers, such as sleep schedule, regular meals with healthy food, elimination of caffeine and sugar, regular exercise, sleep hygiene, meditation or biofeedback, and so on. Our second step is trying supplements such as magnesium (which sometimes is given intravenously because of poor absorption of pills) and CoQ10, which have been proven to be effective both in children and adults. Other, less proven supplements, such as riboflavin, feverfew, and boswellia are also worth trying before starting a daily preventive medication. At the same time, since migraine often causes severe pain, we often prescribe abortive migraine medications, such as sumatriptan or rizatriptan, which are often more effective than ibuprofen and acetaminophen.

It is considered unethical for doctors to prescribe placebo, although we do sometimes prescribe very mild drugs in a small dose (cyproheptadine is one such drug), which is almost the same as prescribing a placebo.

An interesting study of placebo in patients with low back pain was just published in the journal Pain . One group was given the usual treatment and the other received the usual treatment as well as a placebo pill, but they were told that they are being given a placebo. The group that knowingly took placebo had a significant reduction in pain and disability. After three weeks of this trial, the first group was also given a placebo pill and they also had a significant drop in pain and disability. It is possible that the effect is just due to the act of taking a pill, which subconsciously sends a message to the brain that something is being done to fix the problem.

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Medical marijuana was legalized in New York in February of this year. Since then, I’ve prescribed it to over 30 patients and about a third of them have found it to be effective. We are planning an observational study to determine which of the three approved types (inhaled, sublingual, oral) and what ratio of active ingredients (THC/CBD) are preferred by migraine sufferers. Doctors who prescribe medical marijuana do have to take an online training course, but the course does not teach about the optimal use because no one has researched this question. There are also regulatory issues to deal with.

Several sets of guidelines have been published by various medical organizations addressing the proper use of medical marijuana, other than dosing and route of administration. Here are some of the recommendations with my comments:

“The doctor should adhere to current standards of practice and comply with state laws, rules and regulations, which may specify conditions for which a patient may quality.”
Migraine is not one of the conditions listed specifically, but it is often accompanied by neuropathic pain, which is listed.

“The doctor’s office should not be located at a marijuana dispensary or cultivation center. The doctor should not receive financial compensation from or hold a financial interest in marijuana-related businesses or be affiliated with them in any way.”
This one is easy for us.

“The physician should not use marijuana either medicinally or recreationally while actively engaged in the practice of medicine.”
I’ve never tried it.

“There should be an established doctor-patient relationship before the doctor considers the use of medical marijuana.”
I prescribe it only to our established patients.

“The doctor should do a physical exam and gather health history, including documentation of previous therapies used by the patient and information on any personal or family history of substance abuse, mental illness or psychotic disorders. The diagnosis should justify the consideration of medical marijuana.”
All of our patients undergo a thorough evaluation.

“The doctor should review other treatment options. The known benefits and risks of marijuana should be presented, along with the warning that, unlike with FDA-approved drugs, there is variability and lack of standardization in marijuana preparation.”
We use medical marijuana only after other non-drug and drug treatments fail.

“If the medical marijuana is chosen, a specific treatment plan for a limited period of time should be agreed on, with details documented in the medical record. The doctor should instruct the patient not to drive or operate heavy machinery while using marijuana.”
Yes, I do that.

“The patient should be seen for follow-up visits to monitor for efficacy and side effects of medical marijuana.”
This is a standard practice with any treatment.

“Patients with a history of mental health problems, substance abuse or addiction should be referred for further evaluation as needed.”
I typically avoid prescribing medical marijuana to such patients.

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Nausea is a very common symptom that accompanies migraine attacks. Effective treatment of migraine with a drug like sumatriptan often stops the headache, nausea, and other associated symptoms. However, sometimes pain subsides, while nausea does not, or nausea is much more bothersome than the headache. Nausea can also be a side effect of the most effective injectable migraine drug, dihydroergotamine (DHE-45). We often administer this drug in our office after other injectable drugs (magnesium, sumatriptan, ketorolac, dexamethasone, etc) fail. If nausea is already present, we will always give an intravenous injection of a nausea drug such as ondansetron (Zofran) or metoclopramide (Reglan) before giving DHE. Sometimes these drugs are ineffective in preventing nausea and vomiting induced by DHE and we have to look for other options.

Phenothiazine family of drugs, including prochlorperazine (Compazine), chlorpromazine (Thorazine), and promethazine (Phenergan) are very old and effective anti-nausea drugs. However, they have a potential for a rare but devastating side effect, which consists of persistent involuntary movements of the face (grimacing and lip smacking) and body. The onset of this side effect can be delayed, which is why it is called tardive dyskinesia. It is not unusual for these drugs to cause an immediate severe and very unpleasant restlessness (akathisia), which patients sometimes describe as wanting to crawl out of one’s skin. Metoclopramide (Reglan) can also cause these side effects, but less often.

Ondansetron (Zofran) does not cause any such side effects and should be the preferred drug for nausea of migraine, although it is only approved for nausea caused by chemotherapy or radiation and for post-surgical nausea. Since it has become generic and inexpensive, it can be used for other causes of nausea, including migraines. It is available as an injection or as a tablet.

Aprepitant (Emend) is an anti-nausea drug that has a totally different mechanism of action than the medications described above, so it is possible that it can help when other drugs do not or when other drugs cause side effects.

A study just published in Neurology by Dr. Denise Chou and her colleagues describes the use of oral aprepitant in the treatment of DHE-induced nausea in hospitalized patients.

The authors reviewed hourly diary data and clinical notes of patients admitted to the hospital for the treatment of refractory migraine headaches (status migrainosus) with DHE infusions between 2011 and 2015.

They identified 74 such patients, of whom 24 had daily diaries. In 36 of 57 cases in which aprepitant was given, there was a 50% reduction in the number of other anti-nausea medications given to patients. Of 57 patients, 52 reported that the addition of aprepitant improved nausea. Among 21 of 24 patients with hourly diary data, nausea scores were reduced. In all 12 patients with vomiting aprepitant stopped it. Aprepitant was well tolerated and caused no side effects.

The authors concluded that aprepitant can be effective in the treatment of refractory DHE-induced nausea and vomiting. They also suggested that perhaps this drug could be used for nausea of migraine even when DHE is not given. The only problem, and it is a very big problem, is the cost. This drug is not going to be available in a generic form until 2018. A single capsule of Emend costs $105 with a coupon you can get on GoodRx.com. Without a coupon, it is $145. A single vial for injection costs $345, so we are not going to use this drug for nausea due to migraine or DHE for at least two years, when cheaper generic copies become available.

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Hypothyroidism, or under-active thyroid is known to cause headaches or worsen pre-existent migraines. Correcting this deficiency with medications such as Synthroid or Armour Thyroid often improves headaches.

Researchers at the University of Cincinnati College of Medicine tried to determine if having headaches made one more prone to developing hypothyroidism. They examined 8,412 healthy people and checked their thyroid function every 3 years over a 20 year period. They excluded from the group people with past thyroid disease or abnormal thyroid function tests at the first office visit. The diagnosis of a headache disorder was established based on person’s report of “frequent headaches,” by the use of any headache-specific medication, or a physician’s diagnosis of a headache disorder. They also recorded age, sex, body mass index, income, smoking, narcotic use, and medicines that could cause thyroid dysfunction.

Headache disorders were present in about 26% of the population and new onset hypothyroidism developed in 7%. Those who had a headache disorder had a slightly higher risk (1.2 times) of developing hypothyroidism. The researchers concluded that headache disorders may be associated with increased risk for the development of new onset hypothyroidism. These results were published in Headache.

One of my colleagues tells an embarrassing story of his wife’s headaches. She developed them after giving birth to their child, so he attributed them to stress and lack of sleep. When headaches persisted she went to her primary care doctor who discovered that she had an underactive thyroid. The headaches promptly went away with thyroid medicine.

Besides headaches, low thyroid function can cause weight gain, fatigue, constipation, muscle cramps, intolerance of cold, dryness of the skin, memory and concentration difficulties. Many of these symptoms also occur with magnesium deficiency, so both RBC magnesium and thyroid function tests (along with vitamin B12, vitamin D, and routine tests) need to be checked when headaches worsen or new ones develop.

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Migraine with aura is known to be associated with an increased risk of diseases of arteries, such as strokes, heart attacks and diseases of peripheral blood vessels. This risk is further increased by estrogen-containing contraceptives.

A new study by Taiwanese neurologists suggests that migraine with aura also carries a higher risk of blood clots forming in the veins, so called venous thrombosis or deep vein thrombosis (DVT). Venous thrombosis is more likely to occur in obese, people with cancer, smokers, women on birth control pills, and those who are bedridden or sit for a long time, like on a long airplane ride. According to this new study, having migraines with aura increases the risk of this condition by two and half times.

DVT, which most commonly occurs in a deep vein in a leg, can completely resolve on its own without any residual effects. However, it can also cause long-term swelling and poor circulation in the leg and in about 10% of cases, a piece of the blood clot can break off and be carried into the lung. This is called pulmonary embolus and it is fatal in 10% of patients. DVT requires urgent treatment with blood thinners, which can prevent pulmonary emboli.

So, it is important to recognize symptoms of DVT. These include swelling in a leg or an arm, pain or tenderness in the leg when standing or walking, warmth in the area that is swollen or hurts, redness of the skin, and visible enlargement of the veins in the leg or arm.

Symptoms of pulmonary embolus are sudden shortness of breath or cough, rapid breathing, chest pain, back pain, profuse sweating, lightheadedness, and passing out.

Because blood clot can damage valves inside the vein some people develop a post-thrombotic syndrome, which can consist of pain, persistent swelling, darkened skin color, skin sores and varicose veins (enlarged and tortuous veins that sometimes can be seen under the skin).

To reduce the risk of both arterial and venous complications one needs to stop smoking, exercise regularly, maintain normal weight, blood pressure and blood sugar, avoid estrogen-containing contraceptives and hormone replacement therapy, and avoid sitting for prolonged periods of time. Obviously, these measures apply to everyone, but they are particularly crucial for those with migraine with aura.

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One of the most common problems with Botox injections given for chronic migraines is that doctors use the standard protocol without adjusting the dose. One of my patients is an 83 year old woman with chronic migraines who has done exceptionally well with Botox injections with no side effects for the past 16 years. She recently started living in Florida during the winter and had Botox injections given by a local doctor. I provided her with a copy of the injection sites and the total dose, which was 65 units given into 20 sites in the forehead and temples. Her Florida neurologist insisted on giving her the standard 31 injections with 155 units all around the head, neck and shoulders. The result was that she developed drooping of her eyelids and pain and weakness of her neck. It defies common sense to inject a small woman who weighs 90 lbs with the same amount of Botox as a 200-lbs man.

Sticking strictly to the protocol prevents many doctors from addressing clenching and grinding of the teeth (TMJ syndrome), which often worsens migraines. Injecting Botox into the masseter muscles (chewing muscles at the corner of the lower jaw) can have a dramatic effect on TMJ pain and migraines. Other patients may need additional injections into the scalp or upper back, depending on where the pain is felt. Since Botox comes only in 100 and 200 unit vials, if the insurance company approves Botox, it sends us 200 units. Instead of discarding the remaining 45 units, we usually give additional injections into the areas of pain that may not be included in the standard protocol.

Giving injections every 3 months or even every 12 weeks works well for many patients. However, about a quarter of my migraine patients find that the effect of Botox lasts only 10 weeks and in a small number , even less than 10 weeks. Fortunately, some insurance companies allow Botox to be administered every 10 weeks, but many do not. Some even limit injections to every 3 months, and not a day earlier, even though the clinical trials that led to the FDA approval involved giving injections every 12 weeks. Having a week or two of worsening migraines can eliminate the cumulative effect we see with repeated treatments. That is, each subsequent Botox treatment provides better relief than the previous one. This may not the case if headaches worsen before the next treatment is given.

Cosmetic concerns are not trivial since Botox injections can make you look strange – as if you are always surprised or look sinister with the ends of your eyebrows always lifted. This can be easily avoided by injecting a very small amount of Botox into the appropriate muscles above the ends of the eyebrows or a little beyond them. In some patients this can be predicted before the first treatment by looking at the lines seen with lifting of the eyebrows. In others, it becomes apparent only after the first treatment. If the appearance is very unappealing, we ask the patient to return to get two small additional injections for which we do not charge.

To minimize bruising and pain we use very thin needles. A 30-gauge needle is used most often, however an even thinner, 33-gauge needle is also available, but is rarely used (higher number indicates a thinner needle). We recommend using a 33-gauge needles, at least for the forehead, where injections tend to be more painful and where bruising, if it happens, is very visible.

Many dermatologists and plastic surgeons tell their patients not to bend down or do anything strenuous to avoid movement of Botox which may lead to drooping of the eyelids. There is no theoretical or practical evidence for this restriction. Once injected, Botox does not move around freely but stays in the injected area. In my 22 years of injecting Botox, I’ve treated thousands of headache sufferers and fewer than 1% of patients developed drooping eyelids and none were related to bending or any other activities. Drooping is more common in older patients, is always reversible within days or weeks, and sometimes can be relieved by eye drops (aproclonidine).

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Medical marijuana reduces the number of prescriptions written by doctors, according to a recent study published in Health Affairs. The researchers at the University of Georgia in Athens looked at all prescriptions filled by Medicare participants over a four year period for nine conditions for which medical marijuana is used for. These included anxiety, depression, glaucoma, nausea, pain, psychosis, seizures, sleep disorders and spasticity. They compared 17 states and Washington, DC where medical marijuana was legalized with those where it was not. In states with legalized medical marijuana the number of prescriptions dropped by 0.5% providing estimated savings of $165 million a year. Of all approved indications, relief of pain was by far the most common reason medical marijuana was prescribed for. This was a much more dramatic effect than the researchers anticipated. They expected that the mostly elderly patients on Medicare would be more resistant to the idea of using marijuana than younger people.

In a February post I mentioned that I started prescribing medical marijuana to my patients with migraine headaches who also have neuropathic pain as part of their headache. While medical marijuana is not approved for migraines per se, it is approved for neuropathic (i.e nerve-related pain), which many migraine sufferers do have. Burning or stabbing pain indicates the presence of neuropathic pain. So far, I’ve prescribed medical marijuana to about two dozen patients and as expected, the results are mixed. It works well for some, but not other. Most commonly, patients who’ve had positive experience with recreational marijuana tend to request medical marijuana and they tend to do better than those who’ve never tried it.

Research on medical marijuana is complicated by the fact that there is no standard formulation, which means that there is wide variation in the strains of the plant with varying amounts of active and inactive ingredients. In New York State medical marijuana can be ingested, inhaled through a vaporizer or placed under the tongue. We also have various ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), which produce different results. Nevertheless, we do plan to do an observational study of 100 migraine sufferers who also have neuropathic pain. We hope to get an indication as to what route of administration and what THC/CBD ratio work best for migraine patients.

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CGRP migraine drugs remain on track to get an approval from the FDA within two years. My first post on these drugs appeared in 2007. The first product in this family was tested for the prevention and acute treatment of migraines. It reached the final phase 3 trials and was found to be very effective and safe, but a few patients developed minor liver abnormalities on blood tests. In view of these blood test abnormalities, the manufacturer, Merck decided against completing the trials. A similar medicine, also in a tablet form, is now being developed by Allergan (maker of Botox) and it appears to be free of liver problems.

CGRP (calcitonin gene-related peptide) is a chemical that is released in the brain during a migraine attack. Four companies are targeting the CGRP molecule in a different way. Instead of taking a pill during an attack or daily to prevent migraines, they are developing monoclonal antibodies which bind to the CGRP molecule or its receptor and block its action. These drugs are given by injection. Three of the companies, Amgen, Eli Lily, and Teva are testing intramuscular injection every month, while the fourth one, Alder is testing intravenous administration every three months. Eli Lily is also testing their compound for the treatment of episodic cluster headaches.

To date, there have been several thousand patients exposed to these monoclonal antibodies in clinical trials. What is most surprising to me is their outstanding safety. The side effects have been infrequent and mild. All four companies are conducting large-scale phase 3 trials, which will hopefully confirm their safety. Based on the previous studies, there is little doubt that these studies will show that the drugs are highly effective in preventing migraines. Unfortunately, it will be at least two years before these truly innovative medications become available.

While I am very excited about getting a new and a very different treatment for migraine and cluster headache sufferers, my enthusiasm is tempered by the potential cost of these drugs. Business experts project the cost to be between $12,000 and $18,000 a year. By comparison, the $6,000 yearly cost of Botox injections seems cheap. Only about 100,000 out of several million chronic migraine sufferers have been treated with Botox since it was approved for migraines 6 years ago. This is in large part due to the difficulties in getting approval from the insurance companies. Besides extensive paper work from the doctor, they require that the patient first try and fail two or three preventive drugs. The new CGRP drugs are likely to be the last option in this chain and will require even more paperwork. The result is likely to be a great underutilization of these breakthrough drugs, just as it has been happening with Botox.

I am not suggesting that these drugs should be cheap since literally billions of dollars will have been spent by the time these drugs receive approval. If the companies cannot make a profit, the investment in research will dry up and fewer breakthrough drugs will be developed. This is why most new treatments are developed in the US and not Europe, where drug costs are controlled by the government. Hopefully, in a few years the cost will drop as it has happened with another family of highly effective migraine drugs, the triptans.

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Vitamin B12 was the subject of an article in the New York Times by Jane Brody entitled, Vitamin B12 as Protection for the Aging Brain. However, she mentions that “insufficient absorption of B12 from foods may even be common among adults aged 26 to 49” and that the advice to take a vitamin B12 supplement may apply to young people as well. This is particularly true for vegans and vegetarians, as well as people with stomach problems and those on PPIs – drugs for ulcers and heartburn, such as Prilosec, Nexium, Aciphex, etc.

Vitamin B12 deficiency can cause “fatigue, tingling and numbness in the hands and feet, muscle weakness and loss of reflexes, which may progress to confusion, depression, memory loss and dementia as the deficiency grows more severe”. Severe deficiency leads to peripheral and central nervous system damage (so called subacute combined degeneration), which eventually becomes irreversible and leads to death.

Jane Brody does not mention that besides Alzheimer’s, other chronic diseases, such as multiple sclerosis, diabetes, and cancer are also associated with low vitamin B12 levels. Vitamin B12 with vitamin B6 and folic acid has been shown to help some migraine sufferers

You can ask your doctor to check your vitamin B12 level, but unfortunately it is not reliable. Most laboratories cite as normal blood levels of above 200 or 250, but there are reports of rare cases where severe deficiency is present with a level of 700. I recommend taking a supplement if the level is below 500. In severe cases or in people with stomach problems, a monthly injection is a better choice. Patients can easily self-inject vitamin B12, but it does require a doctor’s prescription. Some of my patients feel the need to inject themselves with vitamin B12 more often than once a month. Whenever they start feeling tired or having other symptoms, they take a shot. Unlike some vitamins, such as B6 and A, vitamin B12 does not cause any negative effects even at high levels. As an oral supplement I usually recommend tablets of methylcobalamin, rather than cyanocobalamin form of vitamin B12 because of better absorption. The usual dose is 1 mg (or 1,000 mcg) daily. If you are deficient and stop taking the supplement, the deficiency can return within a few months.

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Living in areas where fracking takes place doubles the risk of having migraines, as well as fatigue and sinus symptoms. Fracking, or hydraulic fracturing, is a water-based method of extracting natural gas from deep under the ground.

Johns Hopkins researchers described these findings in the journal Environmental Health Perspectives. The study was conducted using questionnaires which were completed by 7,785 adults. Among these people, 1,765, or 23% suffered from migraines, 1,930 people or 25% experienced severe fatigue and 1,850 or 24% had symptoms of chronic sinusitis (three or more months of nasal and sinus symptoms). In the general population the incidence of migraines is about 12%.

Previous studies have discovered an association between fracking and increased risk of premature births, asthma attacks and indoor radon concentrations.

It is unclear how fracking results in these health problems. Some possible explanations include air pollution, odors, noise, bright lights, and heavy truck traffic.

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Three times as many women are afflicted by migraines as men, according to many large studies. However, 6% of men do suffer from migraines and that means 9 million American men. However, in our clinic, instead of 75%, over 90% of patients are women. Men are often dragged into the office by their wife, girlfriend, or mother.

A new study presented at the recent meeting of the American Headache Society confirms this observation. Dr. Anne Scher and her colleagues established that men are less likely to see a doctor and when they do see one, they are less likely than women to be given the diagnosis of migraine. Only 59% of men with migraines were given the correct diagnosis, while this number was 77% for women. This is probably due to the perception of migraine as a disease of women. The reasons for misdiagnosis in both sexes include the notion that every migraine sufferer has to have a visual aura (it is present only in about 20%), or that the headache has to be one-sided, or the person has to have nausea. In fact, all of the typical migraine features do not have to be present. It is sufficient to have nausea and throbbing pain or light sensitivity and inability to function normally, or light and noise sensitivity and one-sided throbbing pain, etc.

Migraines are often misdiagnosed as sinus headaches because in some people migraine is accompanied by a clear nasal discharge or because the pain is localized in the area of sinuses. True sinus headaches are usually accompanied by yellow or green nasal discharge.

Migraines can be also mistaken for tension-type headaches, but tension-type headaches are milder and never severe, not accompanied by nausea and other symptoms, and typically respond to over-the-counter medications.

One type of headaches that is significantly more common in men, is cluster headache. Cluster headaches are also often misdiagnosed as migraine or sinus headache. The name comes from the fact that these headaches occur in clusters – every day for a month or two and then they go away for a year or longer. The pain is extremely intense, always one-sided and localized around the eye, usually accompanied by tearing and runny nose on the side of the headache. These headaches tend to wake the person from sleep, but can occur during the day and last anywhere from half an hour to a few hours. Some of the treatments for cluster headaches are different from those for migraines, so a correct diagnosis is crucial. There are many posts on this blog and an article on our site devoted to cluster headaches, so please do a search if you are interested in learning more.

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Intravenous magnesium relieves acute migraine attacks in patients with magnesium deficiency, which is present in half of migraine sufferers, according to the study we published in 1995 in the journal Clinical Science. Infusions not only treat an acute attack, but also prevent migraines. Oral magnesium supplementation is not as effective and helps less than 50% of patients because some patients do not absorb magnesium. Most people get enough magnesium from food, but some migraine sufferers have a genetic defect which prevents them from absorbing magnesium or a genetic defect that leads to an excessive loss of magnesium through kidneys.

Our experience with thousands of patients suggests that the majority of migraine sufferers who are magnesium deficient do improve with oral supplementation, but about 10% do not. These patients need regular infusions of magnesium and these infusions are often life-changing. Magnesium not only treats and prevents migraines, but also relieves muscle cramps, PMS, palpitations, “brain fog”, and other symptoms.

There are many mentions of magnesium on my blog and on the nyheadache.com website, so what prompted another post on this topic is a couple of patients with an unusal experience. I would occasionally see such patients but in the past few weeks, I saw several. These patients tell me that when we give them an infusion of magnesium by “slow push” over 5 minutes they get excellent relief, but when they end up in an emergency room or another doctor’s office where they receive the same amount of magnesium through an intravenous drip over a half an hour or longer, there is no relief.

A likely explanation is that a push results in a high blood level, which overcomes the blood-brain barrier and delivers magnesium into the brain, while during a drip, magnesium level does not increase to a high enough level to reach the brain. Studies have shown that migraineurs not only have a systemic magnesium deficiency, but specifically in their brains. A similar phenomenon has been described with sumatriptan (Imitrex). Researchers discovered that migraine sufferers who did not respond to sumatriptan had a much slower increase in the drug level compared to responders, even though the total amount of the drug absorbed into the blood was the same.

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Recently, a patient of mine reported that cramp bark has significantly improved her menstrual migraines. Cramp bark is a common shrub with red berries. Its bark has been used for over 100 years for muscle cramps, menstrual cramps, fluid retention, and other symptoms. Fortunately, it appears to be very safe and even though no scientific studies have been performed on it, it may be worth trying. I will start recommending it to women with menstrual migraines, menstrual cramping and patients with muscle spasms in their neck and upper back.

The two top herbs I recommend to my migraine patients are feverfew and boswellia. Feverfew has been subjected to scientific studies and seems to help some patients while causing almost no side effects. Boswellia has been reported to help even patients with cluster headaches, but no rigorous studies have been done. However, it is safe and because of its anti-inflammatory properties it can also help joint and muscle aches (see my blog post on Boswellia).

Butterbur, on the other hand is not always safe, so I haven’t been recommending it. Here is one of my blog posts on it.

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Vagus nerve stimulation (VNS) with an electrode implanted in the neck is an FDA-approved treatment for depression and epilepsy, when these conditions do not respond to medications. Since antidepressant and anti-epilepsy medications help migraines, I had six patients (four with migraines and two with cluster headaches) treated with VNS. Two of the four chronic migraine patients and both cluster patients had good relief – results that were published in the journal Cephalagia in 2005. This publication led to the development of gammaCore, a device to stimulate the vagus nerve through the skin, without the need for surgical implantation of an electrode. The New York Headache Center participated in one of the earliest studies of this device and the results were encouraging.

An article published in the current issue of Neurology presents the results of another study of gammaCore. In this first double-blind study 59 adults with chronic migraines (15 or more headache days each month) were given either real VNS or sham treatment for two months. After two months they were all given the real treatment for 6 months. The main goal of the study was to examine the safety and tolerability of this treatment, but the researchers also looked at the efficacy by measuring the change in the number of headache days per 28 days and acute medication use.

Both sham and real treatment were well tolerated with most adverse events being mild or moderate and transient. The number of headache days were reduced by 1.4 days in the real and 0.2 days in the sham group. Twenty-seven participants completed the open-label 6-month phase, which suggests that this treatment might work for half of the patients. However, larger sham-controlled studies are needed to prove that this treatment really works. GammaCore is also being tested for the treatment of cluster headaches. Although it has not been definitively proven to be effective, it is already being sold in some European countries.
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Menopause often brings relief to female migraine sufferers. However, many women have worsening of their migraines during the transition. This is thought to be due to the fluctuating levels of estrogen, which is also responsible for menstrual migraines. Steady levels of estrogen during pregnancy and in menopause lead to a dramatic relief of migraines in two out of three women.

A study published in a recent issue of the journal Headache examined the relationship of headache frequency to the stages of menopause. The study looked at 3446 women with migraines with a mean age of 46. Among women who were premenopausal, 8% had high frequency of headaches (10 or more headache days each month), while during perimenopause as well as menopause, 12% of women had high frequency of migraines. This does not contradict the fact that many women stop having migraines in menopause, but it suggests that among those women who continue having migraines, there are more with high frequency of attacks.

By publishing these findings, the authors wanted to draw attention to the fact that many women may need a more aggressive approach to treatment. In women with high frequency of attacks preventive therapies tend to be more effective than abortive ones. These may include magnesium, CoQ10, Boswellia, and other supplements, as well as preventive medications and Botox injections. At the same time, most women may also need to take abortive therapies, such as triptans.

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Tremor of the hands is usually a benign condition. It is even called, benign essential tremor or, if it runs in the family, benign familial tremor. Patients with tremor are twice as likely to have migraines, so this is why I am writing about it. Tremor is also a symptom of Parkinson’s disease, but these two types of tremor can be easily differentiated. Parkinsonian tremor is a resting tremor, which means that hands shake at rest, while essential tremor occurs in action, like when trying to drink from a cup.

Even though it is benign, essential tremor can be incapacitating and socially embarrassing. Fortunately, in most people it responds to treatment. We usually start with propranolol (Inderal), a drug that belongs to the beta-blocker family, which is used for the treatment of high blood pressure and migraines. If propranolol or another beta-blocker is ineffective or causes side effects (due to low blood pressure or slow pulse), tremor can be treated with epilepsy drugs such as primidone (Mysoline), gabapentin (Neurontin), zonisamide (Zonegran), or an alpha-2 agonist such as clonidine (Catapres), which is a different type of blood pressure medicine.

In rare cases, tremor affects not hands but the voice. I recently treated such a patient. He tried some medications, but when they did not help, he was given Botox injections into the vocal cords. This reduced the tremulousness of his voice, but only partially. Botox can also help with hand tremor, but because there are so many small muscles involved, the results are not very good. Taking careful history revealed that this patient tried only 10 mg of propranolol and when it did not help, he stopped it. I decided to give it another try and built up the dose to 30 mg, which provided complete relief without any side effects. For migraines, we usually go up to 60 to 120 mg of propranolol, but some patients need and tolerate even higher doses.

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A new report presented at the last annual scientific meeting of the American Headache Society in San Diego showed that post-concussion symptoms can be helped by an intravenous infusion of magnesium.

Doctors at the department of neurology at UCLA described six patients with a post-concussion syndrome, who were given an infusion of 2 grams of magnesium sulfate. Three out of six had a significant improvement of their headaches and all had improvement in at least one of the following symptoms: concentration, mood, insomnia, memory, and dizziness.

This was a small study, but it is consistent with other studies that show a drop in the magnesium level following a concussion and also studies in animals that show beneficial effects of magnesium following a head trauma.

Our studies have shown that intravenous magnesium can relieve migraine and cluster headaches in a significant proportion of patients.

Considering how safe intravenous magnesium is and how devastating the effect of a concussion can be, it makes sense to give all patients with a post-concussion syndrome if not an intravenous infusion, at least an oral supplement. I usually recommend 400 mg of magnesium glycinate, which should be taken with food. For faster and more reliable effect, we routinely give patients with migraines, cluster, and post-concussion headaches an infusion of magnesium. Patients who do not absorb or do not tolerate (it can cause diarrhea) oral magnesium, come in to for monthly infusions.

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Medication overuse headache (MOH), which is sometimes called rebound headache, is included in the International Classification of Headache Disorders. However, this is one of several headache types whose existence is still debated. After years of indocrination, most neurologists and headache specialists strongly believe that every drug taken for acute treatment of headaches can cause MOH. However, we have good evidence only for caffeine and for opioid (narcotic) pain medications. It is far from proven in case of triptans (sumatriptan or Imitrex, and other) or NSAIDs (ibuprofen or Advil, naproxen or Aleve, and other).

Last week, I attended the annual scientific meeting of the American Headache Society (AHS) and was happy to see that despite an almost universal acceptance of the diagnosis of MOH, the organizers set up a debate on the existence of MOH. The debaters included two top experts in the field, Drs. Richard Lipton of Montefiore Headache Clinic in the Bronx and Ann Scher of the Uniformed Services University in Bethesda. Dr. Lipton and Scher have collaborated on many research projects and have published many important articles on headaches together, so the debate was friendly and based on facts.

Dr. Scher quoted the American Council on Headache Education, an affiliate of the AHS:

“It is important to know that intake of medications for acute treatment should be limited to less than twice a week. Some methods which can prevent the onset of medication overuse headache include following instructions on how to take medications, avoid use of opioid medications and butalbital combination medications and limit use of simple analgesics to less than 15 days a month and triptans less than 10 days a month”.

And then she posed a question: How many are being harmed vs helped by this advice?

While Dr. Lipton quoted scientific articles supporting the existence of MOH, Dr. Scher’s conclusions reflected my clinical experience that MOH is not a proven entity as it relates to triptans and NSAIDs. I see it only in those who overuse caffeine or caffeine-containing drugs (Excedrin, Fioricet, etc) or narcotic pain killers (Percocet or oxycodone, Vicodin or hydrocodone, and other).

Dr. Scher concluded that, “Since the existence of MOH has not been proven (and may be non-provable for practical purposes), one is obligated to remain agnostic about this entity. And the corollary is that there is no evidence that undertreating will prevent headache frequency progression and may harm more people than help”.

In fact, the same headache experts who limit abortive therapies to twice a week, recommend aggressive abortive therapy for migraines because undertreatment of episodic migraine can lead to its transformation into chronic migraine.

She also indicated that “Quality of evidence for medication withdrawal alone as treatment for MOH is poor” and “Medication withdrawal alone is not clearly better than doing nothing and may be worse”. Meaning that in addition to withdrawal of the acute medication, patients should be given prophylactic treatment.

Studies indicate that after one year, 60% and after two years, 70% of those with chronic migraines (15 or more headache days in a month) revert to episodic ones (less than 15 headache days a month) regardless of treatment. In 15% headaches decrease to less than one a week. This is because fortunately, migraines often improve with time on their own.

We have evidence that Botox injections and some preventive medications can make discontinuation of acute medications easier. We always try to stop Fioricet (butalbital, acetaminophen, and caffeine), Fiorinal (butalbital, aspirin, and caffeine), Excedrin (caffeine, acetaminophen, aspirin) with the help of regular aerobic exercise, biofeedback or meditation, magnesium and other supplements, Botox injections, and sometimes preventive medications.

However, we do have several dozen patients whose headaches are controlled by the daily intake of triptans. These patients have tried given prophylactic medications, Botox injections and other treatments, but find that only triptans provide good relief and eliminate migraine-related disability. The most commented on post on this blog (with 175 comments to date) is one on the daily use of triptans.

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Hemiplegic and basilar migraine are rare types of migraine. Hemiplegic migraine is accompanied by a paralysis of one side of the body. Basilar migraine derives its name from the basilar artery, which supplies blood to the brainstem. Symptoms of brainstem dysfunction (double vision, unsteady gait, vertigo, difficulty speaking) made doctors think that ischemia or lack of blood flow in that artery caused these symptoms. We now know that this is not the case and basilar migraine may be just another form of migraine with aura.

The FDA ruled that sumatriptan (Imitrex), other triptans, and ergotamines (DHE-45, Cafergot) are contraindicated in patients with basilar and hemiplegic migraine because of the unsubstantiated fear that these drugs may cause constriction of blood vessels that might be already constricted resulting in a stroke. There is little evidence that symptoms of hemiplegic and basilar migraine are caused by the constriction of blood vessels. It is most likely due to the dysfunction of the brain cells. In addition, constriction of blood vessels by the triptans is very mild.

A study just published in the journal Headache examined 67 patients with basilar and 13 with hemiplegic migraines who were treated with triptans and dihydroergotamine (DHE-45). None of these patients suffered a stroke or a heart attack.

This is not the first report of the safe use of triptans in the treatment of basilar and hemiplegic migraines. Although the total number of patients reported is small, it appears that triptans and ergots are probably safe in these types of migraines. Some doctors are afraid to prescribe triptans to such patients out of fear of litigation. There is a good chance that the next edition of the classification of headache disorders will no longer include basilar migraine because it is recognized as being just a form of migraine with aura. Ergots and triptans are not contraindicated in migraine with aura.

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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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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 GoodRx.com 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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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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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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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.

onzetratm-xsailtm-photo-1-5-HR

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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, Amazon.com, and Migralex.com.

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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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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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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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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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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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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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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 Migralex.com, Amazon.com, 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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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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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 GoodRx.com 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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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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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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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 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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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.

BH

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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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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 https://www.youtube.com/watch?v=llvUbxEoadQ&authuser=0

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