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Chronic migraine

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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There is little doubt that stem cells, along with genetics and computer science will revolutionize medicine. There are more than a dozen journals devoted to stem cell research and many general and speciality medical journals also publish research on stem cells, which means that a couple of hundred articles are published every month. At first, the research was stymied by the controversy about the fetal sources of stem cells. For the most part this problem has been circumvented by the discovery of other sources, such as umbilical cord, placenta, fat tissue, and other.

In neurology, multiple sclerosis, spinal cord injuries, and strokes have been the main targets of stem cell research. The latest study of stem cells for stroke victims conducted at Stanford by Gary Steinberg and his colleagues produced very encouraging results. This trial included only 18 patients, but they all had their stroke anywhere between 6 months and 3 years before the study – past the usual time where further recovery is expected. Improvement occurred in the majority of patients and the improvement was not affected by the age of the patient or the severity of the stroke. Although stem cells were injected directly into the brain through a small hole that was drilled in the skull, there were no serious complications or side effects. The researchers also noted that stem cells did not replace damaged cells but rather stimulated patients’ own repair mechanisms. This is at odds with the original idea that stem cells by their nature could turn into nerve cells or any other cells in the body to replaced damaged cells.

This stimulating (and anti-inflammatory) effect of stem cells was our reason for conducting a small pilot study of stem cells in patients with refractory chronic migraines, which was described in a previous post. We did not inject cells into the brain, but into the muscles around the head and neck. Three out of 9 patients showed some improvement. We used patients’ own cells extracted from their fat tissue, while the stroke study used cells derived from the bone marrow of a donor. The future of stem cell research clearly lies in the use of such off-the-shelf cells, which have been shown to be safe and are probably more effective than fat-derived cells.

Stem cell lines are being developed to treat different medical conditions – Asterias for spinal cord injury, Pluristem for radiation damage, and many other.

The same team of researchers and SanBio, Inc. the Japanese company that developed these stem cells are conducting another larger controlled trial. You can email stemcellstudy@stanford.edu for information about participating in this trial.

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Chronic pain is known to alter the structure of the brain. Mayo Clinic researchers used MRI scans to examine brains of 29 patients with post-traumatic headaches and compared their scans to those of 31 age-matched healthy volunteers. The average frequency of headaches was 22 days a month. Patients with post-traumatic headaches were found to have thinning of several areas of their cerebral cortex which are responsible for pain processing in the frontal lobes. Cortex covers the surface of the brain and contains bodies of brain neurons. Drs. Chiang, Schwedt, and Chong, who presented their findings at the annual meeting of the International Headache Society held last month in Vancouver, also discovered that the thinning was correlated with the frequency of headaches.

This study did not address possible treatments, but it would make sense that with better control of headaches, this brain atrophy might be reversible. To treat post-traumatic headaches we often use Botox injections, which have been shown to help posttraumatic headaches. Even though Botox is approved only for chronic migraines, many patients with post-traumatic headaches do have symptoms of migraines and can be diagnosed as having post-traumatic chronic migraines (without such a designation insurance companies may not pay for Botox). We also check RBC magnesium, CoQ10 and other vitamin levels, which are often low in chronic headache sufferers and if corrected, can lead to a significant improvement. Epilepsy drugs and anti-depressants can also help.

While the above mentioned treatments can help headaches and potentially could reverse brain atrophy, there is only one intervention that has been shown to increase the thickness of the brain cortex on the MRI scan. This intervention is meditation. And this effect was demonstrated in several studies. An 8-week course of mindfulness-based stress reduction led to a measurable increase in the gray matter concentration of certain parts of the brain cortex. A pilot study of migraine sufferers showed that meditation has a potential not only to restore thickness of the brain, but also to relieve migraines.

In one of my previous blog posts that described a sceintific study of meditation, I mentioned several ways to learn meditation: Free podcasts by a psychologist Tara Brach an excellent book, Mindfulness in Plain English by B. Gunaratana, and several apps – Headspace, 10% Happier, and Calm. You can also take an individual or a group class, which are widely available.

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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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Concussion, even when it is mild, can result in a post-concussion syndrome. The main symptom is a headache and it is present in 60% of people within the first year after a mild traumatic brain injury. In people with personal or family history of migraines these headaches are often post-traumatic chronic migraines. Post-traumatic headaches and other symptoms such as dizziness and difficulty with vision, concentration and memory are often difficult to treat. However, an effective treatment of headaches often leads to an improvement in other symptoms as well.

Treatment with epilepsy drugs (Topamax, Depakote, Neurontin), blood pressure medications (propranolol), or antidepressants (Elavil, Cymbalta) can be effective in some, but not in all and not without side effects. Botox injections have been very effective without any serious side effects in many of my patients and similar results have been published by other doctors (see here and here).

Dr. Sylvia Lucas of University of Washington in Seattle presented her experience with the treatment of posttraumatic headaches with Botox at the annual meeting of the American Headache Society held in Boston last month. She described 15 patients who sustained a mild traumatic brain injury and suffered from chronic migraines for an average of 8 months prior to being treated with Botox. After a series of three Botox treatments given every 3 months most patients had a significant improvement in the number of headache days, as well as improved physical and social functioning, emotional well-being, energy level and a reduction in pain. As expected, no patient experienced any serious side effects.

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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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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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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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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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It was a great privilege to know Elie Wiesel, survivor of Auschwitz, Nobel Peace Prize winner, author of 40 books, university professor, and most importantly, a tireless campaigner for human rights.

Mr. Wiesel suffered from severe daily migraines. Both of his parents and many members of his extended family suffered from headaches. The only year in his life without headaches was when he was in Auschwitz. He was highly functional with a very busy schedule despite his chronic migraines. I invited him to speak about his headaches at the First International Headache Summit held in Tel-Aviv, Israel, on November 16, 2008 and he generously agreed (here is a photo from the event). This is an excerpt from his presentation which was published in the journal Headache:

“Thank you very much, Dr. Mauskop. I’ve been thinking a lot about this topic, and when I consider a topic I tend to return to my primary source: do we find headaches in Scripture? Perhaps you remember the prophet Elishah, a very special man, the disciple of Elijah. The woman who was his host in a certain village was barren, and she was embarrassed to tell him this. Elishah’s servant knew of her distress, however, and he so informed the prophet whom he served. Elishah blessed her with a son. The son grew, and one day when he was in the fields with his father, he cried out, “My head, my head. I have a headache.” Thus, for the first time, headache enters old religious texts. The father asked his servants to bring the boy home, where he suddenly died. His mother ran to the prophet, to Elisha, and said, “I asked you for a living son . . . not for a dead one.” At that point we first bear literary witness to the act of mouth-to-mouth resuscitation. The prophet administered it resuscitation, and the boy lived once again.
When one poses a question, the Talmud may offer what amounts to advice. What happens if a person has a headache? What should he do? You or I would answer, Go to a doctor, but the Talmud advises, Go study Torah. Now, why should a person who has a headache go and study? Is it because when he or she studies, they forget their headache? or maybe they get a different headache. Everything is possible.
Now, I must tell you, Dr. Mauskop, you kindly asked me to come and see you for my headaches. I didn’t come because I did not want to embarrass you, to cause you to have to admit failure, because nothing has ever helped me. I began having headaches—I’m speaking to you as a patient—at age 7. At age 7, I already was taking pills for headache; everybody in my family was! My mother had headaches; my father had headaches; my grandfather had headaches. So I lived with headaches from my childhood on.
But then something bizarre happened: the day I entered Auschwitz, the headaches disappeared. I studied what you told me about pressure, about headaches as the result of pressure. But that seemed a contradiction. If ever I had pressure, it was there. In the camp. Every moment was pressure. But the headaches disappeared.
The moment I arrived at the first orphanage in France, after Liberation, they came back. The first doctor I went to I saw for my headaches. They are still with me. And they are not rare; they are still frequent. I get up every day with a headache, and once a week, I have what I call the “deluxe” version, a real headache. My problem is if I have to give a lecture that day—and I teach full time—or that evening, what do I do? If I take strong pills, I’m afraid it could affect my thought processes. I try to cope. I didn’t come to see you. I thought, why should I give you pain by realizing that you cannot help my own?
At my age, and rather suddenly, I’ve developed other kinds of pains that I didn’t have before. Back pains, hand pains. So I’ve been to all kinds of doctors for these various woes, and—I don’t have to tell you—the interesting part is, usually when you have a new pain, the old pain recedes. Not in my case. My headache is so faithful to me; it’s so loyal that it remains present always.
I got up this morning with a very, very bad headache. So, I said to my headache, “You won’t win.” I speak to my headache; I personalize it. I say, “I know who you are, and I know what you want, and it won’t work.” And the pain says to me, “Let’s see, Wiesel.” And so we fight.
Through my studies, I’ve discovered that many writers and artists and painters have suffered from headaches, and they have had their own distinctive methods of coping. Dumas used to place a wet cloth on his forehead. Hemingway used to do write standing, because this seemed to afford some relief. Many of the great writers had headaches. Perhaps writers have headaches because they are afraid of critics.
And to this day I have not found a way of handling my own headache except in my own fashion, which is to live with it. It hasn’t slowed down my work. I teach full-time, and I am a very obsessive professor. In some 40 years, I don’t think I’ve ever given the same course twice. I want to be the best student in the class. That’s how I learn and grow with the students. And all that with my constant companion, this headache.
Now maybe once I’ve finished, you will have a session and say, “Now what can we do for Elie Wiesel’s headaches?” But don’t bother; even if you were to try, I don’t think you could help. But perhaps you can use my example to encourage your patients. Patients will come to you and say, “Why can’t you help me?” And you can say, “Look. He couldn’t get cured, and nevertheless he works. He goes on, functioning, studying, teaching.”
Maybe psychologically I need the headaches to work? I’m sure some of you have had that idea in mind. Maybe he needs the added challenge . . . this extra burden. In that case, why did I have headaches at age 7? And 8 . . . 9 . . . 10? Hereditary? Sure. Pressure? No. What pressure? School pressure? I was a good student.
So do I need these headaches? Personally, I think not. I think I could work as well without them. Are they part of me? Are they part of my psyche? Is my headache part of who I am? If so, what a terrible analysis . . . what a terrible definition of self! Am I my own pain?
You know Descartes, the philosopher. As a young man I admired him because he was one of the great thinkers of the Middle Ages, helping us emerge from the darkness. He came out with the formula, and I’m sure most of you recall it from school, cogito ergo sum: I think, therefore I am. And later I discovered about Descartes things I didn’t admire that much. He had written a book on science. When he read about the tragic fate of Galileo, he was so afraid of the Inquisition that he didn’t publish his book. Hey, Descartes, that’s no way to behave. You, the philosopher, should be afraid of the tormentor? But he was. So I began reanalyzing, reevaluating Descartes, and concluding that maybe he’s wrong even with his cogito ergo sum! I’m a student of the Talmud. I encourage students to ask questions . . . even to question the questions. And so I thought, Maybe he’s wrong.
I think he is. I would say, “I think, therefore you are.” My thought must involve you. My life must involve you. I am who I am, not because of myself, but because of my attitude towards you. One also could say, “You think, therefore I am.” Your thought challenges mine. Your existence is a challenge to mine. Your life is maybe a question . . . and an answer in relation to my own. Alone, who are we? Nobody is alone.
So, how might I use even the pain of headache for the benefit of someone else? How can I do that? By doing my work, sure. So I go on; I’m a writer; I’m a teacher; I go around the world trying to do my best to improve some conditions here and there, always failing—but it doesn’t matter . . . I will go on trying.
One last thing to add, something perhaps to tell your patients: when a person says, Leave me alone, I have a headache, it’s wrong. Never leave me alone. Never think that you bother me. I may have the worst headache in my life, but if someone needs me, I have no right to say, “But I have a headache.” That is not a sufficient excuse.”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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