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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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