Science of Migraine

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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