Archive
Science of Migraine

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

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

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

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

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

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

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

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

Read More

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

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

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

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

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

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

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

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

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

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

Read More

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).

Read More

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

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

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

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

Read More

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

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

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

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

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

Read More

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

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

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

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

Read More

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.

Read More

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

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

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

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

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

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

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

Read More

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

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

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

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

Read More

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

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

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

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

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

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

Read More