Migraines pill about.

Migraines may be doing more than causing people skull-splitting pain. Scientists have found evidence that the headaches may also be acting like tiny transient strokes, leaving parts of the brain starved for oxygen and altering the brain in significant ways.

A paper describing the work by neuroscientists at the University of Rochester Medical Center appeared online in Nature Neuroscience.

The scientists say the work makes it crucial for migraine sufferers to do everything they can to prevent their headaches. While avoiding severe pain has long been a motivating factor, the scientists say the risk of brain damage makes it imperative to prevent the headaches, by avoiding a person’s triggers for the headaches and by using medications prescribed by doctors to prevent them.

“Normally, the focus of migraine treatment is to reduce the pain. We’re saying that migraines may be causing brain damage, and that the focus should be on prevention, which will stop not only the pain but also minimize potential damage,” said Maiken Nedergaard, M.D., Ph.D., the neuroscientist who led the research team. She is a professor in the Department of Neurosurgery and a member of the Center for Aging and Developmental Biology and worked closely with Takahiro Takano, Ph.D., research assistant professor, who is first author of the paper.

By combining two recently developed imaging technologies, Nedergaard’s team was able to get an unprecedented look at the events that happen in the brain of a mouse as a migraine unfolds. The team uncovered a complex, unexpected tale of supply and demand regarding blood flow and oxygen.

In short, the team found that the brain develops a voracious demand for energy as the organ attempts to restore the delicate chemical balance that is lost in the initial throes of a phenomenon known as cortical spreading depression, which is thought to underlie many migraines.

Even though the brain’s arteries expand dramatically and make a great deal more oxygen-rich blood available to meet the demand for energy, some parts of the brain still wind up experiencing severe oxygen shortage, or hypoxia. This causes parts of brain cells’ sophisticated signaling structures to disintegrate, similar to what occurs when a person has a mini-stroke, or after a severe injury, or when blood flow to the brain is completely stopped, such as during a heart attack.

“In mice, the damage from these episodes looks exactly like the damage that occurs to the brain from repeated TIAs, or transient ischemic attacks,” said Takano. “It’s long been known that patients having a migraine attack are functionally impaired from the pain. It’s also been shown recently that with repeated migraines, a person’s cognitive abilities decrease. But actually doing damage to the brain - that is a surprise.”
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Women with epilepsy who took the seizure drug valporate, which is marketed by Abbott Laboratories under the brand name Depakote, while pregnant increased their risk of having an infant with mental defects, according to a study presented Thursday at the annual meeting of the American Academy of Neurology in Boston, the New York Times reports.

Kimford Meador, professor of neurology at the University of Florida, and colleagues examined 185 infants at age two using standard IQ measures. The mothers of the children had taken either Depakote, GlaxoSmithKline’s Lamictal, Novartis’ Tegretorl or Parke-Davis’ Dilanten (Carey, New York Times, 5/4). The average IQ of the children whose mothers had taken Depakote was 81, compared with an average of 96 for children in the Tegretol group, 94 for the Lamictal group and 95 for the Dilantin group (Gellene, Los Angeles Times, 5/4). After adjusting for the mothers’ IQ scores, the researchers found that the two-year-old children who had been exposed to Depakote scored seven to eight points lower on IQ tests than children of mothers who had taken other seizure medications (New York Times, 5/4).

A score of 100 on the IQ test is average and below 70 is considered mentally retarded, according to researchers. Twenty-four percent of children whose mothers took Depakote had IQs below 70, compared with 13% for Tegretol, 11% for Lamictal and 12% for Dilantin. According to researchers, about 2% of all children have IQs below 70. According to the Los Angeles Times, Depakote also is used to treat migraines and some psychiatric conditions, such as bipolar disorder.

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Meador said that the NIH-funded study did not support a conclusion that all four drugs might cause mental retardation (Los Angeles Times, 5/4). However, he said, “In all, it is compelling evidence that [Depakote] should not be used as a first-line choice for treatment in pregnant women” (New York Times, 5/4). Meador said that women who must take Depakote because they do not respond to other drugs should take the lowest possible dose if they become pregnant. He also urged pregnant women to remain on their epilepsy medication because a seizure could be harmful to them and their fetuses (Los Angeles Times, 5/4).

Other researchers said the findings should be considered preliminary because IQ measures are less reliable in two-year-olds than in older children, the Times reports. Laureen Cassidy, a spokesperson for Abbott, said that for many women, “Depakote may be the only effective seizure control medication, and that decision should be made thoughtfully between physician and patient to fully evaluate the risk verses benefit of treatment.” Depakote’s label now states that the drug “has been associated with birth defects in children of women who have taken it while pregnant,” the Times reports. Researchers plan to continue tracking children through age six (New York Times, 5/4).

Among patients diagnosed with severely disabling migraine, the study found the likelihood of major depression increased 32-fold if the patient also reported other severe symptoms.

“Painful physical symptoms may provoke or be a manifestation of major depression in women with chronic headache, and depression may heighten pain perception,” said study author Gretchen Tietjen, MD with the University of Toledo-Health Science Campus and a member of the American Academy of Neurology. “This relation between migraine and major depression suggests a common neurobiology.”

Tietjen says studies are underway to test whether severe headache, severe physical symptoms and major depression may be linked through dysfunction of serotonin in the central nervous system.

“Regardless of what’s causing the link between migraine and depression, psychiatric disease such as depression complicates headache management and can lead to poorer outcomes for headache management,” said Tietjen.

The study was supported, in part, by the American Headache Society, which estimates 18 million American women are affected by headache.

The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson disease, and multiple sclerosis.

Women with chronic headache, especially migraines, are more likely to be depressed, feel tired, and have a host of other severe physical symptoms, according to a study published in the January 9, 2007, issue of Neurology, the scientific journal of the American Academy of Neurology.

The study involved 1032 women at headache clinics in five states. Of the women surveyed, 593 reported episodic headache (fewer than 15 headaches per month) and 439 had chronic headache (more than 15 headaches per month). Ninety percent of the women were diagnosed with migraines.

The study found women with chronic headache were four times more likely than those with episodic headache to report symptoms of major depression. Chronic headache sufferers were also three times more likely to report a high degree of symptoms related to headache, such as low energy, trouble sleeping, nausea, dizziness, pain or problems during intercourse, and pain in the stomach, back, arms, legs, and joints.

Women who have migraines with visual problems have increased risk for heart disease, according to a study published on Wednesday in the Journal of the American Medical Association, Long Island Newsday reports. For the study, researchers at the Harvard School of Public Health and Brigham and Women’s Hospital analyzed the records of 27,800 women older than age 45 who participated in the Women’s Health Initiative. None of the women had heart disease when they entered the study between 1992 and 1995. Researchers focused on the records of 5,125 women who had a history of migraines. According to the study, participants who had migraines with migraine aura had more than twice the normal risk for major cardiovascular events. Migraine aura “is a visual sensation — like lights flashing or lines zigzagging, with some reports of temporary blindness” — that often lasts for 20 minutes to one hour before migraines begin, Newsday reports. Women who had migraines without migraine aura did not have an increased risk for major cardiovascular events, the study finds. Lead study author Tobias Kurth said that researchers did not determine the cause of the link between migraine aura and heart disease and that the increased risk was small, with about 18 additional cases of heart disease per 10,000 women with migraine aura. Mark Gudesblatt, a neurologist at South Shore Neurologic Associates, said, “It’s an important study because it tells you not to take these things lightly” (Talan, Long Island Newsday, 7/19).

Study Authors Did Not Report Financial Ties

The six authors of the study did not disclose to JAMA that they have consulted for, or received research funds from, pharmaceutical companies that manufacture treatments for heart disease or migraines, the AP/Miami Herald reports. JAMA in January implemented a policy that requires financial disclosures from researchers before acceptance of studies for publication, and an editorial published in the journal last week indicated that “JAMA was getting tougher as a result of … recent breaches” of the policy, the AP/Herald reports. JAMA Editor in Chief Catherine DeAngelis said that journal editors were not aware of the financial ties until the Associated Press informed her about them last week. The authors said they did not report the financial ties because the study does not promote a treatment. JAMA on Tuesday published online a letter from the authors of the study to explain their failure to disclose the financial ties, as well as a response from DeAngelis and a correction. DeAngelis said that the letter, her response and the correction will appear in a future print edition of JAMA. “Let me decide what’s pertinent or not,” DeAngelis said, adding, “Authors should always err on the side of full disclosure.” Kurth in an interview said that the financial ties “do not represent a conflict of interest” (Tanner, AP/Miami Herald, 7/19).