Posts tagged migraines
Articles and news from the latest research reports.
Genetic Mutation Linked with Typical Form of Migraine
A research team led by a Howard Hughes Medical Institute investigator at the University of California, San Francisco has identified a genetic mutation that is strongly associated with a typical form of migraine.
In a paper published on May 1 in Science Translational Medicine, the team linked the mutation with evidence of migraine in humans, in a mouse model of migraine and in cell culture in the laboratory.
The mutation is in the gene known as casein kinase I delta (CKIdelta).
“This is the first gene in which mutations have been shown to cause a very typical form of migraine,” said senior investigator Louis J. Ptáček, an investigator at HHMI and a professor of neurology at UCSF. “It’s our initial glimpse into a black box that we don’t yet understand.”
Migraine, the causes of which are still unknown, affects 10 to 20 percent of all people, and causes “huge losses in productivity, not to mention immense suffering,” said Ptáček. Typical symptoms include a pounding headache; lowered pain threshold; hypersensitivity to mild stimuli including sound and touch; and aura, which Ptáček describes as “a visual sensation that presages the headache to come.”
The paper presents both clinical and basic scientific evidence that the mutation causes migraine.
In the study, the scientists first analyzed the genetics of two families in which migraine was common, and found that a significant proportion of migraine sufferers in the families either had the mutation or were the offspring of a mutation carrier.
In the laboratory, the team demonstrated that the mutation affects the production of the casein kinase I delta enzyme, which carries out a number of vital functions in the brain and body. “This tells us that the mutation has real biochemical consequences,” said Ptáček.
The scientists then investigated the effects of the mutation in a line of mice that carry it. “Obviously, we can’t measure headache in a mouse,” Ptáček noted, “but there are other things that go along with migraine that we can measure.”
Pain threshold, explained Ptáček, can be lowered in mice by the administration of nitroglycerin. The mutant mice had a significantly lower threshold for nitroglycerin-induced peripheral pain than did normal mice.
Another piece of evidence was cortical spreading depression (CSD), a wave of electrical “silence” in the brain that follows electrical stimulation, spreading out from the point of stimulation in a predictable pattern. The researchers found that the mutant mice had a significantly lower electrical threshold for the induction of CSD.
The CSD experiments are “especially intriguing,” said Ptáček, because it is known that CSD spreads through the brain at 3 millimeters per minute. “Functional brain imaging has shown that in the occipital lobes of people with migraine aura, changes in blood flow spread at the same rate.”
Finally, Ptáček and his team found that astrocytes – brain cells that are essential to neuronal functioning and health – from the brains of mutant mice showed increased calcium signaling compared with astrocytes from the brains of normal mice.
“This is significant because we think astrocyte functioning is very, very relevant to migraine,” said Ptáček. “This is an enzyme, and so it modifies proteins. The question is, which protein or proteins does it modify that is relevant to migraine? How does it change astrocyte activity?”
The research “puts us one step closer to understanding the molecular pathway to pain in migraine,” he said. “And, as we come to a clearer understanding, we can start thinking about better therapies. Certain molecules might be targets for new drugs.” There are good drugs now, said Ptáček, “but they only help some patients, some of the time. The need for better treatments is huge.”
The CKIdelta mutation is “far from the only mutation likely to be associated with migraine,” Ptáček cautioned. “There are likely several, in different combinations in different people. This is simply the first one we’ve found.”
MRI shows brain abnormalities in migraine patients
A new study suggests that migraines are related to brain abnormalities present at birth and others that develop over time. The research is published online in the journal Radiology.
Migraines are intense, throbbing headaches, sometimes accompanied by nausea, vomiting and sensitivity to light. Some patients experience auras, a change in visual or sensory function that precedes or occurs during the migraine. More than 300 million people suffer from migraines worldwide, according to the World Health Organization.
Previous research on migraine patients has shown atrophy of cortical regions in the brain related to pain processing, possibly due to chronic stimulation of those areas. Cortical refers to the cortex, or outer layer of the brain.
Much of that research has relied on voxel-based morphometry, which provides estimates of the brain’s cortical volume. In the new study, Italian researchers used a different approach: a surface-based MRI method to measure cortical thickness.
"For the first time, we assessed cortical thickness and surface area abnormalities in patients with migraine, which are two components of cortical volume that provide different and complementary pieces of information," said Massimo Filippi, M.D., director of the Neuroimaging Research Unit at the University Ospedale San Raffaele and professor of neurology at the University Vita-Salute’s San Raffaele Scientific Institute in Milan. "Indeed, cortical surface area increases dramatically during late fetal development as a consequence of cortical folding, while cortical thickness changes dynamically throughout the entire life span as a consequence of development and disease."
Dr. Filippi and colleagues used magnetic resonance imaging (MRI) to acquire T2-weighted and 3-D T1-weighted brain images from 63 migraine patients and 18 healthy controls. Using special software and statistical analysis, they estimated cortical thickness and surface area and correlated it with the patients’ clinical and radiologic characteristics.
Compared to controls, migraine patients showed reduced cortical thickness and surface area in regions related to pain processing. There was only minimal anatomical overlap of cortical thickness and cortical surface area abnormalities, with cortical surface area abnormalities being more pronounced and distributed than cortical thickness abnormalities. The presence of aura and white matter hyperintensities—areas of high intensity on MRI that appear to be more common in people with migraine—was related to the regional distribution of cortical thickness and surface area abnormalities, but not to disease duration and attack frequency.
"The most important finding of our study was that cortical abnormalities that occur in patients with migraine are a result of the balance between an intrinsic predisposition, as suggested by cortical surface area modification, and disease-related processes, as indicated by cortical thickness abnormalities," Dr. Filippi said. "Accurate measurements of cortical abnormalities could help characterize migraine patients better and improve understanding of the pathophysiological processes underlying the condition."
Additional research is needed to fully understand the meaning of cortical abnormalities in the pain processing areas of migraine patients, according to Dr. Filippi.
"Whether the abnormalities are a consequence of the repetition of migraine attacks or represent an anatomical signature that predisposes to the development of the disease is still debated," he said. "In my opinion, they might contribute to make migraine patients more susceptible to pain and to an abnormal processing of painful conditions and stimuli."
The researchers are conducting a longitudinal study of the patient group to see if their cortical abnormalities are stable or tend to worsen over the course of the disease. They are also studying the effects of treatments on the observed modifications of cortical folding and looking at pediatric patients with migraine to assess whether the abnormalities represent a biomarker of the disease.
(Source: eurekalert.org)
Choosing Wisely: AAN Cites Five Things to Question
In 2012, the AAN joined the Choosing Wisely campaign, a project initiated by the American Board of Internal Medicine (ABIM) Foundation to promote appropriate medical decision-making and the stewardship of health care resources. The campaign is designed to help consumers and physicians engage in conversations about the overuse of particular tests, procedures, and treatments and to help patients make smart and effective care choices.
In February 2013, the AAN participated in a news conference with the ABIM Foundation and Consumer Reports, where medical specialties announced their lists of the top five questionable tests and procedures each selected for patients and physicians to consider.
Read AAN’s Five Things Physicians and Patients Should Question
The AAN’s complete recommendations were published online ahead of print in the February 21, 2013, issue of Neurology®.
How Neurology Tests and Procedures Were identified
The AAN established a Choosing Wisely Working Group to develop its list of recommendations. Members of this group were selected to broadly represent varying practice settings and neurological subspecialties. Neurologists with expertise in evidence-based medicine and a broad range of subspecialty disciplines were also included. The working group solicited recommendations from AAN members, which were then rated based upon their judgments of harm and benefit that would result based upon compliance with the recommendation. Based on committee voting and a literature review, candidate recommendations were sent to relevant AAN sections, committees, specialty societies and patient advocacy groups for review and comment. The working group reviewed this feedback and voted on the final top five recommendations, which were approved by the AAN Practice Committee and Board of Directors.
Lightning May Trigger Migraine Headaches
Migraine sufferers know that a variety of influences—everything from stress to hunger to a shift in the weather—can trigger a dreaded headache. A new study published in the journal Cephalalgia, though, suggests that another migraine trigger could be an unexpected atmospheric condition—a bolt of lightning.
As part of the study, Geoffrey Martin of the University of Cincinnati and colleagues from elsewhere asked 90 chronic migraine sufferers in Ohio and Missouri to keep detailed daily diaries documenting when they experienced headaches for three to six months. Afterward, they looked back over this period and analyzed how well the occurrence of headaches correlated with lightning strikes within 25 miles of the participants’ houses, along with other weather factors such as temperature and barometric pressure.
Their analysis found that there was a 28 precent increased chance of a migraine and a 31 precent chance of a non-migraine (i.e. less severe) headache on days when lightning struck nearby. Since lightning usually occurs during thunderstorms, which bring a host of other weather events—notable changes in barometric pressure—they used mathematical models to parse the related factors and found that even in the absence of other thunderstorm-related elements, lightning alone caused a 19 percent increased chance of headaches.
Despite these results, it’s probably a bit premature to argue that lightning is a definitive trigger of migraines. For one, a number of previous studies have explored the links between weather and migraine headaches, and the results have been unclear. Some have suggested that high pressure increases the risk of headaches, while others have indicated that low pressure increases the risk as well. Other previous studies, in fact, have failed to find a link between migraines and lightening, in particular.
NuPathe’s Patch for Migraine Wins FDA Approval
Adults with migraine will soon have a new treatment option — Zecuity, a transdermal, battery-powered sumatriptan patch.
NuPathe, maker of the patch, said the FDA has approved the single-use patch to treat headache pain and nausea caused by migraine, with or without aura.
The patch is applied to the upper arm or thigh during a migraine and can deliver 6.5 mg of sumatriptan over the course of 4 hours once activated by push button.
The treatment system was approved based on the results of a phase III, placebo-controlled trial of 800 patients that showed the sumatriptan delivery method was safe and effective, the drugmaker said in a statement.
The FDA failed to approve a NuPathe application for a transdermal sumatriptan patch called Zelrix in August 2011.
In a complete response letter, the agency asked the company for additional data on Zelrix, citing concerns over the patch’s safety, chemistry, and manufacturing. The FDA’s approval of Zecuity may obviate the need for those additional studies.
The device is contraindicated in patients with heart disease, a history of heart disease or stroke, peripheral vascular disease, transient ischemic attack, blood circulation problems, uncontrolled blood pressure, basilar migraines, contraindication to sumatriptan or parts of the device, or Wolff-Parkinson-White syndrome or similar heart rhythm disturbances.
The system should not be used if taken within 24 hours of using another migraine medication or within 2 weeks of using a monoamine oxidase-A inhibitor.
Triptans, such as sumatriptan, can cause serotonin syndrome, which can be exacerbated when used with certain antidepressants.
Patients with heart disease, a family history of heart disease, stroke, high cholesterol or diabetes, have gone through menopause, who smoke, have had epilepsy or seizures, or are pregnant, nursing, or thinking about becoming a parent should consult a healthcare professional before using Zecuity.
(Image: Corbis)
After nearly 10 years of follow-up of study participants who experienced migraines and who had brain lesions indentified via magnetic resonance imaging, women with migraines had a higher prevalence and greater increase of deep white matter hyperintensities (brain lesions) than women without migraines, although the number, frequency, and severity of migraines were not associated with lesion progression, according to a study appearing in the November 14 issue of JAMA. Also, increase in deep white matter hyperintensity volume was not significantly associated with poorer cognitive performance at follow-up.
Migraine affects up to 15 percent of the general population. “A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain,” according to background information in the article. White matter hyperintensities are associated with atherosclerotic disease risk factors, increased risk of ischemic stroke, and cognitive decline.
Kids who get migraine headaches are much more likely than other children to also have behavioral difficulties, including social and attention issues, and anxiety and depression. The more frequent the headaches, the greater the effect, according to research out now in the journal Cephalagia, published by SAGE.
Marco Arruda, director of the Glia Institute in São Paulo, Brazil, together with Marcelo Bigal of the Albert Einstein College of Medicine in New York studied 1,856 Brazilian children aged 5 to 11. The authors say that this is the first large, community based study of its kind to look at how children’s behavioural and emotional symptoms correlate with migraine and tension-type headaches (TTH), and to incorporate data on headache frequency.
Migraines currently affect about 20 percent of the female population, and while these headaches are common, there are many unanswered questions surrounding this complex disease. Previous studies have linked this disorder to an increased risk of stroke and structural brain lesions, but it has remained unclear whether migraines had other negative consequences such as dementia or cognitive decline. According to new research from Brigham and Women’s Hospital (BWH), migraines are not associated with cognitive decline.
This study is published online by the British Medical Journal (BMJ) on August 8, 2012. “Previous studies on migraines and cognitive decline were small and unable to identify a link between the two. Our study was large enough to draw the conclusion that migraines, while painful, are not strongly linked to cognitive decline,” explained Pamela Rist ScD, a research fellow in the Division of Preventive Medicine at BWH, and lead author on this study.
Source: BWH