Brain fluid dynamics key to migraine mysteries, new therapies

 New research describes for the first time how a spreading wave of disruption and the flow of fluid in the brain triggers headaches, detailing the connection between the neurological symptoms associated with aura and the migraine that follows. The study also identifies new proteins that could be responsible for headaches and may serve as foundation for new migraine drugs.

"In this study, we describe the interaction between the central and peripheral nervous system brought about by increased concentrations of proteins released in the brain during an episode of spreading depolarization, a phenomenon responsible for the aura associated with migraines," said Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the new study, which appears in the journal Science. "These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies."t is estimated that one out of 10 people experience migraines and in about a quarter of these cases the headache is preceded by an aura, a sensory disturbance that can includes light flashes, blind spots, double vision, and tingling sensations or limb numbness. These symptoms typically appear five to 60 minutes prior to the headache.

The cause of the aura is a phenomenon called cortical spreading depression, a temporary depolarization of neurons and other cells caused by diffusion of glutamate and potassium that radiates like a wave across the brain, reducing oxygen levels and impairing blood flow. Most frequently, the depolarization event is located in the visual processing center of the brain cortex, hence the visual symptoms that first herald a coming headache.

While migraines auras arise in the brain, the organ itself cannot sense pain. These signals must instead be transmitted from the central nervous system -- the brain and spinal cord -- to the peripheral nervous system, the communication network that transmits information between brain with the rest of the body and includes sensory nerves responsible for sending information such as touch and pain. The process of communication between the brain and peripheral sensory nerves in migraines has largely remained a mystery.

Fluid Dynamics Models Shed Light on Migraine Pain Origins

Nedergaard and her colleagues at the University of Rochester and the University of Copenhagen are pioneers in understanding the flow of fluids in the brain. In 2012, her lab was the first to describe the glymphatic system, which uses cerebrospinal fluid (CSF) to wash away toxic proteins in the brain. In partnership with experts in fluid dynamics, the team has built detailed models of how the CSF moves in the brain and its role in transporting proteins, neurotransmitters, and other chemicals.

Source: ScienceDaily

Study finds no link between migraine and Parkinson's disease

 Contrary to previous research, a new study of female participants finds no link between migraine and the risk of developing Parkinson's disease. The study is published in the August 21, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"These results are reassuring for women who have migraine, which itself causes many burdens, that they don't have to worry about an increased risk of Parkinson's disease in the future," said study author Tobias Kurth, MD, ScD, from the Institute of Public Health at Charité -- Universitätsmedizin Berlin in Germany.

The study involved 39,312 female participants with an average age of 55 at the start of the study.

A total of 7,321 of the participants reported current or past migraine at the start of the study.

The participants were then followed for an average of 22 years.

During that time, 685 people reported physician-diagnosed Parkinson's disease.

Of those, 128 were people who reported a history of migraine or active migraine, and 557 were people with no migraine.

After adjusting for other factors that could affect risk of developing Parkinson's disease as well as migraine, such as age, physical activity, alcohol use and smoking status, researchers found that people with migraine were no more likely to develop Parkinson's disease than those who did not have migraine.

This result did not change based on how frequently people had a migraine or whether they experienced an aura before the migraine.

An aura is a visual or other sensory disturbance that occurs before the migraine starts, such as seeing bright lights.

"Since this study involved only female health professionals who were primarily white people, more research is needed to determine whether the results will apply to other groups, including men, women and other races, ethnicities and gender identities," Kurth said.

Another limitation of the study is that participants self-reported information on migraine and Parkinson's disease, so it is possible that some information was not accurate. In addition, since Parkinson's disease is often not diagnosed until symptoms are advanced, it's possible that some participants may have developed Parkinson's disease after the end of the study.

Source: ScienceDaily

Drug may stop migraines before headache starts

 When taken at the first signs of a migraine, before headache pain begins, a drug called ubrogepant may be effective in helping people with migraine go about their daily lives with little or no symptoms, according to a new study published in the August 28, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study focused on people with migraine who could tell when an attack was about to happen, due to early symptoms such as sensitivity to light and sound, fatigue, neck pain or stiffness, or dizziness.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in the migraine process.

"Migraine is one of the most prevalent diseases worldwide, yet so many people who suffer from this condition do not receive treatment or report that they are not satisfied with their treatment," said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in Bronx, New York, and Fellow of the American Academy of Neurology. "Improving care at the first signs of migraine, even before headache pain begins, can be a key to improved outcomes. Our findings are encouraging, suggesting that ubrogepant may help people with migraine function normally and go about their day."

The study involved 518 participants who had migraine for at least one year and two to eight migraine attacks per month in the three months before the study. All of the participants regularly experienced signs that a migraine would be starting within the next few hours. Participants were asked to treat two attacks during a two-month period.

Researchers divided participants into two groups. The first group received a placebo for their first set of pre-headache symptoms of migraine, followed by taking 100 milligrams (mg) of ubrogepant for their second instance of symptoms. The second group took ubrogepant for the first instance and placebo for the second instance.

Participants evaluated limitations on their activity in their diary using a scale ranging from zero to five, with 0 meaning "not at all limited -- I could do everything"; 1, "a little limited"; 2, "somewhat limited"; 3, "very limited"; or 4, "extremely limited."

Twenty-four hours after taking the drug or a placebo, 65% of people who took ubrogepant reported themselves as "not at all limited -- I could do everything," or "a little limited," compared to 48% of those who took the placebo.

Researchers found that as early as two hours post-medication, people who took the drug were 73% more likely to report that they had "no disability, able to function normally," than those who took the placebo.

"Based on our findings, treatment with ubrogepant may allow people with migraine who experience early warning signs before a migraine occurs to quickly treat migraine attacks in their earliest stages and go about their daily lives with little discomfort and disruption," said Lipton. "This could lead to an improved quality of life for those living with migraine."

Source: ScienceDaily

Propranolol may reduce ischemic stroke risk in women with migraines

 A medication often used to treat high blood pressure and prevent migraines was associated with a reduction in ischemic stroke risk among women using the drug for migraine prevention, according to a preliminary study to be presented at the American Stroke Association's International Stroke Conference 2025. The meeting is in Los Angeles, Feb. 5-7, 2025, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Propranolol, a beta blocker medication used for treating high blood pressure and preventing migraines, had a stronger protective effect for ischemic stroke risk in women with migraine, particularly those without aura. However, the medication did not have the same protective effect on men.

Migraine headaches are common in the general population, but they occur three times more often in women than in men. This debilitating condition is associated with an increased risk of stroke. While the beta blocker propranolol can be used to prevent migraines, its effectiveness in reducing overall stroke risk is still uncertain.

"Migraine is an often-ignored risk factor for cardiovascular issues. Until recently, preventive treatments for people who have migraines were not available," said lead study author Mulubrhan Mogos, Ph.D., M.Sc., FAHA, an assistant professor at Vanderbilt University School of Nursing in Nashville, Tennessee. "Many women suffer from migraines, and it's important to note that propranolol may be beneficial for these women, particularly those who experience migraine without aura. This is an important discovery for those dealing with migraines."

Mogos also noted that migraine disproportionately affects women from historically under-resourced communities, and this disparity may impact the ability to achieve education goals or maintain stable employment, creating a vicious cycle. While new treatments have proven effective, they may not be accessible to women in these groups due to high costs.

For the study, researchers reviewed more than 3 million electronic health records from two large databases. In separate analyses, researchers identified people with migraine who developed stroke and those with migraine who did not develop stroke (control group). They then assessed whether the individuals were treated with propranolol for migraine and whether that treatment had impacted stroke risk.

"We initially looked at overall stroke and then ischemic stroke specifically. We refined our analysis further by controlling for possible confounders and found the association is significant and stronger for ischemic stroke," Mogos said.

After adjusting for potential variables, such as demographics (age, sex, race), other conditions (high blood pressure, diabetes, etc.) and hormonal factors (use of birth control, pregnancy -- considered separately for each woman) that might affect results the analysis found:

• Propranolol was significantly associated with a reduced risk of ischemic stroke in women with migraine, particularly in those without aura. The risk of developing a stroke was 52% lower for women taking the medication in one database analysis and 39% lower in the other. No stroke risk reduction was seen in men in either analysis group.
• The protective effect of propranolol was stronger for ischemic stroke and in women with migraine without aura. Migraine aura can include disturbances, such as flashing lights, blind spots, zigzag patterns or seeing colored spots. Other symptoms include tingling or numbness in the face or hands, difficulty speaking, dizziness or confusion.
• Secondary analyses showed lower overall stroke rates in women taking propranolol at multiple time points in both databases.

Source: ScienceDaily

New drug to prevent migraine may start working right away

 A drug recently approved to prevent migraine may start working right away, according to a study published in the December 23, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study looked at the drug atogepant, which is a calcitonin gene-related peptide (CGRP) receptor antagonist taken by mouth.

"With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective," said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and a Fellow of the American Academy of Neurology. "Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical."

In the study, people taking the drug atogepant were less likely to have a migraine on the first day of taking the drug compared to those taking a placebo. They also had fewer migraines per week during each of the first four weeks of the study and fewer migraines during the study overall than those taking a placebo.

For this study, researchers looked at the data from three trials on the safety and effectiveness of atogepant over 12 weeks to focus on how rapidly improvements appeared. The ADVANCE trial, which enrolled people with episodic migraine, had 222 people taking the drug and 214 taking placebo. The ELEVATE trial, which enrolled people with episodic migraine who had previously not responded well to other oral preventive treatments, had 151 on the drug and 154 on placebo. The PROGRESS trial, which enrolled people with chronic migraine, had 256 on the drug and 246 on placebo.

People with episodic migraine experience up to 14 migraine days per month. People with chronic migraine experience at least 15 days with headache per month, with at least eight days being characteristic of migraine.

On the first day of the study, 12% of those taking the drug in the first trial, the ADVANCE trial had a migraine, compared to 25% of those taking placebo. In the second trial, the ELEVATE trial, the numbers were 15% and 26%. For the third trial, the PROGRESS trial, the numbers were 51% and 61%.

When researchers adjusted for other factors that could affect the rate of migraine, they found that people taking the drug were 61% less likely to have a migraine in the first trial, 47% less likely in the second trial, and 37% less likely in the third trial.

For the first two trials, the people taking atogepant had an average of one fewer day with migraine per week, compared to an average of less than one-half day fewer per week for those taking the placebo. For the third trial, average migraine days per week declined by about 1.5 days for those taking the drug compared to about one day for those taking the placebo.

Source: ScienceDaily

Drug may prevent some migraine attacks in children and teens

 For children and teens living with migraine, there may be a new preventive treatment, according to a preliminary study released today, February 26, 2025, that will be presented at the American Academy of Neurology's 77th Annual Meeting taking place April 5-9, 2025, in San Diego and online. Researchers found the drug zonisamide, which has been used to treat seizures, may reduce migraine days in this age group. This study does not prove that zonisamide reduces migraine days; it only shows an association.

"Migraine disease is debilitating and can lead to kids having to miss school and other activities," said author Anisa Kelley, MD, of Northwestern University Feinberg School of Medicine in Chicago."

Currently, there is only one FDA-approved migraine preventative medication for this age group. Our results are encouraging, showing zonisamide may be another option for reducing migraine attacks."

For the study, researchers reviewed health records at one institution.

They identified 256 children and teens who had been diagnosed with migraine and prescribed preventative zonisamide.

Of these participants, 28% had difficult-to-treat migraine, which was defined as having migraine disease unsuccessfully treated with two or more previous medications.

Researchers documented the number of headache days per month for each participant both before and after starting zonisamide.

They then divided participants into three subgroups based on how long they took the medication before a follow-up visit with a physician.

The first group followed up in the first month, the second group within two to six months and the third group, after six months.

For all participants, the median number of headache days per month reduced from 18 to six at the first follow-up visit.

When comparing between the groups, the subgroup that followed up within two to six months had the largest reduction with a median decrease of six headache days per month.

Kelley noted that the data suggested the drug was most effective after at least two months of use.

The data also suggested that the drug was effective for both those with difficult-to-treat migraine disease and those without.

"It's very exciting that we may have an effective way to treat difficult migraine disease in children and teens, however it's important to note that our study did have limitations," said Kelley.

"For instance, our study did not compare people taking the medication to people who did not take the medication. Future studies are needed with control groups to confirm our results."

Source: ScienceDaily

Good news for people with migraine who take drugs before or during pregnancy

 There's good news for people with migraine who take common drugs before or during pregnancy -- a new study found no increase in neurodevelopmental disorders such as autism and ADHD in their children. The study, which looked at drugs used for migraine attacks called triptans, is published on May 21, 2025, online in Neurology®, the medical journal of the American Academy of Neurology.

The study does not prove that there is a link between these drugs and neurodevelopment disorders.

"These results are encouraging for people with migraine, who may be taking these drugs before they even know that they are pregnant, and this is helpful information for their physicians, who can make more informed decisions about treating people with debilitating migraine attacks," said study author Hedvig Nordeng, PhD, of the University of Oslo in Norway.

For the study, researchers used health registry records for the entire Norwegian population and identified 26,210 pregnancies in female participants with migraine at the start of pregnancy. Of those, 21,281 people, or over 80%, had taken triptans in the year before they became pregnant and 4,929 of those with migraine had not taken any triptans during that time. For those who took the drugs, researchers divided them into four groups: people who had low use of triptans and stopped using them before pregnancy (42%); people who increased using triptans six months before pregnancy and stopped using them in early pregnancy (31%); people who had moderate triptan use before pregnancy and continued into early pregnancy (21%); and people who used triptans before and during pregnancy (6%).

Then researchers followed the children born for an average of eight years and up until they were 14 years old for some. They checked health registries for diagnoses of neurodevelopmental disorders including autism spectrum disorder, behavioral disorders, learning and intellectual disabilities, speech and language and developmental coordination disorders and attention deficit hyperactivity disorder (ADHD).

Overall, 1,140 children, or 4.3%, were diagnosed with a neurodevelopmental disorder during the study. The most common were ADHD and speech and language disorders. A total of 2.2% of the children of people with the highest use of triptans were diagnosed with ADHD, compared to 2.1% of the children of people with migraine who did not use the drugs. A total of 1.1% of the children of people with the highest use of the drugs were diagnosed with speech and language disorders, compared to 1.0% of children of people who did not use the drugs. When researchers adjusted the results to account for other factors that could affect the risk of neurodevelopmental disorders, such as a parent having a neurodevelopmental disorder, folic acid intake or use of other drugs such as opioids or antidepressants, they found no increased risk for neurodevelopmental disorders among children exposed to triptans prenatally."Migraine affects almost one in five of people of childbearing age," Nordeng said. "While symptoms often improve during pregnancy, about 8% of people experience worsening attacks during pregnancy, which can lead to increased risks of both maternal and fetal complications, so it's vital to have treatment options available."

A limitation of the study was that researchers did not verify that people took their migraine medications, only that they filled their prescriptions, so the actual drug exposure may be different than the estimates.

Source: ScienceDaily