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Migraine research in focus

By Mindo - 19th Jun 2019

Priscilla Lynch presents a round-up of recent topical international research in the area of migraine

Migraines may increase risk of pregnancy complications

Women with migraine and their offspring have greater risks of several adverse pregnancy outcomes than women without migraine, according to the findings of a new study published in Headache.

The Danish study investigated the associations between maternal migraine and risks of adverse pregnancy outcomes in the mother, and birth, neonatal and postnatal outcomes in the offspring using Danish population registries to assemble a cohort of pregnancies among women with migraine and an age – and conception year – matched comparison cohort of pregnancies among women without migraine (from 2005‐2012). They identified 22,841 pregnancies among women with migraine and 228,324 matched pregnancies among women without migraine.

Migraine was associated with an increased risk of pregnancy-associated hypertension disorders (adjusted prevalence ratios (aPR): 1.50 [95% confidence interval (CI): 1.39-1.61]) and miscarriage (aPR: 1.10 [95% CI: 1.05‐1.15]).

Migraine was also associated with an increased prevalence of low birth weight (aPR: 1.14 [95% CI: 1.06‐1.23]), preterm birth (aPR: 1.21 [95% CI: 1.13‐1.30]) and Caesarean delivery (aPR: 1.20 [95% CI: 1.15‐1.25]), but not of small for gestational age offspring (aPR: 0.94 [95% CI: 0.88‐0.99]) and birth defects (aPR: 1.01 [95% CI: 0.93‐1.09]).

Offspring prenatally exposed to maternal migraine had elevated risks of several outcomes in the neonatal and postnatal period, including intensive care unit admission (aRR: 1.22 [95% CI: 1.03‐1.45]), hospitalisation (aRR: 1.12 [95% CI: 1.06‐1.18]), dispensed prescriptions (aRR: 1.34 [95% CI: 1.24‐1.45]), respiratory distress syndrome (aRR: 1.20 [95% CI: 1.02‐1.42]), and febrile seizures (aRR: 1.27 [95% CI: 1.03‐1.57), but not of death (aRR: 0.67 [95% CI: 0.43‐1.04]) and cerebral palsy (aRR: 1.00 [95% CI: 0.51‐1.94]).

Treated migraine was not linked with higher risks of adverse outcomes compared with untreated migraine. This suggests that migraine itself, rather than its treatment, is associated with pregnancy complications.

“Migraine is a disabling condition, common among women of reproductive age. Accumulating evidence shows that migraine in pregnancy may lead to several adverse outcomes in the mother and child, but treatment may alleviate these risks,” said lead author Dr Nils Skajaa, Epidemiologist Department of Clinical Epidemiology, Aarhus University Hospital.

Analysis examines migraine’s link to higher stroke risk

Later onset of migraine with aura (MA), as opposed to onset before the age of 50 years, is associated with an increased risk of stroke, a new US study suggests.

MA was associated with an increased risk of ischaemic stroke in the Atherosclerosis Risk in Communities (ARIC) study, but a recent post-hoc analysis published in Headache reveals unexpected results suggesting that onset of such migraines before age 50 years is not associated with such risk. Later onset of MA was linked with a higher risk, however.

The analysis included 447 MA migraineurs and 1,128 migraineurs without aura (MO) among 11,592 participants (elderly men and women with a history of migraine).

Over 20 years, there was a two-fold increased risk of ischaemic stroke when the age of MA onset was 50 years or older when compared to those with no headache. MA onset before 50 years old was not associated with stroke. Also, MO was not associated with increased stroke risk regardless of age of onset.

In the elderly population in this study, the absolute risk for stroke in MA was 37/447 (8.27 per cent) and in MO was 48/1,128 (4.25 per cent).

“I think clinically this is very meaningful, as many individuals with a long history of migraine are concerned about their stroke risk, especially when they get older and when they have other cardiovascular disease risks,” said lead author Dr X Michelle Androulakis, Chief of Neurology at WJB Dorn VA Medical Centre, in South Carolina, US. “Cumulative effects of migraine alone – with onset of migraine before age of 50 – did not increase stroke risk in late life in this study cohort. On the contrary, the recent onset of migraine at or after age 50 is associated with increased stroke risk in late life.”

This study underscores the importance of the age of onset of MA in assessing stroke risk in older migraineurs.

Study: Men with migraine may have higher oestrogen levels

While it has been known that oestrogen plays a role in migraine for women, new research shows that the female sex hormone may also play a role in migraine for men, according to a small study published in an online issue of Neurology, the medical journal of the American Academy of Neurology.

During their childbearing years, women are three times more likely to have migraine than men.

“Previous research has found that levels of oestrogen can influence when women have migraines and how severe they are, but little is known about whether sex hormones also affect migraine in men,” said study author Dr W P J van Oosterhout of Leiden University Medical Centre in the Netherlands. “Our research found increased levels of oestrogen in men with migraine, as well as symptoms of lower levels of testosterone.”

The study involved 17 men with an average age of 47 years who had a migraine an average of three times a month. None were taking medication known to affect hormone levels. They were compared to 22 men without migraine. All participants were of healthy weight, matched for age and body mass index.

Researchers measured the levels of both estradiol, an oestrogen, and testosterone in the blood. They took four blood samples from each participant on a single day, each three hours apart. For those with migraine, the first blood samples were taken on a non-migraine day and then each day thereafter until the participant had a migraine.

They found that men with migraine had higher levels of oestrogen between migraines, 97 picomoles per litre (pmol/L), compared to 69pmol/L in men without migraine, while testosterone levels were similar for both groups. This resulted in a lower ratio of testosterone to oestrogen between migraines, 3.9, compared with men without migraine, 5.0. Testosterone levels did increase 24 hours before a migraine in men who experienced pre-migraine symptoms like fatigue, muscle stiffness and food cravings.

In addition, participants were surveyed about symptoms that indicated they may have a relative deficiency in testosterone, such as mood, energy and sexual disorders, and researchers found that men with migraine more frequently reported such symptoms and the symptoms were more often severe. A total of 61 per cent of men with migraine reported such symptoms, compared to 27 per cent of men without migraine.

“Further studies are needed in larger populations to validate our findings,” said Dr Van Oosterhout. “The exact role of oestrogen in men with migraine, and whether fluctuations in oestrogen may be associated with migraine activity, like they are in women, needs to be fully investigated.”

Smartphone relaxation app helps some manage migraine

Migraine sufferers who used a smartphone-based relaxation technique at least twice a week experienced on average four fewer headache days per month, a new US study shows.

Developed in part by researchers at New York University School of Medicine, the app, called RELAXaHEAD, guides patients through progressive muscle relaxation (PMR). In this form of behavioural therapy, patients alternately relax and tense different muscle groups to reduce stress.

The study authors said their work, published online in the journal Nature Digital Medicine, is the first to evaluate the clinical effectiveness of an app for treating migraine, and adding an app to standard therapies (such as oral medications) under the supervision of a doctor.

“Our study offers evidence that patients may pursue behavioural therapy if it is easily accessible, they can do it on their own time, and it is affordable,” said study senior investigator and neurologist Dr Mia Minen. “Clinicians need to rethink their treatment approach to migraine because many of the accepted therapies, although proven to be the current, best course of treatment, aren’t working for all lifestyles.”

While migraine patients are often prescribed behavioural therapy alongside drugs, they often do not pursue the therapy even after a doctor’s recommendation because of the expense and inconvenience, says Dr Minen, an Assistant Professor of Population Health and Chief of Headache Research at NYU Langone Health. “Oftentimes they end up only taking medications,” she said.

To see if an app might increase compliance, the research team analysed app use by 51 confirmed migraine patients at NYU Langone Health, all of whom owned smartphones. Participants were asked to use the app for 90 days and to keep a daily record of the frequency and severity of their headaches, while the app kept track of how long and often patients used PMR.

Study participants, on average, had 13 headache days per month, ranging between four and 31. Over a third, 39 per cent, of patients in the study also reported having anxiety, and 30 per cent had depression.

PMR therapy utilising the RELAXaHEAD app dropped to 51 per cent after six weeks, and to 29 per cent after three months. The study authors, who anticipated a gradual decrease in the use of the app, next plan to identify potential ways to encourage more frequent sessions. They also plan to study the best ways to introduce the app into their clinical practices.

Dr Minen says that taken as a whole, the study results suggest that accessible smartphone technologies “can effectively teach patients lifelong skills needed to manage their migraines”.

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