Leah Lawrence

The use of novel, solid-state caloric vestibular stimulation (CVS) device significantly reduced the number of migraine days experienced by adult migraineurs, according to a new randomized, double-blind study published in 

In the study, 100 patients with episodic migraine without aura were randomly assigned to active treatment with the device or to a control placebo arm. Treatments were self-administered by patients twice daily for 3 months.* Patients were instructed to separate treatments by at least an hour. The primary endpoint of the study was the change in monthly migraine days from baseline to the third treatment month.

Patients assigned to treatment with the CVS device had a net therapeutic gain of –2.8 migraine days (

=.012) vs the control arm. At baseline, patients assigned to CVS had a median of 7.7 migraine days; that decreased to 3.9 days after 3 months of treatment. In comparison, control patients had a baseline level of 6.9 migraine days, and after 3 months, that rate decreased only by 1.1 days. In addition, patients assigned to CVS reported a decrease in the use of acute migraine medications.

No serious or unexpected adverse events were reported in either study arm.

“These results indicate that CVS therapy addresses the existing need for new prophylactic therapies for episodic migraine,” Wilkinson and colleagues

 wrote. “This approach appears to be both efficacious and very well tolerated, and further clinical testing is warranted.”

*During active treatment, patients lay on a wedge pillow to help maximize the thermoconvective effect of CVS. Treatments-both active and placebo-were administered via a headset equipped with independently controlled thermoelectric devices attached to aluminum earpieces that fit inside the ear canal. During active treatment, a time-varying saw-tooth waveform was delivered.

1. Wilkinson D, Ade KK, Rogers LL, et al. Preventing episodic migraine with caloric vestibular stimulation: a randomized controlled trial. 

Articles

This study showed that a novel CVS device provided effective, well-tolerated adjuvant prophylactic therapy for a group of adults with episodic migraine.

Caloric Vestibular Stimulation Device Prevented Episodic Migraine

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Although male and female high school athletes had similar knowledge of sports-related concussion (SRC) signs and symptoms, females were more likely to report their concussive symptoms to an authoritative figure, according to the results of a study published in the 

“For both sexes, blurred visions, loss of consciousness, and dizziness were the most recognized SRC symptoms, whereas memory loss, nausea, and fogginess were the most commonly unrecognized SRC symptoms,” wrote Jessica Wallace, PhD, of Youngstown State University, Ohio, and colleagues. “High school athletic department staffs should emphasize symptom knowledge by explaining what each symptom means and incorporate theory-based interventions to overcome stigmas within the male sport culture. Moreover, all school sport programs must encourage optimal reporting environments in which every male or female athlete feels safe and confident in reporting symptoms of SRC to an authoritative figure.”

During the last decade, there has been increased awareness of concussion, and SRC is now recognized as a public health concern among young athletes, according to the study. When SRC goes unidentified or unreported, they can lead to increased risk of subsequent injury and long-term consequences for the injured athlete.

With this study, Wallace and colleagues examined sex differences in knowledge of SRC symptoms and whether males or females were more likely to report suspected SRC.

In the cross-sectional study, 288 high school athletes (68.8% males) completed a validated survey about their knowledge of SRC. The mean age of respondents was 15.6. The survey included identifying symptoms of SRC from a list of 21 symptoms and reasons why athletes would not report their concussion. Knowledge scores ranged from 0 to 21, with 21 indicating greater knowledge. Included sports were football, wrestling, volleyball, basketball and soccer.

The majority of respondents had never sustained a concussion. The researchers found a sex difference in total concussion symptom knowledge (P=0.03). Female respondents had more total SRC symptom knowledge compared with males (average score of 15.06 vs. 14.36).

The most commonly known symptom of SRC was blurred vision, identified by more than 80% of males and females. Fogginess was identified least often.

The top three reasons for not reporting a concussion was similar between males and females:

Several reasons were identified why male athletes were more likely than females to not report a concussion:

They thought their coach would get mad (P<0.01)

Their teammates would think they were weak (P<0.01)

Their coach would think that they were weak (P=0.01)

It was the end of the season and they did not want to miss a game (P

They did not want to lose playing time (P<0.01)

Their team was going to be in the playoffs when it happened (P=0.05)

They did not want to let their team down (P=0.01)

“It is concerning that athletes are still not reporting SRCs because they do not identify them as being serious enough injuries to require medical attention. It is also worrisome that the failure to report a concussion due to fear of removal from play remains an obstacle that needs to be overcome in high school athletics,” the researchers wrote. “Even if concussion knowledge can be increased, the determination and competitive spirit of our athletes cannot be altered.”

Wallace J, et al. Sex differences in high school athletes’ knowledge of sport-related concussion symptoms and reporting behaviors. J Athl Train

The top three reasons for not reporting a concussion was similar between males and females.

Sports-Related Concussion: Barriers to Reporting

Treatment with the anti-calcitonin gene-related peptide (CGRP) drug erenumab resulted in a significantly reduction in the number of monthly migraine days for patients with chronic migraine, according to the results of a phase II study published in 

 Similar reductions were seen for patients assigned to either the 70-mg or the 140-mg dose.

“Because of its favorable safety, tolerability, and efficacy profile in this study, and its once-monthly administration, subcutaneous erenumab has the potential to increase real-world adherence to treatment in patients with chronic migraine,” wrote Stewart Tepper, MD, Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues. “This could address an important unmet need, because just 17–20% of patients with chronic migraine adhere to migraine preventive drugs after 1 year, and non-adherence can lead to worsening of the disorder.”

For several decades, studies have suggested a role for CGRP in migraine, and that targeting the CGRP pathway might help to prevent migraine. Tepper and colleagues conducted this study to determine if erenumab, a fully human monoclonal antibody against CGRP, could prevent migraine in patients with chronic migraine.

The study included patients aged 18 to 65 with chronic migraine, defined at 15 or more headache days per month of which eight or more were migraine days.

Patients were randomly assigned 3:2:2 to subcutaneous placebo (n=286), erenumab 70 mg (n=191), or erenumab 140 mg (n=190) every 4 weeks for 12 weeks. The primary endpoint was change in monthly migraine days from baseline to the last 4 weeks of the double-blind treatment.

At study initiation, patients had mean monthly migraine days of 18.2, 17.9, and 17.8 for the placebo, 70-mg, and 140-mg groups, respectively. Treatment with either dose of erenumab resulted in a 2.5-day greater reduction in monthly migraine days compared with placebo (average reduction of -6.6 vs. -4.2 days; P<0.0001).

“Reductions of headache frequency from baseline of more than 30% and by more than one day per month are generally thought to represent a clinically relevant change,” the researchers wrote. “The reductions in monthly migraine days in this study represent a change of more than 30%, and more than one day per month relative to patients receiving placebo.”

Of the 667 patients who underwent treatment, 637 completed therapy. Four patients withdrew because of adverse events (two in the placebo group and two in the 140-mg group). A similar percentage of patients in the placebo (39%), erenumab 70 mg (44%), and erenumab 140 mg (47%) groups reported adverse events. The most frequently reported events were injection-site pain, upper respiratory tract infection, and nausea. No serious adverse events resulted in treatment discontinuation.

In an editorial that accompanied the study, Maria Adele Giamberardino and Raffaele Costantini, of G D'Annunzio University of Chieti, Italy, wrote that erenumab may be a “promising new therapy for prevention of this highly problematic type of chronic pain.”

They added that selection criteria for patients in the study were strict and excluded patients with most medical comorbidities.

“Future studies should verify whether similar efficacy is maintained with erenumab in the general chronic migraine population, including patients with comorbidities, and whether interference or interactions occur in patients undergoing multiple treatments, especially those with increased risks such as for cardiovascular events, as in the case of concurrent hypertension,” they wrote.

Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial

Challenging chronic migraine: targeting the CGRP receptor

For several decades, studies have suggested a role for CGRP in migraine, and that targeting the CGRP pathway might help to prevent migraine.

CGRP-Targeting Erenumab for Chronic Migraine

Both overweight and underweight individuals are at increased risk for migraine compared with normal weight individuals, according to the results of a meta-analysis published recently in 

“The current study substantiates that obesity and underweight status are associated with an increased risk of migraine, and that age and sex are important covariates of this association,” wrote Bizu Gelaye, PhD, from the Harvard T.H. Chan School of Public Health, and colleagues. “These data suggest that clinicians treating migraine patients should be aware of this association.”

Obesity is considered a possible modifiable risk factor for migraine. Prior studies have shown that the association found between obesity and migraine was greater in younger individuals and in women. Therefore, Gelaye and colleagues hypothesized that age and sex might be important factors in the “migraine–obesity association and that differences in the strength of this association across studies were likely attributable to differences in study methodology.”

The analysis included data from 12 studies including 288,981 participants. Two studies included mostly participants aged 50 or older and the remaining studies were mostly younger participants.

Among the studies, the odds ratio for migraine associated with obesity (BMI of 30 or greater) varied from 0.55 to 2.56. In the pooled estimates, results of the age- and sex-adjusted model showed that compared with normal weight individuals, those with obesity had a 27% increased risk for migraine (odds ratio=1.27; 95% CI, 1.16-1.37; P<0.001). This association remained even after multivariate adjustments.

“While this increased risk is moderate (being of similar magnitude to the risk associated with ischemic heart disease and bipolar disorders), the recognition of this risk is important given that obesity is a potentially modifiable disease risk factor for migraine,” the researchers wrote. “Further, it supports the need for research to determine whether interventions to reduce obesity decrease the risk of migraine.”

The researchers also found that although the age- and sex-adjusted pooled migraine risk was increased in overweight individual (odds ratio=1.08; 95% CI, 1.04-1.12; P<0.001), the association was lost once the data were adjusted.

Finally, the age- and sex-adjusted pooled risk of migraine in those individuals considered underweight (BMI <18.5) was increased by 13% compared with normal weight individuals (odds ratio=1.13; 95% CI, 1.02-1.24; P<0.001).

“Taken together with obesity-related migraine risk, this finding supports that both excessive and insufficient adipose tissue is associated with an increased risk of the migraine,” the researchers wrote.

Body composition status and the risk of migraine: a meta-analysis

Researchers examined two possible risk factors for migraine that potentially can be modified – having obesity and being underweight.

Migraine Risk by Body Composition

Among young patients with ischemic stroke, migraine was associated with cervical artery dissection (CEAD), according to the results of a study published recently in 

“This association persisted after adjustment for traditional vascular risk factors, and it was apparent for the migraine subtype without aura more than for migraine with aura, for men more than for women, and for the younger rather than older age group,” wrote Valeria De Giuli, MD, of the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, UniversitÃ  degli Studi di Brescia, Brescia, Italia, and colleagues. “Our data support consideration of a history of migraine as a marker for increased risk of ischemic stroke caused by CEAD, as well as a putative susceptibility factor for CEAD, regardless of its clinical features.”

The study looked at 2,485 consecutive patients aged 18 to 45 with first-ever acute ischemic stroke taken from the Italian Project on Stroke in Young Adults. Frequency of migraine and presence or absence of aura was assessed. The researchers looked at presence of migraine in patients whose stroke was because of CEAD or from another cause and the characteristics of CEAD-related stroke with or without migraine.

Of the included patients, 13.4% had CEAD ischemic stroke. Migraine occurred more commonly in patients with CEAD stroke compared with non-CEAD stroke (30.8% vs. 24.4%; P=0.01). Data showed that the difference in incidence of migraine was mainly from migraine without aura (24.0% vs. 15.6%; P<0.001). In fact, compared with migraine with aura, migraine without aura was independently associated with CEAD-related stroke (odds ratio=1.74; 95% CI, 1.30-2.33). The association between migraine without aura and CEAD stroke was stronger in men (OR=1.99; 95% CI, 1.31-2.33) and in patients aged 39 or younger (OR=1.82; 95% CI, 1.22-2.71). Frequency of migraine with aura did not differ between the two groups.

“The mechanisms by which migraine might increase the individual propensity to CEAD remain unproven, but there are convincing arguments for common biological pathways underlying the 2 disorders,” the researchers wrote. “Among these, shared genetic susceptibility and endothelial dysfunction seem to be plausible.”

In an editorial that accompanied the study, Patrick D. Lyden, MD, of the department of neurology at Cedars-Sinai Medical Center, discussed several strengths of the study.

“The investigators assiduously searched for multiple stroke causes in each young patient and diligently recorded their observations. Rigorous work is needed to study patients with both migraine and dissection, compared with patients without either disease, and examine agnostically for biological mechanisms in common,” the researchers wrote. “Furthermore, there is the remaining chance that the association between migraine without aura and dissection is just that-chance. Future studies should focus not only on confirming the finding-which really seems robust given the large sample size and thorough evaluation-but also on analyzing biochemical or histologic features in common.”

Association between migraine and cervical artery dissection

. The Italian Project on Stroke in Young Adults. 

Migraine and the risk of carotid artery dissection in the IPSYS Registry. Are they related?

Is there a common biological pathway underlying ischemic stroke and migraine in young patients?

Migraine, Ischemic Stroke in Young Patients

Patients with migraine without aura experienced a long-term reduction in migraine recurrence after undergoing acupuncture compared with patients undergoing a sham procedure.

“True acupuncture manifested persisting superiority and clinically relevant benefits for at least 24 weeks in migraine prophylaxis, including reducing the number of migraine frequency and days with migraine, as well as decreasing pain intensity,” researchers led by Ling Zhao, PhD, of the Acupuncture and Tuina School at Chengdu University, China, and colleagues wrote in 

According to the researchers, multiple studies have shown that true acupuncture is more effective than sham acupuncture in reducing migraine intensity, frequency of attacks, and number of migraine days. However, data are lacking on whether acupuncture can prevent future migraine attacks.

To investigate, Zhao and colleagues conducted a 24-week randomized trial that randomly assigned 249 participants with migraine without aura aged 18 to 65 to true acupuncture or a sham procedure. A third group of participants was placed on a waiting list. Participants undergoing true acupuncture received treatment at four points and those undergoing a sham procedure had treatment at four points not thought to be active for acupuncture.

Participants underwent 4 weeks of treatment and 20 weeks of follow-up. The participants were asked to record migraines in a diary. The primary outcome was change in frequency of migraine attacks from baseline to week 16.

Overall, 245 participants were included in the intent-to-treat analysis and the majority were women. After follow-up, the mean change in frequency of migraines was significantly different among the three groups (P<0.001). Participants assigned to true acupuncture had a mean decrease in frequency of attacks of 3.2 compared with 2.1 for the sham procedure and 1.4 for the waiting list. This translated into a significant improvement for true vs. sham acupuncture (P<0.001) and compared with the waiting list (P<0.001).

In an editorial that accompanied the research, Amy A. Gelfand, MD, of the pediatric headache program at the University of California San Francisco, highlighted several limitations of the study, including the fact that the acupuncturists were not blinded and could have unintentionally communicated group assignment to the participants, potentially affecting the results.

“If the true acupuncture regimen studied in this trial is truly effective for migraine prevention, the logistical barriers inherent in patients being able to access it clinically are likely to be substantial,” Gelfand wrote.

Among those barriers include access to acupuncture that incorporates electrical stimulation, as used in the study, ability to undergo acupuncture daily, as was done in the study, and the lifestyle flexibility to allow for missing partial days of work or school for a month.

“In this regard, acupuncture is not entirely without potential adverse effects,” Gelfand wrote. “Development of a self-administered home acupuncture device, if feasible, could get around a number of these issues. In the meantime, how best to counsel patients about the utility of acupuncture for migraine prevention? It is probably safe to try-it is not clear it is effective. The main risks are likely to their pocketbook and their time.”

The long-term effect of acupuncture for migraine prophylaxis

. A randomized clinical trial. JAMA Intern Med. Epub 2017 February 20.

Studies have shown that true acupuncture is more effective than sham acupuncture in reducing migraine, but it treatment feasible?

Acupuncture for Migraine: a Feasible Option?

The use of analgesics and opioids to treat acute migraine was associated with a higher risk for developing medication overuse headache (MOH) compared with other migraine treatments, according to the results of a literature review.

 “These findings should be of interest to patients, clinicians, and policy-makers as many patients may self-medicate, and the magnitude of analgesic use is potentially higher than what has generally been observed in population-based studies,” researcher Kristian Thorlund, of the department of clinical epidemiology & biostatistics, McMaster University, Hamilton, Ontario, and colleagues, wrote in 

“While our findings are in line with current clinical guidelines and prejudice in favor of targeted migraine-specific pharmacotherapy, they should still only be interpreted as exploratory due to their observational nature.”

MOH is a headache that occurs on 15 or more days per month caused by overuse of medications for migraine or other pain disorders. There are a variety of medications used for the treatment of acute migraines including analgesics, ergots, opioids, and triptans. With this study, Thorlund and colleagues wanted to determine whether any of these classes of medications were more likely to elicit MOH.

They performed a comprehensive literature review of studies that reported MOH according to the International Classification of Headache Disorders. They identified 29 studies for inclusion in their review.

Fourteen studies discussed MOH for both triptans and ergots: four yielded a relative risk in favor of triptans, two yielded no difference, and eight studies yielded an adjusted relative risk in favor of ergots.

Both triptans and ergots appeared favorable for MOH when compared to opioids, the researchers found.

Seven studies discussed MOH for ergots and opioids. Four studies had a relative risk in favor of ergots, one showed no difference, and two studies yielded a relative risk in favor of opioids. The fixed-effect weighted average relative risk was 0.76, suggesting an average 24% relative risk reduction in MOH with ergots compared with opioids.

Eleven studies covered MOH for both triptans and opioids. Five studies favored triptans, one study showed no difference, and five studies yielded a relative risk in favor of opioids. There was a fixed-effect weighted average adjusted relative risk of 0.35, suggesting an average of 65% relative risk reduction in MOH with triptans compared with opioids.

Twelve of the studies included in the review discussed MOH for ergots and analgesics. Eleven of the 12 studies had a relative risk in favor of ergots. The fixed effect weighted average adjusted relative risk, suggesting an average of 59% relative risk reduction in MOH with ergots compared with analgesics.

Finally, the researchers also found that analgesics and opioids appeared to yield a similar risk of MOH. Nine studies discussed MOH for analgesics and opioids. Three studies showed an adjusted relative risk estimate in favor of analgesics, and six studies in favor of opioids. The fixed-effect weighted average adjusted relative risk was 1.09, suggesting an average 9% increased risk of MOH with analgesics compared with opioids.

The researchers suggested that there are several possible reasons for increased MOH associated with analgesic and opioid use, including the fact that analgesics are an over-the-counter medication that patients can self-administer compared with triptans, which are a prescription medication.

Risk of medication overuse headache across classes of treatments for acute migraine

A review examined risk of medication overuse headache across classes of acute migraine treatments.

Migraine Treatment: Medication Overuse Headache 

The use of sphenopalatine ganglion blockade (SPG) in children with migraine headaches is a safe and effective treatment for reducing headache scores, according to the results of a study presented at the Society of Interventional Radiology's 2017 Annual Scientific Meeting. The minimally invasive treatment takes only minutes to provide relief for migraine headaches, the study showed.

“This treatment, performed in an outpatient setting by an interventional radiologist, can safely relieve a child's migraine quickly,” Robin Kaye, MD, section chief of interventional radiology in the department of medical imaging at Phoenix Children's Hospital and a co-author of the study, said in a press release. “By reducing the need for medications that come with serious side effects or intravenous therapies that may require hospital stays, children don't have to miss as much school and can get back to being a kid sooner.”

Although migraines are more commonly discussed in adults, migraines affect about 12% of people aged 12 and younger. SPG is known to be an effective treatment among adults with migraine, but little is known about its use in the pediatric population.

With SPG procedures, a small flexible catheter is inserted into each nostril and local anesthetic is administered to the SPG, a nerve bundle thought to be associated with migraines, located at the back of the nose. Briefly disabling the SPG can disrupt and reset the headache circuit, breaking a cycle of severe migraines and reducing the need for medication. The minimally invasive SPG block takes almost immediate effect with relief potentially lasting for months, researchers said.

In this study, Kaye and colleagues performed 310 SPG procedures in 200 patients with migraine aged 7 to 18. Prior to undergoing SPG, the patients recorded headache scores on a scale of 1 to 10.

The procedure was performed supine with neck in hyperextension and anesthesia of the bilateral nares was accomplished with lidocaine spray and gel. Patients remained supine with neck in hyperextension for 10 minutes. After the procedure, headache scores were recorded again.

The mean headache score decreased more than two points from pre-intervention of 5.55 to 3.28 post-intervention (P<0.0001).

“While it isn't a cure for migraines, this treatment has the potential to really improve the quality of life for many children,” Kaye said. “It can be performed easily, without complications, and gives quick pain relief, which is important to parents who want to see their children happy, healthy, and pain free again. If needed, we can also repeat the treatment if or when the migraine returns.”

The researchers noted that SPG blocks are not a frontline treatment. A child only qualifies for the therapy if he/she has been diagnosed with a severe migraine that has not responded to first-line treatments.

Safety and efficacy of sphenopalatine ganglion blockade in children – initial experience

. Abstract #10. Presented at SIR Annual Scientific Meeting, March 4-9, 2017. 

SPG is known to be an effective treatment among adults with migraine, but little is known about its use in the pediatric population. 