Starling, Amaal J.

Objective To determine the potential impact of erenumab, a human anti‐calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise‐induced angina, and ST depression in a double‐blind, placebo‐controlled study in patients with stable angina due to documented coronary artery disease. Background The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established. Methods An exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo. The primary endpoint was the change from baseline in exercise duration as measured by TET with a noninferiority margin of −90 seconds. Safety follow‐up visits occurred through week 12. Eighty‐eight participants were included in the analysis. Results LS mean (SE) change in TET was −2.9 [14.8] seconds in the erenumab group and 8.1 [14.4] seconds in placebo; adjusted mean (90% CI) treatment difference was −11.0 (–44.9, 22.9) seconds. The CI lower bound (–44.9 sec) did not reach pre‐defined non‐inferiority margin of −90 seconds, demonstrating that TET change from baseline in the erenumab group was non‐inferior to placebo. There was no difference in time to exercise‐induced angina in erenumab and placebo groups (median [90% CI] time of 500 [420, 540] vs 508 [405, 572] seconds; hazard ratio [90% CI]: 1.11 [0.73, 1.69], P = .69) or time to onset of ≥1 mm ST‐segment depression (median [90% CI] time of 407 [380, 443] vs 420 [409,480] seconds; hazard ratio [95% CI]: 1.14 [0.76, 1.69], P = .59). Adverse events were reported by 27% and 32% of patients in erenumab and placebo groups. Conclusions Erenumab did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.

Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) ( p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) ( p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events. Conclusions This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention. Trial registration number NCT02357381

Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4–2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Since then, numerous studies have been performed investigating the short-term and long-term benefits, risks and complications of the use of onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose of this narrative review is to describe the currently available clinical evidence for the use of onabotulinumtoxinA injections for treating patients with chronic migraine.

Efficient eye movements provide a physical foundation for proficient reading skills. We investigated the effect of in-school saccadic training on reading performance. In this cross-over design, study participants (n = 327, 165 males; mean age [SD]: 7 y 6 mo [1y 1 mo]) were randomized into treatment and control groups, who then underwent eighteen 20-minute training sessions over 5 weeks using King-Devick Reading Acceleration Program Software. Pre- and posttreatment reading assessments included fluency, comprehension, and rapid number naming performance. The treatment group had significantly greater improvement than the control group in fluency (6.2% vs 3.6%, P = .0277) and comprehension (7.5% vs 1.5%, P = .0002). The high-needs student group significantly improved in fluency ( P < .001) and comprehension ( P < .001). We hypothesize these improvements to be attributed to the repetitive practice of reading-related eye movements, shifting visuospatial attention, and visual processing. Consideration should be given to teaching the physical act of reading within the early education curriculum.

Migraine preventive medications are used to reduce the frequency, severity, and disability of migraine attacks. Once migraine preventive therapy is initiated, the question of how long to maintain this therapy arises. This article will explore the literature pertaining to the long‐term use of migraine preventive medications, including length of treatment and safety with long‐term exposure.

Background Cluster headache (CH), the most common trigeminal autonomic cephalalgia, is an extremely debilitating primary headache disorder that is often not optimally treated. New evidence‐based treatment guidelines for CH will assist clinicians with identifying and choosing among current treatment options. Objectives In this systematic review we appraise the available evidence for the acute and prophylactic treatment of CH, and provide an update of the 2010 American Academy of Neurology (AAN) endorsed systematic review. Methods Medline, PubMed, and EMBASE databases were searched for double‐blind, randomized controlled trials that investigated treatments of CH in adults. Exclusion and inclusion criteria were identical to those utilized in the 2010 AAN systematic review. Results and Recommendations For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high flow oxygen remain the treatments with a Level A recommendation. Since the 2010 review, a study of sphenopalatine ganglion stimulation was added to the current guideline and has been administered a Level B recommendation for acute treatment. For prophylactic therapy, previously there were no treatments that were administered a Level A recommendation. For the current guidelines, suboccipital steroid injections have emerged as the only treatment to receive a Level A recommendation with the addition of a second Class I study. Other newly evaluated treatments since the 2010 guidelines have been given a Level B recommendation (negative study: deep brain stimulation), a Level C recommendation (positive study: warfarin; negative studies: cimetidine/chlorpheniramine, candesartan), or a Level U recommendation (frovatriptan). Conclusions This AHS guideline can be utilized for understanding which therapies have superiority to placebo or sham treatment in the management of CH. In clinical practice, these recommendations should be considered in concert with other variables including safety, side effects, patient preferences, clinician experience, cost, and the invasiveness of the intervention. Given the lack of Class I evidence and Level A recommendations, particularly for a number of commonly used preventive therapies, further studies are warranted to demonstrate safety and efficacy for established and emerging therapies.