Lawrence C. Newman

Prevalence and Diagnosis of Migraine in Patients Consulting Their Physician With a Complaint of Headache: Data From the Landmark Study

Context.—Headache experts have suggested that to improve the recognition of migraine, patients with a stable pattern of episodic, disabling headache and a normal physical exam should be considered to have migraine in the absence of contradictory evidence. The premise upon which this approach is based—that is, that episodic, recurrent primary headache in the clinic is usually migraine—has not been evaluated in prospective clinical studies.

Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study

BACKGROUND Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine. METHODS In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14 days per month. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1; stratified by sex and use of concomitant preventive drugs) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125, 675 mg TEV-48125, or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Patients reported headache information daily using an electronic diary. Primary endpoints were change from baseline in migraine days during the third treatment cycle (weeks 9-12) and safety and tolerability. The secondary endpoint was change relative to baseline in headache-days during weeks 9-12. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered at ClinicalTrials.gov, number NCT02025556. FINDINGS Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants: 104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125, and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number of migraine-days from baseline to weeks 9-12 was -3.46 days (SD 5.40) in the placebo group, -6.27 days (5.38) in the 225 mg dose group, and -6.09 days (5.22) in the 675 mg dose group. The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days (95% CI -4.07 to -1.55; p<0.0001), whereas the difference between the placebo and 675 mg dose group was -2.64 days (-3.90 to -1.38; p<0.0001). LSM differences in the reduction of headache-days were -2.63 days (-3.91 to -1.34; p<0.0001) between the placebo group and 225 mg dose group and -2.58 days (-3.87 to 1.30; p <0.0001) between the placebo group and the 675 mg dose group. Adverse events occurred in 58 (56%) patients in the placebo group, 44 (46%) patients in the 225 mg dose group, and 57 (59%) patients in the 675 mg dose group; moderate or severe adverse events were reported for 29 (27%) patients, 24 (25%) patients, and 26 (27%) patients, respectively. INTERPRETATION TEV-48125, at doses of 225 mg and 675 mg given once every 28 days for 12 weeks, was safe, well tolerated, and effective as a preventive treatment of high-frequency episodic migraine, thus supporting advancement of the clinical development programme to phase 3 clinical trials. FUNDING Teva Pharmaceuticals.

A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine

Headaches associated with menstruation are often resistant to abortive and preventative medications. We performed an open-label study in 20 female migraineurs, employing oral sumatriptan perimenstrually as short-term prophylaxis of menstrual migraine. In 126 sumatriptan-treated cycles, headache was absent in 52.4% and reduced in severity by 50% or greater in 42%. Breakthrough headaches were rare and significantly reduced in severity compared with baseline headaches.

Posttraumatic Hemicrania Continua

Hemicrania continua is a rare, benign headache disorder characterized by a low‐level baseline hemicranial headache with superimposed exacerbations of more severe pain. Exacerbations last from minutes to days and may be associated with ipsilateral autonomic features such as ptosis, miosis, conjunctival injection, lacrimation, or rhinorrhea; when present, these features tend to be less pronounced than those seen with cluster headache. Response to treatment with indomethacin, in doses ranging from 25 to 300 mg per day, has been deemed a sine qua non of diagnosis. To date, in the majority of instances, hemicrania continua appears to have arisen de novo, without any identifiable trigger. We report four patients in whom the onset of hemicrania continua was temporally linked to head trauma.

EMERGENCY DEPARTMENT EVALUATION OF HEADACHE

Headache is an extremely common complaint in the Emergency Department, accounting for up to 16% of all visits. Although there are more than 300 medical conditions which can produce headache, the vast majority of headache disorders are benign. This article outlines an orderly approach for evaluating patients who present with headaches; in addition, the authors discuss the emergency treatment of the more common types of headache.

Migraine and vestibular symptoms--identifying clinical features that predict "vestibular migraine".

Background.— Migraine and symptoms that may suggest a vestibular disorder (referred to herein broadly as vestibular symptoms—VS) often co‐exist. In part due to a lack of standardized diagnostic criteria, this relationship remains unknown to many physicians.

Reversible Anorgasmia With Topiramate Therapy for Headache: A Report of 7 Patients

Objective.—To describe 7 patients who developed new onset anorgasmia while using topiramate therapy for migraine prophylaxis.

Thunderclap Headache as the Presenting Symptom of Myocardial Infarction

Headache as the presenting symptom of myocardial ischemia has been reported in more than 20 cases. These headaches have been described as of gradual onset, associated with exertion and with EKG changes. We present herein the first case of thunderclap headache occurring at rest as the sole symptom of an acute myocardial infarction.

Reversible anorgasmia with topiramate therapy for migraine

Topiramate is widely used for migraine prevention. Common side effects include fatigue, anorexia, weight loss, cognitive impairment, and paresthesias. Erectile dysfunction in two patents taking topiramate for partial epilepsy was recently reported.1 Herein we report two patients in whom treatment with topiramate resulted in reversible anorgasmia. ### Patient 1. A 52-year-old woman with chronic migraine headaches for 10 years was begun on topiramate 15 mg daily and increased by 15 mg/day every 2 weeks. The patient continued to have three to four headaches per week at doses of 45 mg/day. At 60 mg daily, headache frequency decreased to once monthly; however, at this dose the patient reported the inability to achieve orgasm. She denied prior history of anorgasmia, changes in libido, or other symptoms of sexual dysfunction. She was reluctant to discontinue …

Hemicrania Continua: A Third Case in Which Attacks Alternate Sides

Hemicrania continua (HC) is an uncommon, primary headache disorder characterized by a continuous unilateral headache of moderate intensity with superimposed exacerbations of more severe pain. HC exists in two temporal subtypes, a continuous form in which headaches persist continuously without remission periods, and a less common remitting form in which bouts of continuous headaches are separated by pain‐free remissions. There have been more than 100 prior reports of HC; in the majority of which the headache is strictly unilateral and without side shift. We now report the third patient in whom headaches alternated sides during different attacks.