Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures.

BACKGROUND: Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives. METHODS: Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed. RESULTS: Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo - 0.7; galcanezumab - 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo - 0.2; galcanezumab - 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1-3 (all p < 0.05) and at weeks 1-4 of month 1 compared to placebo (all p < 0.01). CONCLUSION: Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03559257 . Registered 18 June 2018.

Good outcome is possible after months of refractory convulsive status epilepticus: lesson learned.

Determining a prognosis for functional recovery after prolonged status epilepticus can be difficult. Prior case studies have shown that despite seizure control, functional outcomes are typically poor unless a reversible cause is identified. Herein we present a case of idiopathic status epilepticus with a surprisingly good outcome after a 125-day drug-induced coma.

Clobazam for treatment of epilepsy.

INTRODUCTION: The landscape of antiepileptic drugs is constantly evolving with new compounds being released onto the market on a regular basis. Most new agents are, at least initially, approved for use as adjunctive treatment of localization-related (focal) epilepsy, and only rarely are new medications released for other types of epilepsy. Though it has been in use in other countries, clobazam is now approved for use in the USA, and specifically in the treatment of Lennox-Gastaut syndrome, a type of (symptomatic or cryptogenic) generalized epilepsy. AREAS COVERED: This paper discusses the pharmacology of clobazam as well as the definition and nosologic boundaries of Lennox-Gastaut Syndrome. General (adult) neurologists are under the erroneous impression that Lennox-Gastaut syndrome is limited to childhood, and this common misconception indicates a lack of understanding of the group of generalized epilepsies. With this paper, readers will gain a better understanding of the limits of Lennox-Gastaut syndrome and how it evolves with age and what clobazam can contribute to its treatment. EXPERT OPINION: Clobazam offers a new treatment option for patients with refractory epilepsy. It has been found to be a safe, well-tolerated adjunctive antiepileptic medication that has had long-standing international experience in thousands of patients. It is unlikely that clobazam will change treatment strategies radically; nonetheless additional options are always welcome as individual patients can respond to different regimens. Physicians should be comfortable prescribing clobazam because it is a benzodiazepine and has been used extensively outside of the USA.

Advances in functional neuroimaging in dementias and potential pitfalls.

Neuroimaging is continuously advancing at a rapid rate and has progressed from excluding relatively uncommon secondary causes (stroke, tumor) to assisting with early diagnosis and subtype of dementia. Structural imaging has given way to functional, metabolic and receptor imaging.