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With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive and immunomodulatory therapies. There is good evidence thymectomy is beneficial in thymomatous and nonthymomatous disease. Nearly all of the drugs used for MG are considered "off-label." The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis. This article reviews the evidence base and provides a framework for the treatment of myasthenia gravis, highlighting recent additions to the literature.

; and the Zilucoplan MG Study Group IMPORTANCE Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. OBJECTIVE To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)-positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. INTERVENTIONS Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. MAIN OUTCOMES AND MEASURES The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. RESULTS The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change,-2.8; P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change,-2.3; P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. CONCLUSIONS AND RELEVANCE Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab...

Objective: To characterize demographic and clinical features in pregnant women presenting with acute headache, and to identify clinical features associated with secondary headache. Methods:We conducted a 5-year, single-center, retrospective study of consecutive pregnant women presenting to acute care with headache receiving neurologic consultation.Results: The 140 women had a mean age of 29 6 6.4 years and often presented in the third trimester (56.4%). Diagnoses were divided into primary (65.0%) and secondary (35.0%) disorders. The most common primary headache disorder was migraine (91.2%) and secondary headache disorders were hypertensive disorders (51.0%). The groups were similar in demographics, gestational ages, and most headache features. In univariate analysis, secondary headaches were associated with a lack of headache history (36.7% vs 13.2%, p 5 0.0012), seizures (12.2% vs 0.0%, p 5 0.0015), elevated blood pressure (55.1% vs 8.8%, p , 0.0001), fever (8.2% vs 0.0%, p 5 0.014), and an abnormal neurologic examination (34.7% vs 16.5%, p 5 0.014). In multivariate logistic regression, elevated blood pressure (odds ratio [OR] 17.0, 95% confidence interval [CI] 4.2-56.0) and a lack of headache history (OR 4.9, 95% CI 1.7-14.5) had an increased association with secondary headache, while psychiatric comorbidity (OR 0.13, 95% CI 0.021-0.78) and phonophobia (OR 0.29, 95% CI 0.09-0.91) had a reduced association with secondary headache.Conclusions: Among pregnant women receiving inpatient neurologic consultation, more than onethird have secondary headache. Diagnostic vigilance should be heightened in the absence of a headache history and if seizures, hypertension, or fever are present. Attack features may not adequately distinguish primary vs secondary disorders, and low thresholds for neuroimaging and monitoring for preeclampsia are justified. Neurology ® 2015;85:1024-1030 GLOSSARY CI 5 confidence interval; HELLP 5 hemolysis, elevated liver enzymes, and low platelet count; ICHD-3 beta 5 International Classification of Headache Disorders, 3rd edition (beta version); OR 5 odds ratio; PRES 5 posterior reversible encephalopathy syndrome.The most common primary headache disorders have a peak prevalence and incidence at a younger age and affect women disproportionately, particularly during childbearing years.1 The female predilection may be explained by the relationship of headache and sex hormones, particularly estrogen.2 Migraine is the most common disabling primary headache disorder, and, in pregnancy, retrospective and prospective studies consistently demonstrate that by the second trimester, migraine frequency typically improves, although attacks of migraine with aura and aura without headache may not reflect this pattern. [3][4][5][6][7][8][9][10] Acute, severe headache in pregnancy is generally regarded as a "red flag" and a cause for further investigation, particularly when new onset. [11][12][13] Various secondary headache disorders are more likely to occur during this time period, 12 possibly related t...