Objective: During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin‐4 immunoglobulin G‐positive neuromyelitis optica spectrum disorder (AQP4‐IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open‐label extension (OLE; NCT02003144) evaluating eculizumab's long‐term safety and efficacy.Methods: Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis.Results: Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient‐years (PY). Treatment‐related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab‐treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse‐free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab‐treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use.Interpretation: This analysis demonstrates that eculizumab's long‐term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long‐term eculizumab treatment to reduce relapse risk in patients with AQP4‐IgG+ NMOSD. ANN NEUROL 2021;89:1088–1098

Kim H, et al. J Clin Neurol. 2022 Mar;18(2):140-151. https://doi.org/10.3988/jcn.2022.18.2.140

Background and Purpose—: We investigated clinical and radiological characteristics of ischemic stroke patients with Takotsubo-like myocardial dysfunction. Methods—: From multicenter stroke registry database, ischemic stroke patients who underwent transthoracic echocardiography were found. Among these, patients were classified if they had specific ventricular regional wall motion abnormalities discording with coronary artery distribution, such as apical (typical pattern) or nonapical ballooning (atypical pattern), considered as echocardiographic findings of Takotsubo cardiomyopathy. Patients with ischemic heart disease history, myocarditis, or pheochromocytoma were excluded. We compared patients with Takotsubo-like myocardial dysfunction with those without and further performed systematic literature review on those with Takotsubo cardiomyopathy. Results—: This study included 23 patients (0.42%). The mean age was 70.7±13.9 years, with predominance of women (73.9%) and typical pattern of Takotsubo-like myocardial dysfunction (91.3%). They were associated with short-term poor functional outcomes, including high mortality, neurological deterioration, and functional status at discharge, compared with those without (39.1% versus 2.4%, 47.8% versus 7.4%; and median [interquartile range], 5 [5–6] versus 3 [2–4]; all P <0.001). They had a higher inflammatory marker level and lower triglyceride level. Ischemic lesions were more commonly found in the right anterior circulation with specific dominant regions being the insula and peri-insular areas. In addition, a trend toward a remarkable mortality rate and higher prevalence of insular involvement was observed in the propensity-score matching, subgroup fulfilling the strict Takotsubo cardiomyopath criteria, and was as reported in literature review. Conclusion—: Stroke patients with Takotsubo-like myocardial dysfunction may differ from those without in clinical outcomes, laboratory findings, and radiological features.

Objective: We aimed to explore cortical thickness abnormalities in a homogeneous group of patients with migraine without aura and to delineate possible relationships between cortical thickness changes and clinical variables. Methods: Fifty-six female migraine patients without aura and T2-visible white matter hyperintensities and 34 female controls were scanned on a 3T magnetic resonance imager. Cortical thickness was estimated and compared between patients and controls using a whole-brain vertex-by-vertex analysis. Correlation analysis was conducted between cortical thickness of significant clusters and clinical variables. Results: Compared to controls, migraine patients had cortical thickening in left rostral middle frontal gyrus and bilateral post-central gyri. Region-of-interest analysis revealed cortical thickening of bilateral post-central gyri in migraine patients relative to controls. The average thickness of bilateral post-central gyri positively correlated with disease duration as well as estimated lifetime headache frequency. Conclusions: We have provided evidence for interictal cortical abnormalities of thickened prefrontal cortex and somatosensory cortex in female migraine patients without aura. Our findings of greater thickening of the somatosensory cortex in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time may lead to structural changes of the somatosensory cortex through increased noxious afferent input within the trigemino-thalamo-cortical pathway in migraine.