Faculty Bibliography

Introduction: Natalizumab, approved for 300 mg intravenous every-4-weeks dosing, is associated with PML risk. Objective(s): To determine whether natalizumab EID is associated with reduced PML risk compared with SID. Patients and Methods: Average dosing intervals (ADIs) were >= 3 to < 5 weeks for SID and > 5 to <= 12 weeks for EID. The primary analysis assessed ADI in the last 18 months of infusion history. The secondary analysis identified any prolonged period of EID at any time in the infusion history. The tertiary analysis assessed ADI over the full infusion history. Result(s): In primary analyses, median exposure (months) was 44 for SID and 59 for EID. The PML HR (95% confidence interval) was 0.06 (0.01-0.22; P < 0.001) for primary and 0.12 (0.05-0.29; P < 0.001) for secondary analyses; no EID PML cases were observed in tertiary analyses (Kaplan-Meier log-rank test P = 0.02). Discussion(s): NA. Conclusion(s): In JCV Ab + patients, natalizumab EID is associated with a clinically and statistically significant reduction in PML risk as compared with SID.

PURPOSE OF REVIEW/OBJECTIVE:To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). RECENT FINDINGS/RESULTS:Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and, less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

BACKGROUND:The 2015 criteria for diagnosing neuromyelitis optica spectrum disorder (NMOSD) have encouraged several groups across the world to report on their patients using these criteria. The disease typically manifests with severe relapses of optic neuritis, longitudinally extensive myelitis and/or brainstem syndromes, often leading to severe disability. Some patients are seropositive for antibodies against aquaporin-4 (AQP4), others are positive for anti-myelin oligodendrocyte glycoprotein (MOG), while a few are negative for both biomarkers. The disease is complex, and only now are specific therapeutic clinical trials being carried out. The present study adds to the literature through detailed clinical data from 153 medical records of Brazilian patients. METHODS:Retrospective assessment of medical records from nine specialized units in Brazil. RESULTS:NMOSD was more prevalent in females (4.1:1), who had significantly fewer relapses than males (p = 0.007) but presented similar levels of disability over time. African ancestry was associated with higher levels of disability throughout the disease course (p < 0.001), although the number of relapses was similar to that observed in white patients. Concomitant autoimmune diseases were relatively rare in this population (6.5%). Positivity for anti-AQP4 antibodies was identified in 62% of the patients tested, while 3% presented anti-MOG antibodies. Anti-AQP4 antibodies were not associated to worse disease course. The last medical record showed that six patients had died and 13 were wheelchair-bound. Seventy percent of the patients did not respond to first-line therapy (azathioprine and/or corticosteroids), and five patients continued to relapse even after four different courses of treatment. CONCLUSION/CONCLUSIONS:The present study adds to the reports from other countries presenting original data on Brazilian patients diagnosed with NMOSD according to the 2015 criteria.