McKeon, Andrew

Objective To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis. Methods We performed a population‐based comparative study of the incidence and prevalence of autoimmune and infectious encephalitis in Olmsted County, Minnesota. Autoimmune encephalitis diagnosis and subgroups were defined by 2016 diagnostic criteria, and infectious encephalitis diagnosis required a confirmed infectious pathogen. Age‐ and sex‐adjusted prevalence and incidence rates were calculated. Patients with encephalitis of uncertain etiology were excluded. Results The prevalence of autoimmune encephalitis on January 1, 2014 of 13.7/100,000 was not significantly different from that of all infectious encephalitides (11.6/100,000; p = 0.63) or the viral subcategory (8.3/100,000; p = 0.17). The incidence rates (1995–2015) of autoimmune and infectious encephalitis were 0.8/100,000 and 1.0/100,000 person‐years, respectively ( p = 0.58). The number of relapses or recurrent hospitalizations was higher for autoimmune than infectious encephalitis ( p = 0.03). The incidence of autoimmune encephalitis increased over time from 0.4/100,000 person‐years (1995–2005) to 1.2/100,000 person‐years (2006–2015; p = 0.02), attributable to increased detection of autoantibody‐positive cases. The incidence (2.8 vs 0.7/100,000 person‐years, p = 0.01) and prevalence (38.3 vs 13.7/100,000, p = 0.04) of autoimmune encephalitis was higher among African Americans than Caucasians. The prevalence of specific neural autoantibodies was as follows: myelin oligodendrocyte glycoprotein, 1.9/100,000; glutamic acid decarboxylase 65, 1.9/100,000; unclassified neural autoantibody, 1.4/100,000; leucine‐rich glioma‐inactivated protein 1, 0.7/100,000; collapsin response‐mediator protein 5, 0.7/100,000; N‐methyl‐D‐aspartate receptor, 0.6/100,000; antineuronal nuclear antibody type 2, 0.6/100,000; and glial fibrillary acidic protein α, 0.6/100,000. Interpretation This study shows that the prevalence and incidence of autoimmune encephalitis are comparable to infectious encephalitis, and its detection is increasing over time. Ann Neurol 2018;83:166–177

ABSTRACTIntroduction: Multifocal motor neuropathy (MMN) is a motor only, asymmetric onset neuropathy that is relatively treatment‐refractory compared with classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. Methods: We reviewed 35 patients seropositive for GM1 (monosialo‐asialo [immunoglobulin M, IgM; immunoglobulin G, IgG]) and/or GD1b (disialo [IgG, IgM]) autoantibodies having MMN, classic CIDP, or MADSAM. Immune‐treatment responsiveness and clinical course was compared with antibody negative disease controls. Results: Seventy‐nine percent of seropositives with an initial diagnosis of MMN were immunotherapy responsive compared with 46% of seronegatives (P = 0.045). Eight ganglioside antibody positive MMN patients of 19 (42%) developed sensory findings consistent with MADSAM compared with 3 of 41 (7%) seronegative MMN patients (P = 0.003). MMN and MADSAM patients with ganglioside antibody positivity had more sustained treatment responses (P = 0.03). Discussion: Patients initially diagnosed with MMN seropositive for diverse GM1 autoantibodies appear more likely to have sustained treatment response and evolution to MADSAM. Muscle Nerve 57: 1000–1005, 2018

ABSTRACTIntroduction: Neuronal calcium channel antibodies are a biomarker of Lambert‐Eaton syndrome (LES) and cerebellar ataxia. We have encountered several patients with LES and cerebellar ataxia coexisting, and we sought to further define this association. Methods: We reviewed records of patients at our institution with a diagnosis of “Lambert‐Eaton syndrome” and “cerebellar ataxia.” Results: Seventeen patients were identified with LES and ataxia. Presenting symptoms were weakness (8), concurrent weakness and ataxia (4), ataxia (4), and other (1). Nine patients had small‐cell lung carcinoma, 3 of whom had survival greater than 100 months. Immunotherapy responses were best among patients without cancer. Nine of 17 (53%) patients were alive at last follow‐up (median survival 62 months; range, 8–240). Discussion: Calcium channel autoimmunity should be considered in patients with coexisting cerebellar ataxia and myasthenic weakness. Affected patients may survive small‐cell carcinoma or have immunotherapy‐responsive neurological symptoms. Muscle Nerve 58: 29–35, 2018

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Objective To describe an expanded phenotypic spectrum and longitudinal outcome in 256 LGI1‐IgG–seropositive and/or CASPR2‐IgG–seropositive patients. Methods Patients were identified through service neural autoantibody evaluation. Ninety‐five had longitudinal follow‐up (7–456 months; median = 35). Results Among 3,910 patients tested, 196 were LGI1‐IgG positive, 51 were CASPR2‐IgG positive, and 9 were dual positive. Cerebrospinal fluid testing was less sensitive than serum testing, detecting only 24 of 38 (63%) LGI1‐IgG–positive and 5 of 6 (83%) CASPR2‐IgG–positive patients. LGI1‐IgG–positive specimens had higher voltage‐gated potassium channel–IgG immunoprecipitation values (0.33nmol/l, range = 0.02–5.14) than CASPR2‐IgG–positive specimens (0.10nmol/l, range = 0.00–0.45, p < 0.001). Of patients presenting with pain or peripheral nervous system (PNS) manifestations, 39% were LGI1‐IgG seropositive (7% had solely neuropathy or pain). Multivariate analysis identified age as the only significant predictor of central nervous system (CNS) versus PNS involvement (>50 years; odds ratio = 15, p < 0.001). Paroxysmal dizziness spells (PDS), a unique LGI1‐IgG accompaniment (14% of patients), frequently delayed the diagnosis. T2‐mesiotemporal hyperintensity was more common in LGI1‐IgG–positive (41%) than in CASPR2‐IgG–positive patients ( p = 0.033). T1‐bright basal ganglia were confined to LGI1‐IgG–positive patients with faciobrachial–dystonic seizures (9 of 39, 31%). Cancer was found in 44% of LGI1‐IgG/CASPR2‐IgG dual seropositive patients (one‐third thymoma). Response to initial immunotherapy was favorable in 97%; mean modified Rankin score was 3 (range = 1–5) at onset and 1.74 (range = 0–6) at last follow‐up, with 9% having severe refractory disability, 20% being asymptomatic, 28% receiving immunotherapy, and 58% receiving antiepileptic medication. Interpretation Older age is a strong predictor of CNS involvement in patients seropositive for CASPR2‐IgG or LGI1‐IgG. Pain, peripheral manifestations, and stereotypic paroxysmal dizziness spells are common with LGI1‐IgG. Response to initial immunotherapy is often favorable, but some patients remain severely disabled, requiring long‐term immunotherapy and/or antiepileptic medications. Ann Neurol 2017;82:79–92