Pittock, Sean J.

AbstractTo determine whether CSF leucine‐rich glioma‐inactivated 1(LGI1)‐IgG titer, index or IgG subclass has prognostic significance, we tested serum and CSF specimens collected concomitantly from 39 seropositive patients. LGI1‐IgG index was elevated (>1) in 21 patients (54%), suggesting intrathecal synthesis. Patients with worse outcome at last follow‐up (modified Rankin Scale >2) had significantly higher index (median 6.57 vs. 0.5, P = 0.048) compared to those with better outcome. Higher CSF LGI1‐IgG4 subclass‐specific titer and index correlated with worse outcome (P < 0.005 for both). These data suggest that evidence of intrathecal LGI1‐IgG synthesis may correlate with neuronal injury and warrant consideration of aggressive immunotherapy.

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