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.

Delayed diagnosis of immune mediated necrotizing myopathy (IMNM) leads to increased morbidity. Patients with chronic course without HMGCR-IgG (3-hydroxy-3-methylglutaryl-coenzyme-A reductase) or SRP54-IgGs (signal recognition particle) are often challenging to diagnose. Immunotherapy response can also be difficult to assess. We created a statistical model to assist IMNM diagnosis. Electrical myotonia vs fibrillations were reviewed as biomarkers for immunotherapy treatment response. Identified were 119 IMNM cases and 938 other-myopathy patients. Inclusion criteria included all having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and 67% (20/30) of our validation IMNM cohorts, and significantly (p < 0.001) favored IMNM over other myopathies: sporadic inclusion body myositis (odds ratio = 4.78); dermatomyositis (odds ratio = 10.61); nonspecific inflammatory myopathies (odds ratio = 8.46); limb-girdle muscular dystrophies (odds ratio = 5.34) or mitochondrial myopathies (odds ratio = 14.17). Electrical myotonia occurred in IMNM seropositive (HMGCR-IgG 70%, 37/53; SRP-IgG 29%, 5/17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in combination accurately predicted IMNM (97.1% area-under-curve). The model was validated in a separate cohort of 30 IMNM cases. Delayed diagnosis of cases with electrical myotonia occurred in 24% (16/67, mean 8 months; range 0-194). Half (8/19) had chronic course and were seronegative, with high model prediction (>86%) at first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2-124) which reduced from 36% (58/162) of muscles to 7% (8/121; p < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as with median creatine kinase reduction of 1779 U/L (range 401–9238, p < 0.001). Modeling clinical features with electrical myotonia is especially helpful in IMNM diagnostic suspicion among chronic indolent and seronegative cases. Electrical myotonia favors IMNM diagnosis and can serve as an adjuvant immunotherapy biomarker.

Objective:To compare the performance of different respiratory function testing in a multidisciplinary ALS clinic.Methods:Demographics, clinical data, and respiratory testing parameters were abstracted from the medical records of patients who attended a multidisciplinary ALS clinic from 2008-2016. We compared the performance of the three primary respiratory test parameters used by Medicare for the initiation of non-invasive ventilation (NIV), (forced vital capacity (FVC) < 50% predicted, maximum inspiratory pressure (MIP) < 60 cm H20, and abnormal overnight pulse oximetry (OvOx)) on how they related to several clinically relevant attributes.Results:476 subjects were identified who underwent at least one respiratory test. Abnormalities of OvOx, MIP, and FVC occurred at a median of 1.6, 1.5, and 3.8 years from disease onset, respectively (p < 0.00001). Subjects with bulbar-onset ALS exhibited earlier abnormalities in MIP and FVC than in spinal-onset ALS (p <0.005). The median survival after an abnormal OvOx, MIP, or FVC test was 1.4, 1.4, and 0.9 years, respectively (p < 0.0001). Utilizing the ALS Functional Rating Score respiratory subscales, at the time of reported respiratory symptoms there were abnormalities in OvOx (60%), MIP (69%), and FVC (19%). Conversely, when respiratory parameter abnormalities preceded reported respiratory symptoms, this occurred with frequencies in OvOx (79%), MIP (42%) or FVC (24%). Four hundred forty-three subjects (93.1%) developed at least one abnormal respiratory measure meeting Medicare criteria for NIV consideration, but fewer than 50% in our cohort demonstrated NIV use. Improved survival in subjects using NIV was statistically significant in patients with bulbar-onset ALS.Conclusions:Abnormalities in OvOx and MIP perform better than FVC at early detection of neuromuscular respiratory weakness in ALS. Initiation of NIV in patients with respiratory insufficiency may improve overall survival in ALS. In the setting of the COVID-19 pandemic, FVC and MIP have not been routinely performed due to infectious aerosol generation. OvOx, which we now routinely mail to patients’ homes, has been utilized exclusively during the COVID-19 pandemic, and allows for continued remote monitoring of respiratory status of patients with ALS.

Introduction/Aims: The full spectrum of the clinical phenotype of facioscapulohumeral muscular dystrophy (FSHD), beyond skeletal muscle weakness, remains poorly characterized. In this study, we describe systemic manifestations and symptom burden in a large series of FSHD patients.Methods: We performed a retrospective chart review of FSHD patients seen at our institution between 2000 and 2017. We reviewed patients' responses to a comprehensive review of symptoms and the results of diagnostic testing for sensorineural hearing loss, cardiac disease, dysphagia, ocular abnormalities, and respiratory insufficiency. We assessed the association between disease manifestations and age of onset, genetic profile, and disease duration. Results:We identified 87 patients with FSHD. The most common reported symptoms included pain (71%), difficulty sleeping (41%), headaches (27%), and altered mood (24%). When tested, 7 of 16 (44%) patients had sensorineural hearing loss, 20 of 60 (33%) had cardiac arrhythmias or conduction defects, 17 of 45 (38%) had echocardiogram abnormalities, 12 of 25 (48%) had reduced forced vital capacity, and 4 of 10 (40%) had oropharyngeal dysphagia. However, patients with these abnormalities represented 8%, 23%, 20%, 14%, and 5% of total number of patients, respectively, as uniform screening was lacking. Ocular pathology attributable to FSHD was not detected.Discussion: FSHD demonstrates a broad clinical phenotype. Increased vigilance among neurologists to screen for systemic manifestations of the disease is warranted.More uniform screening and future population-based studies are needed to compare findings in FSHD patients with the general population.

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