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Background and Objectives: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study., Methods: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/μL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%)., Results: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/μL in 1,005 patients (83%), 5-49 cells/μL in 200 patients (16%), and ≥50 cells/μL in 13 patients (1%)., Discussion: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/μL, is compatible with GBS after a thorough exclusion of alternative diagnoses., Classification of Evidence: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS., (© 2023 American Academy of Neurology.)

Background and Objectives: The slow and variable disease progression of Becker muscular dystrophy (BMD) urges the development of biomarkers to facilitate clinical trials. We explored changes in 3 muscle-enriched biomarkers in serum of patients with BMD over 4-year time and studied associations with disease severity, disease progression, and dystrophin levels in BMD., Methods: We quantitatively measured creatine kinase (CK) using the International Federation of Clinical Chemistry reference method, creatine/creatinine ratio (Cr/Crn) using liquid chromatography-tandem mass spectrometry, and myostatin with ELISA in serum and assessed functional performance using the North Star Ambulatory Assessment (NSAA), 10-meter run velocity (TMRv), 6-Minute Walking Test (6MWT), and forced vital capacity in a 4-year prospective natural history study. Dystrophin levels were quantified in the tibialis anterior muscle using capillary Western immunoassay. The correlation between biomarkers, age, functional performance, mean annual change, and prediction of concurrent functional performance was analyzed using linear mixed models., Results: Thirty-four patients with 106 visits were included. Eight patients were nonambulant at baseline. Cr/Crn and myostatin were highly patient specific (intraclass correlation coefficient for both = 0.960). Cr/Crn was strongly negatively correlated, whereas myostatin was strongly positively correlated with the NSAA, TMRv, and 6MWT (Cr/Crn rho = -0.869 to -0.801 and myostatin rho = 0.792 to 0.842, all p < 0.001). CK showed a negative association with age ( p = 0.0002) but was not associated with patients' performance. Cr/Crn and myostatin correlated moderately with the average annual change of the 6MWT (rho = -0.532 and 0.555, p = 0.02). Dystrophin levels did not correlate with the selected biomarkers nor with performance. Cr/Crn, myostatin, and age could explain up to 75% of the variance of concurrent functional performance of the NSAA, TMRv, and 6MWT., Discussion: Both Cr/Crn and myostatin could potentially serve as monitoring biomarkers in BMD, as higher Cr/Crn and lower myostatin were associated with lower motor performance and predictive of concurrent functional performance when combined with age. Future studies are needed to more precisely determine the context of use of these biomarkers., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature., Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness method was used to develop consensus recommendations pertaining to 7 treatment topics. In February 2019, the international panel was reconvened with the addition of one member to represent South America. All previous recommendations were reviewed for currency, and new consensus recommendations were developed on topics that required inclusion or updates based on the recent literature. Up to 3 rounds of anonymous e-mail votes were used to reach consensus, with modifications to recommendations between rounds based on the panel input. A simple majority vote (80% of panel members voting "yes") was used to approve minor changes in grammar and syntax to improve clarity., Results: The previous recommendations for thymectomy were updated. New recommendations were developed for the use of rituximab, eculizumab, and methotrexate as well as for the following topics: early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment., Conclusion: This updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for patients with MG worldwide., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To develop formal consensus-based guidance for the management of myasthenia gravis (MG)., Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input., Results: Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy., Conclusion: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide., (© 2016 American Academy of Neurology.)

Whether autoimmune mechanisms play a role in the pathogenesis of inclusion body myositis (IBM) is unknown. Human leukocyte antigen (HLA) analysis in 52 patients, including 17 with autoimmune disorders (AIDs), showed that patients were more likely to have antigens from the autoimmune-prone HLA-B8-DR3 ancestral haplotype than healthy control subjects, irrespective of the presence of AIDs. Patients lacked the apparently protective HLA-DR53 antigen. The results provide further support for an autoimmune basis in IBM.

The sera of patients with Lambert-Eaton myasthenic syndrome (LEMS) contain autoantibodies against several extracellular and intracellular components of the voltage-gated calcium channel (VGCC)/synaptic vesicle release complex. An example of the latter are anti-beta-subunit antibodies (anti-MysB antibodies). We constructed a full-length cDNA clone of a human VGCC beta-subunit to produce purified beta-subunit fusion protein (MysB protein). Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS. The presence of anti-beta-subunit antibodies was closely associated with high titers of P/Q- and N-type VGCC antibodies. Immunization of rats with the purified MysB protein induced high antibody titers, but no signs of neurologic dysfunction were found. We conclude that anti-beta-subunit antibodies are not likely to interfere with ion channel function, but their presence could explain the cross-reactivity of LEMS sera with several subtypes of VGCCs and the lack of correlation between anti-VGCC antibody titer and clinical severity of disease.