Objective:To improve myasthenia gravis (MG) autoantibody testing.Methods:MG serological tests with confirmatory or refuting clinical-electrodiagnostic (EDX) testing and cancer evaluations were reviewed over 4-years (2012-2015). All patients had acetylcholine-receptor-binding (AChR-Bi), modulating (AChR-Mo) and striational (STR) autoantibody testing, and negatives reflexed to muscle-specific-kinase (MuSK). Thymoma and cancer occurrences were correlated with STR and reflexed glutamic-acid-decarboxylase-65 (GAD65), ganglionic-acetylcholine-receptor (alpha-3), collapsin-response-mediating-protein-5 (CRMP5), and voltage-gated-potassium-channel-complex (VGKC) autoantibodies.Results:Of 433 tested, 133 (31%) met clinical-EDX criteria for MG. Best sensitivity (90%) occurred at AChR-Bi>0.02nmol/L, leaving 14 negative (6-ocular-MG, 7-generalized-MG, 1-MuSK-MG) with specificity 90% (31 false-positives). Using AChR-Mo antibodies (>20% loss) specificity was better (92%, 24 false-positives), however sensitivity dropped (85%). Specificity improved (95%) by testing AChR-Mo when AChR-Bi are positives, resulting in 45% reduction of false-positives (31 to 17), maintaining AChR-Bi 90% sensitivity. Cut-off values recommended by area-under-curve analysis did not outperform this approach. AChR-Bi and AChR-Mo values were significantly higher in true-positives. Computed tomography (CT) evaluations in 121 MG revealed 16 thymomas. Historical or subsequent cancers occurred in 22. STR and reflexed autoantibodies were not more common in MG with thymoma or other cancers. Full-body CT (n=34) was performed in those with STR and reflex autoantibody positivity, but without additional cancers found.Conclusion:Accuracy of MG serological testing is improved by reflexing AChR-Bi positive cases to AChR-Mo. STR and other reflexed cancer evaluation autoantibodies did not provide value beyond standard CT-chest imaging at the time of MG diagnosis. Diagnostic certainty is informed by AChR-Bi and AChR-Mo with higher values increasing specificity.

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Background Anti‐cytosolic 5′‐nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results. Methods We first searched for patients, seen in our clinics, tested for anti‐cN1A antibodies between December 2015 and December 2019. We identified 92 patients who were diagnosed with sIBM, according to the 2011 ENMC or Griggs et al criteria. Thereafter, we reviewed and compared the clinical and investigational findings of these patients in relation to their antibody status. Results Anti‐cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value, or presence of myotonic discharges on EMG. Anti‐cN1A antibody positive patients appeared to have more frequent auto‐aggressive inflammation on muscle biopsy but not as an isolated myopathological feature. Conclusions Our study showed that anti‐cN1A antibody positive and negative sIBM patients have similar clinical features and disease severity. Anti‐cN1A antibodies in our sIBM cohort did not correlate with any studied clinical or laboratory parameter and, therefore, were of limited value in the patient's assessment.

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.