Cell‐surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

Abstract

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined.

Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study

“…In this study, we evaluated the rituximab responsiveness 1 month after the standard rituximab treatment, based tocilizumab group, at the time of monthly rituximab therapy initiation in the additional rituximab group, and at 1 month after the last cycle of weekly rituximab therapy in the observation group First-line = at initiation of first-line immunotherapies; RTX = at initiation of standardregimen weekly rituximab; RTX 1 mo = at 1 month from the initiation of weekly rituximab therapy; 1 mo = at 1 month from the baseline time points; 2 mo = at 2 months from the baseline time points; last FU = at the last clinical follow-up point on the fact that timely control of disease is essential to improve outcomes in AE [35], and that early discrimination of drug responsiveness is fundamental in the considering further treatment options. In this study, clinical improvement from standard-regimen rituximab was reported in 85/176 (48.3 %) patients [29/55 (52.7 %) for the anti-NMDA-R encephalitis subgroup].…”

Paraneoplastic neurologic disorders in small cell lung carcinoma

“…Thus the frequency of the entire range of PNDs and neuronal antibodies in SCLC has not been determined systematically. Furthermore, with the recent discovery of a new category of disorder mediated by autoantibodies against neuronal cell surface proteins such as NMDA receptor and LGI1, 8 it is important to determine whether these antibodies are present in SCLC PNDs.…”

Neuronal antibodies in pediatric epilepsy: Clinical features and long‐term outcomes of a historical cohort not treated with immunotherapy

“…In adults, autoantibodies to essential neuronal proteins such as the N ‐methyl‐ d ‐aspartate receptor (NMDAR) and the voltage gated potassium channel (VGKC)‐complex antigen, leucine rich glioma inactivated 1 (leucine rich glioma inactivated 1 (LGI1), are now widely recognized as an important treatable cause of encephalitis 1, 2. Patients present with memory loss, confusion, and seizures in limbic encephalitis with predominantly LGI1 antibodies3, 4 and neuropsychiatric features, movement, and autonomic symptoms in NMDAR‐Ab (antibody) encephalitis 5, 6.…”