The Search for Autoimmune-Associated Epilepsy Continues - Are We Getting Closer to Our Target?

Clinical Features Which Predict Neuronal Surface Autoantibodies in New-Onset Focal Epilepsy: Implications for Immunotherapies McGinty RN, Handel A, Moloney T, et al. J Neurol Neurosurg Psychiatry. 2020;92(3):291-294. doi:10.1136/jnnp-2020-325011 Objective: To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy and evaluate the value of immunotherapy in this clinical setting. Methods: Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy. Results: A total of 10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. Nine of 23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (P <.0001). Multivariate analysis identified 6 features which predicted autoantibody positivity (area under the curve = 0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, magnetic resonance imaging limbic system changes, and the absence of conventional epilepsy risk factors. Eleven (79%) of 14 patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score = 0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (P <.05). Conclusions: Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggest immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis. : Antibodies Contributing to Focal Epilepsy Signs and Symptoms Score. de Bruijn M, Bastiaansen AEM, Mojzisova H, et al. Ann Neurol. 2021;89(4):698-710. doi:https://doi.org/10.1002/ana.26013. Objective: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology and to create a score to preselect patients requiring testing. Methods: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. Results: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty (3.4%) patients had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-d-aspartate receptor, and 13 had antiglutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10 000 IU/mL). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% CI = 19.6-3332.2, P <.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, P =.0005), behavioral changes (OR = 12.3, 95% CI = 3.2-49.9, P =.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, P =.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, P =.009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, P =.005). The internally validated C-statistic was 0.95 and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%. Interpretation: Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. © The Author(s) 2021.