Clinical features which predict neuronal surface autoantibodies in new-onset focal epilepsy: implications for immunotherapies

Abstract

ObjectiveTo 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.MethodsProspective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.Results10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. 9/23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (p<0.0001). Multivariate analysis identified six features which predicted autoantibody positivity (area under the curve=0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, MRI limbic system changes and the absence of conventional epilepsy risk factors. 11/14 (79%) 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<0.05).ConclusionsSeizure 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 suggests 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.

Autoimmune encephalitis: clinical spectrum and management

“…However, only recently have studies combined accurate clinical phenotyping with the autoantibody results in unselected populations. 23 24 These largely concur with our routine clinical experience: patients who have unselected new-onset seizures, neuronal surface autoantibodies and an immunotherapy-responsive syndrome typically have mild features of autoimmune encephalitis, such as cognitive and mood features, specific seizure semiologies, dysautonomia and limbic MRI changes. This clinically-driven assessment approach aims to limit unfruitful or equivocal immunotherapy trials in patients attending epilepsy clinics.…”

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

“…For instance, focal epileptic seizures or behavioral changes may occur in isolation at onset but often evolve rapidly to status epilepticus and/or encephalopathy, which can help diagnostically to distinguish from isolated epilepsy, psychiatric disorders, or typical neurodegenerative dementia (30)(31)(32). Different scoring systems have been designated to help clinicians determine the likelihood of autoantibody detection in patients with different neurological manifestations (33)(34)(35). Viral-like prodromes or vaccinations are not uncommon at or before symptom onset (26)(27)(28)36).…”

Brain FDG‐PET findings in glutamic acid decarboxylase antibody‐associated epilepsy

“…Some of them are: adult onset of seizures above 30 years old, antiepileptic drug‐resistance, new‐onset refractory status epilepticus, no risk factors for seizures, personal or familiar history of autoimmune diseases, neuropsychiatric changes, autonomic dysfunction, viral prodrome, recent or past neoplasia, or evidence of central nervous system (CNS) inflammation by lumbar puncture or MRI. It is important to highlight that there are no strict criteria to diagnose autoimmune‐associated epilepsy 5,6 …”