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

J Neurol Neurosurg Psychiatry. 2021 Mar;92(3):291-294. doi: 10.1136/jnnp-2020-325011. Epub 2020 Nov 20.


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: 10.5% (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).

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 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.

Keywords: autoimmune encephalitis; epilepsy; neuroimmunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / blood*
  • Cohort Studies
  • Encephalitis / blood
  • Encephalitis / etiology
  • Epilepsies, Partial / blood*
  • Epilepsies, Partial / immunology*
  • Epilepsies, Partial / therapy
  • Female
  • Humans
  • Immunotherapy*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Predictive Value of Tests
  • ROC Curve
  • Young Adult


  • Autoantibodies
  • Nerve Tissue Proteins