Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis

Epilepsy Behav. 2016 Dec:65:18-24. doi: 10.1016/j.yebeh.2016.10.016. Epub 2016 Nov 15.

Abstract

Objective: To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies.

Methods: Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption.

Results: Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p<0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p<0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p<0.05) over time.

Conclusions: Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.

Keywords: Epilepsy; GAD65 autoantibodies; Immunotherapy; Limbic encephalitis; Paraneoplastic autoantibodies.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Case-Control Studies
  • Cognition Disorders / blood
  • Cognition Disorders / immunology
  • Cognition Disorders / therapy*
  • Epilepsy / blood
  • Epilepsy / immunology
  • Epilepsy / therapy*
  • Female
  • Follow-Up Studies
  • Glutamate Decarboxylase* / blood
  • Humans
  • Immunotherapy / methods*
  • Limbic Encephalitis / blood
  • Limbic Encephalitis / immunology
  • Limbic Encephalitis / therapy*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Retrospective Studies
  • Seizures / blood
  • Seizures / immunology
  • Seizures / therapy*

Substances

  • Autoantibodies
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2