Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy

Epilepsy Behav. 2018 Mar;80:331-336. doi: 10.1016/j.yebeh.2018.01.021. Epub 2018 Feb 9.

Abstract

Glutamic acid decarboxylase (GAD) antibody-associated encephalitis causes both acute seizures and chronic epilepsy with predominantly temporal lobe onset. This condition is challenging in diagnosis and management, and the incidence of GAD antibody (Ab)-related epilepsy could be much higher than commonly believed. Imaging and CSF evidence of inflammation along with typical clinical presentations, such as adult onset temporal lobe epilepsy (TLE) with unexplained etiology, should prompt testing for the diagnostic antibodies. High serum GAD Ab titer (≥2000U/mL or ≥20nmol/L) and evidence of intrathecal anti-GAD Ab synthesis support the diagnosis. Unlike other immune-mediated epilepsies, antiglutamic acid decarboxylase 65 (GAD65) antibody-mediated epilepsy is often poorly responsive to antiepileptic drugs (AEDs) and only moderately responsive to immune therapy with steroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX). Long-term treatment with more aggressive immunosuppressants such as rituximab (RTX) and/or cyclophosphamide is often necessary and may be more effective than current immunosuppressive approaches. The aim of this review is to review the physiology, pathology, clinical presentation, related ancillary tests, and management of GAD Ab-associated autoimmune epilepsy by searching the keywords and to promote the recognition and the initiation of proper therapy for this condition.

Keywords: Autoimmune encephalitis; Autoimmune epilepsy; Limbic encephalitis; Paraneoplastic limbic encephalitis.

Publication types

  • Review

MeSH terms

  • Adult
  • Antibodies / blood*
  • Autoantibodies / blood
  • Carboxy-Lyases
  • Encephalitis / diagnosis
  • Encephalitis / immunology*
  • Epilepsy / diagnosis
  • Epilepsy / drug therapy
  • Epilepsy / immunology*
  • Epilepsy, Temporal Lobe / blood
  • Epilepsy, Temporal Lobe / drug therapy
  • Epilepsy, Temporal Lobe / immunology*
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Limbic Encephalitis / diagnosis
  • Limbic Encephalitis / immunology*
  • Limbic Encephalitis / pathology
  • Personality
  • Seizures / diagnosis
  • Seizures / drug therapy
  • Seizures / immunology
  • Temporal Lobe
  • Treatment Outcome

Substances

  • Antibodies
  • Autoantibodies
  • Immunoglobulins, Intravenous
  • Carboxy-Lyases
  • Glutamate Decarboxylase