Importance: The literature on neural autoantibody positivity in epilepsy has expanded over the last decade, with an increased interest among clinicians in identifying potentially treatable causes of otherwise refractory seizures.
Observations: Prior studies have reported a wide range of neural autoantibody positivity rates among various epilepsy populations, with the highest frequency reported in individuals with focal epilepsy of unknown cause and new-onset seizures. The antibodies in some cases are of uncertain significance, and their presence can cause conundrums regarding therapy.
Conclusions and relevance: There is likely some role for neural autoantibody assessment in patients with unexplained epilepsy who lack clear evidence of autoimmune encephalitis, but the clinical implications of such testing remain unclear owing to limitations in previous published studies. A framework for study design to bridge the current gaps in knowledge on autoimmune-associated epilepsy is proposed.