Neuronal surface and intracellular antibody testing in patients with long-term epilepsy

We aimed to investigate the frequency of neuronal surface and intracellular antibodies in individuals with long-term epilepsy and the associated clinical and laboratory characteristics.

We tested sera from 223 patients with epilepsy without signs of autoimmune encephalitis and 12 patients with epilepsy and a subacute onset of additional neurological symptoms. All had epilepsy lasting at least one year. We compared clinical and laboratory characteristics between those with and without antibodies. Additionally, we assessed the ACES and APE scores, and ONES checklist for identifying patients with antibodies.

Only one of 223 patients with epilepsy and no autoimmune encephalitis signs (0.4%) had antibodies, presenting with drug-resistant mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) and GAD antibodies. She had no improvement after surgical treatment (Engel IV). Of the 12 patients with subacute onset of additional neurological symptoms, four (33.3%) had antibodies: two anti-GAD, one anti-LGI1, and one anti-Hu. Antibody-positive patients showed later epilepsy onset, had more seizure frequency fluctuations, cutaneous drug reactions, and electrographic seizures compared to antibody-negative patients. All of them had TLE, and anti-GAD cases had refractory unilateral MTLE-HS, musicogenic seizures, and temporal hypermetabolism on interictal FDG-PET. The ONES checklist had the highest sensitivity and specificity to identify patients with antibodies.

All patients with long-term epilepsy and neuronal antibodies had TLE, with 60% exhibiting MTLE-HS associated with GAD antibodies. Neuronal antibodies were rarely detected (0.4%) among patients with isolated long-term epilepsy, but when present, they were associated with specific clinical and laboratory features.

Neuronal antibodies are biological markers of autoimmune encephalitis, a condition that causes sudden and rapidly worsening cognitive decline, changes in mental state, and psychiatric symptoms, often accompanied by seizures and other neurological issues. In our study, we investigated how often these antibodies appear in patients with isolated long-term epilepsy and what clinical or laboratory characteristics are associated with them. We found neuronal antibodies only in patients with temporal lobe epilepsy. These antibodies were rare (0.4%) among patients with long-term epilepsy alone and were linked to specific clinical and laboratory features.