Abstracts

Rationale: Anti-neuronal antibodies represent an increasingly recognized cause of epilepsy. Observational and retrospective data have shown that not only do autoimmune epilepsies tend to be refractory to antiepileptic drugs (AEDs), but antibodies targeting intracellular antigens harbour a worse prognosis and exhibit a poorer response to immunotherapy than those targeting cell-surface receptors. We compared patients with antibodies to anti-Ma2 to patients with leucine-rich glioma inactivated-1 (LGI1) to explore the potential differences between epilepsy secondary to each of these antibody subtypes.Methods: We gathered the clinical and EEG data on nine patients with autoimmune epilepsy, including three patients with anti-Ma2 antibodies and six patients with LGI1 antibodies.Results: All anti-Ma2 patients required admission to the ICU at some point during their illness, while only 1/6 patients with LGI1 did. Status epilepticus occurred in 3/3 anti-Ma2 patients and 1/6 LGI1 patients. Other neurological symptoms (narcolepsy, ophthalmoplegia, behavioural changes) were frequent among anti-Ma2 patients. Epilepsy was the predominant feature in most LGI1 patients, with mild cognitive impairment being a frequent accompanying feature. In 2/3 of anti-Ma2 patients, an underlying malignancy (testicular tumour) was identified and removed, whereas none of the LGI1 patients had a malignancy. Patients in both groups required multiple AEDs (average of 6 in patients with anti-Ma2, 4 in LGI1), with poor response in all but 1 patient with LGI1. 3/5 patients with LGI1 showed marked improvement in their seizure control after receiving immunotherapy (steroids and/or IVIg and/or PLEX), while only 1/3 patients with anti-Ma2 showed transient response to IVIg, which may have reflected a previously existing pattern of fluctuation in seizure frequency. 5/6 LGI1 patients exhibited faciobrachial or crural tonic or dystonic seizures at some point during their course. Seizure semiology suggestive of temporal lobe onset was present in 4/6 LGI1 patients and 2/3 anti-Ma2 patients. EEG revealed multifocal interictal spikes and multifocal ictal onsets in 3/3 anti-Ma2 patients. Meanwhile, there were rare or absent interictal epileptiform discharges in 5/6 LGI1 patients. One patient with anti-Ma2 underwent vagal nerve stimulation due to the refractory and multifocal nature of the epilepsy, with minimal improvement in seizure frequency.Conclusions: Patients with anti-Ma2 antibodies exhibited a more malignant course compared to patients with LGI1 antibodies. Seizures were refractory to AEDs in the majority of LGI1 patients and all anti-Ma2 patients. Anti-Ma2 patients showed a poorer response to immunotherapy than LGI1 patients, and exhibited multifocal epileptogenic foci.