AbstractObjectiveStereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo‐EEG) may miss seizure onset elsewhere. We hypothesized that stereo‐EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2‐year outcomes of patients who underwent single‐fiber SLAH after stereo‐EEG and evaluated whether stereo‐EEG SOPs predict postoperative seizure freedom.MethodsThis retrospective five‐center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo‐EEG followed by single‐fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2‐year Engel I classification or recurrent seizures before then, stratified by SOP category.ResultsFifty‐eight patients were included, with a mean follow‐up duration of 39 ± 12 months after SLAH. Overall 1‐, 2‐, and 3‐year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low‐voltage fast activity or low‐frequency repetitive spiking, had a 46% 2‐year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log‐rank test, p = .00015).SignificancePatients who underwent SLAH after stereo‐EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.