Electroclinical features and dynamic network connectivity of orbitofrontal epilepsy

OBJECTIVE: Orbitofrontal epilepsy (OFE) is rare and underrecognized. This study aims to characterize electroclinical features and dynamic network connectivity of OFE and subtypes. METHODS: We retrospectively analyzed 17 patients with OFE who underwent stereoelectroencephalographic (SEEG) electrode implantation and epilepsy surgery at our center. Thirteen patients with available ictal SEEG recordings were further categorized into lateral (LOFE, n = 6), medial (MOFE, n = 5), and posterior (POFE, n = 2) subtypes. Clinical semiology, scalp electroencephalographic (EEG), neuroimaging, and SEEG data were analyzed. Directed functional connectivity was evaluated in 22 seizures from 13 patients using pairwise nonlinear regression across ictal stages. RESULTS: The mean seizure duration was 68.4 s. Semiology was heterogeneous, with impaired consciousness being the most common manifestation (47.1%), frequently evolving into elementary motor phenomena (62.5%) or automatisms (37.5%). Hyperkinetic behavior (23.5%) and focal to bilateral tonic-clonic seizures (29.4%) were also observed. This heterogeneity may relate to propagation to frontal, cingulate, insular, and temporal regions. In 13 patients with available ictal SEEG recordings, EEG seizure activity preceded clinical onset, with a mean electroclinical delay of 28.9 s. LOFE most often showed nonspecific auras and early motor manifestations; MOFE was associated with autonomic auras and automatisms; and POFE frequently presented with fear auras. Functional connectivity increased from early to late ictal periods and remained elevated postictally. Connectivity differences between LOFE and MOFE were confined to the seizure onset and early propagation phases, with LOFE showing stronger lateral frontal interactions and MOFE stronger medial frontal-cingulate/insula interactions. SEEG resolved frequent mislocalizations by scalp EEG/imaging. Most patients achieved favorable outcomes (Engel class I: 84.6%, mean follow-up = 52.1 months, 11/13), and focal cortical dysplasia was the most common pathology (76.9%, 10/13). SIGNIFICANCE: OFE subtypes tend to show different semiological features and preferential connectivity patterns, potentially related to differential engagement of frontal-limbic networks. Targeted SEEG is associated with accurate localization and generally favorable outcomes in this cohort.