The Five Sign: A hand posture suggesting insulo-opercular involvement in focal seizures.

OBJECTIVE: The Five Sign is a previously underrecognized ictal hand posture characterized by full extension and spreading of the fingers. We aimed to determine its localizing value and underlying network basis in patients with drug-resistant focal epilepsy. METHODS: We retrospectively analyzed 510 patients with drug-resistant focal epilepsy, including 34 patients exhibiting Five Sign-positive seizures. The association between Five Sign and epileptogenic zone (EZ) localization was quantified using sensitivity, specificity, likelihood ratios, and odds ratios. Hierarchical cluster analysis was performed to characterize co-occurring semiological features, and the relationship between the temporal evolution of the Five Sign and EZ distribution was examined. Multimodal evaluation included interictal Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) group analysis and stereoelectroencephalography (SEEG)-based epileptogenicity mapping. RESULTS: Five Sign demonstrated a strong preferential association with insulo-opercular (IO) epilepsy, showing the highest prevalence in IO cases (23.7%) and the highest positive predictive value for IO localization (64.7%). The presence of Five Sign significantly increased the likelihood of IO localization (p < .001). Hierarchical cluster analysis revealed a distinct temporal organization of Five Sign seizures, with aura symptoms typically preceding the sign, orofacial, tonic, and autonomic manifestations co-occurring with it, and complex motor behaviors emerging afterward. Temporal phase analysis showed that early-phase Five Sign was strongly associated with IO EZs, whereas later-phase Five Sign was more frequently associated with extra-insular EZs (p < .01). Group-level 18F-FDG-PET analysis revealed hypometabolism centered in the anterior-mid-dorsal insula with extension to striatum and medial pulvinar. Epileptogenicity mapping demonstrated convergent seizure-onset involvement within the IO region and premotor cortex, supporting a distributed motor-related network. SIGNIFICANCE: The Five Sign is a highly specific semiological marker of IO epilepsy and reflects engagement of a distinct cortico-subcortical network centered on the posterior IO region. Recognition of the Five Sign may refine presurgical localization hypotheses and guide invasive monitoring strategies.