The Five Sign: A hand posture suggesting insulo‐opercular involvement in focal seizures
Xiangzhi Lu, Weiyuan Luo, Zhengbo Zhao, Baotian Zhao, Chao Zhang, Xiu Wang, Jiajie Mo, Zhong Zheng, Xiaoqiu Shao, Jianguo Zhang, Kai Zhang, Wenhan HuAbstract
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 ( 18 F‐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 18 F‐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.