OBJECTIVE: Clinical observation of autonomic signs during seizures can aid in localizing the epileptogenic zone (EZ). We performed a systematic review and meta-analysis to evaluate the localizing value of ictal cutaneous phenomena-piloerection, sweating, pallor, and flushing-in focal epilepsy and their relevance to presurgical evaluation. METHODS: Following PRISMA guidelines, a systematic search of PubMed and EMBASE was conducted up to June 1, 2025. We included studies describing spontaneous ictal cutaneous signs identified via video-EEG in patients with focal epilepsy. We assessed risk of bias using QUADAS-2, confidence in EZ localization, and certainty of evidence using GRADE. A meta-analysis was performed to calculate summary odds estimates where data were available. RESULTS: Piloerection (31 studies; 100 patients) exhibited the most robust evidence, with 92% of patients showing temporal lobe involvement (High GRADE evidence). Ictal pallor (3 studies; 13 patients) was strongly associated with temporal lobe epilepsy (76.9%), showing a specific tendency toward left-sided lateralization and favorable post-surgical outcomes. Flushing (4 studies; 9 patients) was associated with posterior quadrant involvement (High GRADE evidence), whereas evidence linking it to the temporal lobe was of low GRADE. Ictal sweating (9 studies; 11 patients) was primarily observed in temporal lobe cases, but conclusions were limited by insufficient surgical validation and high heterogeneity. Most of the included literature consisted of case reports, with a high risk of selection and assessment bias. CONCLUSIONS: Ictal cutaneous symptoms offer distinct localizing utility in epilepsy. Piloerection and pallor serve as reliable "red flags" for temporal lobe involvement, whereas flushing is indicative of a posterior quadrant origin. Despite the limitations of current evidence-primarily retrospective case reports-these autonomic signs provide valuable supporting data for multimodal localization of the epileptogenic zone.
Rocamora et al. (2026) studied this question.