Localizing value of cutaneous ictal phenomena: A systematic review

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.

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.

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.

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.