Serum α-Synuclein in Pediatric Refractory Epilepsy: Correlation with Diagnosis and Clinical Severity

<i>Background and Objectives:</i> Epilepsy is a common neurological disrupt that involves recurring seizures. α-Synuclein (α-Syn), one of the most abundant proteins in the nervous system, is implicated in both neurodegenerative conditions and epilepsy. This study aimed to assess serum α-Syn levels in children with drug-resistant epilepsy (DRE) and explore the relationship with diagnosis and clinical severity. <i>Materials and Methods:</i> This cross-sectional study was carried out at the Pediatric Neurology Outpatient Clinic of Beni-Suef University Hospital. It involved 30 children with DRE, 30 with drug-responsive epilepsy, and 30 age- and sex-matched healthy controls. Serum α-Syn levels were evaluated using enzyme-linked immunosorbent assay (ELISA). <i>Results:</i> Serum α-Syn levels were significantly higher in children with epilepsy compared to healthy controls (<i>p</i> < 0.001), with significantly high levels observed in drug-resistant cases versus drug-responsive ones (<i>p</i> < 0.001). Receiver operating characteristic (ROC) investigation confirmed that α-Syn effectively distinguished epilepsy patients from healthy controls, yielding an area under the curve (AUC) of 0.773. It also successfully differentiated between drug-responsive and drug-resistant epilepsy, with an AUC of 0.858. Further analysis revealed significant positive correlations between serum α-Syn levels and the frequency of hospitalizations due to seizures, the number of anti-epileptic drugs (AEDs) prescribed, and monthly seizure frequency (<i>p</i> = 0.018, 0.009, and <0.001, respectively). In contrast, α-Syn levels were negatively associated with the time since the last seizure and the age at seizure onset (<i>p</i> = 0.001 and 0.016, respectively). <i>Conclusions:</i> Serum α-Syn levels are elevated in epilepsy patients, particularly those with drug-resistant epilepsy, suggesting its potential role as a biomarker for disease severity and treatment resistance.