Serum α-synuclein and IL-1β are increased and correlated with measures of disease severity in children with epilepsy: Potential prognostic biomarkers?

Abstract

Background The search for noninvasive biomarkers of neuroinflammation and neurodegeneration has focused on various neurological disorders, including epilepsy. We sought to determine whether alpha-synuclein and cytokines are correlated with the degree of neuroinflammation and/or neurodegeneration in children with epilepsy and with acquired demyelinating disorders of the central nervous system (CNS), as a prototype of autoimmune neuroinflammatory disorders. Methods We analyzed serum and exosome levels of alpha-synuclein and serum proinflammatory and anti-inflammatory cytokines among 115 children with epilepsy and 10 acquired demyelinating disorders of the CNS and compared to 146 controls. Patients were enrolled prospectively and blood was obtained from patients within 48 h after acute afebrile seizure attacks or relapse of neurological symptoms. Acquired demyelinating disorders of the CNS include acute disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica spectrum disorders, and transverse myelitis. The controls were healthy age-matched children. The serum exosomes were extracted with ExoQuick exosome precipitation solution. Serum alpha-synuclein levels and serum levels of cytokines including IFN-beta, IFN-gamma, IL-1 beta, IL-6, IL-10 and TNF-alpha were measured using single and multiplex ELISA kits. Data were analyzed and compared with measures of disease severity, such as age at disease onset, duration of disease, and numbers of antiepileptic drug in use. Results Serum alpha-synuclein levels were significantly increased in patients with epilepsy and acquired demyelinating disorders of the CNS compared to controls (both, p < 0.05) and showed correlation with measures of disease severity both in epilepsy (p < 0.05, r = 0.2132) and in acquired demyelinating disorders of the CNS (p < 0.05, r = 0.5892). Exosome alpha-synuclein showed a significant correlation with serum alpha-synuclein (p < 0.0001, r = 0.5915). Serum IL-1 beta levels were correlated only with the numbers of antiepileptic drug used in children with epilepsy (p < 0.001, r = 0.3428), suggesting drug resistant epilepsy. Conclusions This is the first study in children demonstrating that serum alpha-synuclein levels were significantly increased in children with epilepsy and with acquired demyelinating disorders of the CNS and correlated with measures of disease severity. Serum IL-1 beta levels showed significant correlation only with drug resistance in children with epilepsy. Thus, these data support that serum levels of alpha-synuclein and IL-1 beta are potential prognostic biomarkers for disease severity in children with epilepsy. CNS, central nervous system.