The search for noninvasive biomarkers of neuroinflammation and neurodegeneration has focused on various neurological disorders, including epilepsy. We sought to determine whether α-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. We analyzed serum and exosome levels of α-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 α-synuclein levels and serum levels of cytokines including IFN-β, IFN-γ, IL-1β, IL-6, IL-10 and TNF-α 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. Serum α-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 α-synuclein showed a significant correlation with serum α-synuclein (p < 0.0001, r = 0.5915). Serum IL-1β 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. This is the first study in children demonstrating that serum α-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-1β levels showed significant correlation only with drug resistance in children with epilepsy. Thus, these data support that serum levels of α-synuclein and IL-1β are potential prognostic biomarkers for disease severity in children with epilepsy. CNS, central nervous system.

中文翻译：

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癫痫患儿的血清α-突触核蛋白和IL-1β升高并与疾病严重程度的测量相关：潜在的预后生物标志物？

寻找神经炎症和神经变性的非侵入性生物标志物的重点在于各种神经系统疾病，包括癫痫病。我们试图确定α-突触核蛋白和细胞因子是否与癫痫和获得性中枢神经系统脱髓鞘疾病（CNS）患儿的神经炎症和/或神经变性程度相关，作为自身免疫性神经炎性疾病的原型。我们分析了115名癫痫患儿和10名获得性中枢神经系统脱髓鞘疾病患儿的血清和外泌体α-突触核蛋白水平以及血清促炎和抗炎细胞因子，并与146名对照进行了比较。对患者进行前瞻性研究，并在急性发热性癫痫发作或神经系统症状复发后48小时内从患者中采血。获得性中枢神经系统脱髓鞘疾病包括急性播散性脑脊髓炎，多发性硬化症，视神经频谱炎和横贯性脊髓炎。对照组是年龄匹配的健康儿童。用ExoQuick外泌体沉淀溶液提取血清外泌体。使用单一和多重ELISA试剂盒测量血清α-突触核蛋白水平和血清细胞因子水平，包括IFN-β，IFN-γ，IL-1β，IL-6，IL-10和TNF-α。分析数据并将其与疾病严重性的度量标准进行比较，例如疾病发作的年龄，疾病的持续时间以及使用的抗癫痫药的数量。与对照组相比，患有癫痫和中枢神经系统获得性脱髓鞘疾病的患者的血清α-突触核蛋白水平显着增加（均为p <0。05）并显示与癫痫（p <0.05，r = 0.2132）和中枢神经系统获得性脱髓鞘性疾病（p <0.05，r = 0.5892）的疾病严重程度相关。外泌体α-突触核蛋白与血清α-突触核蛋白显着相关（p <0.0001，r = 0.5915）。血清IL-1β水平仅与癫痫患儿使用的抗癫痫药的数量相关（p <0.001，r = 0.3428），表明耐药的癫痫病。这是第一项针对儿童的研究，表明儿童癫痫和获得性中枢神经系统脱髓鞘疾病的患儿血清α-突触核蛋白水平显着升高，并与疾病严重程度相关。癫痫患儿的血清IL-1β水平仅与耐药性显着相关。从而，这些数据支持血清α-突触核蛋白和IL-1β水平是癫痫儿童疾病严重程度的潜在预后生物标志物。中枢神经系统，中枢神经系统。