BACKGROUND There is paucity of studies on predictors of seizures in Wilson disease with neurological manifestation (WDNM), and none has evaluated the role of copper (Cu) induced oxidative stress, proinflammatory and excitotoxicity in the genesis of seizure. OBJECTIVES To report frequency, refractoriness, and outcome of seizure in WDNM. We also evaluate role of Cu induced oxidative stress, excitotoxicity and cytokines in predicting seizures. METHODS The diagnosis of WDNM was based on clinical, MRI, KF ring and 24 h urinary Cu. Detailed clinical examination including severity of WD, occurrence of seizure, seizure semiology, antiepileptic drug (AED) and breakthrough seizures were noted. Cranial MRI and electroencephalography findings were noted. Serum free-Cu, oxidative stress markers (glutathione, total antioxidant capacity, malondialdehyde), glutamate and cytokines (interleukin 6, 8 and 10 and tumour necrosis factor α) were measured by atomic absorption spectrophotometer, spectrophotometer, fluorometer and flow cytometer respectively, and correlated with seizures. Patients were treated with zinc with or without penicillamine, and those with epilepsy received second-generation antiepileptic drugs (AEDs). RESULTS Out of 110 patients with WDNM, 16(14.5%) had seizures; focal in 11(68.7%) and generalized in 5(31.3%). Patients with seizure had higher serum free-Cu (35.87 ± 1.34 vs 31.72 ± 0.68; P = 0.02), severe dystonia (P = 0.04), and more frequent cortical (100% vs 6.4%; P < 0.01) and subcortical (81.3% vs 20.2%; P < 0.01) lesions on MRI compared to those without seizure. Oxidative stress markers (glutathione, total antioxidant capacity, malondialdehyde), cytokines and glutamate were elevated in WDNM compared to controls. On multivariate logistic regression analysis, cortical involvement (OR = 105.49; 95%CI = 8.74-1272.39; P < 0.01) and number of MRI lesions (OR = 1.99; 95% CI = 1.11-3.57; P = 0.02) were independent predictors of seizure. The seizures were controlled with single and dual AEDs in seven patients each, and two patients needed three AEDs. All the patients had seizure remission for a median follow up of 66(24-180) months. CONCLUSION About one-sixth WDNM patients have seizures especially in those with cortical and extensive MRI lesions. Seizures are easily controlled by AEDs.

中文翻译：

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威尔逊病发作的预测因素：一项临床放射学和生物标志物研究。

背景技术关于具有神经学表现（WDNM）的威尔逊病中癫痫发作的预测因子的研究很少，并且还没有评估铜（Cu）引起的氧化应激，促炎性和兴奋性毒性在癫痫发作中的作用。目的报告WDNM的发作频率，难治性和癫痫发作结果。我们还评估了铜诱导的氧化应激，兴奋性毒性和细胞因子在预测癫痫发作中的作用。方法WDNM的诊断基于临床，MRI，KF环和24 h尿铜。记录了详细的临床检查，包括WD的严重程度，癫痫发作的发生，癫痫发作的符号学，抗癫痫药（AED）和突破性癫痫发作。记录了颅骨MRI和脑电图检查结果。血清游离铜，氧化应激指标（谷胱甘肽，总抗氧化能力，丙二醛），用原子吸收分光光度计，分光光度计，荧光计和流式细胞仪分别测定谷氨酸和细胞因子（白细胞介素6、8和10以及肿瘤坏死因子α），并与癫痫发作相关。患者接受含或不含青霉素的锌治疗，患有癫痫的患者接受第二代抗癫痫药（AED）。结果在110例WDNM患者中，有16例（14.5％）发作。集中在11（68.7％），泛泛在5（31.3％）。癫痫发作患者的血清游离铜水平较高（35.87±1.34 vs 31.72±0.68; P = 0.02），重度肌张力障碍（P = 0.04），皮层皮质癌（100％vs 6.4％; P <0.01）和皮层下病变（81.3）更常见％vs 20.2％； P <0.01）MRI病变与无癫痫发作的病变相比。氧化应激指标（谷胱甘肽，总抗氧化能力，丙二醛），与对照组相比，WDNM中的细胞因子和谷氨酸盐升高。在多因素logistic回归分析中，皮层受累（OR = 105.49; 95％CI = 8.74-1272.39; P <0.01）和MRI病变数目（OR = 1.99; 95％CI = 1.11-3.57; P = 0.02）是独立的预测因子癫痫发作。癫痫发作由一次和两次AED控制，每例7例，两名患者需要3例AED。所有患者均发作缓解，中位随访66（24-180）个月。结论大约六分之一的WDNM患者出现癫痫发作，尤其是那些皮质和广泛MRI病变的患者。癫痫发作很容易被AED控制。11-3.57；P = 0.02）是癫痫发作的独立预测因子。癫痫发作由一次和两次AED控制，每例7例，两名患者需要3例AED。所有患者均发作缓解，中位随访66（24-180）个月。结论大约六分之一的WDNM患者出现癫痫发作，尤其是那些皮质和广泛MRI病变的患者。癫痫发作很容易被AED控制。11-3.57；P = 0.02）是癫痫发作的独立预测因子。癫痫发作由一次和两次AED控制，每例7例，两名患者需要3例AED。所有患者均发作缓解，中位随访66（24-180）个月。结论大约六分之一的WDNM患者出现癫痫发作，尤其是那些皮质和广泛MRI病变的患者。癫痫发作很容易被AED控制。