Objective

To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain.

Methods

A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected.

Results

The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026).

Conclusion

There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

中文翻译：

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威尔逊病患者不同疾病分期不同致病因素的研究

客观的

研究威尔逊病（WD）患者在不同阶段，大脑中存在不同的致病因素，如金属沉积、氧化应激和炎症反应。

方法

共有 32 名未经治疗的 WD 患者和 10 名正常对照者参加了该研究。使用改良的 Young 量表评估神经系统症状。进行了肝功能、金属代谢、磁敏感加权成像（SWI）、弥散张量成像（DTI）和磁共振波谱（MRS）检查。临床疾病分期根据影像学结果分为金属沉积期、纤维损伤期和神经元坏死期。24小时尿铜、血清铜、血清铁含量；以及过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GSH-PX)、丙二醛 (MDA)、一氧化氮 (NO)、一氧化氮合酶 (NOS)、超氧化物歧化酶 (SOD)、白细胞介素 (IL-1) 和肿瘤的水平检测到坏死因子α（TNF-α）。

结果

神经元坏死期WD患者尿铜含量低于金属沉积期（P  = 0.011）和纤维损伤期（P  = 0.023）。 纤维损伤阶段WD患者NOS（P  = 0.039）和NO（P = 0.047）含量高于正常对照组，而GSH-PX（P  = 0.025）和CAT（P  = 0.041）在神经元坏死阶段较低。在神经元坏死阶段，IL-1（P  = 0.030）和TNF-α水平高于正常对照（P  = 0.042）。纤维损伤患者神经症状评分（P = 0.013）和神经元损伤高于金属沉积（P  = 0.026）。

结论

WD的不同阶段有不同的致病因素。在神经元坏死阶段，WD 患者的铜沉积减少。在纤维损伤和神经元坏死阶段，WD患者存在氧化应激损伤。在神经元坏死阶段，WD 患者有炎症反应。