Ortiz Juan Fernando, Morillo Cox Álvaro, Tambo Willians, Eskander Noha, Wirth Martín, Valdez Margarita, Niño Maria
Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Medicine, Universidad San Francisco de Quito, Quito, ECU.
Cureus. 2020 Nov 16;12(11):e11509. doi: 10.7759/cureus.11509.
Wilson's disease (WD) is an autosomal recessive disease that presents mainly with hepatic, neurological, and psychiatric manifestations. Neurological manifestations have been described in the past. Nevertheless, the pathophysiology and the clinical relevance of these manifestations have not been described in great detail in the medical literature. We aim to consolidate the knowledge about the neurological manifestations of WD and present the pathophysiology of each neurological manifestation of the disease. We will give a brief definition, the provenance, and the pathophysiology of the neurological conditions. We collected data from the National Library of Medicine (PubMed) using regular keywords and medical subject headings. Studies were selected applying the following inclusion/exclusion criteria: (1) studies that used exclusively human subjects, (2) papers published in English, and (3) papers from 1990 onward. The exclusion criteria were (1) studies that used animals, (2) papers not published in English, and (3) papers published before 1990. Additional studies were included via reference lists of identified papers and related articles featured in PubMed and Google Scholar. Copper toxicity is the principal factor for brain degeneration seen in WD. Parkinsonism seen in WD has been associated with a nigrostriatal dopaminergic deficit. Resting tremor may have the same pathophysiology as parkinsonism. Action tremor is related to an accumulation of copper in the cerebellum's vermis and hemispheres. At the same time, essential tremor can be explained due to affection of the dentate nucleus. Choreoathetosis is produced due to increased activity of the direct pathway. We did not find specifically associated pathophysiology related to dysarthria. We assume that multiple parts of the brain are involved in that problem. Putamen nucleus damage is the leading cause that explains dystonia seen in WD along with the globus palidus. We did not find a specific localization for seizures in WD, but the pathology seems to be related to decreased levels of B6 and direct toxicity of copper on the brain.
威尔逊病（WD）是一种常染色体隐性疾病，主要表现为肝脏、神经和精神方面的症状。过去已有关于神经症状的描述。然而，这些症状的病理生理学及临床相关性在医学文献中尚未得到详细阐述。我们旨在整合有关WD神经症状的知识，并阐述该疾病各神经症状的病理生理学。我们将简要介绍神经疾病的定义、来源及病理生理学。我们使用常规关键词和医学主题词从美国国立医学图书馆（PubMed）收集数据。研究选择采用以下纳入/排除标准：（1）仅使用人类受试者的研究；（2）英文发表的论文；（3）1990年以后发表的论文。排除标准为：（1）使用动物的研究；（2）非英文发表的论文；（3）1990年以前发表的论文。通过已识别论文的参考文献列表以及PubMed和谷歌学术搜索中特色的相关文章纳入其他研究。铜毒性是WD中所见脑变性的主要因素。WD中出现的帕金森症与黑质纹状体多巴胺能缺陷有关。静止性震颤可能与帕金森症具有相同的病理生理学。动作性震颤与小脑蚓部和半球中铜的蓄积有关。同时，原发性震颤可归因于齿状核受累。舞蹈手足徐动症是由于直接通路活性增加所致。我们未发现与构音障碍具体相关的病理生理学。我们推测该问题涉及大脑的多个部位。壳核损伤是解释WD中所见肌张力障碍的主要原因，苍白球也与之相关。我们未发现WD中癫痫发作的特定定位，但病理似乎与维生素B6水平降低以及铜对大脑的直接毒性有关。
