Movement disorders are a prominent and common feature in many autoantibody-associated neurological diseases, a group of potentially treatable conditions that can mimic infectious, metabolic or neurodegenerative disease. Certain movement disorders are likely to associate with certain autoantibodies; for example, the characteristic dyskinesias, chorea and dystonia associated with NMDAR antibodies, stiff person spectrum disorders with GAD, glycine receptor, amphiphysin or DPPX antibodies, specific paroxysmal dystonias with LGI1 antibodies, and cerebellar ataxia with various anti-neuronal antibodies. There are also less-recognized movement disorder presentations of antibody-related disease, and a considerable overlap between the clinical phenotypes and the associated antibody spectra. In this review, we first describe the antibodies associated with each syndrome, highlight distinctive clinical or radiological 'red flags', and suggest a syndromic approach based on the predominant movement disorder presentation, age, and associated features. We then examine the underlying immunopathophysiology, which may guide treatment decisions in these neuroimmunological disorders, and highlight the exceptional interface between neuronal antibodies and neurodegeneration, such as the tauopathy associated with IgLON5 antibodies. Moreover, we elaborate the emerging pathophysiological parallels between genetic movement disorders and immunological conditions, with proteins being either affected by mutations or targeted by autoantibodies. Hereditary hyperekplexia, for example, is caused by mutations of the alpha subunit of the glycine receptor leading to an infantile-onset disorder with exaggerated startle and stiffness, whereas antibodies targeting glycine receptors can induce acquired hyperekplexia. The spectrum of such immunological and genetic analogies also includes cerebellar ataxias and some encephalopathies. Lastly, we discuss how these pathophysiological considerations could reflect on possible future directions regarding antigen-specific immunotherapies or targeting the pathophysiological cascades downstream of the antibody effects.

中文翻译：

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神经元抗体引起的运动障碍：综合征方法、遗传相似性和病理生理学。


运动障碍是许多自身抗体相关神经系统疾病的一个突出且常见的特征，这些疾病是一组可以治疗的、类似于感染性、代谢性或神经退行性疾病的潜在疾病。某些运动障碍可能与某些自身抗体有关；例如，与NMDAR抗体相关的特征性运动障碍、舞蹈症和肌张力障碍，与GAD、甘氨酸受体、两性蛋白或DPPX抗体相关的僵直人谱系障碍，与LGI1抗体相关的特异性阵发性肌张力障碍，以及与各种抗神经元抗体相关的小脑性共济失调。还存在较少被认识的抗体相关疾病的运动障碍表现，以及临床表型和相关抗体谱之间相当大的重叠。在这篇综述中，我们首先描述与每种综合征相关的抗体，强调独特的临床或放射学“危险信号”，并根据主要运动障碍表现、年龄和相关特征提出一种综合征方法。然后，我们检查潜在的免疫病理生理学，这可能指导这些神经免疫性疾病的治疗决策，并强调神经元抗体和神经变性之间的特殊界面，例如与 IgLON5 抗体相关的 tau 蛋白病。此外，我们详细阐述了遗传运动障碍和免疫状况之间正在出现的病理生理学相似之处，即蛋白质要么受到突变的影响，要么被自身抗体靶向。 例如，遗传性神经亢进症是由甘氨酸受体的α亚基突变引起的，导致婴儿期发病的疾病，伴有过度惊吓和僵硬，而针对甘氨酸受体的抗体可以诱发获得性神经亢进症。这种免疫学和遗传类比的范围还包括小脑性共济失调和一些脑病。最后，我们讨论这些病理生理学考虑因素如何反映有关抗原特异性免疫疗法或针对抗体效应下游病理生理级联的可能的未来方向。