The pathophysiology of complex neuroimmunological diseases, such as multiple sclerosis and autoimmune encephalitis, remains puzzling — various mechanisms that are difficult to dissect seem to contribute, hampering the understanding of the processes involved. Some rare neuroimmunological diseases are easier to study because their presentation and pathogenesis are more homogeneous. The investigation of these diseases can provide fundamental insights into neuroimmunological pathomechanisms that can in turn be applied to more complex diseases. In this Review, we summarize key mechanistic insights into three such rare but paradigmatic neuroimmunological diseases — Susac syndrome, Rasmussen encephalitis and narcolepsy type 1 — and consider the implications of these insights for the study of other neuroimmunological diseases. In these diseases, the combination of findings in humans, different modalities of investigation and animal models has enabled the triangulation of evidence to validate and consolidate the pathomechanistic features and to develop diagnostic and therapeutic strategies; this approach has provided insights that are directly relevant to other neuroimmunological diseases and applicable in other contexts. We also outline how next-generation technologies and refined animal models can further improve our understanding of pathomechanisms, including cell-specific and antigen-specific CNS immune responses, thereby paving the way for the development of targeted therapeutic approaches.

多发性硬化症和自身免疫性脑炎等复杂神经免疫疾病的病理生理学仍然令人费解——各种难以剖析的机制似乎都在起作用，阻碍了对相关过程的理解。一些罕见的神经免疫疾病更容易研究，因为它们的表现和发病机制更加同质。对这些疾病的研究可以提供对神经免疫病理机制的基本见解，进而可以应用于更复杂的疾病。在这篇综述中，我们总结了对三种罕见但典型的神经免疫疾病——Susac 综合征、Rasmussen 脑炎和 1 型发作性睡病——的关键机制见解，并考虑了这些见解对其他神经免疫疾病研究的意义。在这些疾病中，人类的发现、不同的调查方式和动物模型的结合使得证据的三角测量能够验证和巩固病理机制特征并制定诊断和治疗策略；这种方法提供了与其他神经免疫疾病直接相关并适用于其他情况的见解。我们还概述了下一代技术和改进的动物模型如何进一步提高我们对病理机制的理解，包括细胞特异性和抗原特异性 CNS 免疫反应，从而为靶向治疗方法的开发铺平道路。不同的调查方式和动物模型使证据的三角测量能够验证和巩固病理机制特征并制定诊断和治疗策略；这种方法提供了与其他神经免疫疾病直接相关并适用于其他情况的见解。我们还概述了下一代技术和改进的动物模型如何进一步提高我们对病理机制的理解，包括细胞特异性和抗原特异性 CNS 免疫反应，从而为靶向治疗方法的开发铺平道路。不同的调查方式和动物模型使证据的三角测量能够验证和巩固病理机制特征并制定诊断和治疗策略；这种方法提供了与其他神经免疫疾病直接相关并适用于其他情况的见解。我们还概述了下一代技术和改进的动物模型如何进一步提高我们对病理机制的理解，包括细胞特异性和抗原特异性 CNS 免疫反应，从而为靶向治疗方法的开发铺平道路。