Fundamental mechanistic insights from rare but paradigmatic neuroimmunological diseases

In this Review, Wiendl et al. consider how the study of rare but paradigmatic neuroimmunological diseases, including Susac syndrome, Rasmussen encephalitis and narcolepsy type 1, is providing fundamental insights into disease mechanisms that can be applied to more complex, heterogeneous neuroimmunological diseases such as multiple sclerosis. 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.

Automated summary

This review discusses how insights from rare neuroimmunological diseases can provide fundamental understanding of disease mechanisms that can be applied to more complex diseases, and how these insights can be relevant to the study of other neuroimmunological diseases.