Neurologic immune-related adverse events from immune checkpoint inhibitors: recent advances and future prospectives

Immune checkpoint inhibitors (ICI) have transformed cancer therapy but can disrupt immune tolerance, causing immune-related adverse events (irAE) in various organs. ICI-induced neurological irAE encompass a heterogeneous spectrum of central and peripheral nervous system disorders. A recently proposed diagnostic algorithm recommends first excluding alternative etiologies, then confirming neuroinflammation using laboratory or radiological evidence. The clinical presentation of neurological irAE is often atypical and may go unrecognized in routine practice, and the impact of irAE on morbidity and mortality is disproportionately high, particularly in phenotypes with overlapping cardiac or respiratory involvement. These facts, along with the early onset, rapid progression, and frequent corticosteroid-refractoriness characteristic of many neurological irAE, underscore the need for heightened clinical vigilance and rapid initiation of immunomodulatory therapy. Targeted biologics are also under active investigation in response to the growing recognition of corticosteroid-refractory neurological irAE. Triple M syndrome-the concurrent occurrence of ICI-induced myasthenia, myositis, and myocarditis-represents the most severe and life-threatening irAE. Certain high-risk populations, including patients with pre-existing neurological autoimmune diseases, thymoma, or paraneoplastic neurologic syndromes, may be predisposed to this and other severe neurological irAE. Future research should focus on refining predictive biomarkers, including autoantibody profiles, cytokine signatures, and neuro-injury markers.