Neurological adverse events of immune checkpoint inhibitors: A practical guide to diagnosis with a focus on neuroimaging findings

The use of immune checkpoint inhibitors (ICIs), a class of oncologic therapies that enhance anti-tumor immunity, may be complicated by the occurrence of neurologic immune-related adverse events (n-irAEs). ICI-induced neurotoxicities predominantly affect the peripheral nervous system, manifesting as myositis, polyradiculoneuropathies and cranial neuropathies and, less frequently, involve the central nervous system, typically as encephalitis or myelitis. The diagnosis of n-irAEs relies on the exclusion of alternative etiologies - such as cancer dissemination, chemotherapy-induced neurotoxicities, and neuroinfections - and the recognition of specific clinical syndromes. Neuroradiological investigations, particularly magnetic resonance imaging (MRI), play a crucial role in ruling out differential diagnosis, mainly cancer dissemination. Furthermore, MRI can support the clinical suspicious of an immune-mediated process by demonstrating indirect signs of neuroinflammation, including tissue edema and gadolinium enhancement. Nuclear medicine techniques, such as position emission tomography and scintigraphy, may also aid in the assessment of ICI-induced encephalitis and parkinsonism. Despite the recognized clinical relevance of imaging investigations in the diagnosis of n-irAEs, a detailed characterization of neuroradiological features of ICI-induced neurotoxicities remains limited. In this Review, we provide a comprehensive description of the imaging findings associated with n-irAEs and summarize the diagnostic work-up of these challenging disorders, emphasizing the central role of neuroimaging in their evaluation.