Neurological immune-related adverse events of immune-checkpoint inhibitors: an updated review

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy across multiple tumor types and disease stages. By reinvigorating antitumor immune responses, these agents may also lead to the emergence of immune-related adverse events (irAEs), including a distinct spectrum of neurological toxicities. Although rare, neurological irAEs are clinically significant due to their diagnostic complexity, potential severity, and risk of long-term neurological sequelae or death. Neurological complications of ICI therapy involve the central nervous system, peripheral nervous system, and skeletal muscle, with immune-related myositis, polyradiculoneuropathy, and encephalitis representing the most frequent and severe entities. Clinical presentations are often heterogeneous and may mimic classical neurological disorders, posing diagnostic challenges even for experienced neurologists and underscoring the need for early recognition and multidisciplinary management. Prognosis varies according to the underlying pathophysiological mechanisms, with nonspecific inflammatory forms generally responding favorably to immunosuppressive treatment, while paraneoplastic-like syndromes are more frequently associated with persistent disability. Patients with preexisting or latent autoimmune neurological disorders represent particularly complex populations, as ICIs may unmask latent paraneoplastic neurological syndromes, and patients with myasthenia gravis seem at increased risk of ICI-induced myositis and myocarditis. High-dose glucocorticoids remain the cornerstone of nirAE management; however, emerging pathophysiology-driven therapies offer the potential to improve outcomes in severe cases while preserving antitumor efficacy.