Central nervous system complications of immune checkpoint inhibitors: A comprehensive review

The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management. Indeed, the therapeutic options are sometimes unfamiliar and may be further complicated by the lack of recommendations in the event of failure of a well-managed first-line treatment. Finally, the attribution of ICIs to certain CNS disorders is controversial and may lead to an incorrect decision to discontinue or contraindicate treatment, resulting in an irremediable loss of opportunity for the patient. Therefore, the aim of this review is to present known/suspected CNS nirAEs induced by ICI, their diagnostic approach and management through therapeutic advice for optimal treatment and rechallenge opportunities. • Neurological immune related adverse event (nirAE) are rare (1-5% of patients) but severe side effect of immunotherapy • Prompt recognition and management of CNS nirAE is necessary to reduce morbidity and mortality of ICI-treated patients especially for encephalitis and extensive myelitis. • Imputability of ICI to certain CNS disorders is controversial and lead to wrong to discontinuation or contraindication, resulting in a loss of opportunity for patient. • Rechallenge is feasible in most of grade 1-3 nirAE cases even for grade 4 endocrine adverse event like hypophysitis