Neurologic complications of immune checkpoint inhibitors

Abstract

Introduction: Immune checkpoint inhibitors (ICI) are associated with a wide spectrum of neurologic immune-related adverse events (irAEs) including meningo-encephalitis, myasthenia gravis and various neuropathies. Although relatively rare, they often present significant diagnostic complexity and may be under-recognized. Permanent neurologic deficits and/or fatality have been described but improvement is noted in most cases with ICI discontinuation and immunosuppressive therapy.Areas covered: This review highlights the most frequently reported ICI-associated neurologic toxicities with a particular focus on those that may be more severe and/or fatal. Data from case series and pharmacovigilance studies is leveraged to provide an overview of associated clinical features, expected outcomes and appropriate management. Various immunobiologic triggers have been proposed to explain why certain patients might develop neurologic irAEs and are also briefly discussed.Expert opinion: All providers who care for patients with cancer should be made aware of common neurologic irAEs and able to recognize when prompt evaluation and consultation with appropriate specialists are indicated. Symptoms suggestive of encephalitis, myasthenia-gravis or an acute polyradiculopathy such as Guillain-Barre Syndrome (GBS) in patients exposed to these agents warrant immediate attention with a low threshold for hospitalization to expedite work-up and monitor for severe and/or life-threatening manifestations.

Keywords: Anti-CTLA4; anti-PD1; anti-PDL1; encephalitis; immune checkpoint inhibitor; immunotherapy; ipililumab; meningitis; myasthenia gravis; neurotoxicity; nivolumab; pembrolizumab.