Neurologic complications of immune checkpoint inhibitors: A comprehensive review

Cancer is characterized by uncontrolled cell proliferation, often leading to invasion of adjacent tissues and onset of metastasis. Therapeutic options include surgical intervention, chemotherapy, radiotherapy, and targeted therapies, with immune checkpoint inhibitors (ICIs) emerging as a revolutionary approach. ICIs, like anti-CTLA-4 (e.g., ipilimumab) and anti-PD-1/PD-L1 (e.g., pembrolizumab and nivolumab), enhance antitumor immune responses by blocking inhibitory mechanisms within T-cells. Despite benefits, ICIs can elicit immune-related adverse effects (irAEs), manifested by dermatologic, gastrointestinal, endocrine, and neurological toxicities. Although neurological complications are relatively uncommon, they are becoming increasingly noted and range from mild symptoms to life-threatening states. These are categorized into central nervous system (CNS) disorders, such as encephalitis, meningitis, and demyelination, and peripheral nervous system (PNS) manifestations, including neuropathies, myasthenia gravis, and Guillain-Barré syndrome. Early diagnosis and treatment are vital to prevent undue morbidity, as delay can lead to permanent disability. This study seeks to clarify immunological mechanisms of ICI function, epidemiological features of related disorders, clinical presentation, diagnostic tests, therapy, and future directions of investigation, and highlights clinical implications and potential avenues for active clinical and translational research.