Immune Checkpoint Inhibitor-Induced Central and Peripheral Neurotoxicity: Case Series and Literature Review

Immune checkpoint inhibitors (ICIs) have been instrumental in the management of primary thoracic and non-thoracic metastatic malignancies, making them a mainstay of cancer therapy due to their long-term clinical benefits. However, they are also associated with several immune-related adverse events (irAEs), including neurological irAEs (nirAEs). Central neurotoxicities induced by ICI use include meningoencephalitis, focal encephalitis, myelitis, and aseptic meningitis, whereas peripheral neurotoxicities include ICI-associated myopathy, myasthenia gravis, and inflammatory neuropathy. The occurrence of irAEs and nirAEs can have long-term effects on survival due to the development of cognitive impairment, aphasia, physical debility, and potential dependence on tracheostomy and gastrostomy in the long term, and should be anticipated at any time following ICI therapy. Discontinuation of ICIs and administration of high-dose corticosteroids are first-line treatment options; however, cessation of ICIs increases the risk of malignancy progression. Rechallenging with ICIs therefore warrants a careful risk-benefit analysis. In this case series, we present four cases of central and peripheral neurotoxicity induced by ICI therapy to illustrate the diverse clinical presentations, prognoses, and outcomes, and to advance the discussion on discontinuation and rechallenging of ICIs in cancer patients.