Neurological Immune-related Adverse Events of Immune Checkpoint Inhibitors: A Single-center Retrospective Study
Luca Marsili1, Kevin Duque1, Samuel Marcucci2, Martina Chirra1, Joseph LaPorta1, Jesus Abanto1, Alberto Vogrig3, Alberto Espay1
1University of Cincinnati, 2UC Health Department of Neurology and Rehabilitation Medicine, 3University of Udine

To evaluate the frequency of neurological-immune-related adverse events (n-irAES) and the associated demographic/clinical characteristics of oncological patients treated with immune-checkpoint inhibitors (ICIs) at the University of Cincinnati (UC).

ICIs have revolutionized cancer treatment at the expense of adverse events (AEs) due to their boosting effect on anti-tumor immunity. N-irAEs include meningitis, encephalitis, demyelinating diseases, vasculitis, neuropathy, neuro-muscular junction disorders, and myopathy. The frequency of n-irAEs is still largely unknown. There also remains uncertainty on the management and clinical outcome of patients developing ICIs-related n-irAEs. 

Retrospective, single-center chart review of electronic health records of all patients treated with ICIs at UC between 2011-2023. Demographic/clinical data were collected on patients who developed at least one n-irAEs. Fisher’s exact test, t-test and Mann-Whitey test were performed accordingly.


Of 1677 patients receiving treatment with ICIs at UC there were 27 cases (1.62%) of ICIs-n-irAEs (74% male, 91% white; mean±SD age 63.1±1.5 years). The most frequent ICI associated with n-ir-AEs was pembrolizumab (53%). The most frequent n-ir-AEs were neuropathy (35.5%), followed by encephalitis (22.6%), and demyelinating diseases (16%). The most frequent tumors associated with n-ir-AEs were skin melanoma (40.7%), followed by urothelial carcinoma (15%), and non-small cell lung cancer (11%). N-ir-AEs occurred after 6.7±7.9 infusions (median, 19 days; IQR 8-29). ICIs were discontinued in 64% of cases after n-ir-AEs (continued in milder n-irAEs) and restarted (same ICIs) only in 14% of cases after n-ir-AEs resolution. A total of 15 cases (55%) died, mostly due to underlying disease progression (86%).


ICIs-related n-irAEs are rare, life-threatening conditions occurring in the early treatment phase, in specific solid tumors, potentially reversible if promptly recognized. Questions that will require further research include the clinical and demographic risk factors associated with ICIs leading to n-ir-AEs and the appropriate timing of ICIs reinitiation after discontinuation.