Cranial Nerve Disorders Associated with Immune Checkpoint Inhibitors

Objective: To describe the spectrum, treatment, and outcome of cranial nerve disorders associated with immune checkpoint inhibitors (Cn-ICI). Methods: This nationwide retrospective cohort study on Cn-ICI (2015-2019) was conducted using the database of the French Refence Center. In addition, a systematic review of the literature (MEDLINE, Scopus, and Web of Science) for records published between 2010-2019 was performed following the PRISMA guidelines, using the search terms “cranial nerve” or “neuropathy” or “palsy” and “immune checkpoint inhibitors”. Results: Among 67 cases with ICI-related neurological toxicities diagnosed in our Reference Center, 9 patients with Cn-ICI were identified (7 men, 78%; median age 62 years [range: 26-82]). Patients were receiving a combination of anti-CTLA-4 and anti-PD-1/PD-L1 (n=5, 56%), or anti-PD-1 antibodies alone (n=4, 44%). Cn-ICI involved optic (n=3), vestibulocochlear (n=3), abducens (n=2), facial (n=2), and oculomotor nerve (n=1). Two patients had involvement of 2 different cranial nerves. Treatment comprised corticosteroids (n=8, 89%), ICI permanent discontinuation (n=7, 78%), plasma-exchange (n=2, 22%), and IVIG (n=1, 11%). Median follow-up was 11 months (range: 1-41). In 3 cases (33%) neurological deficit persisted/worsened despite treatment: 2 optic and 1 vestibulocochlear. Among cases from the literature and the present series combined (n=39), the most commonly affected cranial nerves were facial (n=13, 33%), vestibulocochlear (n=8, 21%), optic (n=7, 18%), and abducens (n=4, 10%). Trigeminal, oculomotor, and glossopharyngeal nerves were less frequently affected (total n=7). Conclusion: Cranial nerve disorders can complicate treatment with ICIs. Approximately one third of the patients had persisting deficits, most frequently involving hearing and vision loss.