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Abstract
Objective To describe the spectrum, treatment, and outcome of cranial nerve disorders associated with immune checkpoint inhibitor (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 and 2019 was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the search terms cranial nerve or neuropathy or palsy and immune checkpoint inhibitors.
Results Among 67 cases with ICI-related neurologic toxicities diagnosed in our reference center, 9 patients with Cn-ICI were identified (7 men, 78%, median age 62 years [range 26–82 years]). Patients were receiving a combination of anti–cytotoxic T-lymphocyte antigen 4 and anti–programmed cell death 1 (PD-1)/PD-1 ligand (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 (n = 1) nerves. 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 IV immunoglobulin (n = 1, 11%). Median follow-up was 11 months (range 1–41 months). In 3 cases (33%), neurologic 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.
Glossary
- Cn-ICI=
- cranial nerve disorders after ICI;
- CTLA-4=
- cytotoxic T-lymphocyte antigen 4;
- GBS=
- Guillain-Barré syndrome;
- ICI=
- immune checkpoint inhibitor;
- IDON=
- idiopathic demyelinating optic neuritis;
- IVIG=
- IV immunoglobulin;
- PD-L1=
- PD-1 ligand;
- PD-1=
- programmed cell death 1;
- PLEX=
- plasma exchange;
- PRISMA=
- Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received May 13, 2020.
- Accepted in final form October 12, 2020.
- © 2020 American Academy of Neurology
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