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Abstract
Objective To determine the clinical and laboratory features of immune checkpoint inhibitor (ICPI)–associated autoimmune encephalitis (ICPI-AIE), an increasingly recognized adverse event with ICPI treatment.
Methods We searched PubMed, The Cochrane Library, and Embase for ICPI-AIE cases from the first description in 2015 until January 2020 using standard bibliographic measures including PRISMA guidelines and preregistration with PROSPERO.
Results Thirty-nine studies met inclusion criteria, resulting in 54 patients with ICPI-AIE (mean age 58.6 years; 43% female). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred after a median of 3.0 treatment cycles, but very early and late presentations were common. Nonlimbic AIE was roughly twice as frequent as limbic AIE (p < 0.05). The most common laboratory abnormalities included bitemporal fluid-attenuated inversion recovery lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on CSF analysis. Intraneuronal antibodies were more frequent than neuronal surface antibodies and a significant predictor for lack of improvement after first-line immunotherapy (p < 0.05).
Conclusions ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the pathophysiologic mechanisms, the epidemiology, and the best treatment approaches associated with ICPI-AIE.
Glossary
- ADEM=
- acute disseminated encephalomyelitis;
- AIE=
- autoimmune encephalitis;
- BM+=
- with brain metastases;
- BM–=
- without brain metastases;
- CASPR2=
- contactin-associated protein-like 2;
- CTLA-4=
- cytotoxic T lymphocyte-associated antigen-4;
- FLAIR=
- fluid-attenuated inversion recovery;
- ICPI=
- immune checkpoint inhibitor;
- IVIg=
- IV immunoglobulin;
- NSCLC=
- non-small cell lung cancer;
- PD-1=
- programmed cell death-1 protein;
- PD-L1=
- PD-1 ligand;
- PICO=
- patients, intervention, comparison, outcome;
- PLEX=
- plasma exchange;
- PRISMA=
- Preferred Reporting Items for Systematic Reviews and Meta-Analyses;
- SREAT=
- steroid-responsive encephalopathy associated with autoimmune thyroiditis
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.
↵* V. Nersesjan and O. McWilliam contributed equally.
This review was preregistered at PROSPERO: crd.york.ac.uk/prospero/display_record.php?RecordID=139838.
- Received September 2, 2020.
- Accepted in final form March 11, 2021.
- © 2021 American Academy of Neurology
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