Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature

Immune checkpoint inhibitors (ICI) are a novel class of antineoplastic treatment that enhances immunity against tumors. They are associated with immune adverse events, and several neurological syndromes have been described, including multiple sclerosis and atypical demyelination. We performed a systematic literature review of case reports with neurological immune adverse events that presented with central nervous system demyelination, up to December 2019. We found 23 cases: seven with myelitis, four isolated optic neuritis, one neuromyelitis optica spectrum disorder, five multiple sclerosis, and six with atypical demyelination. Ipilimumab was the most frequently used ICI (11/23). The median time to develop symptoms from the onset of ICI was 6.5 weeks [range 1.0–43.0], and from last ICI dose was 14 days [range 0–161]. Anatomopathological examination was performed in four cases, with the finding of a T-cell mediated immune response. Outcomes were generally favorable after immunosuppression: 18 patients had improvement or a full recovery, three patients did not respond to treatment, three patients died, and in one, treatment was not reported. We describe the patients' clinical presentation, treatment administered, and outcomes. We further speculate on possible pathophysiological mechanisms and discuss potential treatments that may be worth investigating.

Optic neuritis at the nexus of peripheral autoimmunity and central nervous system demyelination: a nationwide cohort study

Background Long-term course of optic neuritis is heterogeneous and varies across populations. We aim to investigate immune-related determinants that predict conversion of optic neuritis (ON) to multiple sclerosis (MS) or neuromyelitis optica (NMO) in a nationwide cohort. Methods We conducted the population-based cohort study using data from Taiwan’s National Health Insurance Research Database. Incident ON cases during 2003~2014 were followed until the end of 2015. Pediatric and adult sub-cohorts were examined separately. The associations between immune-related comorbidities or treatment and outcomes were analyzed using Cox proportional hazards models. Results A total of 11923 adult and 1365 pediatric ON patients were enrolled. The rates of conversion to MS were 2.7% for adult and 3.1% for pediatric ON with median follow-up duration of 6.3 and 7.3 years respectively, while 1.2% of pediatric and adult ON evolved to NMO. Comorbid systemic lupus erythematosus was associated with increased risks of subsequent development of MS in adult (adjusted hazard ratio [aHR], 2.80; 95% CI, 1.04-7.49) and pediatric ON patients (aHR, 21.65; 95% CI, 1.29-363.4). Adult ON patients were at increased risks of NMO if comorbid with myasthenia gravis (aHR, 9.13; 95% CI, 1.20-69.45) or Sjogren’s syndrome (aHR, 4.71; 95% CI, 1.74-12.76). Conclusion ON could be the sentinel event linking several peripheral autoimmune comorbidities to distinct forms of central nervous system demyelination. The clinical context in which ON occurs should be taken into account in the care and counseling of these patients.