Clinical characteristics, management and outcomes in immune checkpoint inhibitor-induced central nervous system demyelinating disease.
This systematic review pooled 60 published cases of immune checkpoint inhibitor-associated central nervous system demyelinating disease, characterizing presentations, timing, management, outcomes, and a 16.7% relapse frequency.
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This systematic review pooled 60 published cases of immune checkpoint inhibitor-associated central nervous system demyelinating disease, characterizing presentations, timing, management, outcomes, and a 16.7% relapse frequency.
Research significance
The evidence shows that most reported patients received corticosteroids and discontinued checkpoint inhibition, with 71.7% reported to have favorable outcomes; it is reasonable but not proven to hypothesize that early syndrome recognition, antibody testing, and prompt individualized immunosuppression could reduce neurological morbidity or relapse.
Source abstract
BACKGROUND: The expanding clinical use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurological immune-related adverse events, among which central nervous system demyelinating disease (ICI-CDD) represents a rare but clinically severe complication. Current evidence remains largely confined to case reports and small case series, highlighting the need for a comprehensive characterization of this condition. METHODS: A systematic review and pooled analysis of published case reports and case series were conducted by searching English-language databases from inception to March 28, 2026, for literature related to ICI-CDD. RESULTS: A total of 60 patients with ICI-CDD from 39 publications were included, with a median age of 58.5 years (range: 9-81 years) and a slight male predominance (58.3%, 35/60). Most patients were seronegative for demyelinating antibodies; among those with detectable antibodies, aquaporin-4 antibody was the most common specificity. Clinical presentations included myelitis (48.3%, 29/60), optic neuritis (31.7%, 19/60), and meningoencephalomyelitis (6.7%, 4/60). Longitudinally extensive transverse myelitis (lesions spanning ≥ 3 vertebral segments) occurred in 62.5% (25/40) of patients. Optic neuritis was typically painless and predominantly bilateral. The median time to ICI-CDD onset was 3 months (range: 0.5-60 months) after treatment initiation, following a median of 4 ICI cycles (range: 1-95). The most frequently associated malignancies were lung cancer and melanoma, with PD-1 inhibitors being the most commonly implicated ICI class (51.7%, 31/60). First-line management predominantly involved corticosteroids (98.2%, 55/56) and ICI discontinuation (80.0%, 48/60). Most patients (71.7%, 43/60) achieved favorable outcomes following immunotherapy, whereas disease relapses occurred in 16.7% (10/60) of cases. CONCLUSIONS: ICI-CDD should be suspected in patients receiving ICI therapy who present with unexplained paraparesis, sensory deficits, sphincter dysfunction, visual loss, or visual field defects. Detection of demyelinating antibodies facilitates early identification of ICI-CDD and prompt initiation of personalized immunosuppressive therapy, thereby improving clinical outcomes.