Angioinvasion severity and admission GCS predict outcomes in invasive central nervous system fungal infections

Central nervous system (CNS) invasive fungal infections caused by Aspergillus spp. and Mucorales are associated with high mortality and severe neurological disability, but predictors of functional outcome remain poorly defined. We compared clinical features, neuroimaging patterns, and outcomes among rhino-orbital-cerebral mucormycosis (ROCM), rhino-cerebral aspergillosis (RA), and cerebral aspergillosis (CA), and identified prognostic factors for mortality and functional outcome.

We performed a retrospective cohort study of 57 adults with proven or probable invasive CNS fungal infection (28 ROCM, 13 RA, 16 CA) treated between January 2018 and April 2025. An exploratory imaging-based angioinvasion severity score (0-3) was constructed from three radiographic markers: internal carotid artery involvement, cerebral infarction, and intracranial hemorrhage. The primary outcome was all-cause mortality during follow-up; 90-day mortality was also assessed. The secondary outcome was 90-day unfavorable functional outcome, defined as modified Rankin Scale (mRS) 3-6. Multivariable analyses used Cox regression, Firth penalized logistic regression, and proportional odds ordinal logistic regression.

ROCM had the highest 90-day mortality (43% vs. 7.7% in RA and 6.3% in CA; p = 0.009) and the lowest rate of favorable 90-day functional outcome (50% vs. 92% and 81%; p = 0.012). Moderate-to-severe angioinvasion (score ≥2) was associated with worse 90-day ordinal disability (common OR 8.61, 95% CI 1.87-39.58; p = 0.006). Lower admission Glasgow Coma Scale (GCS) score independently predicted mortality (adjusted HR 0.77, 95% CI 0.67-0.88; p < 0.001) and unfavorable functional outcome (adjusted OR 0.68, 95% CI 0.36-0.91; p = 0.006). After adjustment for angioinvasion burden and GCS, fungal phenotype was not independently associated with prognosis. The prediction model for unfavorable functional outcome showed good discrimination (AUC 0.888).

Higher angioinvasion severity was associated with worse neurological functional outcome, whereas admission GCS independently predicted both mortality and unfavorable functional outcome. These findings may assist early risk stratification and treatment planning in invasive CNS fungal infection.