White Matter Functional Disconnection Predicts Long-Term Disability and Early Mortality in Spontaneous Intracerebral Hemorrhage

BACKGROUND AND OBJECTIVES: Spontaneous intracerebral hemorrhage (ICH) has the highest short-term mortality among stroke subtypes, and progress in treatment has been hindered by the limited accuracy of current prognostic tools. We investigated whether white matter functional disconnection severity, estimated using a normative lesion network mapping framework integrating direct electrical stimulation and resting-state functional MRI data from previously published independent Data sets, improves prediction of 6-month functional outcome measured with the modified Rankin Scale (mRS). METHODS: We analyzed 97 patients with spontaneous ICH. Ordinal logistic regression models were used to evaluate the association between domain-specific disconnection severity and 6-month mRS, and to compare traditional functional outcome in patients with primary intracerebral hemorrhage and ICH scores with connectivity-enriched models incorporating disconnection measures. RESULTS: White matter functional disconnectivity was significantly associated with 6-month functional outcome (mRS; P < .001; Nagelkerke's R2 = 0.507). Integrating disconnection severity into the functional outcome in patients with primary intracerebral hemorrhage and ICH scores improved predictive performance in both cases (Nagelkerke's R2 = 0.615 vs 0.389 and 0.651 vs 0.434, respectively), with the connectivity-enriched ICH score achieving the strongest overall fit across all models tested. Exploratory analyses showed associations between domain-specific disconnection severity, residual functional deficits, and early mortality. CONCLUSION: Assessment of white matter functional disconnection severity seems to be a promising approach for predicting long-term disability after ICH, although prospective validation in larger multicenter cohorts is required before clinical implementation. The findings suggest that different brain networks exhibit variable vulnerability to injury and differential potential for functional recovery.