The interrelation between acute ischemic stroke, persistent disability, and uncertain prognosis underscores the need for improved methods to predict clinical outcomes. Traditional approaches have largely focused on analysis of clinical metrics, lesion characteristics, and network connectivity, using techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). However, these methods are not routinely used in acute stroke diagnostics. This study introduces an innovative approach that not only considers the lesion size in relation to the National Institutes of Health Stroke Scale (NIHSS score), but also evaluates the impact of disrupted fibers and their connections to cortical regions by introducing a disconnection value. By identifying fibers traversing the lesion and estimating their number within predefined regions of interest (ROIs) using a normative connectome atlas, our method bypasses the need for individual DTI scans. In our analysis of MRI data (T1 and T2) from 51 patients with acute or subacute subcortical stroke presenting with motor or sensory deficits, we used simple linear regression to assess the explanatory power of lesion size and disconnection value on NIHSS score. Subsequent hierarchical multiple linear regression analysis determined the incremental value of disconnection metrics over lesion size alone in relation to NIHSS score. Our results showed that models incorporating the disconnection value accounted for more variance than those based solely on lesion size (lesion size explained 44% variance, disconnection value 60%). Furthermore, hierarchical regression revealed a significant improvement (p < 0.001) in model fit when adding the disconnection value, confirming its critical role in stroke assessment. Our approach, which integrates a normative connectome to quantify disconnections to cortical regions, provides a significant improvement in assessing the current state of stroke impact compared to traditional measures that focus on lesion size. This is achieved by taking into account the lesion’s location and the connectivity of the affected white matter tracts, providing a more comprehensive assessment of stroke severity as reflected in the NIHSS score. Future research should extend the validation of this approach to larger and more diverse populations, with a focus on refining its applicability to clinical assessment and long-term outcome prediction.

Background/Objectives: Early and accurate prediction of stroke severity is crucial for optimizing guided therapeutic decisions and improving outcomes. This study investigates the predictive value of lesion size and functional connectivity for neurological deficits, assessed by the National Institutes of Health Stroke Scale (NIHSS score), in patients with acute or subacute subcortical ischemic stroke. Methods: Forty-four patients (mean age: 68.11 years, 23 male, and admission NIHSS score 4.30 points) underwent high-resolution anatomical and resting-state functional Magnetic Resonance Imaging (rs-fMRI) within seven days of stroke onset. Lesion size was volumetrically quantified, while functional connectivity within the motor, default mode, and frontoparietal networks was analyzed using seed-based correlation methods. Multiple linear regression and cross-validation were applied to develop predictive models for stroke severity. Results: Our results showed that lesion size explained 48% of the variance in NIHSS scores (R² = 0.48, cross-validated R² = 0.49). Functional connectivity metrics alone were less predictive but enhanced model performance when combined with lesion size (achieving an R² = 0.71, cross-validated R² = 0.73). Additionally, left hemisphere connectivity features were particularly informative, as models based on left-hemispheric connectivity outperformed those using right-hemispheric or bilateral predictors. This suggests that the inclusion of contralateral hemisphere data did not enhance, and in some configurations, slightly reduced, model performance—potentially due to lateralized functional organization and lesion distribution in our cohort. Conclusions: The findings highlight lesion size as a reliable early marker of stroke severity and underscore the complementary value of functional connectivity analysis. Integrating rs-fMRI into clinical stroke imaging protocols offers a potential approach for refining prognostic models. Future research efforts should prioritize establishing this approach in larger cohorts and analyzing additional biomarkers to improve predictive models, advancing personalized therapeutic strategies for stroke management.