Title:Stroke recovery phenotyping through network trajectory approaches and graph neural networks

Abstract:Stroke is a leading cause of neurological injury characterized by impairments in multiple neurological domains including cognition, language, sensory and motor functions. Clinical recovery in these domains is tracked using a wide range of measures that may be continuous, ordinal, interval or categorical in nature, which presents challenges for standard multivariate regression approaches. This has hindered stroke researchers' ability to achieve an integrated picture of the complex time-evolving interactions amongst symptoms. Here we use tools from network science and machine learning that are particularly well-suited to extracting underlying patterns in such data, and may assist in prediction of recovery patterns. To demonstrate the utility of this approach, we analyzed data from the NINDS tPA trial using the Trajectory Profile Clustering (TPC) method to identify distinct stroke recovery patterns for 11 different neurological domains at 5 discrete time points. Our analysis identified 3 distinct stroke trajectory profiles that align with clinically relevant stroke syndromes, characterized both by distinct clusters of symptoms, as well as differing degrees of symptom severity. We then validated our approach using graph neural networks to determine how well our model performed predictively for stratifying patients into these trajectory profiles at early vs. later time points post-stroke. We demonstrate that trajectory profile clustering is an effective method for identifying clinically relevant recovery subtypes in multidimensional longitudinal datasets, and for early prediction of symptom progression subtypes in individual patients. This paper is the first work introducing network trajectory approaches for stroke recovery phenotyping, and is aimed at enhancing the translation of such novel computational approaches for practical clinical application.