Derivation and Validation of Subtypes of Concussion: A Systematic Review

Concussion is a highly prevalent and heterogeneous injury. Subtyping has been increasingly used to parse this heterogeneity by identifying clinically meaningful subgroups of individuals with concussion. Despite several concussion subtyping studies published in recent years, no consistent findings have emerged, largely due to variation in samples, injury contexts, and subtyping approaches. This systematic review aims to summarize literature concerning the derivation of patient subtypes of concussion across all populations and contexts of acquiring injury. Additional aims include summarizing methodologies, features, and populations that have been used for subtyping and identifying common pipeline limitations. Specifically, we tackle the central question of whether the subtyping methodologies that have been applied to concussion thus far have effectively identified clinically meaningful categories or insights. We examine 30 studies subtyping a total of 188,498 individuals found on Embase, PubMed, and Web of Science as of February 4, 2025, that have applied subtyping analysis to humans who have sustained a concussion. Extracted items include sample characteristics, methodological details, features used for subtype derivation and validation, and subtype ordering across those features. Risk of bias was assessed using a modified version of the Cochrane Collaboration's Tool for assessing risk of bias in randomized trials adapted for cluster analysis. We identified a strong association between memory, sleep, stress, and social connectedness with overall subtype favorability within a study. We also identified missing data handling and validation method as areas for which studies frequently employ inadequate approaches, and a disproportionate representation of males and White individuals in samples. Limitations of this review include risk of bias from including studies with low statistical rigor and an absence of a theoretically validated approach for synthesizing results by meta-analysis. Addressing the gaps identified in this review will help future studies derive subtypes that more effectively advance our understanding of concussion heterogeneity.