Lesioned hemisphere‐specific phenotypes of post‐stroke fatigue emerge from motor and mood characteristics in chronic stroke

Background and purpose Post-stroke fatigue commonly presents alongside several comorbidities. The interaction between comorbidities and their relationship to fatigue is not known. In this study, we focus on physical and mood comorbidities, alongside lesion characteristics. We predict the emergence of distinct fatigue phenotypes with distinguishable physical and mood characteristics.

Methods In this cross-sectional observational study, in 94 first time, non-depressed, moderate to minimally impaired chronic stroke survivors, the relationship between measures of motor function (grip strength, nine-hole peg test time), motor cortical excitability (resting motor threshold), Hospital Anxiety and Depression Scale and Fatigue Severity Scale-7 (FSS-7) scores, age, gender and side of stroke was established using Spearman's rank correlation. Mood and motor variables were then entered into a k-means clustering algorithm to identify the number of unique clusters, if any. Post hoc pairwise comparisons followed by corrections for multiple comparisons were performed to characterize differences among clusters in the variables included in k-means clustering.

Results Clustering analysis revealed a four-cluster model to be the best model (average silhouette score of 0.311). There was no significant difference in FSS-7 scores among the four high-fatigue clusters. Two clusters consisted of only left-hemisphere strokes, and the remaining two were exclusively right-hemisphere strokes. Factors that differentiated hemisphere-specific clusters were the level of depressive symptoms and anxiety. Motor characteristics distinguished the low-depressive left-hemisphere from the right-hemisphere clusters.

Conclusion The significant differences in side of stroke and the differential relationship between mood and motor function in the four clusters reveal the heterogenous nature of post-stroke fatigue, which is amenable to categorization. Such categorization is critical to an understanding of the interactions between post-stroke fatigue and its presenting comorbid deficits, with significant implications for the development of context-/category-specific interventions.