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

Post-stroke fatigue commonly presents alongside several co-morbidities. The interaction between co-morbidities and their relationship to fatigue is not known. Here we focus on physical and mood comorbidities, alongside lesion characteristics. We predict the emergence of distinct fatigue phenotypes with distinguishable physical and mood characteristics. 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 scores and Fatigue Severity Scale – 7 scores age, gender and side of stroke was established using Spearman’s rank correlation. Mood and motor variables were then entered into k-means clustering algorithm to identify number of unique clusters, if any. Post-hoc pairwise comparisons followed by corrections for multiple comparisons was performed to characterise differences between clusters in the variables included in k-means clustering. Clustering analysis revealed a 4-cluster model to be the winning model (average silhouette score of 0.311). There was no significant difference in FSS-7 scores between the 4 high-fatigue clusters. 2 clusters consisted of only left hemispheric strokes, and the remaining two were exclusively right hemisphere strokes. Factors that differentiated hemisphere-specific clusters was the level of depressive symptoms and anxiety. Motor characteristics distinguished the low-depressive left from right hemispheric clusters. The significant differences in side of stroke, and the differential relationship between mood and motor function in the 4 clusters reveals the heterogenous nature of post-stroke fatigue, which is amenable to categorisation. Such categorisation is critical for understanding the interactions between post-stroke fatigue and its presenting comorbid deficits, with significant implications for development of context/category specific interventions.