Predicting Modafinil-Treatment Response in Poststroke Fatigue Using Brain Morphometry and Functional Connectivity

Abstract

Background and Purpose— Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods— Twenty-six participants with severe fatigue (multidimensional fatigue inventory–20 ≥60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results— Multiple regression analysis showed that baseline multidimensional fatigue inventory–20 score (β=0.576, P =0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (β=−0.424, P =0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r 2 =0.52, area under the receiver operator characteristic curve=0.939). Conclusions— Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: ACTRN12615000350527.

Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue

“…Furthermore, we selected participants that were eligible (MRI safety) and consented to the imaging arm of this study. There were no significant differences in fatigue scores between those participants that were included in the imaging study and those who only participated in the main MIDAS trial 58 .…”

Post-stroke fatigue: a scoping review

“…Most of the interventional studies have a medium to high risk of bias. Table 2 shows only two studies in white cells (indicating low risk of bias) but both have small sample size consisting of 34 (MIDAS study 63 – 68 ) and 64 randomised patients 61 respectively.…”

Neuroimaging Parameters Are Not Associated With Chronic Post-stroke Fatigue in Young Stroke Patients

“…Using these techniques, it has been reported that lower global efficiency in an apathy-related subnetwork was an independent risk factor for post-stroke apathy ( 14 ). Recent study showed that functional connectivity of the fronto-striato-thalamic network predicted the response for chronic PSF treatment with modafinil ( 15 ). However, in this study structural connectivity that provide structural basis for the functional interactions between brain regions, was not examined.…”