Risk Factors and Imaging Mechanisms of Fatigue After Mild Ischemic Stroke: An Exploratory Study From a Single Chinese Center

Abstract

Objective: To explore the biochemical risk factors and imaging mechanisms of post fatigue after mild ischemic stroke among a Chinese population.Methods: Forty consecutive patients with mild ischemic stroke within onset of 14 ± 2 days were enrolled between March and June 2018. The clinical information, scale data, biomarkers in peripheral venous blood, and imaging data during hospitalization and follow-up period were collected.Results: Patient age (range 34–78) was positively correlated with the prevalence of fatigue (p = 0.009). Both blood norepinephrine and serotonin levels during hospitalization were negatively correlated to the prevalence of post-stroke fatigue (model 1 p = 0.009 and model 2 P = 0.043, respectively). Infarct of right cerebral hemisphere is positively correlated with the occurrence of fatigue after mild ischemic stroke (p = 0.020). Compared to non-fatigue patients, amplitude of low-frequency fluctuation (ALFF) was lower in several areas of brain in stroke patients with fatigue, including the right orbital inferior frontal, right inner orbital frontal, right frontal, right triangular frontal inferior, right anterior and lateral cingulate, and right medial frontal gyruses. Analysis of the difference in functional connectivity between the fatigue and non-fatigue groups found no cluster.Conclusions: Frontal lobe-related neural pathways may play an essential role in the regulation of fatigue after mild ischemic stroke. Abnormal neural circuits may reduce the levels of neurotransmitters such as serotonin and norepinephrine and lead to post-stroke fatigue.

Neuroimaging correlates of post-stroke fatigue: A systematic review and meta-analysis

“…Twenty-nine studies (n = 3709 participants) assessed whether lesion lateralization was associated with PSF. 9, Of these, 24 showed no association, 3 reported a higher prevalence of PSF with right-sided stroke, 29,34,38 and 1 showed a higher prevalence of PSF in right-sided stroke at 6-month follow-up but not at baseline. 43 One study reported higher rates of general and mental fatigue in those with left-sided lesion lateralization.…”

“…Seven studies assessed brainstem lesions. 29,33,38,44,47,48,51 1131 One found fewer brainstem lesions in the fatigued group. 47 Another showed thalamus and/or brainstem lesions were associated with increased PSF risk.…”

“…Nine studies assessed cortical lesions. 1,8,33,38,[44][45][46][47][48] 1748 One showed a small effect size for higher cognitive fatigue. 8 Insula Two studies assessed insula lesions.…”

“…21 A second study in 16 post-stroke patients reported fractional ALFF was lower in several brain areas in PSF, including the right frontal, right inner orbital frontal, right orbital inferior frontal, right triangular frontal inferior, right anterior and lateral cingulate, and right medial frontal gyri. 38 A third small study (n = 12) used fMRI to show that reduced network functional connectivity in the ipsilesional rostral middle frontal cortex was associated with higher fatigue severity. 52 Two studies assessed the effect of modafinil on fMRI functional connectivity (FC) in PSF, 55,56 using data from the double-blind MIDAS-II trial (n = 36), which showed modafinil 200 mg daily reduced PSF compared to placebo.…”

“…A trend for a higher number of these lesions in the fatigued group was observed. 38 Infratentorial Infratentorial Five studies assessed infratentorial lesions. 1,7,9,44,46 729 Two found an increased risk of PSF associated with infratentorial lesions.…”