Association of Lesion Location and Fatigue Symptoms After Ischemic Stroke: A VLSM Study

Abstract

Background:Poststroke fatigue (PSF) is a common symptom in stroke survivors, yet its anatomical mechanism is unclear. Our study was aimed to identify which brain lesions are related to the PSF in patients with acute stroke.MethodPatients with first-ever acute ischemic stroke consecutively admitted from the first affiliated hospital of the University of Science and Technology of China (USTC) between January 2017 and June 2020. Fatigue was scored using the Fatigue Severity Scale. All the participants were assessed by 3.0 T brain MRI including diffusion-weighted imaging. The infarct lesions were delineated manually and transformed into a standard template. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and the occurrence and severity of fatigue. The same analyses were carried out by flipping the left-sided lesions. Multivariate logistic regressions were applied to verify the associations.ResultsOf the 361 patients with acute stroke, 142 (39.3%) patients were diagnosed with fatigue in the acute phase and 116 (35.8%) at 6 months after the index stroke. VLSM analysis indicated clusters in the right thalamus which was significantly associated with the occurrence and severity of PSF at 6-month follow-up. In contrast, no significant cluster was found in the acute phase of stroke. The flipped analysis did not alter the results. Multivariate logistic regression verified that lesion load in the right thalamus (OR 2.67, 95% CI 1.46–4.88) was an independent predictor of 6-month PSF.ConclusionOur findings indicated that lesions in the right thalamus increased the risk of fatigue symptoms 6 months poststroke.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

“…In a recent meta-analysis, 6 lesions in the thalamus were associated with greater likelihood of fatigue (odds ratio (OR) = 1.76 (1.09, 2.85)) in people with chronic stroke, but no associations between hemisphere of stroke or cortical versus subcortical lesions were found. A recent large (n = 361) study, 38 using diffusion-weighted magnetic resonance imaging, also found significant associations between thalamic lesions and the likelihood (OR = 2.67 (1.46, 4.88)) and severity of fatigue at 6 months post-stroke. More sensitive brain imaging methods and precise delineation of lesions are needed to confirm neuroanatomical associations with fatigue.…”

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

“…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. 42 Sixteen studies had group data or summary data suitable for meta-analysis.…”

Mechanisms of Post-Stroke Fatigue: A Follow-Up From the Third Stroke Recovery and Rehabilitation Roundtable

“…Over the last 2 decades several small studies (see review 47 ) have investigated the relationship between lesion characteristics and PSF with inconclusive results partly due to the variations in scales, metrics of lesion characteristics, small sample size, and variations in time points. Recently, a meta-analysis 48 of 14 studies assessing PSF, and a large scale (n = 361) structural MRI study 49 both concluded that a lesion in the thalamus significantly increased the likelihood of reporting PSF 6 months post-stroke. Extending beyond lesion location, another study examined if structural dysconnectivity associated with the lesion explains PSF, and found no relationship.…”

“…67,68 Exercise may ameliorate some of the peripheral (aerobic deconditioning and muscle atrophy) and central disturbances (alterations in cerebral blood flow, cellular energy stores, and neural circuit activity) that potentially contribute to PSF. 36-71 In a small RCT using a combination of 12-weeks of cognitive training and exercise, addition of exercise reduced fatigue compared to control subjects that received cognitive training alone. 16 A recent systematic review explored whether exercise impacts fatigue using the FSS.…”