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

 So you identified fatigue as coming from stroke. Useless, you did NOTHING to cure the fatigue that stroke patients have.

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

Xiaoxiao Zhang¹, Hongjuan Fang², Ding Ma³, Yunyun Duan³, Zhaozhao Wang⁴, Ning Zhang^5,6* and Chunxue Wang^5,6,7*

• ¹Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ²Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ³Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ⁴Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
• ⁵Department of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ⁶China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ⁷Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China

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.

Introduction

Stroke is one of the three leading causes of death and the third primary cause of disability worldwide. Post-stroke fatigue is a multi-dimensional emotional and perceptual experience (1), with a high prevalence and a wide range of influences (2). The health hazards of early fatigue and subjective mental fatigue have been overlooked for a long time. Only in recent years, researchers have found that post-stroke fatigue is the main sequelae of stroke (2–6). Most severe stroke patients are disabled and it is hard to accurately evaluate the symptom of post-stroke fatigue. Compared to severe stroke, patients with mild ischemic stroke generally show no obvious motion disability. However, many studies have shown that fatigue significantly lowers the life quality in survivors of mild ischemic stroke and is also a predictor of death after stroke (1, 7–9), which make such patients an ideal candidate for post-stroke fatigue study. Effective diagnosis and treatment of post-stroke fatigue can improve the quality of life for patients with mild ischemic stroke (10–13). In this consideration, it is crucial to understand the pathogenesis of post-stroke fatigue.

The pathogenesis of fatigue after mild ischemic stroke is highly complicated, and there have been limited studies on its biological and imaging mechanisms. Post-stroke fatigue has been confused with post-stroke depression for a long time. In recent years, it has been considered as two different but similar diseases. Although the occurrence of post-stroke depression is known to be related to monoamine neurotransmitters (norepinephrine, serotonin, dopamine), it is unclear if this association is seen in post-stroke fatigue. In a study of neuroanatomical pathway of monoamine neurotransmitter imbalance after stroke, Hama and associates pointed out that the monoamine neural network can be divided into catecholamine and serotonin, which are anatomically and functionally related, and may affect the occurrence of fatigue and emotional disorder after stroke (14). In the present study, we choose these three kinds of monoamine biomarkers to explore the possible mechanisms of post-stroke fatigue.

In the non-stroke fatigue population, it is found that central fatigue may be caused by the failure of integration of marginal input and motor function in the basal ganglia, which affects the striatum thalamus frontal cortex system (15). The relationship between the occurrence of post-stroke fatigue and stroke characteristics (such as its location, type, and neurological deficit) is still unclear (16). Therefore, this study used functional magnetic resonance imaging (fMRI) to explore whether there is abnormal neuronal activity (decrease or increase) in patients with post-stroke fatigue, and whether there is interruption in brain network connection that affects the release of related neurotransmitters.

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