Post-Stroke Fatigue: History
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Subjects: Neurosciences
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Seungwon Kwon

Post-stroke emotional disorders encompass depression, anxiety, emotion control disorder, anger control disorder, and fatigue that occurs after a stroke. Post-stroke fatigue (PSF) is one of the most common emotional disorders, and the previous studies suggested that 16%–85% of stroke patients experience PSF.

  • post-stroke fatigue
  • depression
  • cognitive dysfunction

1. Introduction

Despite the improvements made in the survival rate of patients with stroke [1], these patients still experience physical disability, as well as cognitive, emotional, and behavioral disorders as sequelae [2], all of which significantly reduce the quality of life of survivors [2]. In the past, stroke treatment strategies mainly focused on physical conditions such as motor or sensory disorders. However, with the recent improvements in the quality of life of survivors, the importance of managing emotional and mood disorders, which are non-physical disorders, has also been highlighted [3].
Post-stroke emotional disorders encompass depression, anxiety, emotion control disorder, anger control disorder, and fatigue that occurs after a stroke [3]. Post-stroke fatigue (PSF) is one of the most common emotional disorders, and the previous studies suggested that 16%–85% of stroke patients experience PSF [4][5][6][7]. PSF is known to adversely affect the overall prognosis of patients with stroke. In one review, PSF was shown to lead to physical deconditioning and reduced self-efficacy in physical performance, poor participation, and outcomes in rehabilitation programs, reduced social participation, poor quality of life, functional limitations, and increased mortality [7][8].
Thus, establishment of an effective treatment strategy for PSF is essential for efficient recovery of stroke survivors. However, a clear explanation of the pathophysiology of PSF, which will serve as the basis for establishing a treatment strategy, is still lacking. The relationships among age, sex, type of stroke, severity of neurological deficits, accompanying symptoms (e.g., depression, sleep disturbance, etc.), autonomic nervous system abnormalities, inflammation, and neuroendocrine dysregulation have been highlighted in a recent study [7]. However, the results of some studies are contradictory, highlighting the need for additional research. Moreover, since the pathophysiology and treatment application for each type of stroke are different [9], the factors contributing to the development of fatigue symptoms may differ even after the same stroke, and information on these seems to be lacking.

2. Discussion

Demographic characteristics, stroke-related characteristics, and laboratory test results were collected from patients hospitalized for treatment after stroke for one year at a medical institution. After analyzing the differences in characteristics between the PSF and control groups, the stroke-related factors that had a significant effect on PSF were investigated. A total of 178 stroke patients who met the selection criteria were analyzed. The number of patients assigned to the PSF group was 96 (53.9%). This finding was consistent with the 57% prevalence of PSF reported in a previous study [10], which is thought to indicate some degree of homogeneity with the participant characteristics in the previous study.
The multiple linear regression analysis confirmed that the degree of depression evaluated by the PHQ-9 score and the degree of inflammation evaluated by the ESR were significantly related to fatigue in all stroke patients. Among these, the relationship between depression and PSF requires attention. The association between PSF and depression [10][11][12][13] has been suggested several times in previous studies, and it was also confirmed in this study. These findings indicate that depression plays important roles in the development of PSF. The PHQ-9 is the most widely used screening tool for depression, and the higher the score, the more severe the depression [14]. A total score of nine or more was defined as depression [14]. In this study, the average PHQ-9 score of the PSF group was 11.10 ± 6.0, a value that can be considered to indicate a post-stroke depressive state. This trend was similar in both patients with ischemic and hemorrhagic stroke.
To this end, we analyzed the results of various laboratory tests such as biochemical, endocrine, lipid, general hematological, and inflammatory marker tests. The results confirmed that hs-CRP, ESR, and PLR, which are representative inflammatory markers, show significant positive association with the severity of fatigue in all types of stroke patients and hemorrhagic stroke patients. Among them, we initially focused on hs-CRP. Hs-CRP has been used to predict the prognosis of cardiovascular [15] and cerebrovascular disorders [16]. A previous study also suggested that PSF 6 months after a stroke was linked to elevated plasma hs-CRP levels upon admission, and this outcome is in line with the findings of the present study [17]. Another inflammatory marker, PLR, has been recently gaining attention as an indicator that reflects the inflammatory state of the body, and is also used as a prognostic predictor in cancer patients [18][19][20], cardiovascular disease patients [21][22], stroke patients [23], and coronavirus disease-19 (COVID-19) patients. It is also attracting attention as a predictor of cytokine storm in patients infected with COVID-19 in the context of a pandemic [24][25]. An existing review [26] has already introduced evidence related to the association between PSF and various inflammatory cytokines. That review [26] raised the possibility that stroke-related inflammatory processes could affect the formation of fatigue symptoms after stroke; however, further studies are needed. The results of this study, therefore, are meaningful in that they confirmed that the occurrence of fatigue in stroke patients and stroke-related inflammatory processes have a significant relationship.
In addition, to explain the relationship between stroke-related inflammatory processes and PSF, various interleukins and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), which are difficult to use in daily clinical settings, were used as indicators. On the other hand, in this study, the novel inflammatory markers PLR, MLR, and NLR, which can be calculated easily by performing general hematology tests and differential counts that are frequently used in general clinical settings, were utilized. Therefore, the results of this study can be helpful in determining whether to apply stroke-related inflammation-associated measures when establishing a treatment strategy for patients complaining of PSF in front-line clinical settings.
As a result, only depression showed a significant association in ischemic stroke patients, but depression and stroke-related inflammation were confirmed to be significantly associated with hemorrhagic stroke. Although the number of patients with hemorrhagic stroke was relatively small and no definite conclusions can be drawn yet, the results suggest that not only do the two types of strokes have different mechanisms of disease development [9]; they may also require different treatment strategies for fatigue symptoms.
This study had several limitations. First, since only inpatients of a single medical institution were investigated, the overall severity of stroke is likely to be higher than that among outpatients. Therefore, in future studies, it may be necessary to reconfirm the results of this study by expanding the survey group to outpatients. Second, the PHQ-9 scores used to evaluate depression show limitations in yielding specific and detailed information when they are widely used as screening tools. Therefore, in future studies, it is necessary to use the Beck Depression Inventory [27] or the Hamilton Depression Rating Scale [28] to evaluate depressive symptoms. Lastly, since this study was conducted as an observational cross-sectional study as well as a retrospective medical record analysis study, there are limitations in causal inference. In the future, causality inference through prospective studies will need to be conducted.
Despite these limitations, this study is meaningful in that it extensively analyzed various physical and mental factors that affect the occurrence of PSF. The results showed that it was possible to reconfirm the importance of previously known mental factors such as depression, and to confirm the relationship between various cytokines and PSF through inflammatory markers such as hs-CRP, ESR, and PLR, which are convenient to use in clinical settings. In the future, studies that can supplement the limitations of this study should be conducted to identify more confirmatory factors for PSF. These efforts are expected to contribute to the development of new treatment strategies for PSF.

This entry is adapted from the peer-reviewed paper 10.3390/healthcare9111586

References

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