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Poststroke Fatigued----A Review

Mar 19, 2022

Anners Lerdal, RN, PhD, Linda N. Bakken, RN, MSc,

Siren E. Kouwenhoven, RN, MPhil, Gunn Pedersen, RN, Marit Kirkevold, RN, PhD, Arnstein Finset, Cand Psychol, PhD (C), and Hesook S. Kim, RN, PhD


Department of Health Sciences (A.L., L.N.B., S.E.K., G.P., H.S.K.), Buskerud University College, Drammen; Research Center (A.L.), Oslo University HospitaldAker, Oslo; Institute of Nursing Science

and Health Sciences (M.K.) and Department of Behavioral Medicine (A.F.), University of Oslo, Oslo, Norway; and Institute of Public Health (M.K.), Aarhus University, A'rhus, Denmark



Contact: joanna.jia@wecistanche.com / WhatsApp: 008618081934791




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Abstract

Although fatigue is a common complaint after stroke, relatively little is known about how poststroke fatigue is experienced and what its related factors are. An in-depth understanding is necessary to develop effective and patient-centered poststroke rehabilitation programs. This review was undertaken to provide a comprehensive synthesis of knowledge from the literature concerning the description, definition, and measurement of fatigue and its relationship to sociodemographic and clinical factors. A search in PubMed, CINAHL, EMBASE, and PsychInfo was performed using ‘‘stroke’’ or ‘‘cerebrovascular accident’’ as medical subject headings in combination with ‘‘fatigue’’ as a keyword. Descriptions of fatigue revealed multiple dimensions of the phenomenon. Although no specific theoretical definition of fatigue as a post-stroke condition was found, a case definition has recently been published to be used as a tool to determine the presence of fatigue in post-stroke patients. Poststroke fatigue is most frequently measured by using the general fatigue scales such as the Fatigue Severity Scale and a Fatigue Visual Analogue Scale, as there is no scale developed to measure poststroke fatigue specifically. Age, sex, living conditions, and personality were associated with poststroke fatigue, albeit with some conflicting findings. Conflicting results also were found in the relationships between fatigue and stroke-related characteristics such as stroke location/type, the number of strokes, and neurological deficits. There is an indication that pre-stroke and poststroke fatigue are related. Possible antecedent components identified are personal factors, biomarkers, stroke characteristics, pre-stroke fatigue, and comorbidity. As knowledge regarding post-stroke fatigue remains limited, there is a need to continue empirical research with various theoretical orientations. J Pain Symptom Manage 2009;38:928e949. © 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.


Key Words: Fatigue, stroke, review, etiology, rehabilitation



Introduction


Stroke is the third most common cause of death in the world and the most frequent cause of disability in elderly people. Early mobilization and rehabilitation after the stroke are important strategies when trying to prevent permanent disability and help patients attain the best possible level of functioning and quality of life. Despite fatigue being one of the most common complaints after stroke, relatively little is known about how fatigue is experienced after stroke; its related factors; and its consequences for the rehabilitation process, performance of activities of daily living (ADLs), and quality of life.1 Fatigue has been described as a feeling of a lack of physical and mental energy.2e4 However, as fatigue is generally a subjective feeling, it may coexist with mental or physical symptoms and various impairments after stroke. The etiology of fatigue is often believed to be multifactorial, and the multidimensional nature of fatigue creates difficulties for both clinicians and researchers in describing and assessing the patient’s condition and implementing the best treatment.


Two methods have been used to measure fatigue in stroke patients: self-reported measures and performance-based measures. Because of the subjective nature of the concept of fatigue, different inventories of self-reported measures are mostly used to estimate the magnitude of the phenomenon, for example, the Fatigue Severity Scale(FSS),6 the Fatigue Impact Scale, and the vitality subscale of the Short Form-36 (SF-36).8 Some performance-based measures are focused on either physical or cognitive outcomes. In the research on fatigue in patients with neurological diseases, many instruments have been used in adults with multiple sclerosis (MS). The instruments intended to measure physical fatigue indirectly rely on a physiological definition of the phenomenon, for example, motor fatigue as measured by the ability to perform muscle contractions over time.9 Cognitive fatigue may be measured using tests of cognitive performance with sustained attention.10.Performance-based measures focus on behavioral outcomes and rely on objective indicators.


Although there are several published review articles regarding fatigue in stroke,1,11e13 these articles are not based on a systematic review of the literature. To offer a comprehensive evaluation of the state of the knowledge on this topic, this review was undertaken to address the following questions:

1) How is fatigue after stroke described, defined, and measured?

2) How is fatigue after stroke-related to personal factors, stroke characteristics, and preexisting conditions?

3) What are the relationships of poststroke fatigue with coexisting clinical factors such as pain, depression, sleep disturbance, cognitive status, motor functioning, dependency, and anxiety?

4) How does fatigue affect the stroke patient’s life?

5) Is there research evidence for fatigue-relieving strategies?



Procedures for the Search and Review


A computer-aided search in PubMed, CINAHL, EMBASE, and PsychInfo was performed in August 2007, which was updated on January 20, 2009. "Stroke"(in PubMed and EM- BASE), "cerebrovascular accident"(in PsychIn- fo), and "cerebral vascular accident " (in CINAHL) were used as medical subject headings in combination with "fatigue" as a word in the abstracts or the title in all four databases. The search retrieved 236 publications, with 191 duplicates in one or two databases. Publications that did not report findings based on empirical data were excluded.


All abstracts were reviewed by two re- searchers (AL and HSK). In addition, abstracts in the journals Stroke, Neurology, Psychosomatic Research, and Journal of Neurology, Neurosurgery, and Psychiatry published between January 1997 and January 2009 were manually reviewed in an effort to identify articles on fatigue in stroke patients. The total set of identified published reports were then screened for inclusion in this review by the following criteria: 1) the report must be concerned with poststroke fatigue, 2) it should report findings from empirical research, 3) it was published before January 20, 2009, and 4) it was published in English or Norwegian. This report is based on a review of 33 published articles obtained through these procedures that met the inclusion criteria.


1

2

3

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ADL ¼ activities of daily living; BDI-PC ¼ Beck Depression Inventory for Primary Care; CIS ¼ checklist individual strength; DSM-IV ¼ Diagnostic and Statistical Manual for Mental Disorders, fourth edition;
FIS ¼ Fatigue Impact Scale; FSS ¼ Fatigue Severity Scale; GT ¼ grounded theory; HC ¼ health control; HRQoL ¼ health-related quality of life; IADL=instrumental ADL; MDD ¼ major depressive disorder;
MIND ¼ minor depressive disorder; MQ ¼ Maastricht Questionnaire; NODEP ¼ no depressive disorders; OR ¼ odds ratio; RCT ¼randomized controlled trial; RIA ¼ reversible ischemic attacks; SF-12 ¼ Short
Form-12; SF-36 ¼ Short Form-36; SCI-P ¼ Structured Clinical Interview for DSM-IV; SSEE ¼ Short Self-Efficacy for Exercise scale; SOEE ¼ short outcome expectations for exercise; VAS ¼ visual analog scale.


The findings from the review are presented according to the research questions in five sections, with discussions regarding the findings integrated into each section.


The Characteristics of Fatigue After Stroke


Although the general characterization of fatigue seems to apply in describing poststroke fatigue, there were some differences in the way poststroke fatigue was described in a few qualitative studies carried out with poststroke patients. Descriptions of fatigue revealed different dimensions of the phenomenon, with problems related to self-control and emotional instability, reduced mental capacity, and perceived reduction in energy needed to read a book and participate in physical activities.17 Poststroke fatigue was characterized as starting or occurring without any specific exertion. Fatigue after stroke was characterized as a hidden dysfunction, invisible to other people, and as unpredictable, as the patient’s capacities were not known or were variable or fluctuating,17 and have been reported as the most frequent symptom three months after stroke.47 In a qualitative study of six women and nine men interviewed at 3, 6, and 12 months after a stroke event, a new form of fatigue was reported. This was related to the feeling of becoming exhausted without any specific reason.15 Because of their fatigue after stroke, some stated that they had difficulty making plans for the day.


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In addition, the patients viewed fatigue as problematic during the rehabilitation process, whereas the health care workers did not address fatigue as a problem.15 Similarly, fatigue was viewed to play a central role and created frustration that was experienced as overwhelming and unable to be controlled in a descriptive study of five young patients aged between 37 and 54 years.36 These patients became very emotional and sensitive to what people said and it affected their total life situation; when receiving a lot of information, they tired faster than before. Although these findings suggest poststroke fatigue to have somewhat distinct characteristics from general fatigue, there is a need for further clarification regarding the exact features that may or may not differentiate poststroke fatigue from general fatigue. The Definition and Measurement of Fatigue in Stroke A theoretical definition of fatigue specififically related to stroke was not found. In the area of MS, however, a consensus conference of researchers and clinicians defined fatigue as ‘‘a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities.’’48 Even though this definition was developed to describe fatigue in MS, it is generic in the way it describes fatigue as a subjective experience and is consistent with Staub and Bogousslavsky’s1 definition of fatigue as ‘‘a feeling of early exhaustion developing during mental activity, with weariness, lack of energy, and aversion to effort.’’ Furthermore, the subjective description implies that the patient’s self-reporting is the basis for measuring the phenomenon.


A case definition has recently been published to be used as a tool to determine the presence of fatigue in poststroke patients in hospitals and for patients living in the community.28 The different measures used in estimating the intensity of fatigue after stroke are shown in Table 2. The most frequently used instruments include the FSS and single items in the form of a 10 mm visual analog scale (VAS). As the table shows, the different scales were developed to measure different dimensions of fatigue such as concentration and motivation49 and the affective and somatic aspects50 of fatigue. None of the scales used in the stroke population have been developed specififically for measuring fatigue after stroke. A recent study30 in which 55 patients with stroke were interviewed evaluated the SF-36v2 (vitality subdimension), the Profile of Mood States, the Fatigue Assessment Scale (FAS), and the Multidimensional Fatigue Symptom Inventory. All four scales were found to be valid and feasible for application to stroke patients. However, the FAS showed the highest test-retest reliability but the poorest internal consistency as assessed by Cronbach’s alpha values (0.58 at T1 and 0.62 at T2).


These scales, in addition to the Brief Fatigue Inventory, were chosen by the research team based on their having the best face validity of 52 fatigue scales. Surprisingly, the FSS, which is the most frequently used instrument in stroke studies and which has shown high internal consistency (Cronbach’s alpha ¼ 0.89),37 was not among the scales evaluated in this report. Whether or not the general fatigue scales are appropriate to capture poststroke fatigue in reliable and valid manners is the question that needs to be addressed in relation to the definition of poststroke fatigue vis-a`-vis the general definition of fatigue. In addition, although various fatigue scales used in the poststroke fatigue studies measure the degree or intensity, the question remains regarding the cutoff points for determination of the presence of fatigue as many studies were concerned with prevalence rather than the variation in intensity.


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CFS ¼ chronic fatigue syndrome; CIS ¼ checklist individual strength; HC ¼ healthy controls; MS ¼ multiple sclerosis; MQ ¼ Maastricht Questionnaire; POMS ¼ Profifile of Mood States; SLE ¼ systemic lupus erythematosus; SF-36/12 ¼ Short Form 36/12.


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AED ¼ astheno-emotional disorder; CIS ¼ checklist individual strength; FIS ¼ Fatigue Impact Scale; FSS ¼ Fatigue Severity Scale; HAMD ¼ Hamilton Depression Rating Scale; MFI-20 ¼ multidimensional fatigue inventory; MVEQ ¼ Maastricht Vital Exhaustion Questionnaire; VAS ¼ Visual Analogue Scale.


Prevalence of Fatigue


Fatigue is among the most prevalent symptoms after stroke,26,54 with prevalence rates shown in Table 3. In a study from The Netherlands focusing on depression,23 70% of patients reported fatigue within the first month after a stroke. Schepers et al.37 demonstrated that 51% of patients reported fatigue when admitted to the hospital, whereas a longitudinal study from Denmark showed that 59% of the patients reported fatigue 10 days after stroke onset.20 These are the only studies found that reported the prevalence of fatigue in the acute phase. In a Swedish sample one year after stroke, 53% of patients reported experiencing fatigue that specififically started after the stroke.14 In two other Swedish studies one year after stroke, the prevalence rate of having astheno-emotional syndrome diagnosed by a neurologist was 72%e77%.16,54 In another Swedish follow-up study of 3,805 patients in the Swedish RiksStroke register examined two years after a stroke, 39% reported that they ‘‘often’’ or ‘‘always’’ felt tired,25 whereas 40% reported fatigue at two-year follow-up in the Danish study.20 In a prospective study after patients were diagnosed with reversible ischemic attacks over a median period of 58 months to identify those who developed a stroke, 51% of those diagnosed with stroke during the study period experienced severe fatigue compared with 16% of those not diagnosed with stroke.40 The longitudinal cohort study from Denmark showed that the proportion of patients with severe fatigue varied between 59% and 38% during the two years of follow-up.20 Various studies using fatigue inventories have reported prevalence rates ranging from a low of 42% to a high of 75%, and a study using a VAS format reported 57% of patients classified as having fatigue (see Table 3).


Only two studies were found that tracked stroke patients’ fatigue experience over time. Although one of the studies showed that over the course of their admission to the hospital, and six months and one year after stroke, the prevalence of fatigue increased over time,37 the proportion of fatigue cases was relatively stable over time except for a higher proportion in the acute phase in the second study.20 Only 17% of the patients did not have fatigue at any time point, whereas 45% had sporadic fatigue (defined as having fatigue at one or two time points).37 The findings from a longitudinal case-control study indicated that seven years after a stroke, patients retrospectively reported more change in fatigue than controls; however, this change was not statistically significant.21 Conversely, in a cross-sectional study of Swedish stroke patients, the proportion of individuals with fatigue was relatively similar across poststroke time points at 3e6, 7e9, and 10e13 months.26 As shown in Table 3, the prevalence of fatigue ranges between 38% and 77%. An important question is whether this variation is due to the different measures and cutoff points used to distinguish between fatigue and no fatigue cases. FSS was the most frequently used fatigue measure in stroke studies. All studies that reported the prevalence of fatigue used mean FSS scores greater than 4.0 to indicate fatigue, although none of these studies explained the rationale for this cutoff point. Interestingly, most recently published MS studies have used an FSS mean score of 5.0 as the cutoff value.


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In addition, fatigue in the general population in Norway has been estimated using different cutoff values (4.0 and 5.0), suggesting the possible overestimation of fatigue cases in the general population.56 As there is controversy regarding the cutoff value for the presence of fatigue when using FSS and other fatigue measurement tools, it is critical to standardize the cutoff value for use in descriptive comparison studies. The literature indicates that fatigue is a major issue confronting stroke patients, as suggested by the finding that more than one-third of stroke patients are likely to experience fatigue at some time after stroke. One area of knowledge regarding prevalence that is lacking is the nature of modulation of the fatigue experience in poststroke patients over time. In addition, there is a lack of knowledge regarding the nature of the fatigue experience in stroke patients and how it might be similar to or different from general fatigue or fatigue in long-term conditions such as chronic fatigue syndrome. It is critical to know about the specific characteristics of fatigue in stroke to begin to understand the mechanisms and potential interventions that could be tested.

1642040450(1)

ADS ¼ activities of daily living; BMI ¼ body mass index; CI ¼ confidence interval; NIHSS ¼ National Institutes of Health Stroke Scale; NS ¼ not statistically significant; OR ¼ odds ratio; SSS ¼ Scandinavian Stroke Scale.


Fatigue in Relation to Personal Factors, Stroke Characteristics, and Preexisting Conditions


Studies correlating factors that may be antecedents to poststroke fatigue are shown in Table 4. Personal Factors Although some studies have reported a relationship between increasing age and the risk of fatigue 25,37, others have reported no relationship.14,16,18,26,29,33 Several studies of fatigue in the general population show a higher proportion of fatigue among women;56,57 however, there is conflicting evidence about the relationship between gender and poststroke fatigue, as some researchers report no differences between men and women,14,16,18,26,33 whereas others report a higher proportion of fatigue among women.25,37 A higher proportion of fatigue cases among patients who are single compared with those who are married or cohabitate has been reported,25 whereas another study reported no relationship.37 Findings from several studies indicated that those patients who experience fatigue after stroke are more likely to be unemployed16,33 or have lost or changed jobs compared with those with no fatigue after the stroke.18 Three studies reported no significant relationship between the level of education and poststroke fatigue.18,33,35In a prospective study of stroke patients from The Netherlands, researchers investigated the locus of control (i.e., the degree to which the patients perceive the development of their health as an output of their own behavior) and its relationship to fatigue.37 The findings suggest that those who believed that their health was determined largely by the actions of physicians reported higher levels of fatigue than those who believed that their own actions were more important.


Stroke Characteristics


The major stroke-related characteristics studied in relation to poststroke fatigue were stroke location/type, number of strokes, and neurological deficits. A study of young adults with cerebral infarction reported higher fatigue scores among patients with basilar artery infarction.33 No other studies showed any relationship between fatigue and stroke location14,16,18,26,33,37 or fatigue and stroke type.14,16,25,37 One study reported a relationship between the number of strokes and fatigue,25 reporting a lower proportion of fatigue among patients who had a first stroke compared with those who had a recurrent stroke. Some studies have reported a significant relationship between neurological impairment and fatigue,16,18 whereas others have not found a significant relationship.14,26 Neurological deficits related to visual fields and facial palsy were significant predictors of fatigue in one study.14 When stroke patients with fatigue in a Korean sample were compared with patients with no fatigue, there was a higher proportion of dysarthria, decreased appetite, and inappropriate and excessive laughing in the fatigue group.18 Glader et al.25 found that fatigue two years after stroke was less prevalent among patients with no speech impairment compared with those with speech impairment at admission, but there was no relationship to the level of consciousness at admission.


Pre stroke Fatigue


As fatigue is a common experience in the general population, there has been some interest in examining the relationship between pre-and post-stroke fatigue to determine whether post-stroke fatigue is actually stroke-related. In a randomized controlled study testing the effects of flfluoxetine on fatigue, the presence of pre-stroke fatigue was related to fatigue after stroke (r ¼ 0.40,P < 0.01).19A survey of 220 consecutive outpatients conducted by the same Korean researchers showed that among the 57% who had fatigue approximately 15 months after stroke, 36% also had fatigue before the stroke.18Among patients with pre-stroke fatigue, 58% experienced an increase and 28% a decrease in fatigue severity. In a longitudinal study of cardiovascular disease in the United States, individuals who reported higher levels of exhaustion had more than twice the risk (hazard ratio [HR] ¼ 2.42, P < 0.001) for stroke 5e7 years later than those who reported low exhaustion.42 That study also showed that individuals with moderate exhaustion scores had a higher risk for stroke than those with lower exhaustion scores (HR ¼ 1.66, P < 0.001). Furthermore, current smoking was a significant risk among those with middle or high levels of exhaustion. Findings from a prospective survey in The Netherlands (mean follow-up time 50.9 months; range 9.5e62.7 months) showed that feelings of exhaustion increased the risk of stroke (relative risk ¼ 1.3).38 The association remained unchanged after controlling for confounding variables such as sex, total cholesterol level, blood pressure, smoking habits, and body mass index.


Preexisting Morbidities


Few studies examined the relationship between preexisting morbidities such as cardiovascular disease, diabetes, other neurological conditions, and stroke or stroke-related experiences including fatigue. No significant relationships were found for cardiovascular disease, and conflicting findings were reported for diabetes.14,18,33 Naess et al.33 reported a significant relationship between migraine and poststroke fatigue. In summary, the literature indicates inconclusive associations between post-stroke fatigue and personal variables, stroke-related characteristics, and preexisting conditions. There is con- afflicting findings regarding associations between post-stroke fatigue and personal and demographic factors such as age, sex, level of education, living situation, and employment status. Furthermore, stroke-related factors such as stroke type, location, and number were shown to have inconclusive associations with post-stroke fatigue. There may be an association between pre-stroke fatigue and poststroke fatigue. This association, however, is difficult to validate because of a high degree of unreliability in retrospectively obtained pre-stroke fatigue data. It appears essential to evaluate possible relationships between pre-and post-stroke fatigue to understand the component of fatigue that is specififically stroke-related. Therefore, it can be concluded that the antecedents to poststroke fatigue are not well known, there appear to be no known characteristics that differentiate pre and poststroke fatigue, and the course of fatigue over time is not well understood.


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Associations Between Coexisting Clinical Factors and Poststroke Fatigue


Studies with findings regarding other clinical factors related to poststroke fatigue are shown in Tables 5 and 6. Pain For patients one year after the stroke, the pain was not significantly associated with fatigue.14 However, stroke patients with pain do report more fatigue.25 In a qualitative study of stroke patients’ pain experiences, fatigue was reported mainly among patients with continuous pain or those with tension-type headaches.58



Depression


Depression has been considered one of the most critical concomitant poststroke experiences associated with fatigue. Not only do these two types of experiences coexist but also are common shared experiences, making it difficult to differentiate between them as independent conditions. This issue is applicable in stroke patients as well as in other patient populations.

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In a study of 200 Italian patients with first-ever stroke who were surveyed for depression three months after their stroke using the Structured Clinical Interview of the Diagnostic and Statistical Manual for Mental Disorders, fourth edition-P,41 the scores for fatigue or loss of energy tended to be significantly higher among patients who had a minor depressive disorder than among those who had no depressive disorder. Similar findings were found in a Belgian study in which neurocognitive and somatic symptoms were assessed in relation to their discriminant contribution to the diagnosis of post-stroke depression.23 The study showed that reduced appetite, psychomotor retardation, and fatigue contributed significantly to identifying patients who had poststroke depression. A relationship between depression and high levels of fatigue has been shown in several other studies.19,25,33,37,45 The odds ratio for having fatigue one year after stroke when having depression was 3.2 (95% confidence interval: 1.7e6.0).14 In a Swedish study, 49% of patients with fatigue one year after stroke were diagnosed with depression compared with 39% in the total sample.16 This was similar in a Korean study, with 34% of patients depressed among those with fatigue approximately 15 months after stroke.18 When a stepwise linear regression analysis was performed separately for the group of stroke patients and the group of controls, and after controlling for sickness impact score on ambulation, depression scores accounted for 11% of the variance in fatigue scores for stroke patients compared with 56% of the variance for the control group.46 A similar finding was reported in a multivariate regression analysis where the patients’ handicap score at discharge predicted their depression score but not their fatigue score.25


Anxiety


Only a couple of studies examined the relationship between fatigue and anxiety. Glader et al.25 reported that patients with anxiety also had a tendency to report more fatigue, whereas Naess et al.33 compared those with and without anxiety in their study of young adults with ischemic stroke, noting that 71% had fatigue among those with anxiety and only 37% had fatigue among those without anxiety. A Norwegian study of quality of life among young adults with ischemic stroke showed that fatigue was weakly related to mental health and more strongly related to physical health.34


Sleep


Fatigue is more likely in patients who report sleep disturbance.14 Among patients with fatigue after stroke, 22% reported insomnia compared with 11% in the no fatigue group (P < 0.005).18 However, another study of patients one year after stroke found no association between fatigue and sleep problems.37 Self-report of sleep problems may be less valid and reliable than an assessment of sleep problems by objective measures, and the type of insomnia may vary with the patient’s fatigue experience. One of the major points of discussion in the general literature on fatigue is the possible link between fatigue and depression. As indicated by findings on poststroke fatigue, there is a trend for the co-occurrence of fatigue with depression and fatigue with anxiety. However, the findings are not conclusive, and there is a need to differentiate the nature of subjective experience and specific psychological and physiological processes associated with fatigue, depression, and anxiety. This is critical because associations found in the literature could be attributed to confounding effects from the instruments used to measure these phenomena. Two other concomitant conditions that seem to be associated with fatigue in stroke, namely, sleep disturbances and daytime physical functioning, are important areas for further study, as an understanding of poststroke fatigue and patient experience is critical in developing interventions.


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Impact of Poststroke Fatigue


The literature suggests that the major impact of poststroke fatigue seems to be on patients’ functioning and dependency. Although stroke patients are often affected by the presence of paralysis in carrying out the ADLs, fatigue seems to further impact their functioning in a variety of ways. A survey of exercise beliefs in the United States showed that patients with fatigue had both lower self-efficacy expectations and outcome expectations for exercise.39 Furthermore, 68% of studied patients agreed or strongly agreed that fatigue influenced their daily activities. Other studies also have shown that those with a balance impairment and less confidence in performing ADLs without falling (low falls efficacy) have higher fatigue scores31 and more perceived unmet demands.55 A study showed that those who have fatigue one year after a stroke have a higher degree of dependency compared with those with no fatigue.


14 Similar findings have been reported two years after stroke.25 Furthermore, a study in The Netherlands of stroke patients two years after stroke showed that the patients with higher perceived disability were more likely to have higher fatigue scores.46 A prospective study of first-ever stroke patients showed that fatigue one year after stroke independently predicted a decline in mobility function two years later.44 In a qualitative study of the consequences of living with stroke, patients described feelings about the need for help and the lack of ability to master their daily life due to fatigue.17 Family members took more responsibility for planning, organizing, and performing family-related activities because of reduced physical capacity. A qualitative prospective study of 11 right hemisphere stroke patients interviewed at one week, one month, three months, and six months after stroke found that all patients described physical and mental fatigue.59 Furthermore, fatigue was the main reason for not engaging in activities. Those who were inactive stated that their lack of interest and tendency to tire easily were the main reasons for inactivity. In contrast, others have shown that fatigue after stroke was not related to the performance of daily activities, as measured by the Barthel Index.16,45 However, contradictory findings within these studies were evident.


Although a higher fatigue level was associated with a greater degree of handicap, there was also no relationship between fatigue and instrumental ADLs.16,45 The lack of association between fatigue and function as measured by the Barthel Index, despite relationships between fatigue and more complex ADLs,16,45 indicates that poststroke fatigue might have more impact on performing activities that are more energy consuming, such as shopping and going to parties, than less energy-demanding activities, such as getting dressed and going to the toilet. The fatigue also affected their sexual activity and capacity to work full time.16 Other studies have also found a decrease in sexual performance related to fatigue after stroke.18 The survey showed that their satisfaction with life as a whole, their leisure situations, and their contact with friends and acquaintances were influenced by their fatigue one year after the stroke.


Patients with high levels of fatigue after stroke rated their general health lower than those with less or no fatigue.25 In an intervention study of patients with brain injury (mainly stroke patients), general fatigue level predicted the patient’s percentage age-predicted maximal heart rate, indicating that fatigue influenced the patient’s ability to work hard.22 However, in a randomized factorial design study, patient fatigue did not have any effect on gait performance in the hospital corridor, the suburban street, or in a mall.27 Similar findings were reported in a study aimed at describing the relationship between household and community activity profiles, fatigue, and cardiovascular fitness.32 no statistically significant relationship between fatigue and these variables was found, indicating that fatigue is not directly related to the oxygen consumption rate (VO2), at least in inactive stroke patients. Another study found that a higher proportion of those stroke patients who reported that they always felt tired had died between one and three years after the stroke (17% vs. 7%).25 The findings in these reports suggest that poststroke fatigue seems to have an impact on functioning in terms of the types of functioning and activities. Poststroke fatigue also seems to affect patients’ lives in relation to sexual, leisure, and social activities. However, the findings are inconsistent and lack theoretical underpinnings to explain the processes by which fatigue affects patients’ daily living.


Fatigue-Relieving Interventions


Only one intervention study was found that specififically targeted fatigue using a drug, in which the use of fluoxetine for fatigue was tested in a double-blind, placebo-controlled study.19 However, fluoxetine showed no effect on reducing post-stroke fatigue, suggesting that serotonergic system dysfunction is not a potential mechanism for post-stroke fatigue.19 Another study43 examined differences in pain and fatigue from constraint-induced movement therapy designed to improve mobility between a group receiving treatment in the subacute phase of stroke compared with a group receiving this therapy in the chronic phase. There was no significant difference between these two groups with regard to pain or fatigue, indicating that the timing for implementing constraint-induced movement therapy was not critical. This study, however, did not target fatigue for specific interventions. In chronic fatigue syndrome, where the evidence base is larger, cognitive behavioral therapy and, to some degree, performing regular physical exercises have been shown to be effective in treating fatigue.5 This paucity of studies examining intervention strategies for poststroke fatigue indicates the low level of attention to fatigue as a clinical problem that needs to be therapeutically attended to. It seems critical that there is a need to develop strategies to address post-stroke fatigue and test such strategies for their effectiveness, given the high prevalence of post-stroke fatigue and its apparent effects on patients’ lives.


Summary


The literature on poststroke fatigue indicates that knowledge regarding this phenomenon is still at a foundation stage. To develop a comprehensive understanding to move toward effective interventions, empirical research with various theoretical orientations must continue.

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Fig. 1. The biopsychosocial model of poststroke fatigue.


The theory of unpleasant symptoms developed by Lenz et al60 is used to present a poststroke fatigue model. This model consists of three components: antecedents, fatigue experiences, and effects, as shown in Fig. 1. The antecedent component is represented by five categories of factors: personal factors, biomarkers, stroke characteristics, pre-stroke fatigue, and chronic diseases. The key personal factors are age, sex, living conditions, and personality, as these are shown in the literature to have some association with poststroke fatigue, albeit with some conflicting findings. Although associations between fatigue and bio physiological markers have not been studied specififically in poststroke fatigue, there is some evidence that levels of cytokines, selected proteins, and other serum factors are involved in stress responses and sickness behaviors such as apathy and sleepiness.61e64 Thus, it is necessary to include this category as an antecedent. Various stroke characteristics such as location, type, and number of occurrences may be associated with post-stroke fatigue experience, as shown in some studies. Two studies of patients with chronic fatigue syndrome have shown a reduction in the subcortical gray matter when compared with healthy controls.65,66 Similar studies on patients with poststroke fatigue may discover possible precipitating factors. Pre-stroke fatigue as an antecedent factor is an important consideration in understanding post-stroke fatigue, as there is evidence that they are related. However, the exact nature of the relationship is not clear. The comorbidities of stroke, especially chronic diseases such as cardiovascular disease, diabetes, chronic anemia, and chronic respiratory disease, may have an impact on fatigue by either aggravating or masking it.


These five categories of antecedent factors have been identified as possible areas for further study. The component of fatigue experience addresses the conceptualization of fatigue in relation to intensity, quality, timing, fluctuation, and long-term trajectory. Lenz et al60 identifield intensity, timing, distress, and quality as the key dimensions of unpleasant symptoms. These five dimensions for poststroke fatigue encompass the experience associated with how it is experienced at one time and how it is experienced over time. The fluctuation dimension refers to how it changes throughout the day and night or during a certain specified time, whereas the trajectory dimension refers to how the experience changes over a long poststroke period. A longitudinal understanding is important because stroke is an illness condition with a specific trajectory.67 This component also includes possible concomitants of stroke, including anxiety, depression, and sleep disturbance.


Co-occurrence of these experiences, as well as differentiation of fatigue from these experiences, will further clarify the nature of the poststroke fatigue experience. The third component of this model is outcomes or effects, consisting of two categories: functioning in daily life and one’s participation in various ADLs, including physical, instrumental, sociocognitive, and leisure activities. As many stroke patients experience deficits in functioning because of the neuromuscular insults of stroke, it is important to understand how fatigue further influences their functioning. In addition, it is important to assess the impact of fatigue on quality of life, as it may be associated with function as well as with how one experiences fatigue independent of other factors. This model is useful in reflecting on the state of the science regarding post-stroke fatigue and in specified areas in need of further investigation. However, the model only serves as a framework for how fatigue is experienced rather than as a theory of the mechanism of how post-stroke fatigue develops.


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References


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3. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol 1988;45:435e437.
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