Journal of Pain and Symptom Management
Volume 38, Issue 6 , Pages 928-949, December 2009

Poststroke Fatigue—A Review

  • Anners Lerdal, RN, PhD

      Affiliations

    • Department of Health Sciences, Buskerud University College, Drammen, Norway
    • Research Center, Oslo University Hospital—Aker, Oslo, Norway
    • Corresponding Author InformationAddress correspondence to: Anners Lerdal, RN, PhD, Department of Health Sciences, Buskerud University College, P.O.B. 7053, 3007 Drammen, Norway.
    • ,
  • Linda N. Bakken, RN, MSc

      Affiliations

    • Department of Health Sciences, Buskerud University College, Drammen, Norway
    • ,
  • Siren E. Kouwenhoven, RN, MPhil

      Affiliations

    • Department of Health Sciences, Buskerud University College, Drammen, Norway
    • ,
  • Gunn Pedersen, RN

      Affiliations

    • Department of Health Sciences, Buskerud University College, Drammen, Norway
    • ,
  • Marit Kirkevold, RN, PhD

      Affiliations

    • Institute of Nursing Science and Health Sciences, University of Oslo, Oslo, Norway
    • Institute of Public Health, Aarhus University, Århus, Denmark
    • ,
  • Arnstein Finset, Cand Psychol, PhD (C)

      Affiliations

    • Department of Behavioral Medicine, University of Oslo, Oslo, Norway
    • ,
  • Hesook S. Kim, RN, PhD

      Affiliations

    • Department of Health Sciences, Buskerud University College, Drammen, Norway

Accepted 9 April 2009. published online 07 October 2009.

Article Outline

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 key word. Descriptions of fatigue revealed multiple dimensions of the phenomenon. Although no specific theoretical definition of fatigue as a poststroke condition was found, a case definition has recently been published to be used as a tool to determine the presence of fatigue in poststroke 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 prestroke and poststroke fatigue are related. Possible antecedent components identified are personal factors, biomarkers, stroke characteristics, prestroke fatigue, and comorbidity. As knowledge regarding poststroke fatigue remains limited, there is a need to continue empirical research with various theoretical orientations.

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

 

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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.2, 3, 4 However, as fatigue is generally a subjective feeling, it may coexist with mental or physical symptoms and various impairments after stroke.1 The etiology of fatigue is often believed to be multifactorial,5 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,7 and the vitality subscale of the Short Form-36 (SF-36).8 Some performance-based measures are focused on either physical or cognitive outcome. 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, 11, 12, 13 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?

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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 EMBASE), “cerebrovascular accidents” (in PsychInfo), 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 researchers (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 was 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 (see Table 1) obtained through these procedures that met the inclusion criteria.

Table 1. Overview of All Articles Included in the Review: Research Questions, Research Design, Fatigue Measurements, and Major Findings
No.Studies or ArticlesResearch QuestionsDesignFatigue MeasurementsResults
1Appelros14Describe the frequencies of pain and fatigue and their predictorsProspective and retrospective. Baseline (in hospital) (n=388) and 1 year after stroke (n=253), first-ever stroke patients.One item asking if they had experienced fatigue that started after the stroke and that the patient felt was related to the strokeProportion of fatigue cases: 53%. Multivariate analysis showed that higher levels of dependency were significantly related to fatigue cases (OR 1.58) and that depression was related to fatigue cases although not at a significant level.
2Bendz15To describe the implications of having a stroke from the patients' and the health care workers' perspectiveQualitative phenomenographic approach. Data from patients (n=15) and their medical records.Interviews 3, 6, and 12 months after strokeThe patients experienced fatigue influencing their rehabilitation process and expressed as that coming suddenly and without any specific reason. Fatigue was ignored in the health care workers’ recordings.
3Carlsson et al.16To explore the consequences of a mild stroke in terms of impairment, disability, and handicap 1 year after strokeLongitudinal study. Consecutively recruited. n=63 younger than 75 years, first-ever stroke patients.Interviews semi-structuredA proportion of 72% experienced fatigue.
4Carlsson et al.17To explore how persons with astheno-emotional syndrome 1 year after a mild stroke experienced the consequences of the syndrome in everyday lifeQualitative study using Grounded Theory. Fifteen patients were strategically sampled.Interviews semi-structuredMental fatiguability was the most common symptom. Fatigue mpacted on the patients' independence and their performance of activities.
5Choi-Kwon et al.18To elucidate the characteristics of and the factors associated with poststroke fatigueCross-sectional study of 220 outpatients in Korea that were recruited consecutively, mean 15 months poststroke.FSS, fatigue VAS, and FISProportion of poststroke fatigue: 57% and prestroke fatigue: 38%. Prestroke fatigue, performance of daily activities, and depression were independently related to poststroke fatigue.
6Choi-Kwon et al.19To evaluate the therapeutic effect of fluoxetine on poststroke fatigue
Experimental study with a random assignment of 83 patients with poststroke fatigue to the intervention group (n=40) or the placebo group (n=43).

FSS, fatigue VASNo difference in the proportion of patients with poststroke fatigue between the groups 3 months after the intervention.

Intervention: 20mg fluoxetine per day in 3 months.

7Christensen et al.20To examine the associations between patients' characteristics and poststroke fatigue and its course during 2 yearsLongitudinal cohort study of 165 first-ever stroke patients assessed 10 days, 3 months, and 1 and 2 years after stroke.Multidimensional fatigue inventoryThe proportions of general severe fatigue were 59%, 44%, 38%, and 40% at different time points. Poor functional outcome was associated with higher levels of fatigue. Poststroke fatigue was mainly related to increased levels of physical fatigue. No difference in the level of reduced motivation and mental fatigue between the stroke patients and the healthy general population.
8Dam21To examine the frequency of depression for affective symptoms and possible predictors of depression 7 years after strokeCohort study. Reexamination of the stroke cohort (n=166) and controls (n=41).One item concerning their changes in fatigue during the 7-year period with four response alternativesCompared with controls, the patients did not report statistically significant increase in the level of fatigue during the last 7 years, while they did report more subjective mood instability and irritability than the controls.
9Dawes et al.22To examine the perceived exertion in patients with brain injury (including stroke) and to examine intensity and performance and other possible variables influencing the exercise intensity achievedCase-control study. Patients with brain injury (n=30) recruited consecutively and a purposively, and a sample of healthy controls (n=19) matched for age, sex, and habitual activity.The Profile of Mood States—fatigue domainLevel of fatigue predicted maximum heart rate but not the peak bicycle power output.
10de Coster et al.23Assess the sensitivity of individual depressive symptoms and their contribution to the diagnosis of poststroke depressionLongitudinal study. Patients with first-ever stroke (n=206) were interviewed within the first month after stroke and after 3, 6, 9, and 12 months.Fatigue assessed by item no. 13 in the Hamilton Rating Scale for depressionThe proportion of fatigue was 70% at 3 months after stroke. The fatigue item showed high discriminative properties in relation to depression.
11Gandiga et al.24To evaluate the effect of transcranial direct current stimulation on health controls and stroke patientsRCT. Patients with chronic stroke (n=14) and healthy controls (n=8) participated.Fatigue VASElderly health controls reported lower level of fatigue than the chronic stroke patients.
12Glader et al.25To determine the prevalence of poststroke fatigue and to examine the impact of such fatigue on daily life and on survivalLongitudinal prospective cohort study. Data from a national registry of stroke patients assessed at 3 months after stroke and a 2-year follow-up questionnaire (n=3667).Fatigue was measured by the one item: “Do you feel tired?” with four response alternatives
High.degree of dependency, being single and being women were related to fatigue. Fatigue 2 years after stroke was related to self-reported general health, anxiety, pain, and depressive symptoms.


More patients who were always tired at 3 months had died at 2-year follow-up.

13Ingles et al.26To determine the frequency and characteristics of poststroke fatigue and its subjective impact on functioningCross-sectional study. Eighty-eight patients between 3 and 13 months after stroke and 56 elderly patients participated in the study.FISA higher prevalence of fatigue in stroke patients than the control (68% vs. 36%). No gender difference in fatigue among stroke patients, whereas women had a higher rate than men in the control. No relationship between fatigue and depression, but the impact of fatigue on functional abilities was modified by depression. Forty percent reported that fatigue was either their worst or one of their worst symptoms.
14Lord et al.27To study the effect of environment and a secondary task on gait parameters among individuals with strokeCross-sectional study. Convenience sample recruited through community stroke groups.Multidimensional Fatigue InventoryFatigue scores among participants were higher than normative values. Level of fatigue was not related to gait performance.
15Lynch et al.28To develop a case definition for poststroke fatigue and to test its psychometric propertiesReview of literature, analysis of qualitative interviews, and reliability testing the definition. Case definition for hospital patients and for community patients. Good test-retest reliability (kappa, 0.78) and interrater reliability (kappa 0.82).
16Mayo et al.29To assess the feasibility of a generic health measure to create coded functional status indicators and compare the characterization of a stroke populationSurvey—case-control study. The sample consisted of 604 patients with stroke and 488 healthy controls.SF-12Differences in mental health were most strongly attributed to higher levels of fatigue.
17Mead et al.30To identify and test fatigue scales' reliability and validity in measuring fatigue in stroke patientsCross-sectional study testing four fatigue scales among 55 stroke patients who also were interviewed.SF-36 (vitality subscale), Profile of Mood States, Fatigue Assessment Scale, and Multidimensional Fatigue Symptom InventoryAll four scales were valid and feasible to administer. FAS showed the best test-retest results but the poorest internal consistency.
18Michael et al.31To quantify fatigue among chronic hemiparetic stroke patients and to explore the relationships of fatigue to cardiovascular fitness, mobility deficit severity, ambulatory activity patterns, social support, and self-efficacy for fallsCross-sectional study. Sixty stroke patients with mild to moderate hemiparetic gait deficit.FSS, fatigue VAS and falls efficacyFatigue was related to falls efficacy and scores on the Berg Balance Scale. The higher the fatigue scores, the lower the social support and the poorer the falls efficiency scores.
19Michael and Macko32To describe household and community ambulatory activity profiles, in terms of step counts and step intensity level, and determine whether these profiles are related to fitness or self-reported fatigueA randomized exercise intervention study. Seventy-nine stroke patients with mild to moderate hemiparetic gait deficit.FSSForty-two percent of the sample rated their fatigue as severe (FSS≥4). No statistically significant association between fitness, step activity, and fatigue.
20Naess et al.33To analyze fatigue in young adults with cerebral infarction and associations with functional state, cognitive dysfunctions, and social factorsCase-control study. One hundred ninety-two patients (15–49 years), after primary or secondary stroke, 1.4–12.3 years after the stroke (mean 6.0), and 212 healthy controls.FSSFatigue was higher in the stroke patients compared with the healthy controls (51% versus 32%). Fatigue was independently associated with depression, reduced function, and basilar artery infarction.
21Naess et al.34To evaluate HRQoL among young adults with ischemic stroke on long-term follow-upCase-control study. One hundred ninety stroke patients (mean age 47.8 years, 1.4–12.3 years after the stroke) and 215 healthy controls (mean age 51.1 years).FSS and SF-36Fatigue was reported by 52% of the patients. Those with fatigue had lower SF-36 scores for all subscales.
22Purebl et al.35To investigate the relationships between depressive symptoms and vital exhaustion among patients with cardiovascular disordersCross-sectional survey. A subgroup of 1,749 with self-reported cardiovascular disorders.Hungarian adaptation of the 21-item Maastricht Vital Exhaustion QuestionnaireThe proportion of severe fatigue among the respondents with stroke was 74.6%. Depression and exhaustion showed moderate correlation. Depressive symptoms were related to vital exhaustion.
23Røding et al.36To describe how younger stroke patients experienced rehabilitation and the time after stroke and to develop hypotheses about their life situationQualitative, GT, descriptive study with five young stroke patients (aged 37–54).InterviewFatigue was an essential part in their lives—viewed to be overwhelming and uncontrollable and created frustration. Impact on their family, social life, sexuality, and ability to work full time.
24Schepers et al.37To describe the course of fatigue during the first year after stroke and determine the relation between fatigue at 1 year after stroke and personal characteristics and poststroke impairmentsProspective longitudinal study. Patients (n=228) recruited consecutively at a rehabilitation center. Data from 167 patients were available for the analysis.FSS (severe fatigue=mean FSS scores>4)The proportions of severe fatigue were 52% (baseline), 64% (6 months), and 70% (12 months), with 17% with no fatigue at all measurement points. Twenty-nine percent of those with severe fatigue at 1 year were depressed. In multivariate analysis, only age, depression, and level of locus of control—powerful others subscale (believe in physicians)—were significant predictors of higher levels of fatigue.
25Schuitemaker et al.38To investigate whether vital exhaustion is a precursor of first stroke while controlling for other cardiovascular risk factorsA prospective cohort study. Adult population. One hundred sixty-seven participated in the RCT and 458 in the monitoring study.Maastricht Interview Vital Exhaustion scaleFeelings of vital exhaustion increased the risk of stroke. Might be a side effect of other risk factors.
26Shaughnessy et al.39To test a hypothesized model that considered the relationship between self-efficacy and outcome expectations for exercise, demographic variables, exercise history before stroke, and physician influences on physical activity in patients after strokeA cross-sectional survey study. n=312.SSEE, SOEEFatigue influences ADL and self-efficacy for exercise. Fatigue, race, and self-efficacy significantly influenced outcome expectations accounting for 34% of the variance.
27Sorensen et al.40To examine the quality of life and social prognosis after RIAA long-term prospective study. After baseline data were obtained, the patients were approached at 6-month intervals. Median follow-up time was 58 months.Interviews and questionnairesFatigue was present in more than 59% of the patients who only had RIA. RIA was related to psychological dysfunction and quality of life.
28Spalletta et al.41To detect the frequency of clinically rated DSM-IV depressive symptoms and the diagnostic validity of depressive disorders in stroke patients suffering from MDD, MIND, and NODEPCross-sectional. Two hundred first-ever stroke patients. Between 3 weeks and 3 months after stroke.DSM-IV (SCID-P)A gradient of severity of somatic symptoms of depression, with the highest severity found in MDD patients and lowest severity in NODEP patients. Fatigue or loss of energy and insomnia were higher in MIND patients than in NODEP patients.
29Schwartz et al.42To examine the synergism between vital exhaustion and cigarette smoking in producing ischemic strokeNational prospective cohort study in the United States of 13,066 participants in the years 1987–1989 and 1990–1992.MQ—vital exhaustionParticipants who scored in the upper quartile of vital exhaustion had a risk for stroke compared to those with a low score on vital exhaustion.
30Underwood et al.43To study the changes in pain and fatigue status among people receiving constraint-induced movement (CIM) therapyRandomized 2-group design. Stroke patients with minimal elbow, hand, and wrist range of motion in extension. One group received CIM therapy for 2 weeks at 3–9 months after stroke (n=18), the comparison group at 1 year after stroke (n=14).Single-item VAS with rating 1–10, 1=no fatigue and 10=absolute exhaustionThe participants in the CIM therapy did not report any statistically significant change in level of fatigue during treatment, and no differences in level of fatigue between the two groups were found.
31van de Port et al.44To identify clinical determinants that deteriorate mobility after strokeLongitudinal prospective cohort study with 205 patients, 1 and 3 years after first-time stroke.Rivermead Mobility Index and FSSAn association between mobility decline and fatigue was found. Fatigue predicted decline in mobility between 1 and 3 years.
32van de Port et al.45To determine the longitudinal association of poststroke fatigue with ADL, instrumental ADL, and HRQoLProspective longitudinal cohort study. Stroke patients consecutively admitted for inpatient rehabilitation (n=223). Data collected at 6, 12, and 36 months after first-ever stroke.FSS (severe fatigue defined as FSS>4)Fatigue was not related to ADL at 6 and 36 months. Significant association with performance of activities. The proportion of severe fatigue was 68% (6 months), 74% (12 months), and 58% (36 months). Fatigue is longitudinally spuriously associated with IADL and independently with HRQoL.
33van der Werf et al.46To assess whether severe fatigue was still a frequent complaint in a group of non-institutionalized outpatients who had suffered a stroke at least 1 year before the study—compared with age-matched control groupCross-sectional mailed questionnaire survey. Patients were asked to find an age-matching HC. One hundred thirty-eight patients received the questionnaire. Sixty-five percent responded and 37% of HC.CIS 8-item range: 1–7 (CIS) cutoff 40. BDI-PC (excluded somatic and performance items). Seven subscales of the Sickness Impact Scale (SIP). These seven subscale scores were added together for a total score (SIP-7-total). The SIP alertness behavior score was used to measure experienced neuropsychological problemsFatigue was the main complaint in 50% of the patients and among 16% of the HC and elevated fatigue in 51% of the stroke patients in contrast to 12% of the HC. The time since stroke was not related to fatigue. No significant relationship between fatigue and depression. Only 38% of the patients with extreme fatigue had elevated depression scores. In multivariate analysis, Sickness Impact Profile scale explained 34% of the variance in CIS fatigue, BDI-PC added another 11% and SIP alertness added 3%. BDI-PC explained the most variance in CIS fatigue (56%).

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

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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 has 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. 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 specifically 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 hospital 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 analogue 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 specifically 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=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-à-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.

Table 2. Self-Reported Fatigue Measurements Used in Stroke Populations
MeasurementDeveloperInitial PopulationDimensions and/or SubscalesNo. of ItemsStroke Studies
Checklist of Individual Strenth (CIS)Vercoulen et al.49MS, CFS, HC
1) Subjective fatigue, 2) concentration, 3) motivation, 4) physical activity level

24van der Werf et al.46
Fatique Assessment Scale (FAS)Michielsen et al.51WorkersSeverity10Lynch et al.28 Mead et al.30
Fatique Severity Scale (FSS)Krupp et al.6MS and SLEFatigue severity9Choi-Kwon et al.18 Choi-Kwon et al.19 Michael et al.30 Michael and Macko32 Naess et al.33 Naess et al.34 Schepers et al.37 van de Port et al.44 van de Port et al.45
Fatique Impact Scale (FIS)Fisk et al.7MS, CFS patients with hypertension
Perceived impact on 1) cognitive, 2) physical, 3) psychological functioning

40Choi-Kwon et al.18 Ingles et al.26
Masstricht Questionnaire (MQ)Appels et al.52Myocardial infarctionVital exhaustion: fatigue, irritability, stress (inability to cope), and feeling of demoralization Purebl et al.35 Schuitemaker et al.38 Schwartz et al.42
Multidimensional Fatigue Inventory (MFI-20)Smets et al.50Cancer patients, CFS and HC
1) General health, 2) physical fatigue, 3) mental fatigue, 4) reduced motivation, 5) reduced activity

20Christensen et al.20
Multidimensional Fatigue Symptom Inventory (MFIS—general)Smets et al.50Cancer patients
1) Global, 2) somatic, 3) affective, 4) cognitive, 5) behavioral symptoms of fatigue (not used in stroke patients)

6Lord et al.27 Lynch et al.28
One-item questions For example, “…have you experienced fatigue?”1Appelros14 Dam21 de Coster et al.23 Glader et al.25 Shaughnessy et al.39 Sorensen et al.40
POMSMcNair et al.53
1) Fatigue—inertia, 2) vigor—activity, 3) depression—dejection, 4) tension—anxiety, 5) anger—hostility, 6) confusion—bewilderment

65Dawes et al.22 Lynch et al.28 Mead et al.30
SF-36/12 Vitality subscaleWare et al.8Patients with different chronic illnessesEnergy level and fatigue4Lynch et al.28 Mayo et al.29 Mead et al.30
VAS Used in many different types of populations 1Choi-Kwon et al.18 Choi-Kwon et al.19 Michael et al.31 Underwood et al.42

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

Prevalence of Fatigue 

Fatigue is among the most prevalent symptoms after stroke,26, 54 with prevalence rates shown in Table 3.

Table 3. Overview of Studies Reporting Prevalence Rates of Severe Fatigue After Stroke
StudySample and Sample SizeFatigue Instrument UsedPrevalence of Fatigue Reported
Appelros14Swedish—population of first-ever stroke in a municipality (253)One item asking if they had experienced fatigue that started after the stroke53% at 1 year
Carlsson et al.16First-ever stroke patients <75 years consecutive admission to a Swedish hospital (75)AED72% at 1 year
Carlsson et al.54First-ever stroke patients and their spouses’ consecutive admission to a Swedish hospital (56)AED77% at 1 year
Choi-Kwon et al.18Consecutive subjects from a Korean outpatient clinic (220)VAS (severe=7–10) FSS, FIS (cutoff value not given)
38% prestroke


57% (between 3 and 27 months)

Christensen et al.20First-ever stroke patients’ consecutive admission to a Danish hospital (165)MFI-20 (severe=general fatigue sum score≥12)
59% at 10 days


44% at 3 months


38% at 1 year


40% at 2 years

Dam21Follow-up study in Denmark (99)One item asking if they were experiencing fatigue
de Coster et al.23The Maastricht University Hospital Stroke Registry (206)One item from the HAM-D70% within 1 month
Ingles et al.26Consecutively recruited from a hospital (88)FIS68%, 3–13 months after stroke
Lynch et al.28Patients in acute phase or rehabilitation—both inpatients and from the community (55)Case definition36%, 10–217 days after stroke
Michael et al.31A community sample of patients with mild to moderate hemiparetic gait deficits in Baltimore (53)
FSS.(mean>4) VAS

46%, 6–166 months after stroke (mean=10.3 months)
Michael and Macko32Community sample of patients with chronic hemiparetic stroke in Baltimore (79)FSS (mean>4)42%, 6–120 months after stroke (mean=10 months)
Naess et al.33Community sample in Norway, aged 15–49 years (192)FSS (mean>4)51% (1.4–12.3 years after stroke)
Schepers et al.37Dutch—consecutive admissions to rehabilitation center (228)FSS (mean>4)51.5% at admission; 64.1% at 6 months; 69.5% at 1 year
Purebl et al.35Stroke patients identified in a national representative sample in Hungary (501)MVEQ (mean 2.58)74.6%
van de Port et al.45Consecutive patients from an inpatient rehabilitation clinic in The Netherlands (223)FSS (mean>4)68% at 6 months; 74% at 12 months; 58% at 36 months
van de Port et al.45Consecutive patients from an inpatient rehabilitation clinic in The Netherlands (168)FSS (mean>4)53% at 36 months
van der Werf et al.46Stroke patients admitted to a hospital in The Netherlands (90)CIS (sum score>40)50% (mean time since stroke=2 years)

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

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 at one year after stroke, 53% of patients reported experiencing fatigue that specifically 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%–77%.16, 54 In another Swedish follow-up study of 3,805 patients in the Swedish Riks-Stroke 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 3–6, 7–9, and 10–13 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 the 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. In addition, fatigue in the general population in Norway has been estimated using different cutoff values (4.0 and 5.0), suggesting 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.

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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.

Table 4. Studies Reporting on the Relationship Between Sociodemographic Variables, Stroke Characteristics, Comorbidity, and Poststroke Fatigue
Antecedent Variables or ConditionsStudies and Findings
Personal factorsAgeAppelros,14 NS; Carlsson et al.16 NS; Choi-Kwon et al.18 NS; Glader et al.25P<0.001; Ingles et al.26 NS; Lynch et al.28 NS; Naess et al.33 NS; Schepers et al.37P=0.02
SexAppelros,14 NS; Carlsson et al.16 NS; Choi-Kwon et al.18 NS; Glader et al.25 women>men P=0.01; Ingles et al.26 NS; Lynch et al.28P=0.02; Mayo et al.29 women>men; OR=1.6; 95% CI: 1.1–2.2; Naess et al.33 NS; Purebl et al.35 NS; Schepers et al.37 NS
Marital statusGlader et al.25 single>married/cohabitant P<0.001; Schepers et al.37 NS
Employment statusCarlsson et al.16P=0.05; Choi-Kwon et al.18P<0.05; Naess et al.33P=0.002
Cohabitant statusAppelros,14 NS; Glader et al.25 living at home with social support/in institution before the stroke>living alone, P<0.01
Level of educationChoi-Kwon et al.18 NS; Naess et al.33 NS
Stroke characteristicsLocationAppelros,14 NS; Carlsson et al.16 NS; Choi-Kwon et al.18 NS; Ingles et al.26 NS; Lynch et al.28 NS; Naess et al.33 NS; Schepers et al.37 NS
TypeAppelros,14 NS; Carlsson et al.16 NS; Schepers et al.37 NS; Glader et al.25 NS; Lynch et al.28 NS
Number of strokesGlader et al.25 recurrent>first ever, P=0.003
Time after strokeIngles et al.26 NS
NIHSSAppelros,14 facial palsy OR=1.8; P=0.04; arm paresis OR=1.5; P=0.02
SSSCarlsson et al.16 NS
Neurological deficitChoi-Kwon et al.18 dysarthria, P<0.01; inappropriate and excessive laughing, P<0.01; Ingles et al.26 NS; Naess et al.33 NS
Prestroke fatigue Choi-Kwon et al.18R=33.46; P<0.01; Choi-Kwon et al.19r=0.40; P<0.01; Schwartz et al.42 risk factor for stroke, P<0.001; Schuitemaker et al.38 risk factor for stroke, P=0.002
LifestyleCigarette smokingChoi-Kwon et al.18P<0.05; Naess et al.33 NS
High use of alcoholChoi-Kwon et al.18 NS
BMINaess et al.33 NS
Primary ADLs before stroke Glader et al.25 dependency before the stroke, P<0.001
ComorbidityCardiovascular diseasesAppelros,14 NS; Choi-Kwon et al.18 NS; Naess et al.33 NS
DiabetesAppelros,14 NS; Choi-Kwon et al.18 NS; Naess et al.33P=0.008
MigraineNaess et al.33P=0.003
Primary ADLs before strokeGlader et al.25 dependency before the stroke, P<0.001

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

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 level of education and poststroke fatigue.18, 33, 35

In 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, 25, 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.

Prestroke Fatigue 

As fatigue is a common experience in the general population, there has been some interest in examining the relationship between pre- and poststroke fatigue to determine whether poststroke fatigue is actually stroke related. In a randomized controlled study testing the effects of fluoxetine on fatigue, the presence of prestroke fatigue was related to fatigue after stroke (r=0.40, P<0.01).19 A 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.18 Among patients with prestroke 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]=2.42, P<0.001) for stroke 5–7 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=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 9.5–62.7 months) showed that feelings of exhaustion increased the risk of stroke (relative risk=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 poststroke fatigue and personal variables, stroke-related characteristics, and preexisting conditions. There are conflicting findings regarding associations between poststroke 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 poststroke fatigue. There may be an association between prestroke fatigue and poststroke fatigue. This association, however, is difficult to validate because of a high degree of unreliability in retrospectively obtained prestroke fatigue data. It appears essential to evaluate possible relationships between pre- and poststroke fatigue to understand the component of fatigue that is specifically 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 Table 5, Table 6.

Table 5. Studies Reporting Findings Regarding Clinical Factors Related to Poststroke Fatigue
Clinical VariableInstrument UsedStudies
PainOne itemAppelros,14 NS; Glader et al.25P<0.01
DepressionCES-DSchepers et al.37P<0.001
BDIChoi-Kwon et al.19P<0.01
HADS-DLynch et al.28P=0.006
MADRSNaess et al.33P<0.001
GDSChoi-Kwon et al.18 OR: 2.67; P<0.05 (multivariate analysis); Ingles et al.26 β=0.75 (multivariate analysis)
DSM-IVAppelros,14 OR=3.2; P<0.001 (univariate analysis); Carlsson et al.16P<0.001; Spalletta et al.41P=0.001
One item self-perceived depressionGlader et al.25P<0.001
Anxiety and other emotional statusHADS-ALynch et al.28P=0.004
MADRSNaess et al.33P<0.001
One itemGlader et al.25P<0.01
Sleep disturbanceOne item asking about sleep disturbanceAppelros,14 OR=2.9; P=0.001 (univariate analysis); Choi-Kwon et al.18P<0.05; Schepers et al.37 NS
Cognitive statusMMSAppelros,14 NS; Carlsson et al.16 NS; Naess et al.33 NS; Schepers et al.37 NS
Trail making test-BSchepers et al.37 NS
Motor functioningRankin scoreNaess et al.33P<0.001
Motricity IndexSchepers et al.37 NS
RPEDawes et al.22 NS
%APMHRDawes et al.22 β=−0.41; P<0.05
Berg BalanceMichael et al.31 NS
Ambulatory activityMichael et al.31 NS
Falls efficacyMichael et al.31P=0.007
Gait speedLord et al.27 NS
Walking velocityMichael et al.31 NS
RMIvan de Port et al.44P=0.04
DependencyMRSAppelros,14 OR=1.4; P<0.001; Choi-Kwon et al.18 OR=3.25; P<0.05 (multivariate analysis)
OHSCarlsson et al.16P<0.001; Ingles et al.26 NS
MHLCSchepers et al.37 powerful others scale; P=0.002

%APMHR=percentage of age-predicted value; BDI=Beck Depression Inventory; CES-D=Center for Epidemiological Studies Depression Scale; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, fourth edition; GDS=Geriatric Depression Scale; HADS=The Hospital Anxiety and Depression Scale; MADRS=Montgomery and Åsberg Depression Rating Scale; MHLC=Multidimensional Health Locus of Control Scale; MMS=Mini-Mental State Examination; MRS=Modified Rankin Scale; NS=not statistically significant; OHS=Oxford Handicap Scale; OR=odds ratio; RMI=Rivermead Mobility Index; RPE=Rating of Perceived Exertion.

Table 6. Studies Reporting on the Impact of Poststroke Fatigue on Function and Quality of Life
VariablesInstrument UsedStudies
Quality of lifeHQoLNaess et al.34 physical functioning, P<0.001; role—physical, P<0.001; bodily pain, P<0.001; general health, P<0.001; vitality, P<0.001; social functioning, P<0.001; mental health, P<0.05
General health statusGlader et al.25P<0.01
FunctioningADLsCarlsson et al.16 NS; Glader et al.25P<0.001; Ingles et al.26 NS; van de Port et al.45
IADLsGlader et al.25P<0.001; Mayo et al.29P<0.05; van de Port et al.45 NS (multivariable analyses)
FAIvan de Port et al.45P=0.032
Speech impairmentGlader et al.25P<0.001
General healthGlader et al.25P<0.001
Self-efficacy expectationsShaughnessy et al.39
SIPvan der Werf et al.46P<0.001; van de Port et al.45P<0.001
Fatality Glader et al.25 always>never/sometimes, OR: 1.85, P<0.001

FAI=Frenchay Activity Index; HQoL=health-related quality of life; IADLs=instrumental activities of daily living; NS=not statistically significant; OR=odds ratio; SIP=Sickness Impact Profile Scale.

Pain 

For patients one year after the stroke, 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.

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 poststroke 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: 1.7–6.0).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 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 on 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 at 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 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 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.

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Fatigue-Relieving Interventions 

Only one intervention study was found that specifically 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 poststroke fatigue, suggesting that serotonergic system dysfunction is not a potential mechanism for poststroke 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. It seems critical that there is a need to develop strategies to address poststroke fatigue and test such strategies for their effectiveness, given the high prevalence of poststroke fatigue and its apparent effects on patients' lives.

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Summary 

The literature on poststroke fatigue indicates that knowledge regarding this phenomenon is still at a foundation stage. To develop comprehensive understanding to move toward effective interventions, empirical research with various theoretical orientations must continue. 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, prestroke 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 biophysiological markers have not been studied specifically 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.61, 62, 63, 64 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 poststroke fatigue experience, as shown in some studies. Two studies of patients with chronic fatigue syndrome have shown a reduction in subcortical gray matter when compared with healthy controls.65, 66 Similar studies on patients with poststroke fatigue may discover possible precipitating factors. Prestroke fatigue as an antecedent factor is an important consideration in understanding poststroke 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 identified 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, psychocognitive, 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 poststroke fatigue and in specifying 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 poststroke fatigue develops.

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Acknowledgments 

We acknowledge the support and assistance provided by various staff members of Buskerud Hospital in Drammen and Oslo University Hospital—Aker in Oslo, Norway, in carrying out this research project.

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References 

  1. Staub F, Bogousslavsky J. Fatigue after stroke: a major but neglected issue. Cerebrovasc Dis. 2001;12:75–81
  2. Lerdal A. Energy, fatigue and perceived illness in individuals with multiple sclerosis: A multi-method approach. Doctoral Dissertation, Department of Behavioural Science in Medicine, University of Oslo, Unipub AS; 2005;
  3. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988;45:435–437
  4. Lee KA, Lentz MJ, Taylor DL, Mitchell ES, Woods NF. Fatigue as a response to environmental demands in women's lives. Image J Nurs Sch. 1994;26:149–154
  5. Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006;367:346–355
  6. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The Fatigue Severity Scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46:1121–1123
  7. Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994;18(Suppl 1):S79–S83
  8. Ware J, Snow KK, Kosinski M. SF-36 Health survey: Manual and interpretation guide. Lincoln, RI: Quality Metric Incorporated; 2002;
  9. Ponten EM, Stal PS. Decreased capillarization and a shift to fast myosin heavy chain IIx in the biceps brachii muscle from young adults with spastic paresis. J Neurol Sci. 2007;253:25–33
  10. Schwid SR, Tyler CM, Scheid EA, et al. Cognitive fatigue during a test requiring sustained attention: a pilot study. Mult Scler. 2003;9:503–508
  11. Colle F, Bonan I, Gellez Leman MC, Bradai N, Yelnik A. Fatigue after stroke. Ann Readapt Med Phys. 2006;49:361–364
  12. De Groot MH, Phillips SJ, Eskes GA. Fatigue associated with stroke and other neurologic conditions: implications for stroke rehabilitation. Arch Phys Med Rehabil. 2003;84:1714–1720
  13. Barker-Collo S, Feigin VL, Dudley M. Post stroke fatigue—where is the evidence to guide practice?. N Z Med J. 2007;120:U2780
  14. Appelros P. Prevalence and predictors of pain and fatigue after stroke: a population-based study. Int J Rehabil Res. 2006;29:329–333
  15. Bendz M. The first year of rehabilitation after a stroke—from two perspectives. Scand J Caring Sci. 2003;17:215–222
  16. Carlsson GE, Moller A, Blomstrand C. Consequences of mild stroke in persons <75 years—a 1-year follow-up. Cerebrovasc Dis. 2003;16:383–388
  17. Carlsson GE, Moller A, Blomstrand C. A qualitative study of the consequences of ‘hidden dysfunctions’ one year after a mild stroke in persons <75 years. Disabil Rehabil. 2004;26:1373–1380
  18. Choi-Kwon S, Han SW, Kwon SU, Kim JS. Poststroke fatigue: characteristics and related factors. Cerebrovasc Dis. 2005;19:84–90
  19. Choi-Kwon S, Choi J, Kwon SU, Kang DW, Kim JS. Fluoxetine is not effective in the treatment of post-stroke fatigue: a double-blind, placebo-controlled study. Cerebrovasc Dis. 2007;23:103–108
  20. Christensen D, Johnsen SP, Watt T, et al. Dimensions of post-stroke fatigue: a two-year follow-up study. Cerebrovasc Dis. 2008;26:134–141
  21. Dam H. Depression in stroke patients 7 years following stroke. Acta Psychiatr Scand. 2001;103:287–293
  22. Dawes H, Scott OM, Roach NK, Wade DT. Exertional symptoms and exercise capacity in individuals with brain injury. Disabil Rehabil. 2006;28:1243–1250
  23. de Coster L, Leentjens AF, Lodder J, Verhey FR. The sensitivity of somatic symptoms in post-stroke depression: a discriminant analytic approach. Int J Geriatr Psychiatry. 2005;20:358–362
  24. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006;117:845–850
  25. Glader EL, Stegmayr B, Asplund K. Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden. Stroke. 2002;33:1327–1333
  26. Ingles JL, Eskes GA, Phillips SJ. Fatigue after stroke. Arch Phys Med Rehabil. 1999;80:173–178
  27. Lord SE, Rochester L, Weatherall M, McPherson KM, McNaughton HK. The effect of environment and task on gait parameters after stroke: a randomized comparison of measurement conditions. Arch Phys Med Rehabil. 2006;87:967–973
  28. Lynch J, Mead G, Grieg C, et al. Fatigue after stroke: the development and evaluation of a case definition. J Psychosom Res. 2007;63:539–544
  29. Mayo NE, Poissant L, Ahmed S, et al. Incorporating the International Classification of Functioning, Disability, and Health (ICF) into an electronic health record to create indicators of function: proof of concept using the SF-12. J Am Med Inform Assoc. 2004;11:514–522
  30. Mead G, Lynch J, Greig C, et al. Evaluation of fatigue scales in stroke patients. Stroke. 2007;38:2090–2095
  31. Michael KM, Allen JK, Macko RF. Fatigue after stroke: relationship to mobility, fitness, ambulatory activity, social support, and falls efficacy. Rehabil Nurs. 2006;31:210–217
  32. Michael K, Macko RF. Ambulatory activity intensity profiles, fitness, and fatigue in chronic stroke. Top Stroke Rehabil. 2007;14:5–12
  33. Naess H, Nyland HI, Thomassen L, Aarseth J, Myhr KM. Fatigue at long-term follow-up in young adults with cerebral infarction. Cerebrovasc Dis. 2005;20:245–250
  34. Naess H, Waje-Andreassen U, Thomassen L, Nyland H, Myhr KM. Health-related quality of life among young adults with ischemic stroke on long-term follow-up. Stroke. 2006;37:1232–1236
  35. Purebl G, Birkas E, Csoboth C, Szumska I, Kopp MS. The relationship of biological and psychological risk factors of cardiovascular disorders in a large-scale national representative community survey. Behav Med. 2006;31:133–139
  36. Røding J, Lindstrom B, Malm J, Ohman A. Frustrated and invisible—younger stroke patients' experiences of the rehabilitation process. Disabil Rehabil. 2003;25:867–874
  37. Schepers VP, Visser-Meily AM, Ketelaar M, Lindeman E. Poststroke fatigue: course and its relation to personal and stroke-related factors. Arch Phys Med Rehabil. 2006;87:184–188
  38. Schuitemaker GE, Dinant GJ, Van Der Pol GA, Verhelst AF, Appels A. Vital exhaustion as a risk indicator for first stroke. Psychosomatics. 2004;45:114–118
  39. Shaughnessy M, Resnick BM, Macko RF. Testing a model of post-stroke exercise behavior. Rehabil Nurs. 2006;31:15–21
  40. Sorensen PS, Marquardsen J, Pedersen H, Heltberg A, Munck O. Long-term prognosis and quality of life after reversible cerebral ischemic attacks. Acta Neurol Scand. 1989;79:204–213
  41. Spalletta G, Ripa A, Caltagirone C. Symptom profile of DSM-IV major and minor depressive disorders in first-ever stroke patients. Am J Geriatr Psychiatry. 2005;13:108–115
  42. Schwartz SW, Carlucci C, Chambless LE, Rosamond WD. Synergism between smoking and vital exhaustion in the risk of ischemic stroke: evidence from the ARIC study. Ann Epidemiol. 2004;14:416–424
  43. Underwood J, Clark PC, Blanton S, Aycock DM, Wolf SL. Pain, fatigue, and intensity of practice in people with stroke who are receiving constraint-induced movement therapy. Phys Ther. 2006;86:1241–1250
  44. van de Port I, Kwakkel G, van WI, Lindeman E. Susceptibility to deterioration of mobility long-term after stroke: a prospective cohort study. Stroke. 2006;37:167–171
  45. van der Port I, Kwakkel G, Schepers VP, Heinemans CT, Lindeman E. Is fatigue an independent factor associated with activities of daily living, instrumental activities of daily living and health-related quality of life in chronic stroke?. Cerebrovasc Dis. 2007;23:40–45
  46. van der Werf SP, van den Broek HL, Anten HW, Bleijenberg G. Experience of severe fatigue long after stroke and its relation to depressive symptoms and disease characteristics. Eur Neurol. 2001;45:28–33
  47. Skaner Y, Nilsson GH, Sundquist K, Hassler E, Krakau I. Self-rated health, symptoms of depression and general symptoms at 3 and 12 months after a first-ever stroke: a municipality-based study in Sweden. BMC Fam Pract. 2007;8:61
  48. Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and multiple sclerosis: Evidence-based management strategies for fatigue in multiple sclerosis. Washington, DC: Paralyzed Veterans of America; 1998;
  49. Vercoulen JH, Swanink CM, Fennis JF, et al. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994;38:383–392
  50. Smets EM, Garssen B, Bonke B, de Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995;39:315–325
  51. Michielsen HJ, De VJ, Van Heck GL. Psychometric qualities of a brief self-rated fatigue measure: the Fatigue Assessment Scale. J Psychosom Res. 2003;54:345–352
  52. Appels A, Hoppener P, Mulder P. A questionnaire to assess premonitory symptoms of myocardial infarction. Int J Cardiol. 1987;17:15–24
  53. McNair DM, Lorr M, Dropplemann LF. Profile of Mood States (POMS). San Diego, CA: Educational and Industrial Testing Service; 1992;
  54. Carlsson GE, Forsberg-Warleby G, Moller A, Blomstrand C. Comparison of life satisfaction within couples one year after a partner's stroke. J Rehabil Med. 2007;39:219–224
  55. van de Port I, van den Bos GA, Voorendt M, Kwakkel G, Lindeman E. Identification of risk factors related to perceived unmet demands in patients with chronic stroke. Disabil Rehabil. 2007;29:1841–1846
  56. Lerdal A, Wahl A, Rustoen T, Hanestad BR, Moum T. Fatigue in the general population: a translation and test of the psychometric properties of the Norwegian version of the Fatigue Severity Scale. Scand J Public Health. 2005;33:123–130
  57. Loge JH, Ekeberg O, Kaasa S. Fatigue in the general Norwegian population: normative data and associations. J Psychosom Res. 1998;45:53–65
  58. Widar M, Ek AC, Ahlstrom G. Coping with long-term pain after a stroke. J Pain Symptom Manage. 2004;27:215–225
  59. Sisson RA. Life after a stroke: coping with change. Rehabil Nurs. 1998;23:198–203
  60. Lenz ER, Pugh LC, Milligan RA, Gift A, Suppe F. The middle-range theory of unpleasant symptoms: an update. ANS Adv Nurs Sci. 1997;19:14–27
  61. Kelley ML, Sellick S, Linkewich B. Rural nonphysician providers' perspectives on palliative care services in northwestern Ontario, Canada. J Rural Health. 2003;19:55–62
  62. Konsman JP, Parnet P, Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Trends Neurosci. 2002;25:154–159
  63. Capuron L, Gumnick JF, Musselman DL, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology. 2002;26:643–652
  64. Vollmer-Conna U. Acute sickness behaviour: an immune system-to-brain communication?. Psychol Med. 2001;31:761–767
  65. Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004;4:14
  66. de Lange FP, Kalkman JS, Bleijenberg G, et al. Neural correlates of the chronic fatigue syndrome: an fMRI study. Brain. 2004;127:1948–1957
  67. Kirkevold M. The unfolding illness trajectory of stroke. Disabil Rehabil. 2002;24:887–898

 This project is funded by the Research Council of Norway (RCN) for 2006–2010. Dr. A. Lerdal has received funding from the RCN (Grant 19256), the Norwegian Nurses Organization, and the U.S.-Norway Fulbright Foundation.

 This paper is a product stemming from the research project Post-Stroke Fatigue for which Dr. H. S. Kim is the project director and Drs. Grethe Eilertsen, A. Lerdal, and Heidi Ormstad are the principal researchers.

PII: S0885-3924(09)00732-5

doi:10.1016/j.jpainsymman.2009.04.028

Journal of Pain and Symptom Management
Volume 38, Issue 6 , Pages 928-949, December 2009

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