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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 26-October-2007, Vol 120 No 1264

Post-stroke fatigue—where is the evidence to guide practice?
Suzanne Barker-Collo, Valery L Feigin, Margaret Dudley
Abstract
A significant proportion of stroke survivors suffer from persistent and significant fatigue which is linked to reduced independence and case fatality. Despite its high prevalence and detrimental effects, studies of post-stroke fatigue (PSF) interventions are scarce. Only one randomised controlled trial of post-stroke fatigue treatment (i.e. fluoxetine) was identified, and though improving post-stroke emotional incontinence and depression in patients with fatigue this did not improve PSF itself. Despite there being no literature on its efficacy, patient and family education/counselling has been identified as an important rehabilitation intervention for the management of stroke-related fatigue, which has been found effective in other patient groups (i.e. cancer, multiple sclerosis, and those with traumatic brain injury). Factors contributing to the lack of evidence for PSF management are identified and it is concluded that there is a need to better differentiate those most likely to suffer PSF, to validate existing assessments of fatigue, and to evaluate the efficacy of fatigue management and treatment strategies in stroke survivors.

Post-stroke fatigue and its impact

Stroke is the second most common cause of death worldwide and the leading cause of disability in adults, having an enormous physical, psychological, and financial impact.1,2 A significant proportion of stroke survivors (39–72%) suffer from persistent and significant fatigue affecting their daily lives, with significant differences in prevalence likely related to varying definitions and methods of assessing fatigue, as well as sampling of different populations.3–8
Defining post-stroke fatigue (PSF) is a challenge as it represents a complex interaction of biological, psychosocial, and behavioral phenomena.9 Subjective fatigue is commonly defined as a feeling of early exhaustion or tiredness developing during either mental or physical activity, or both, with weariness, lack of energy, and aversion to effort.5,10 One recent systematic review of self-reported instruments for fatigue assessment defines fatigue as “An unpleasant physical, cognitive, and emotional symptom described as a tiredness not relieved by common strategies that restore energy.”11
By its very definition, fatigue involves behavioural and work performance decrement, and is characterised by distress and decreased functional status related to reduced energy.12 Post-stroke fatigue, either cognitive and/or physical, often poses a barrier to return to work and other daily activities, quality of life, and rehabilitation, especially during the first year after stroke onset.4,5,13-16 Indeed, it has been shown that fatigue is associated with profound deterioration of several aspects of everyday life.3,7
In a 2-year stroke follow-up population-based Swedish study,3 fatigue independently predicted decreased functional independence, institutionalisation, and case-fatality. Similarly, a case-control study in the Netherlands17 found that PSF correlates significantly with functional disability and neuropsychological deficits. Furthermore, PSF may impede full participation in a rehabilitation program.14
Interestingly, stroke survivors with less severe physical or cognitive disability tend to rate fatigue as a more severe symptom,4,9,18 which, according to de Groot et al,19 may be related to the relative lack of other post-stroke sequelae and greater expectation for full recovery and differing demands of daily life in these patients.

Prevalence and natural history

Of 4023 2-year stroke survivors in Sweden,20 366 (10%) reported always feeling tired and 1070 (29.2%) additional survivors were often tired. Two years post stroke approximately 40% of patients report that they are “always” or “often” fatigued.3,4,17
The frequency of self-reported fatigue is roughly twice as high in patients post stroke as it is in matched controls, and 27% of stroke survivors experience fatigue every day.4 Although fatigue is known to persist for months and even years post-stroke,4,17 the time which has elapsed since the stroke occurred can not explain levels of fatigue.4,17
In a Canadian case-control study, fatigue was also not related to stroke severity, or lesion location.4 In that study, 40% of the stroke group reported that fatigue was either their worst or one of their worst symptoms. Although most of these studies evaluated fatigue in elderly stroke survivors, there is some evidence suggesting that post-stroke fatigue is more prevalent in younger that in older patients.3
In regards to the time course of PSF, a recent study of 167 survivors of first-ever stroke,7 assessed fatigue at admission, 6-months post-stroke, and 1-year post stroke and found it to be present in 51.5%, 64.1%, and 69.5%, respectively. Fatigue was present at all three assessments in 37.7% of patients, and absent on all three assessments in 17.4% of patients.
Although fatigue is often seen as a result of sleep apnoea, post-stroke depression, and disability,6,21,22 a concept of 'primary' post-stroke fatigue has been proposed.5 According to this concept, fatigue may develop in the absence of depression or significant cognitive sequelae, and may be linked to attentional deficits resulting from specific damage to the reticular formation and related structures involved in the subcortical attentional network.
Fatigue is one of the symptoms of depression, but does not include the accompanying inappropriate feelings of anhedionia, worthlessness, hopelessness, or suicidal ideation.23 There is evidence that the presence of post-stroke fatigue is independent of depression.3 In a 2-year follow-up of post-stroke fatigue, of 3667 patients who were not depressed, 10% (n =366) always felt tired, while an additional 29.2% (n=1070) often felt tired.3 When depression and fatigue do co-occur, the impact of fatigue on functional abilities is strongly influenced by depression.4
In addition to depression, PSF must also be differentiated from symptoms of executive disturbances such as apathy. Executive dysfunction is typified by an inability to engage in goal-directed behaviours, of which difficulty initiating behaviour may be a symptom.24 Thus, a patient with executive dysfunction may express an intention to engage in a particular behaviour but not actually be able to initiate that behaviour without assistance, which may be viewed by others as patient apathy. This is very different from the individual with fatigue who would typically state that they cannot engage in an activity due to their fatigue, and who is able to initiate behaviour if she/he desires to do so, but may not be able to complete the behaviour due to fatigue.
Anxiety may also present as fatigue, though anxiety may be differentiated using techniques such as SWIKIR (Somatic Symptoms, Worries, Irritability, Keyed-up or on edge, Initial insomnia, and Relaxation Difficulties), whereby anxiety disorder is present if 3 or more symptoms are reported.25

Measuring post-stroke fatigue

Many unidimensional and multidimensional scales have been developed attempting to measure the nature, severity, and impact of fatigue in a range of clinical populations.10,11,26 Different scales purport to measure different aspects of fatigue and it has been suggested that measures developed to measure fatigue in one clinical condition may not be justified for other clinical conditions.10 However, it has also been suggested that “since fatigue is an unspecific symptom there should not be need for adopting disease specific fatigue scales for each individual disease.”26 In this situation the choice of the most appropriate fatigue measurement scale to be used for research or clinical practice should be determined by aspects of fatigue that need to be measured.10
While there is no consensus on which fatigue scales are most appropriate for use in the assessment of fatigue in stroke survivors, the most commonly used in stroke populations10 include the Visual Analogue Scale (used in three studies);15,27,28 Fatigue Severity Scale (used in five studies);4,7,15,27,29 Checklist Individual Strength (used in one study);17 and quality of life fatigue subscales, including SF-36 (used in three studies)30-32 and Newcastle Stroke specific Quality of Life measure (used in one study).33
Of these, two objective assessment tools (Fatigue Severity Scale and Checklist Individual Strength) have been recently recommended by de Groot et al19 to quantify fatigue characteristics for initial diagnosis and to monitor the outcome of fatigue treatment in stroke survivors, although it was mentioned that “scales or measures used in the study of fatigue in other patient populations may also prove useful for application to post-stroke fatigue.”
Electromyography has also been used to evaluate neuromuscular fatigue post-stroke,34 but this measurement has limited value in the overall evaluation of post-stroke fatigue in which multiple dimensions of fatigue are usually involved.
Right hemispheric strokes have been implicated in fatigue because of disconnection between the right insula and frontal lobe or anterior cingulated cortex.35 Fatigue has also been associated with damage to the brainstem and thalamic regions—affecting the reticular activating formation that regulates wakefulness.5,36 However, these physical associations with fatigue are inconsistent,4 and do not explain the widespread incidence of fatigue post stroke.
Other identified predictors of post-stroke fatigue include living alone or in an institution, impairment in activities of daily living (ADL), and recurrent stroke.3 Although older female stroke survivors were more likely to report fatigue in one study,3 no association between fatigue and demographic variables was found in other studies.4,17 Given these multiple potential causes of post-stroke fatigue, any assessment of fatigue must be multidimensional, and treatment approaches are likely to be differentially beneficial in different etiologically defined subgroups.

Fatigue management— what is available?

Despite the high prevalence of post-stroke fatigue and its detrimental effects, studies for post-stroke fatigue interventions are scarce. Indeed, a search of the United Kingdom’s National Clinical Guidelines for Stroke (2nd edition)37 and its tables of evidence reveals no evidence on treatments for fatigue, nor is there any mention of fatigue as a condition requiring treatment.
Fatigue is not mentioned in the New Zealand guidelines for stroke management,38 yet it has been emphasised that intervention studies are urgently needed for this potentially treatable sequelae of stroke.3–7,15,39
Because the causes of fatigue are multidimensional and interrelated, a considerable range of fatigue management options are available, including cause-specific treatments, pharmacological intervention, and non-pharmacological interventions, including educational programs. For example, stroke patients who have been inactive and/or ill for periods of time may have nutritional or metabolic deficits resulting in fatigue.
Treating anaemia and supporting nutrition, or correcting electrolyte and fluid imbalances may make positive differences for these patients. In addition, comorbidities common to older adults such as arthritis, thyroid function changes, respiratory disease, altered glucose metabolism, or cardiovascular disease may contribute to fatigue and their treatment may lessen fatigue symptoms.40
Use of psychostimulants and antidepressants (where fatigue is intermingled with depression) may offer some relief from the symptoms of fatigue related to HIV and multiple sclerosis.41,42 When stroke causes low initiation and psychomotor retardation, which may be interpreted as motor fatigue or executive dysfunction, tricyclic antidepressants such as methylphenidate have been successfully used to improve functional independence and mood.4,43
Several non-pharmacological interventions have also been linked to reduced fatigue including therapeutic recreation and social activities, and complementary activities such as biofeedback,44 relaxation and meditation,45 music,46,47 and pet therapy;48 which are thought to offer benefits through distraction and stress reduction which may ameliorate the impact of fatigue. Their specific benefits in alleviation of post-stroke fatigue in randomised controlled trials have yet to be established.
We have been able to identify only one randomised controlled trial of fatigue management in stroke survivors.27 In that small (n=83) double-blind placebo-controlled trial, consecutive outpatient stroke survivors (average 14 months post stroke) were randomly assigned to either fluoxetine (antidepressant of the selective serotonin reuptake inhibitor class) 20 mg/day (n=40) or placebo (n=43) given over 3 months. Follow-up evaluations at 3 and 6 months after the beginning of the treatment, included the Visual Analogue Scale (mean score 5.4±2 at baseline) and Fatigue Severity Scale (mean score 4.4±1.2 at baseline).
Percent change in the fatigue scales and the proportion of patients with fatigue did not differ between the treatment groups at either follow-up assessments. However, fluoxetine significantly improved post-stroke emotional incontinence and depression in patients with fatigue. The authors concluded that post-stroke fatigue may be associated with diverse aetiologies (but not closely related to serotonergic dysfunction), and that further studies are required to elucidate the causative factors to find an appropriate treatment for post-stroke fatigue.

Psychoeducation for fatigue management

It has been suggested that studies are needed to evaluate whether rehabilitation strategies that include not only fitness and mobility interventions, but also social/behavioural and self-efficacy components, are associated with reduced fatigue and increased ambulation.15
Despite there being no literature on its efficacy, patient and family education and counselling has been identified as the most important rehabilitation nursing intervention for the management of stroke-related fatigue.14 Indeed, it has been suggested that patient education regarding post-stroke fatigue should be made available for patients, their caregivers, and families.14,19 This general approach to fatigue management is of particular relevance in the absence of a clear causal mechanism.
Such programmes typically provide anticipatory guidance about the likely experience of fatigue with the goal of diminishing distress and misunderstanding if fatigue occurs; helping to maintain a sense of control. Identification of fatigue-provoking activities, problem-solving and identification of fatigue management strategies are also provided, including energy conservation strategies (e.g., prioritizing, sleep hygiene, pacing, delegating, scheduling rest) and establishing appropriate balance between rest and activity.
Individually tailored increased physical activity may be beneficial in overcoming the self-perpetuating cycle of inactivity, deconditioning, and fatigue commonly observed in stroke survivors.19 As stated by Clarke and Lacasse49 the goal of fatigue management is to equip patients with multiple self-help strategies to successfully alleviate or lessen fatigue throughout the disease process.
Unfortunately, there is no literature on the impact of educational programmes for fatigue post-stroke. There is, however, a literature available from other populations, including patients with cancer, multiple sclerosis, and those with traumatic brain injury. For instance, in cancer survivors, Fawzy50 found that those who received a 6-hour intervention involving education on health promotion, stress management, and coping skills resulted in significantly greater decrease in fatigue compared with controls. In addition, Keyes51 found that participation in a single 60-minute psycho-educational fatigue management session produced significantly lower levels of behavioural, sensory, cognitive, and total fatigue compared to a control condition.
There is evidence of the effectiveness of educational fatigue management in multiple sclerosis.52–54 In a recent evaluation of a 16-hour fatigue management education programme, participants rated the programme highly or very highly, and there was a trend towards significant improvement in quality of life measures which may have resulted from small sample size (N=10 with 2 drop-outs).55
In a recent traumatic brain injury study,56 seven participants with acquired brain injury participated in an 8-session educational programmed for post-injury fatigue. Quality of life as measured by the SF-36 improved significantly; there was a small non-significant drop in scores on the Brain Injury Fatigue Scale that was not linked to changes in mood.
Comprehensiveness (targeting multiple causes of fatigue), involvement of caregivers and family members, individual tailoring, relative simplicity, and non-pharmacological content are some of the clear advantages of these educational programmes.

Factors contributing to the problem

Several factors are likely to contribute to the lack of evidence for post-stroke fatigue management. First and foremost, as noted earlier, there is no accepted definition of fatigue, and “no single measure of fatigue adequately captures the complexity of the phenomenon.”9 Furthermore, while there are a number of measures specific to fatigue that can be used, none of these have been validated in stroke populations. Indeed, only one stroke-specific quality of life measure has been developed to include a subscale for fatigue consisting of three items.33
In addition to this difficulty in quantifying fatigue, the causes of post-stroke fatigue differ from person to person and may include physical causes such as pain, disease, anaemia, inactivity, or other health problems.57 It has been proposed that post-stroke fatigue may result from the combined effects of organic brain lesions and psychosocial stress related to changes in life situation.58,59
Given these multiple potential causes of post-stroke fatigue, any assessment of fatigue must be multidimensional, and treatment approaches are likely to be differentially beneficial in different etiologically defined subgroups.
Finally, as previously noted, stroke survivors with less severe physical or cognitive disability tend to rate fatigue as a more severe symptom. Related to this is the possibility that difficulties with fatigue are less likely to become apparent while an inpatient, becoming evident only when one attempts to take-up his/her previous activities. This is reflected in increased reports of fatigue over the first year post-stroke.7
Where to from here?
The above literature identifies fatigue as a prevalent debilitating and distinct sequelae of stroke that has detrimental effects not only on the quality of life and other functional outcomes in these patients but also impedes their effective rehabilitation.
While a number of challenges remain in the assessment and treatment of post-stroke fatigue, the existing literature from other population groups could act as a springboard to much needed research in this area. In particular, there is a need to better differentiate those most likely to suffer post-stroke fatigue, to validate existing assessments of fatigue, and to evaluate the efficacy of fatigue management and treatment strategies in stroke survivors.

Competing interests: None.
Author information: Suzanne Barker-Collo1, Valery L. Feigin2, Margaret Dudley3
  1. Senior Lecturer, Department of Psychology, Faculty of Science, The University of Auckland
  2. Associate Professor, Clinical Trials Research Unit, School of Population Health and Department of Medicine, School of Population Health, Faculty of Health & Medical Sciences, The University of Auckland
  3. Research Fellow, Clinical Trials Research Unit, School of Population Health and Department of Medicine, School of Population Health, Faculty of Health & Medical Sciences, The University of Auckland
Correspondence: Suzanne Barker-Collo PhD, Department of Psychology, Faculty of Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand. Fax: +64 9 373 7450; email: s.barker-collo@auckland.ac.nz
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