Review
Frequency and natural history of fatigue after stroke: A systematic review of longitudinal studies

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Abstract

Background

Fatigue is a common and distressing symptom after stroke. Stroke survivors and health professionals need to know whether fatigue is likely to improve, or get worse over time; and whether there is a temporal association with depression or anxiety, which might provide a target for treatment,

Aims and objectives

To systematically review all longitudinal observational studies which have assessed fatigue on at least two separate time points after stroke onset to determine its frequency, natural history and temporal relationship with anxiety and/or depression.

Method

We systematically searched MEDLINE, EMBASE, CINAHL and PsychInfo using the keywords “fatigue” and “stroke” and their associated terms or synonyms. Data were extracted regarding time points after stroke where fatigue was assessed, frequency of fatigue at each time point and any reported associations with anxiety and/or depression.

Results

101 full texts were retrieved after scrutinising the titles and abstracts. Nine fulfilled our inclusion criteria. Fatigue was assessed at a variety of time points after stroke (from admission—to 36 months). The frequency of fatigue ranged from 35%–92% at the first time point. Frequency of fatigue declined across time points in seven of the studies (n = 764) and increased in two studies (n = 195). Three papers found significant associations between fatigue and mood at the same time point. The single study investigating temporal associations between fatigue and mood disorders reported that depression predicted subsequent fatigue.

Conclusions

Fatigue is present soon after stroke onset and remains common in the longer term. There is little evidence regarding the temporal relationship between fatigue and mood: this is an area where further research is needed.

Introduction

Fatigue can be defined as a chronic subjective “feeling of lack of energy, weariness and aversion to effort” [1]. After stroke, fatigue is common and distressing to patients, for example, a recent study reported that 43% of stroke survivors felt they were not receiving enough help for fatigue [2]. Fatigue is an independent predictor of institutionalisation [3], [4] and, for stroke survivors under the age of 60 years, an independent predictor of being unable to return to paid work [5].

It is crucial to understand the natural history of fatigue after stroke. Stroke survivors need to know whether their fatigue is likely to improve over time, stay the same or progressively get worse so they can plan their future e.g. returning to work or resumption of previous leisure activities. Health care professionals need to know how many stroke survivors are likely to be fatigued at different time points so services can be planned accordingly. Researchers need to know whether fatigue starts immediately after stroke and how long it lasts, in order to decide how soon after stroke an intervention for fatigue should be delivered (if one could be developed).

Longitudinal studies have major advantages over cross sectional studies when studying the natural history of a condition or symptom because they report changes within individuals as well as the proportion of patients at a particular time point who have a symptom. Therefore longitudinal studies of post-stroke fatigue could tell us if fatigue is a stable symptom or whether it fluctuates over time. Longitudinal studies can also provide information about whether fatigue affects all patients for a short period of time or a small number of patients over an extended period; cross-sectional studies are unable to provide this information [6].

Several cross-sectional papers have demonstrated an association between fatigue and depression after stroke. [7], [8], [9], [10] leading to the suggestion that fatigue is a symptom of post-stroke depression [11], [12]. However, identifying an association between these two symptoms at a particular time point does not necessarily mean that one symptom causes the other, or vice versa; it is equally plausible that a third factor might cause both symptoms [13]. Longitudinal studies can potentially provide evidence regarding the direction of any observed association between fatigue and mood disorders i.e. whether depression precedes fatigue or vice versa [14]. Understanding the direction of causality is important because if depression precedes fatigue then identifying and treating depression might prevent or reduce the risk of developing post-stroke fatigue.

There are several published non systematic narrative reviews of fatigue after stroke [1], [15], [16], [17], [18], [19]. Systematic reviews are scientifically more robust and are consequently considered to be more objective sources of information and less prone to bias and error than traditional narrative reviews [20], [21]. The single previous systematic review used narrow search terms and so may have missed studies. Furthermore, the searches were performed in 2009, and we know of other studies on post-stroke fatigue that have been published since then [22].

The aim of this systematic review was to identify all longitudinal observational studies of fatigue after stroke to determine the frequency of fatigue, its natural history and the temporal relationship between fatigue and mood disorders.

Section snippets

Searches

Searches were conducted in MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1937) and PsychInfo (from 1806) on 7th April 2011 using keywords “fatigue” and “stroke” and their associated terms or synonyms. The same search terms were used in this review as in the published Cochrane systematic review [23] of interventions for post-stroke fatigue (Appendix 1).

Definition of stroke

Stroke was defined as “a clinical syndrome characterised by rapidly developing clinical symptoms and/or signs of focal, and at times

Results

The electronic search identified 7046 citations before duplicates were removed. The full texts of 101 potentially relevant papers were retrieved. A further seven papers were retrieved following scrutiny of the reference lists of papers (reviews, qualitative, cross-sectional and longitudinal studies) where the main topic was fatigue after stroke (Fig. 1).

Of these 108 papers, 99 were excluded. The main reasons for excluding a study were a) it was a review and contained no original research b) it

Discussion

This systematic review of longitudinal studies of post-stroke fatigue has demonstrated that the frequency of fatigue varied substantially between studies, with estimates ranging from 35% to 92% at first time point, probably reflecting the heterogeneity between the studies regarding the methods of recruitment and their methods of assessing fatigue.

Fatigue appears to be a persistent symptom after stroke at least for the first 36 months. The proportion of patients with fatigue at the beginning and

Conclusion

Fatigue is a common symptom post-stroke and is likely to persist in the long term for patients who develop it. This review explored the possibility of depression being a cause of fatigue but found insufficient evidence in the literature. Therefore it is vital for preventative and management strategies to be developed for those suffering from fatigue. For these interventions to be made possible potential causes of post-stroke fatigue must be further investigated.

Conflicts of interest

None.

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    This work was supported by a Chief Scientist Office of the Scottish Government grant.

    1

    Centre of Clinical Brain Sciences, Bramwell Dott Building, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, United Kingdom.

    2

    Geriatric Medicine, University of Edinburgh, Room S1642, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, United Kingdom. Tel.: + 44 131 242 6369/6481; fax: + 44 131 242 6370.

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