Prevalence of fatigue in patients 3 months after stroke and association with early motor activity: a prospective study comparing stroke patients with a matched general population cohort

The main finding from the study was, a higher prevalence of fatigue in stroke patients even after careful matching with a general population sample. Prevalence of fatigue three months after stroke was around one third, using either FSS-7 with a cut off ≥ 4.0, or using the HUNT3-survey questionnaire with a cut off ≥ 5. The prevalence is lower than most previous studies where prevalence was most often reported in the range of 50 %. There are several possible reasons for this difference. Most obviously, use of different questionnaires and different cut-offs to define fatigue will affect prevalence findings. However, a further possible explanation may be the older patient population in our study compared with other studies. Younger patients may be more aware of fatigue due to increased likelihood of wanting to return to work, more social activities, and higher activity levels [9, 12, 47]. We did not find compelling support for our hypothesis that more early motor activity would be associated with decreased likelihood of PSF. Our analysis confirms previous findings that pre-stoke fatigue, depression and pain are important predictors. Time in bed almost reached statistical significance in the model, with 95 % CI for OR ranging from 1.00 (no association) to 1.04 (4 % greater odds of having fatigue for every 5.4 min of extra bed rest).

The stroke patients were about three times more likely to report fatigue than their community-living counterparts who had not experienced stroke. Our results also showed that the stroke patients had more than double the likelihood of having at least one other disease prior to their stroke compared to the general population, and more than double the likelihood of having three or more other diseases. This finding suggests that the higher prevalence of PSF may be at least in part related to the stroke population being in poorer health even before they had a stroke. The previous literature on the association between pre-stroke co-morbidities and fatigue is not clear. A study in young patients found an association between PSF and both diabetes mellitus and myocardial infarction [32], while two other studies found no such association [14, 15]. PSF is a serious problem which clearly warrants better monitoring and management. Our findings suggest that pre-stroke health is an important factor in development of PSF.

Our findings hint at the possibility that early inactivity may be associated with fatigue at three months. This may be similar to the finding that more time in bed, but not less time in higher level activities, was predictive of worse functional outcome three months after stroke [48]. Previous bed rest studies have shown bed rest in general is not a benign treatment, but harmful to health [49, 50]. One possible mechanism by which bed rest could lead to higher levels of fatigue is the loss of cardiorespiratory fitness (CRF). CRF declines rapidly with bed rest [51], and is related to fatigue scores [52]. However, a recent review of cross-sectional studies found neither current physical activity levels nor CRF explained the level of fatigue experienced by people after stroke [53]. The risk of immobility-related complications increases with increased amounts of bed rest [54] suggesting that an association between fatigue and time in bed might also be explained by an increased prevalence of post-stroke complications. The reverse causal pathway is also plausible, whereby early activity is dependent on the absence of fatigue. Despite our non-significant finding, we argue that further research is still needed to investigate how early fatigue and early inactivity are related to the problem of debilitating PSF.

A recent study found that patients with stroke, who had more effortful movement as determined by movement velocity during a timed hand movement task, were found to have increased likelihood of fatigue [22]. The authors proposed that the relationship could be due to either a simple effort-fatigue relationship or because both fatigue and reduced movement speed may result from an alteration in motor cortex excitability. With this finding in mind alongside our own results, PSF may be largely explained by a combination of poor pre-stroke health, effects of the brain injury (including early inflammatory effects), issues secondary to stroke during the acute phase (including medications, sleep problems and complications), depression, pain, the harmful consequences of too much inactivity, and increased effort of movement related to motor impairment.

Strengths of our study of PSF prevalence are the largely unselected stroke sample and the appropriate and well-matched control group. The main limitations of our study are that important confounding variables may be missing from the regression models such as cognitive function, medications and sleep disorders [19]. However, all models were adjusted for the most common and significant predicting variables after stroke. Secondly, there may be bias introduced because participants excluded due to lost to follow-up (n = 7), illness/cognitive decline/too tired (n = 86), or failure to complete pre-stroke fatigue, pain or depression questionnaires (n = 34) was potentially non-random. This group was likely to include the least healthy among the cohort. Thirdly, our measures of activity early after stroke may not adequately represent activity, or inactivity, of importance in preventing the development of PSF. All studies of PSF are limited by the multidimensional nature of fatigue and the inadequacies of the fatigue measurement tools used. Pre-stroke fatigue was measured with a different questionnaire to PSF, which may compromise our study, and early PSF was not measured. Finally, as the stroke units were all in Norway where national guidelines strongly recommend promotion of early out of bed activity, there may not have been sufficient between-individual spread of inactivity/activity levels for the role of early motor activity in predicting PSF to be revealed. The likelihood that the amount of bedrest is closely related to stroke severity and pre-stroke function also poses a challenge in this and future studies. Carefully controlling for these confounders as in the present study, using pre-stroke mRS and NIHSS in the models, is helpful but may still be inadequate. These limitations may have resulted in the lack of support for our second hypothesis.

Some previous research supports there being a difference between mental and physical fatigue, particularly after stroke. The impact of a stroke (irrespective of whether ischemic or haemorrhagic) taxes the central nervous system and increases the level of cognitive strain, which may be interpreted as fatigue. Stroke patients may be physically capable of participating in rehabilitation exercises or physical activity, but feel unable to engage in the activity due a depletion of cognitive reserves or higher vascular burden. Global increases in allostatic load coupled with negative affect may further compound this problem. Drawing a distinction between mental and physical fatigue is currently difficult and controversial and was not attempted in our study. However, we suggest further research along these lines may yield important knowledge and facilitate management of the problem of PSF in the future.

PSF presents management challenges with few options currently available with proven effectiveness [55]. A combined cognitive therapy and graded exercise program has shown promise in alleviating fatigue, as well as cognitive therapy alone [56, 57]. However these trials are small and more research is needed on the effect of multifactorial approaches including exercise programs. It is apparent from the results of observational studies that improvement of general health and management of depression, sleep and pain should all help alleviate PSF. We also suggest that determining the appropriate amount of time spent on bed-rest versus out of bed activities early after stroke warrants urgent further investigation in relation to fatigue [31].