Stroke poses a significant public health concern, with approximately 60–70% of individuals unable to resume their previous lifestyle after stroke (1). Poststroke fatigue (PSF) emerges as a common symptom following stroke, with reported prevalence ranging between 23 and 85% in the literature (2, 3). Described as early exhaustion accompanied by weariness, lack of energy, and reluctance to exertion, poststroke fatigue persists during physical or mental activity and often remains unaffected by rest (2–5). This fatigue detrimentally impacts quality of life and workability and is even linked to a heightened mortality risk (6–8). Despite its profound implications, poststroke fatigue receives relatively little attention, with no specific treatments currently available (9).

When a stroke occurs, it can induce profound shifts in the brain’s function and structure. It disrupts the delicate balance of neural networks. Moreover, the immune system’s response to a stroke can also exacerbate fatigue. As part of the body’s natural response to injury, an inflammatory process is activated, potentially flooding the system with inflammatory cytokines, fostering a protective response but also contributing to a pervasive sense of exhaustion (2, 10, 11). Emotional well-being is compromised following a stroke, with depressive mood, anxiety, and stress frequently taking hold. These psychological states are closely entwined with fatigue. Moreover, cognitive efforts become disproportionately taxing after a stroke and the strenuous journey of adjusting to new physical and cognitive limitations demands substantial mental exertion, which can compound feelings of fatigue (12, 13). Disorders such as sleep apnoea and insomnia, which are prevalent in stroke survivors, together with the sleep changes due to hospitalization can impair the restorative quality of sleep, leaving individuals grappling with fatigue during the daylight hours. Furthermore, a reduction in physical activity after a stroke is another contributing factor. It can result in a decline in muscle strength, intensifying the sensation of fatigue. Hitherto, the body’s metabolic and hormonal milieu may be altered by a stroke, leading to shifts in energy levels and influencing how fatigue is perceived (12, 13).

The complexity of PSF is further amplified by changes in neuroplasticity after a stroke, which can affect the excitability of cortical neurons. An imbalance may arise between excitatory and inhibitory signals in the brain, either ramping up neural activity or causing a lull, each contributing to fatigue in its own way (2, 11).

The connectivity between different brain regions may be reshaped, potentially altering the efficiency with which these areas communicate. Such changes are thought to impact the personal experience of fatigue (2, 11).

It is important to note that these mechanisms are not mutually exclusive and can interact in complex ways to contribute to the experience of poststroke fatigue. Furthermore, individual differences in genetics, pre-stroke health status, and the location and severity of the stroke can influence the development and severity of PSF. Ongoing research is aimed at better understanding these mechanisms to improve the management and treatment of poststroke fatigue. After a stroke, the brain undergoes a range of neuroplastic changes as it attempts to recover and reorganize its functions. These changes can affect the excitability of cortical neurons, potentially leading to alterations in how signals are transmitted across neural networks. It is thought that in some individuals, these alterations might contribute to the onset or exacerbation of fatigue symptoms.

PSF can significantly interfere with the rehabilitation process for stroke survivors. Its impact may affect not only the physical aspect of recovery but also cognitive and emotional well-being. Fatigue can decrease a patient’s ability to actively participate in rehabilitation sessions. Patients may find it difficult to complete exercises or engage in activities for the duration required to achieve optimal outcomes. This reduced participation can slow progress and decrease the overall effectiveness of the rehabilitation program (4, 14). PSF is not just physical but also cognitive. Patients experiencing cognitive fatigue may have difficulty focusing, remembering instructions, and performing tasks that require cognitive effort. This can interfere with cognitive rehabilitation efforts and impede recovery in cognitive functions such as memory, attention, and executive functions. Fatigue can exacerbate psychological conditions such as depressive mood and anxiety, which are common after a stroke (4, 13, 14). These conditions can further reduce motivation and engagement in rehabilitation. Moreover, the frustration of dealing with persistent fatigue can lead to decreased morale and motivation, critical components of successful rehabilitation treatments.

The recent consensus among experts underscores the imperative of early recognition of poststroke fatigue in stroke patients, advocating for intervention targeting modifiable factors. Key priorities include employing appropriate tools for clinical identification and examination, elucidating its pathophysiology, and exploring therapeutic avenues such as neuromodulation, therapeutic exercise, psychoeducation, and pharmacology (15).

To the best of our knowledge, the association between poststroke fatigue in the early stages poststroke and functional outcomes remains inadequately explored (5). Given its potential to impede engagement in physical and social activities and rehabilitation, this aspect assumes paramount importance (16–18). A recent retrospective study highlights the correlation between poststroke fatigue at admission and functional outcomes (19).

In this prospective study, we investigate the impact of initial poststroke fatigue on the functional recovery of stroke survivors enrolled in a neurorehabilitation program. Specifically, we assess the trajectory of fatigue over the first 6 months and examine the influence of stroke subtype (ischemic or hemorrhagic).

This study represents the first attempt to prospectively assess whether poststroke fatigue correlates with functional outcomes following a subacute rehabilitation period. Our findings revealed that poststroke clinically significant fatigue (CSF) was present in approximately 40% of patients at baseline, with a higher proportion observed in hemorrhagic stroke compared to ischemic stroke cases. Notably, the binary logistic regression analysis confirmed the predictive value of CSF at baseline on functional recovery and outcomes 6 months poststroke (19). Patients presenting with CSF at baseline demonstrated a higher probability of experiencing poor recovery.

Regarding outcome measurements obtained using the Barthel Index for Activities of Daily Living (BIADL), it appears that this probability varies between ischemic and hemorrhagic strokes, with the early presence of CSF being a risk factor for impaired improvement in hemorrhagic stroke. Despite similar improvements in functional measures (NIHSS, BIADL, and MRS) among ischemic and hemorrhagic patients, fatigue exhibited less improvement during the rehabilitation period in ischemic stroke cases, while significant improvement was observed in the hemorrhagic stroke group. This discrepancy cannot solely be attributed to initial stroke severity (which was the worst in the hemorrhagic group) or age and sex distribution (similar in both groups), suggesting potential differences in how the two stroke types affect the brain and potentially the networks governing fatigue (2–4, 11). In ischemic and hemorrhagic strokes, the processes of tissue damage, damage size and location, edema, inflammation, and blood not yet reabsorbed may be different and/or have a different time course, and this may cause different perceptions of fatigue. The specific mechanisms underlying fatigue induction in different stroke populations warrant further investigation (15).

Comorbidities such as hypertension, diabetes mellitus, depression, pain, and medication usage may independently contribute to fatigue (20–23). However, due to the limited sample size of our study, a formal analysis of these factors’ impact on our results was not conducted. While there is evidence suggesting an interrelationship between depressive mood, pain, and fatigue, indicating a symptom cluster, this does not necessarily imply shared aetiologies. Instead, it indicates that these factors are not entirely independent and warrant further exploration with larger cohorts to discern their individual effects on functional outcomes (10, 13, 20–26).

This study is subject to several limitations: (1) medications commonly prescribed for stroke patients, including sedatives, antiepileptics, pain medications, and antidepressants, may independently contribute to fatigue and may be differentially prescribed between ischemic and hemorrhagic strokes; (2) exclusion of patients unable to communicate their symptomatology, such as those with aphasia or altered states of consciousness (10, 26–28); (3) other conditioning factors, such as neuroanatomical/biological aspects and unexamined comorbidities, likely influence the effects of fatigue on functional outcomes, particularly the lack of improvement in fatigue despite neurorehabilitation in ischemic strokes (15–17, 19, 28). Our data confirm the evolution of poststroke fatigue and associated factors reported elsewhere (25, 29–31).

In conclusion, our data support the notion that early poststroke fatigue negatively impacts future outcomes and exhibits a distinct time course between ischemic and hemorrhagic strokes. Further studies are warranted to validate our findings and enhance their generalizability. Therefore, it is imperative to devise strategies during the acute and subacute phases poststroke to mitigate this detrimental effect and improve patient functions and quality of life.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Hospital Universitario Severo Ochoa, Madrid, ref.: A1434. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

AJ-B: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. VS-L: Conceptualization, Data curation, Formal analysis, Investigation, Writing – review & editing. MD: Conceptualization, Investigation, Methodology, Validation, Writing – review & editing. EO: Investigation, Writing – review & editing. NL-A: Conceptualization, Investigation, Methodology, Writing – review & editing. AM: Writing – review & editing. JT: Formal analysis, Funding acquisition, Methodology, Writing – review & editing. AO: Conceptualization, Data curation, Methodology, Supervision, Validation, Writing – original draft, Writing – review & editing.