Frustrated by Fatigue: Stroke Survivors Deserve Action Now!

Poststroke fatigue is defined by Lynch and colleagues as a sense of fatigue, or a lack of energy, or an increased need to rest every day or nearly every day, that leads to difficulty taking part in everyday activities.¹ Clinically significant fatigue is experienced by 23%-77% of stroke survivors.² This invisible symptom has been described as one of the most frustrating poststroke sequelae and is associated with poor quality of life, dependency, institutionalization, social isolation and mortality.^3,4 The new scientific statement by the American Heart Association, Poststroke Fatigue: Emerging Evidence and Approaches to Management by Hinkle and colleagues², reviews the state of the science and highlights profuse gaps in knowledge especially related to the measurement, etiology, and clinical management of poststroke fatigue.

The multidimensionality of post-stroke fatigue

One of the challenges to understanding and elucidating mechanisms for poststroke fatigue emphasized by the scientific statement is the multidimensional nature of the fatigue. Poststroke fatigue can vary by individual and be characterized as physical fatigue, mental fatigue, or social fatigue. Fatigue can occur at any phase in stroke recovery and persist for many years post stroke.⁵ Fatigue in stroke is often associated with demographic factors such as older age and female gender but can occur in any age or gender. Poststroke fatigue is associated with neurological and physical deficits such as motor dysfunction, weakness, and speech disturbances; however, stroke survivors describe their fatigue as excessive and chronic and often unrelated to exertion levels. Other medical comorbidities such as diabetes or heart failure or medication side effects also may contribute to fatigue. Additionally, depression, sleep disturbances such as sleep apnea, and poststroke pain are associated with poststroke fatigue. It is important to note, however, that while there is overlap between poststroke fatigue and depression, these are known to be distinct poststroke sequelae. While these are key areas for stroke clinicians to assess and intervene, none of these factors fully explain fatigue symptoms among stroke survivors.

Measurement of poststroke fatigue

The variation among measures and timing of assessment has contributed to the wide range of prevalence of fatigue among stroke survivors. Assessment of poststroke fatigue is limited due to several challenges. First, fatigue is a subjective assessment as there are presently no objectives markers of fatigue. While several subjective measures of fatigue exist in the literature, none are stroke specific. The vast majority was developed for assessment of fatigue in cancer populations, some of which have been validated for use with stroke survivors. In addition, as noted in the scientific statement, measures that include items regarding weakness may be invalid in a stroke population. Second, the multidimensional nature of poststroke fatigue creates measurement debate. For example, some measures differentiate types of fatigue (e.g. physical, mental, emotional, social) and others define fatigue as a single concept. Another challenge concerns the stroke survivors themselves. Stroke survivors tend to adjust their behaviors and self expectations to manage the fatigue symptoms. For example, they plan time for naps or other rest periods, reduce activity, or alter their expectations of what they can accomplish in a particular time period to be less than it was prestroke. This can lead to confusion for stroke survivors when asked to endorse particular symptoms of fatigue on Likert-style standardized questionnaires. Their answers would differ based on whether or not they adjusted their activity and accomplishment expectations. This presents a challenge for stroke clinicians and researchers to develop a more accurate, stroke specific, valid and reliable measure of poststroke fatigue.

Etiology of poststroke fatigue

As highlighted in the scientific statement, the pathophysiology of post-stroke fatigue is currently unknown. Given the multidimensional nature of poststroke fatigue, it is likely a heterogeneous phenomenon, with individual biological, psychological, social, and behavioral contributors. However, substantial evidence suggests that fatigue is not due to increased physical effort associated with functional disability from the stroke but may have a more centrally mediated or systemic origin. The scientific statement discusses biologic mechanisms that have been studied and show promise for additional mechanistic inquiry such as altered cortical excitability, genetics, inflammation, plasma glutamate levels, and serum glucose levels. Additional potential pathways such as genomic, epigenetic, proteomic, metabolomic and bioenergetic pathways should also be explored in future studies.

Clinical management of poststroke fatigue

Interventions for poststroke fatigue currently consist of treating any underlying clinical reasons for fatigue such as correcting nutritional deficits, anemia, or fluid and electrolyte imbalances, reestablishing activity, treatment of poststroke depression with antidepressants, or addressing sleep disorders.6 There are presently no efficacious interventions for idiopathic poststroke fatigue.6 This scientific statement makes clear that there is a dearth of well-conducted studies on which to base clinical treatment recommendations for poststroke fatigue.

A call to action

This scientific statement is an important wake-up call to stroke clinicians and the scientific community that there is much work to be done to reduce the prevalence of poststroke fatigue. The state of the science regarding poststroke fatigue has such gaping holes that it needs to be a funding priority area in stroke research. There is a clear lack of biomarkers linked to the pathophysiology of poststroke fatigue that can guide individualized patient therapeutics. This is a rally cry for better measures, better understanding of the etiology, and ultimately better clinical management of poststroke fatigue in order to improve the health and quality of life for stroke survivors. Stroke survivors deserve action now!