Better Understanding of Fatigue After STroke

Stroke is worldwide the second most common cause of death following heart attack and the leading cause of disability. Post-stroke fatigue (PSF) is a common complication after stroke and can be defined as 'an overwhelming exhaustion or tiredness, not related to exertion, which does not typically improve with rest'. Fatigue following stroke can be divided into early (\< 3 months) and late (\> 3 months) fatigue. PSF can have a considerable impact on a person's everyday activities and quality of life, participation in the rehabilitation process and levels of caregiver burden. Yet no efficient treatment exists to prevent or cure PSF because the pathophysiology remains unclear and seems to be multifaceted.

Autonomic dysfunction is a common complication after stroke, associated with higher morbidity and mortality. An easy tool to measure the function of the autonomic nervous system (ANS) is heart rate variability (HRV), which is defined as the beat-to-beat variation of the heart rate (= interbeat interval (IBI)). It is the result of alterations in the sympathetic and parasympathetic nervous system. In recent systematic reviews, authors stipulate that HRV can be regarded as a prognostic factor for short- and long-term stroke outcomes. HRV can be derived from 24 hours, 5 minutes (short-term) and \< 5 minutes (ultra-short-term) measurements by applying time-domain and frequency-domain indices.

Autonomic dysfunction has been related to chronic fatigue syndrome, in addition to fatigue in multiple sclerosis, Parkinson's disease and myasthenia gravis. However, to the best of our knowledge, the relationship between autonomic dysfunction and PSF has not yet been fully investigated.

Fatigue is also common in cardiovascular diseases, especially in patients with heart failure (HF). HF can contribute to fatigue after stroke, independently of stroke.

Cardiac complications after acute ischemic stroke (AIS), such as arrhythmias, cardiac dysfunction and myocardial injury, are frequent. The so-called 'stroke-heart syndrome', a concept introduced in 2018, describes a broad spectrum of cardiac changes observed in 10-20% of patients with AIS within the first month after stroke onset, with a peak in the first 72 hours. A dysregulation in the neural-cardiac control after stroke is suspected to be the cause of the cascade leading to cardiac complications, in which autonomic dysfunction and inflammation seem to be part of the underlying mechanism.

Based on previous studies and by analogy with other neurological diseases, the investigators hypothesize that autonomic dysfunction following AIS contributes to PSF and that patients presenting heart failure as a complication following AIS have an increased risk of PSF.

To confirm this hypothesis, the investigators will conduct a prospective, interventional study where patients who are hospitalized at the Stroke Unit, within 72 hours after stroke symptom onset, will be included. Evaluation will take place of (a) the relationship between autonomic dysfunction (HRV) and early and late PSF, and of (b) the relationship between cardiac dysfunction and early PSF and late PSF.

There will also be an investigation into following elements:

* the association between early and late PSF and (a) certain inflammatory markers at admission (CRP, NLR), (b) stroke localization and (c) baseline imaging markers of brain frailty.
* the role of pre-existing fatigue + pre-existing or post-stroke newly diagnosed cognitive impairment, depression and sleep disturbances on the course of PSF.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18
* First-ever (suspicion of) ischemic stroke based on clinical examination and/or brain imaging
* Onset \< 72h at time of inclusion
* Admitted at the stroke unit of CHU Brugmann and UZ Brussel
* Ability to participate in assessment of fatigue, cognitive, mood and sleep disturbances
* Ability to undergo MRI of the brain

Exclusion Criteria:

* Unable to speak French, Dutch or English
* Pre-existing stroke or other structural brain lesion
* Life expectancy \< 1 year
* Severe language impairment or dementia impeding assessment of fatigue, cognitive, mood and sleep disturbances
* Pregnancy or wish to become pregnant