Background
Experimental and clinical data suggest a detrimental effect of sleep deficiency/sleep
fragmentation on stroke outcome. In rodents, sleep fragmentation and sleep deprivation
induced in the acute phase of stroke enhance the extension of the lesion and impair
functional recovery - inversely, sleep-promoting drugs have a positive effect on functional
recovery. In humans, a negative effect of sleep deficiency and sleep fragmentation due to
sleep-disordered breathing (SDB), restless legs syndrome (RLS) and insomnia on stroke outcome
has also been suggested but only insufficiently tested.
SDB is found in 50-70% of patients with transient ischemic attacks and acute ischemic stroke.
Patients with SDB demonstrate a more rapid progression of stroke severity as well as higher
blood pressure and longer hospitalization in the acute phase of stroke. Over time, they also
exhibit a higher mortality. Functional outcome is also negatively affected by the presence of
SDB. Moreover, SDB was shown to represent an independent risk for hypertension and
cardiovascular morbidity and mortality, and for stroke.
The frequency of insomnia in patients with stroke in a prospective study achieved 68% in the
acute phase decreasing to 49% after 18 months. However, systematic large scale observational
studies on the frequency of insomnia in stroke patients are lacking. Sleep duration after
stroke has been assessed in few studies only (e.g. in patients with paramedian thalamic
stroke), in some of them a good correlation with actigraphic measurements was found.
Moreover, over the last three decades a link was found between sleep deficiency and
fragmentation and cardiocerebrovascular morbidity and mortality based on epidemiological
data. In particular, short sleepers (e.g. sleep duration < 6 hours) and poor sleepers
(reporting a non-restorative sleep) presented a higher risk of cardiovascular events
including death, coronary heart disease and stroke. Insomnia and sleep duration in the
general population were also reported to predispose to an increased risk of hypertension,
cardiovascular events and mortality.
A high association between RLS and stroke was demonstrated in a few studies. RLS was found in
12% of 137 patients after stroke and predicted a worse outcome. Few case reports reported
high numbers of periodic limb movements during sleep (PLMS), which are often associated with
RLS, in stroke patients. An association of RLS/PLMS with hypertension, cardiovascular
diseases and stroke was also discussed in recent years. However, the large scale data on the
impact of RLS for the stroke outcomes are lacking.
The possible mechanisms linking sleep deficiency, poor sleep and sleep fragmentation with
cardiovascular disorders (including stroke) are multiple and include an elevated sympathetic
activation, procoagulatory and inflammatory changes, increased atherosclerosis, and changes
in cerebral hemodynamics and oxygenation. However, the clinical relevance and the association
with clinical outcomes needs further investigation.
Objective
The aim of this study is to assess the impact of sleep deficiency and sleep fragmentation
resulting from insomnia, SDB or RLS on the frequency of new cerebro- and cardiovascular
events after stroke or TIA including death of any cause, and clinical outcome within one and
two years after stroke.
Primary objective of the study is the assessment of the frequency of all-cause deaths and new
cerebro- and cardiovascular events within 24 months after stroke or transient ischemic attack
in patients with and without sleep deficiency/fragmentation.
The main secondary objective is an assessment of clinical outcome 12 months after stroke in
patients with and without sleep deficiency/fragmentation.
Methods
Patients with acute ischemic stroke or TIA will be recruited at two Neurology Departments in
Switzerland (Inselspital Bern & Neurocenter of Southern Switzerland Lugano). Two groups will
be formed based on the presence or absence of sleep deficiency/fragmentation assessed at one
month following stroke by questionnaires and telephone interviews. Examinations (at baseline
& 3, 12 and 24 months follow up after stroke) will include standardized and validated
questionnaires assessing stroke outcome (independence and activities of daily living) as well
as insomnia, RLS, risk for sleep apnea, depression and apathy. Additional non-invasive
physiological assessments will be performed in about every fifth of all recruited patients in
the acute phase of stroke and after 3 and 12 months. They include ambulatory blood pressure
measurements and wrist activity assessing 24h physical activity patterns over 3 weeks,
assessment of arterial stiffness/endothelial function and basic cognitive performance.
