Diurnal variation of clock genes expression and other sleep-wake rhythm biomarkers among acute ischemic stroke patients.

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/ß), PER1, and PER3) showed significant time-of-day variation in both patients' and controls' groups, except expression of NR1D1 (Rev-erbα/ß) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/ß) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important.

BACKGROUND: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. OBJECTIVE: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. METHODS: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or >10. RESULTS: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. CONCLUSIONS: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.