Pathophysiology of Central Apnoeas in Stroke Patients

Study Overview
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Brief Summary
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40% of patients with Sleep Disorder Breathing (SDB) appearing during the acute phase of stroke show a respiratory pattern characterized by central apnoeas and/or periodic breathing. Clinical studies conducted in patients with hearth failure and central apnoeas have demonstrated the pathogenetic central role of hypersensitivity of central and peripheral chemoreceptors in association with baroreflex hypersensitivity, expression of hyperactivity of sympathetic nervous system. The joint study of chemoreflexes and baroreflexes in patients with central apneas during the acute and subacute phase of ischemic stroke represents, to our knowledge, a novelty in literature, that should supply useful elements to clarify the pathogenesis and the clinical and prognostic significance of these disorders. Investigators expect a difference in the analysis of the baroreflexes and chemoreflexes in patients with ischemic stroke/transient ischemic attack (TIA) and central apnoeas than patients with ischemic stroke not accompanied by respiratory problems and compared with healthy controls.

Detailed Description
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Investigators expected to include in the study of 120 patients, aged between 35 and 75 years, belonging to the following diagnostic categories: 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of central apnoea (central apnoea index> 10 / h, or Cheyne-Stokes breathing for more than 30% of total sleep time or mixed apneas with central apnoeas> 50% of total apneas) 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of obstructive sleep apnea (apnea-hypopnea index> 20 / h) 30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of sleep respiratory disorders at polysomnography 30 healthy controls matched for age, sex, race and BMI. For the study of the baroreflexes, patients will be subjected to continuous monitoring of ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory rate and ventilation by pneumotachograph. The tests will be performed in the supine position and then repeated in a sitting position. Data from such monitoring will be used for analysis of the harmonic components of the cardiac rate (RR interval) and the variability of blood pressure and respiratory rate, through the method of auto regressive analysis. For the study of central chemoreceptors, investigator will use the steady-state hypercapnic test, which measures the ventilatory response to hypercapnia at a constant level of Oxygen partial pressure (PaO2). The ventilatory response to hypercapnia is calculated by the method of linear regression and is represented by the angular coefficient of the straight line that describes the variation of ventilation for each variation of alveolar carbon dioxide partial pressure (PCO2). For the study of peripheral chemoreceptors will be used the single-breath or transient hypercapnia test. The patient makes a single deep breath of a gas mixture containing 85% O2 and 15% CO2 and then resume normal breathing. It is expected, therefore, a period of 3 seconds, required because the gases contained in the mixture may come from the pulmonary circulation to the peripheral circulation, at the level of peripheral chemoreceptors. The ventilation is recorded within the next 20-30 seconds, because in this time interval is evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of response of the central chemoreceptors greater than 1 minute.

Official Title
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Central Apnoeas in the Course of Transient Ischemic Attack/Ischemic Stroke: Clinical, Prognostic, Pathophysiological Elements.

Conditions
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Central Apnoeas, Stroke Patients

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥35 years old and < 75 years old with clinical diagnosis of TIA or ischemic stroke admitted in a Stroke Unit within 2 days from onset of symptoms signed Informed Consent Exclusion Criteria: Patients with unstable clinical situation (cardio-respiratory or life-threatening medical conditions) currently on continuous positive airway pressure (CPAP) or on CPAP during the last 3 months before stroke with non-ischemic events (intracerebral/subarachnoid haemorrhage) Patients with coma/stupor

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Central Apnoeas Patients<br>• 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of central apnoea (central apnoea index> 10 / h, or Cheyne-Stokes breathing for more than 30% of total sleep time or mixed apneas with central apnoeas> 50% of total apneas) | |
| Obstructive apnoea patients<br>• 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of obstructive sleep apnea (apnea-hypopnea index> 20 / h) | |
| No SDB patients<br>• 30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of sleep respiratory disorders at polysomnography | |
| Healthy controls<br>• 30 healthy controls matched for age, sex, race and BMI. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baroreflexes | For the study of the baroreflexes, patients will be subjected to continuous monitoring of ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory rate and ventilation by pneumotachograph. The tests will be performed in the supine position and then repeated in a sitting position. Data from such monitoring will be used for analysis of the harmonic components of the RR interval and the variability of blood pressure and respiratory rate, through the method of auto regressive analysis. | 3 months | 
| Chemoreflexes | For the study of central and peripheral chemoreceptors, investigator will use the steady-state hypercapnic test, which measures the ventilatory response to hypercapnia at a constant level of PaO2, and the single-breath test in wich the subject makes a single deep breath of a gas mixture containing 85% O2 and 15% CO2 and then resume normal breathing. The ventilation is recorded within the next 20-30 seconds, because in this time interval is evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of response of the central chemoreceptors greater than 1 minute. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnoea-hypopnoea index (AHI) | Assessing prognosis and spontaneous temporal evolution of central apnoeas in patients with cerebral ischemic events. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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central apnoeas, stroke