University of Zurich
Zurich Open Repository and Archive
Central periodic breathing during sleep in 74 patients with acute
ischemic stroke - Neurogenic and cardiogenic factors
Siccoli, M M; Valko, P O; Hermann, D M; Bassetti, C L
Siccoli, M M; Valko, P O; Hermann, D M; Bassetti, C L (2008). Central periodic breathing during sleep in 74
patients with acute ischemic stroke - Neurogenic and cardiogenic factors. Journal of Neurology,
Postprint available at:
Posted at the Zurich Open Repository and Archive, University of Zurich.
Originally published at:
Journal of Neurology 2008, 255(11):1687-1692.
CENTRAL PERIODIC BREATHING IN 74
PATIENTS WITH ACUTE ISCHEMIC STROKE -
NEUROGENIC VERSUS CARDIOGENIC
Massimiliano M. Siccoli, MD
Philipp O. Valko, MD
Dirk M. Hermann, MD
Claudio L. Bassetti, MD
Department of Neurology, University Hospital of Zurich, Switzerland
Prof. Claudio L. Bassetti
Department of Neurology
University Hospital of Zurich
Tel.+41 44 255 55 03
Fax+41 44 255 46 49
Key words: Cheyne-Stokes respiration, ischemic stroke, left ventricular function, autonomic
nervous system, insula
Word count: 4249 (including title page, references, and tables)
Colum title: Central Periodic Breathing in Acute Ischemic Stroke
Objectives: The aims of our study are 1) to better characterize central periodic breathing
during sleep (CPBS) and its clinical relevance in acute stroke, 2) to better define the role of
brain damage in its pathogenesis.
Methods: We included 74 consecutive patients admitted within 96 hours after stroke onset.
Stroke severity on admission, stroke outcome at discharge and stroke topography were
assessed. ECG and transesophageal echocardiography were performed. Nocturnal breathing
was assessed with an ambulatory device the first night after admission. CPBS severity was
represented as absolute time and percentage of recording time.
Results: Age was 63±13 [25-82], 49 (66%) were male. Thirty (41%) patients showed CPBS
during ≥10% and 7 (9%) during ≥50% of recording time. CPBS severity was associated with
age (p=0.017), stroke severity (p=0.008), ECG abnormalities (p=0.005) and lower left
ventricular ejection fraction (p<0.0001). CPBS severity was higher in patients with extensive
hemispheric strokes (n=6, p<0.0001), and significantly lower in patients with partial strokes
involving the left insula (n=5, p<0.0001) and the mesencephalon (n=5, p=0.002).
Conclusions: CPBS is a frequent phenomenon in acute ischemic stroke, and is associated
with older age, stroke severity/extension, and lower left ventricular function. The lower
occurrence of CPBS in left insular and mesencephalic stroke suggests a major role of distinct
brain areas in the modulation of respiratory phenomena accompanying acute stroke, and
emphasize the role of acute brain damage in their pathogenesis.
Central periodic breathing (CPB) - or Cheyne-Stokes breathing, characterized by
cyclic fluctuations in breathing drive in a gradual waxing-and-waning fashion  - result from
a variety of conditions affecting the neuronal network involved in respiratory control.
CPB during wakefulness and/or sleep have been reported in patients with brainstem or
bilateral extensive hemispheric stroke and impaired level of consciousness [2-4]. More recent
studies in stroke patients report a variable prevalence (6-38%) for CPB during sleep (CPBS)
[4-8], a spontaneous recovery of these breathing pattern after stroke [6,9,10] and an
association with large ischemic lesions and poor functional outcome [11,12].
In both patients with and without stroke, CPBS has been linked to increased
respiratory CO2 sensitivity [13,14] and left ventricular dysfunction [15,16]. CPBS has also
been reported in patients with unilateral lesions of variable topography without disturbed level
of consciousness or overt heart failure [4,10,17]. Although these observations clearly suggest
a major role of distinct brain areas in the regulation of respiratory response to ischemic brain
damage, the mechanisms leading to CPBS in association with a new-onset ischemic brain
lesion remain poorly known.
Following a preliminary retrospective observation on three patients (University
Hospital of Berne) , we performed a systematic and prospective assessment of CPBS in a
new larger series of patients with the aim 1) to better characterize this breathing pattern and
its clinical relevance in acute stroke, 2) to better define the role of brain damage in its
Patients. Seventy-four consecutive adult patients with first-ever acute ischemic stroke
were prospectively included. The study design was approved by the local ethical committee,
and written informed consent was obtained from patients or relatives. Patients with very
severe strokes (National Institutes of Health Stroke Scale  [NIHSS]>20),
intracerebral/subarachnoid haemorrhage, coma/stupor, life-threatening medical conditions
Clinical and radiological evaluation. Cardiovascular risk factors including family
history, arterial hypertension (defined as BP >140/90 mmHg measured ≥3 times prior to
stroke), diabetes (defined as fasting glucose level >140 mg/dl), smoking status,
hypercholesterinemia (defined as cholesterol level >250 mg/dl), obesity (defined as Body-
Mass-Index (BMI) ≥25 kg/m2) and previous history of heart failure/coronary heart disease were
Clinical stroke assessment included NIHSS and modified Rankin disability Scale 
at hospital discharge.
An ECG was performed on admission, Holter ECG and transesophageal echocardiography
during the hospitalization.
Stroke topography was assessed in the acute phase according to clinical and
radiological criteria by CT scan examination and/or MR imaging. A detailed topographic
description of the ischemic region according to clinically identifiable subtypes  and
vascular territories  was performed.
Nocturnal breathing. Overnight respirography was performed with a validated 
portable device (Autoset® Embletta PDS, ResMed) during the first night after admission. The
recording was considered to be successful if ≥60 minutes with nasal flow and at least one chest
band signal were present. The analysis was performed automatically and corrected manually
according to previously described standard criteria . Chaotic signals automatically scored
from the computer as events were carefully checked manually, and, if not clearly classifiable,
were not considered as respiratory events and excluded. Apnea was defined by a cessation of
oro-nasal airflow ≥10 seconds, hypopnea by a reduction of oro-nasal airflow ≥10 seconds by
≥50%, or ≥30% when associated with an oxygen desaturation ≥4%. Apnea-hypopnea-index (AHI)