Multiple system atrophy presenting with acute respiratory failure due to diaphragmatic dysfunction

Sleep related respiratory dysfunction and vocal cord paralysis are considered to be the major factors responsible for respiratory failure in multiple system atrophy (MSA). We report a patient initially presenting with alveolar hypoventilation culminating in respiratory failure, ultimately diagnosed as MSA. No central sleep apnea or marked paralysis of the vocal cords was noted. The most likely cause for the respiratory failure was thought to be the weakness of respiratory musculature. This case emphasizes the need that MSA should be added to the differential diagnosis of unexplained hypercapnic respiratory failure.     

Laryngeal inputs in defensive airway reflexes in humans

Stimulation of laryngeal receptors is the natural starting point of defensive airway reflexes including the cough reflex, expiration reflex, spasmodic panting, and apnoea with laryngospasm. Although several different types of laryngeal receptors have been reported, the laryngeal irritant receptors are considered to play the most essential role in elicitation of defensive airway reflexes. Based on the knowledge that the laryngeal irritant receptors are stimulated by water solutions lacking chloride anions, we have developed an experimental method to elicit defensive airway reflexes with a direct instillation of distilled water onto the laryngeal mucosa in humans. Using this experimental method, we studied the characteristics of defensive airway reflexes in lightly anaesthetized patients with multiple system atrophy (MSA). The reflex responses to water stimulation observed in these patients were characterized by apnoea with laryngospasm while the cough reflex was never elicited. Endoscopic images of the larynx in these patients were also characterized by laryngeal oedema. Considering the pathological changes occurring in the central nervous system and the laryngeal mucosa, it is possible that the defensive airway reflexes may be modified by central and/or peripheral mechanisms in patients with MSA.     

肛门和尿道括约肌肌电图对多系统萎缩的诊断和鉴别诊断价值

肛门和尿道括约肌肌电图对多系统萎缩（MSA）具有诊断和鉴别诊断价值。本文综述了两种检查方法的解剖及病理生理基础、方法学、正常和异常表现以及在神经系统疾病中的诊断及鉴别诊断价值。目前,两种检查方法对多系统萎缩诊断及鉴别诊断价值仍存在争议,对MSA诊断的特异性及敏感性,二者差异与临床特点的相关性,以及是否可以互相弥补尚未见报道。肛门和尿道括约肌肌电图在MSA时表现为神经源性损害的改变,在怀疑MSA时该项检查可作为常规的电生理检测手段,对于鉴别诊断以及两者之间的相互关系尚有进一步研究的空间。     

Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Barcelona Multiple System Atrophy Study Group

We prospectively studied the sleep patterns and laryngeal function of 20 patients with multiple system atrophy and found sleep disturbances in all subjects and vocal cord abduction dysfunction in 14 (70%). In three patients with nocturnal stridor and complete vocal cord abductor dysfunction, continuous positive airways pressure eliminated laryngeal stridor, obstructive apnoea, and haemoglobin desaturation.     

A case of multiple systemic atrophy (MSA) analyzed by acoustic sound for nocturnal inspiratory stridor]

A 70-year old woman was admitted because of sleep maintenance insomnia with severe respiratory sounds during sleep. Polysomnography (PSG) revealed frequent respiratory events, particularly hypopneas, throughout the night associated with severe oxygen desaturation, and inspiratory stridor, which was shown to have a high-pitched frequency by acoustic sound analysis. She also presented fine finger tremor due to parkisonism, increased bilateral tendon responses, cerebellar ataxic gait, and dysautonomia. Therefore, we concluded that she suffered from multiple systemic atrophy (MSA). Nasal continuous positive airway pressure (nCPAP) treatment was successful. Characteristic PSG findings and analysing the snoring sound are important in the early diagnosis of sleep-related disordered breathing in MSA.     

Sleep apnoea in heart failure: To treat or not to treat?

Heart failure (HF) and sleep apnoea are common disorders which frequently coexist. Two main types of apnoea occur: one is obstructive which, through recurring episodes of snoring, hypoxaemia, large negative intra‐thoracic pressures and arousals from sleep leading to downstream inflammatory and autonomic nervous system changes, is thought to be a causative factor to the development of systemic hypertension and HF. The other type of apnoea, Cheyne–Stokes respiration with central sleep apnoea (CSR‐CSA), is characterized by an oscillatory pattern of ventilation with a prevailing hyperventilation‐induced hypocapnia, often in the absence of significant hypoxaemia and snoring, and is thought to be a consequence of advanced HF‐related low cardiac output, high sympathetic nervous system activation and pulmonary congestion. CSR‐CSA may be a compensatory response to advanced HF. Rostral fluid shift during sleep may play an important role in the pathogenesis of both obstructive sleep apnoea (OSA) and CSA. Studies of positive airway pressure (PAP) treatment of OSA and CSA in HF have shown short‐term improvements in cardiac and autonomic function; however, there is no evidence of improved survival. Loop gain may provide useful marker of continuous PAP (CPAP) responsiveness in patients with central apnoea. A greater understanding of the pathophysiology of the interaction between obstructive and central apnoea and the various types of HF, and the mechanisms of therapies, such as PAP, is required to develop new strategies to overcome the disabling symptoms, and perhaps improve the mortality, that accompany HF with sleep apnoea.     

多系统萎缩非运动症候的临床研究

目的总结多系统萎缩(multiple system atrophy,MSA)以非运动症候和运动症候为首发症状的构成比和MSA非运动症候的具体症候构成比。方法选择MSA患者31例,其中MSA-P型18例,MSA-C型13例。进行详细病史记录和神经系统体检,记录运动症候及非运动症候具体表现及出现时间。结果 23例MSA以非运动症候首发。非运动症候的首发症状以快速眼动睡眠异常、排尿障碍、性功能障碍及直立性低血压常见。31例MSA患者均有非运动症候表现。以直肠功能障碍(93.5%)、排尿障碍(90.3%)、直立性低血压(64.5%)、睡眠呼吸暂停(61.3%)、快速眼动睡眠异常(48.4%)最为常见。MSA-P型与MSA-C型在年龄、性别、首发病程、就诊病程及非运动症候构成比较,差异无统计学意义(P>0.05)。结论 MSA患者普遍存在自主神经功能障碍等非运动症候表现,且以首发症状多见。MSA-C型患者中以非运动症候起病较MSA-P型患者更为多见。     

Periodic leg movement, sleep fragmentation and central sleep apnoea in two cases: reduction with Clonazepam

Two subjects presented with periodic leg movement (PLM) syndrome during sleep that was characterized by marked sleep fragmentation and repetitive short central apnoeas. Treatment of PLM using Clonazepam, a benzodiazepine with hypnotic properties, markedly reduced the sleep fragmentation due to PLM and, despite its depressant properties on the central nervous system, controlled the repetitive central apnoeas. These two observations, although rare, give insight into the role of non-ventilatory variables in the development of sleep apnoea. Significant sleep fragmentation should be considered when assessing factors leading to respiratory instability during sleep and/or the pathophysiology of sleep apnoea syndromes.     

Continuous positive airway pressure therapy in sleep apnoea

Sleep apnoea is associated with increased mortality and morbidity. The treatment goal is to reduce the neurocognitive and cardiovascular sequelae. CPAP therapy in sleep apnoea is discussed in two parts in the article. The first part will consider CPAP therapy in the more common form of sleep apnoea (i.e. obstructive or mixed sleep apnoea) and the second part will consider CPAP therapy in central sleep apnoea. Alternative positive airway pressure modalities are discussed. CPAP therapy has been extensively studied and it remains the mainstay of treatment in obstructive sleep apnoea, as it is still the most consistently efficacious and safe option. However, its major disadvantage is that it does not confer a cure to this disorder and hence therapy is generally life long with its usual treatment compliance problems. As such, there are continuous improvement strategies. The role of CPAP therapy in central sleep apnoea is more limited. There has been increasing data on the beneficial effect of CPAP on central sleep apnoea/Cheyne-Stokes respiration in congestive heart failure. Evidence for CPAP therapy in sleep apnoea has evolved significantly over the last decade. However, more research and publication of large-scale long-term randomized trials of treatment in sleep apnoea to assess patient-orientated outcomes and preferences are necessary.     

Sleep apnoea: Finnish National guidelines for prevention and treatment 2002-2012

(1) After negotiations with the Finnish Ministry of Social Affairs and Health, a national programme to promote prevention, treatment and rehabilitation of sleep apnoea for the years 2002-2012 has been prepared by the Finnish Lung Health Association on the basis of extensive collaboration. The programme needs to be revised as necessary, because of the rapid development in medical knowledge, and in appliance therapy in particular. (2) Sleep apnoea deteriorates slowly. Its typical features are snoring, interruptions of breathing during sleep and daytime tiredness. Sleep apnoea affects roughly 3% of middle-aged men and 2% of women. In Finland, there are approx. 150,000 sleep apnea patients, of which 15,000 patients have a severe disease, 50,000 patients are moderate and 85,000 have a mild form of the disease. Children are also affected by sleep apnea. A typical sleep apnea patient is a middle-aged man or a postmenopausal woman. (3) The obstruction of upper airways is essential in the occurrence of sleep apnoea. The obstruction can be caused by structural and/or functional factors. As for structural factors, there are various methods of intervention, such as to secure children's nasal respiration, to remove redundant soft tissue, as well as to correct malocclusions. It is possible to have an effect on the functional factors by treating well diseases predisposing to sleep apnoea, by reducing smoking, the consumption of alcohol and the use of medicines impairing the central nervous system. The most important single risk factor for sleep apnoea is obesity. (4) Untreated sleep apnoea leads to an increase morbidity and mortality through heart circulatory diseases and through accidents by tiredness. Untreated or undertreated sleep apnoea deteriorates a person's quality of life and working capacity. (5) The goals of the Programme for the prevention and treatment of sleep apnoea are as follows: (1) to decrease the incidence of sleep apnoea, (2) to ensure that as many patients as possible with sleep apnoea recover, (3) to maintain capacity for work and functional capacity of patients with sleep apnoea, (4) to reduce the percentage of patients with severe sleep apnoea, (5) to decrease the number of sleep apnoea patients requiring hospitalisation and (6) to improve cost effectiveness of prevention and treatment of sleep apnoea. (6) The following means are suggested for achieving the goals: (1) to promote prevention of obesity, weight loss and weight control; (2) to promote securing of nasal respiration in child patients and removal of obstructing redundant soft tissues; (3) to promote the correction of children's malocclusions, (4) to enhance knowledge about risk factors and treatment of sleep apnoea in key groups, (5) to promote early diagnosis and active treatment, (6) to commence rehabilitation early and individually as a part of treatment and (7) to encourage scientific research. (7) On the national level, the occurrence of sleep apnoea can be prevented, for example, by encouraging weight control. The programme gives examples of such measures and appeals to various authorities and voluntary organisations to reinforce their collaboration. Preventive measures should be individualised, and based on due consideration. (8) The efficacy of diagnosing sleep apnoea should be increased. Attention should be paid to the symptoms of risk group patients at different units of the primary and occupational health care. Even mild forms of the disease should be treated appropriately. Diagnosis and treatment of the disease involve cooperation between the primary and specialised health-care sectors. Methods of treatment are (1) treatment of obesity, (2) positional therapy, (3) reduction of the use of medicines impairing the central nervous system, (4) reduction of smoking and the consumption of alcohol, (5) devices affecting the position of the tongue and lower jaw, (6) treatment with Continuous Positive Airway Pressure (CPAP-treatment), (7) surgical methods of treatment and (8) rehabilitation. (9) The hierarchy of referrals in the prevention and treatment of sleep apnoea should be revised to accord a greater role to the primary health-care sector. Good exchanges of information and cooperation between the primary health care and specialised medical-care sectors should be developed. Hospitals districts in cooperation with provincial governments and municipalities should ensure that different levels of the health-care system are capable of fulfilling the tasks assigned to them appropriately. (10) Rehabilitation of sleep apnoea should be goal-orientated and cover all forms of rehabilitation: medical, occupational and social. Rehabilitation should prevent the effects caused by the disease. Thus, it is possible to support self-care, increase the patient's resources and improve quality of life. (11) Information and training should be directed primarily towards health-care personnel, patients and their families. Organisations should produce materials for health and patient education as well as organising training events. To support the activities. financing will be needed from organisations such as Finland's Slot Machine Association. The Social Insurance Institution should disseminate information about questions of social security. Regional direction and training will mainly be the responsibilities of hospital districts, provincial governments and local health centres. The media will play an important role in the dissemination in-depth information about prevention and treatment of sleep apnoea.     

Percutaneous coronary intervention for central sleep apnoea with ischaemic cardiomyopathy

Central sleep apnoea is often recognized in patients with heart failure. Although the medical treatment to improve cardiac function is effective for sleep apnoea, direct evidence that improved cardiac function ameliorates sleep apnoea has not been reported due to the fact that a particular drug may affect a multitude of organs. We present a chronic heart failure patient with central sleep apnoea whose nocturnal desaturation was improved by percutaneous coronary intervention that resulted in improved cardiac function. This is the first case where percutaneous coronary intervention improved sleep apnoea, suggesting that the improved cardiac function led to amelioration of sleep apnoea.     

Sleep disordered breathing: management update

The term sleep disordered breathing encompasses a spectrum of abnormalities, including snoring, obstructive sleep apnoea (OSA), central sleep apnoea (CSA), respiratory‐related arousals and hypoventilation. This review focuses on both OSA and CSA. It provides a clinical update of recent advances in the diagnosis, management and prognosis of these two conditions. An increasing array of treatment modalities, particularly for OSA, broadens the opportunity for personalised therapy tailored to the individual patient.     

Sleep-Disordered Breathing—Do We Have to Change Gears in Heart Failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)—with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea—such as implantable phrenic nerve stimulators—also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea.     

Pickwickian syndrome and hypersomnia with periodic respiration]

A classical definition of Pickwickian syndrome associates alveolar hypoventilation, obesity and hypersomnia with periodic breathing. Obesity in itself is enough to explain the alveolar hypoventilation and some of the sleep disorders, but in fact all three elements of this syndrome are intricated. Obesity, whether associated with a Pickwickian syndrome or not, affects ventilatory mechanics similarly. With the cause of sleep disorders are associated central ventilatory pauses, appearing periodically followed by phases of apnoea secondary to buccopharyngial hypotony. The alveolar hypoventilation is therefore the consequence of obesity and periodic apnoea. It also results from a low respiratory frequency considering that the tidal volume is also decreased. These different elements suggest some disorder of the centers controling ventilation. One can describe different nosological forms, all having as a common factor hypersomnia with periodic respiration, the latter being a determining factor in the diagnosis. Therapy, including weight reduction and symptomatic treatment of alveolar hypoventilation, is now augmented by new drugs acting on the central nervous system.     

High prevalence and persistence of sleep apnoea in patients referred for acute left ventricular failure and medically treated over 2 months.

AIMS: Cardiac failure patients were studied systematically using polysomnography 1 month after recovering from acute pulmonary oedema, and again after 2 months of optimal medical treatment for cardiac failure. METHODS AND RESULTS: This prospective study of consecutive patients was conducted in a cardiac care unit of a university hospital. V o(2)measurements and left ventricular ejection fraction were recorded. Thirty-four patients, initially recruited with pulmonary oedema, improved after 1 month of medical treatment to NYHA II or III. They were aged less than 75 years and had a left ventricular ejection fraction less than 45% at the time of inclusion. Age was 62 (9) years, body mass index= 27 (5) kg x m(-2)and an ejection fraction= 30 (10)%. Eighteen of the 34 patients (53%) had coronary artery disease. Twenty-eight of the 34 had sleep apnoea syndrome with an apnoea+hypopnoea index >15 x h(-1)of sleep. Thus, the prevalence of sleep apnoea in this population was 82%. Twenty-one of 28 (75%) patients had central sleep apnoea and seven of 28 (25%) had obstructive sleep apnoea. Patients with central sleep apnoea had a lower Pa co(2)than those with obstructive sleep apnoea (33 (5) vs 37 (5) mmHg, P<0.005). Significant correlations were found between apnoea+hypopnoea index and peak exercise oxygen consumption (r= -0.73, P<0.01), and apnoea+hypopnoea index and Pa co(2)(r= -0.42, P = 0.03). When only central sleep apnoea patients were considered, a correlation between apnoea+hypopnoea index and left ventricular ejection fraction was also demonstrated (r= -0.46, P<0.04). After 2 months of optimal medical treatment only two patients (both with central sleep apnoea) showed improvement (apnoea+hypopnoea index <15 x h(-1)). CONCLUSIONS: We have demonstrated a high prevalence of sleep apnoea, which persisted after 2 months of medical treatment, in patients referred for acute left ventricular failure. Central sleep apnoea can be considered a marker of the severity of congestive heart failure.     

Das Schlafapnoe-Syndrom in der Rehabilitation

Sleep-related breathing disorders are a common finding in patients undergoing cardiological rehabilitation. Sleep apnoea is recognized as a major risk factor for cardiovascular disorders. The diagnosis of sleep-related breathing disorders begins with taking a thorough sleep medicine-related patient history and answering dedicated questionnaires. The second step involves portable monitoring to assess oxygen saturation, heart rate, respiratory flow and effort. Portable monitoring is able to detect the severity of the breathing disorder and forms the basis on which to refer the patient for further sleep laboratory diagnosis or, in the case of positive results, to initiate appropriate treatment. In order to exclude a sleep-related breathing disorder, to distinguish between obstructive and central sleep apnoea, or to diagnose other sleep disorders a cardiorespiratory polysomnography in a sleep laboratory is required. Polysomnography is also needed if comorbidities are present. Appropriate and prompt treatment of sleep-related breathing disorders can shorten cardiological rehabilitation and improve outcomes in this patient group.     

Sleep apnoea syndrome and cardiac failure

Despite recent therapeutic advances, chronic cardiac failure is still associated with a significant morbidity and mortality. Sleep apnoea syndrome is common in this population, affecting almost half of these patients. However, it is rarely diagnosed and treated. There are two types of sleep apnoea syndrome, which can sometimes co-exist: the obstructive apnoea syndrome with collapse of the upper airways, and the central apnoea syndrome with cyclical Cheyne-Stokes respiration, linked with anomalies of central control. Apnoea leads to sympathetic stimulation and an increase in the left ventricular post-charge which can alter cardiac function and the prognosis. Diagnosis of sleep apnoea syndromes is now made with small ambulatory oxymeters which do not disturb sleep and which allow precise detection of episodes of desaturation. Treatment with positive pressure ventilation brings an improvement in daytime symptoms (fatigue, drowsiness) as well as an improvement in cardiac function. Screening for sleep apnoea is thus essential in patients with chronic heart failure, especially in those resistant to optimal drug treatment, in order to improve their management.     

Increased mortality risk in congestive heart failure patients with comorbid sleep apnoea: 10‐year follow up

We aimed to determine the mortality rates of a congestive heart failure (CHF) research cohort during a 10‐year follow up and compare survival between those with CHF only (controls), CHF and central sleep apnoea, and CHF and obstructive sleep apnoea. There was a significant detriment of survival in patients with CHF/central sleep apnoea compared with both CHF/obstructive sleep apnoea patients (mean survival time difference 3.8 years, P = 0.005) and controls (mean survival time difference 4.0 years, P = 0.01).     

Cardiac diastolic function and hypercapnic ventilatory responses in central sleep apnoea.

Hyperventilation is the key factor contributing to the development of idiopathic nonhypercapnic central sleep apnoea (ICSA), where left ventricular systolic function is normal. ICSA is reported to occur in 20% of patients with left ventricular diastolic dysfunction, in whom elevated pulmonary vascular pressures and resultant increased pulmonary vagal afferent traffic may contribute to hyperventilation. The contribution of the two potential mechanisms responsible for the hyperventilation seen in the following ICSA was measured: 1) left ventricular diastolic dysfunction-induced pulmonary hypertension; and 2) increased peripheral and central hypercapnic ventilatory responses (HCVR). The pulmonary artery pressure, left ventricular diastolic function and chemosensitivity to hypercapnia were measured during wakefulness in 16 subjects with ICSA. All subjects had systolic pulmonary artery pressures <3.99 kPa (<30 mmHg) and only four had diastolic dysfunction. All subjects had elevated peripheral and central HCVR compared with historical normal control subjects. Diastolic dysfunction correlated with increasing age but not with HCVR or markers of central sleep apnoea severity. Idiopathic nonhypercapnic central sleep apnoea is likely to be dependent upon raised hypercapnic ventilatory responses, and not pulmonary hypertension due to left ventricular diastolic dysfunction.     

Diagnostic approaches to respiratory sleep disorders

Sleep disordered breathing (SDB) comprises a number of breathing disturbances occurring during sleep including snoring, the obstructive sleep apnoea/hypopnea syndrome (OSAHS), central sleep apnoea (CSA) and hypoventilation syndromes. This review focuses on sleep disordered breathing and diagnostic approaches in adults, in particular clinical assessment and overnight assessment during sleep. Although diagnostic approaches to respiratory sleep disorders are reasonably straightforward, they do require a degree of clinical acumen when it comes to assessing severity and management options. Diagnosing respiratory sleep disorders on clinical features alone has limitations. Monitoring and measuring respiration during sleep has undergone many advances in the last 40 years in respect of quality and validity, largely regarding OSAHS. Despite the improvement in our diagnostic standards and recognition of sleep disordered breathing, many limitations still need to be overcome. Apart from assessing the individual patient, population screening for sleep disorders continues to preoccupy health professionals and policy makers in many countries. Research in the field is pushing current boundaries in terms of simplifying diagnosis and enhancing screening for sleep disordered breathing in large populations. At present, a number of these newer approaches require further validation.