Respiratory disorders in patients with neurological diseases may be a result of damage to different parts of the respiratory rhythm generator and controlling structures responsible for generation of respiratory movements (neuromuscular disorders). Vascular damage to the respiratory center may lead to central respiratory disturbances. Neurodegenerative disease can damage the respiratory center (Cormican, 2004), as well as demyelinating lesions (Auer, 1996) located within the respiratory center. Damage of the axons projecting from respiratory center to spinal cord a-motoneurons (cervical spine trauma, demyelinating plaques in multiple sclerosis) can cause respiratory disorders. Damage to the a-motor neurons of the spinal cord (amyotrophic lateral sclerosis, post-polio syndrome) leads to respiratory failure (Aboussouan, 2005). Similarly, peripheral nerve conduction abnormalities (Guillian-Barre syndrome and congenital polyneuropathy) may lead to hypoventilation and respiratory failure. Disorders of the neuromuscular transmission (myasthenia gravis, botulinum toxin poisoning) and primary muscle disorders (myopathies, muscular dystrophy) can cause respiratory disorders. Physiological sleep, especially REM sleep phase, is a period vulnerable to the occurrence of respiratory disorders. Often the first sign of respiratory failure in the course of neurological diseases is sleep-disordered breathing (Katz, 2009; Landon, 2006). Due to the risk of significant respiratory complications, often fatal, in the course of certain neurological diseases (amyotrophic lateral sclerosis, glycogenosis type II), it is advisable to closely monitor the sleep-disordered breathing among such patients (Bach, 2004; Birnbaum, 2009). Early detection of sleep-disordered breathing, thanks to the possibilities of non-invasive respiratory therapy in the earlier stages of the disease, can significantly improve the quality of life of patients and their prognosis (Bourke, 2003; Farrero, 2005; Mustfa, 2006; Bourke, 2006; Katz, 2009; Ambrosino, 2009). An interesting fact is the presence and influence of breathing disorders in neurological diseases not associated in their pathophysiology with respiratory problems. Examples of such diseases include Alzheimer's disease, Parkinson's disease and epilepsy. Sleep-disordered breathing can often worsen the course of these diseases. The main group of neurological disorders often associated with respiratory disorders are neuromuscular diseases.
Sleep-disordered breathing and respiratory failure are a common consequence of neuromuscular diseases. Respiratory failure as a result of the underlying disease is more prominent during physiological sleep. Ventilation disorders caused by weakening of breathing muscles occur mostly in patients at REM sleep stage. Physiological relaxation of most of the body muscles (except diaphragm and oculomotory muscles, Tabachnik, 1981) and respiratory drive instability may be the cause of breathing disorders during this phase of sleep. It was confirmed in patients with neuromuscular diseases in which blood saturation was measured (Bourke, 2002; Katz, 2009). Sleep-disordered breathing in patients with neuromuscular diseases can be either of central or obstructive origin. The most common type of sleep-disordered breathing in these patients are central hypoventilation and central apneas.
Motor neuron disease leads to progressive muscle weakness, including respiratory muscles. This results in decreased breathing exertion and hypoventilation (Lyall, 2001). The course and severity of respiratory distress affects the clinical course of disease. First of all, bulbar form of amyotrophic lateral sclerosis is associated with more rapid development of respiratory failure (Hadjikoutis, 2001). Respiratory failure develops in a significant majority of patients with motor neuron disease and is a major cause of mortality. Studies concerning sleep disorders and sleep-disordered breathing in motor neuron disease often differ significantly. Some studies indicate a significantly higher incidence of sleep-disordered breathing in the early stages of the disease (Santos, 2003) and fragmentation of sleep (Arnulf, 2000) with the absence or substantial reduction of the duration of REM sleep and increased number of arousals (Takekawa, 2001). Sleep-disordered breathing was mainly of central origin (Santos, 2003; Bourke, 2002). The severity of respiratory distress tended to decrease with time of disease; in patients with disease lasting less than 1 year AHI = 23, while in patients suffering from more than 2 years AHI = 16. Other studies in the early stages of the disease (Kimura, 1999; Ferguson, 1996, David, 1997) do not show significantly higher incidence of SDB. Some authors have postulated the relationship between the number of apneas during sleep and the clinical course (bulbar form) (Santos, 2003; Kimura, 1999), others did not observed similar corelations (Ferguson, 1996). The incidence of SDB in the early stages of motor neuron disease is estimated from 16 to 76.5% (Bourke, 2002). The reasons for such divergent results are due to small study groups of patients (usually not exceeding 20 persons), a different methodological approach (polysomnography vs. portable devices) and a different stage of the disease and its clinical course. Summarizing the results of these studies it is clear that sleep-disordered breathing in patients with motor neuron disease in the early stages of the disease are mostly represented in the form of shallow breaths of central origin, arising from the failure of the diaphragm muscle contraction. Obstructive disorders are rare and are associated rather with the bulbar form (Bourke, 2002). With disease progression the severity of respiratory distress during the day and during sleep increases. Most researchers (Kimura, 1999; Bourke, 2002; Bourke, 2003; Santos, 2003; Mustfa, 2006; Ozsancak, 2008; Ambrosino, 2009) suggest that early detection of major breathing problems during sleep is important and early qualification for home treatment of patients with non-invasive ventilation methods should be performed (Bourke, 2003; Santos, 2003; Mustfa, 2006; Ozsancak, 2008; Ambrosino, 2009). Along with the improvement of technical devices and their increased availability, treatment should be introduced as soon as possible (Ozsancak, 2008; Ambrosino, 2009). A number of studies in patients with motor neuron disease proved a beneficial effect of using non-invasive ventilation during sleep on the quality of life and prognosis (Bourke, 2003, 2006; Moustfa, 2006). Randomized study of 41 patients with motor neuron disease using non-invasive ventilation during sleep (Bourke, 2006) showed a significant increase in their quality of life and its prolongation, for an average 205 days compared with the control group. The greatest benefit was found in the group of patients with less severe involvement of bulbar muscles (Bourke, 2006). Due to the nature of SDB in patients with motor neuron disease (mainly central hypoventilation), the optimal screening study evaluating the severity of respiratory distress seems to be, both in terms of accessibility and sensitivity, overnight oximetry.
Sleep-disordered breathing in patients with Duchenne muscular dystrophy has a characteristic clinical course (Barbe, 1994). In children under 10 years mostly obstructive apneas occur, while in older children, with the development of disease, the apneas of central origin predominate (Smith, 1989; Suresh, 2005). The occurrence of obstructive sleep apnea and snoring at a younger age is associated with frequent enlargement of the tongue (Barbe, 1994; Suresh, 2005)
and a relatively good function of the respiratory muscles. With age, symptoms of respiratory muscle failure develop and lead to sleep- apneas of central type. The study of 34 patients aged from 1 to 15 years showed the presence of daily symptoms of sleep-disordered breathing in 64%. Polysomnographic studies have shown obstructive SDB incidence in 31% (median age 8 years ) and central type SDB in 32% (median age 13 years) (Suresh, 2005). The non-invasive ventilation therapy during sleep significantly reduced the number of episodes of breathing problems, an average of 11 per hour in 5 years. The authors recommend polysomnography study in patients under 10 years of age with symptoms of sleep-disordered breathing. In children above 10 years of age, with early signs of respiratory distress, polysomnographic studies must be performed. Treatment with non-invasive home night ventilation should begin as early as possible (Suresh, 2005; Katz, 2009). In children with Duchenne muscular dystrophy the best predictor of outcome is the vital capacity, respiratory parameters during sleep are of less importance. Recommendations of the American Thoracic Society (2006) include: a history of breathing problems during sleep during each visit, regardless of age, in the case of a patient immobilized in a wheelchair polysomnographic evaluation once a year. When polysomnography is not feasible it is recommended to control overnight pulse oximetry (Kirk, 2000) and evaluate arterial gasometry during follow-up visits.
There are no large systematic studies on sleep -disordered breathing in other types of muscular dystrophies. Recently published study analyses SDB in 51 patients with facioscapulohumeral muscular dystrophy (Della Marca, 2009). 22 patients had abnormal breathing during sleep, 13 of them had obstructive breathing disorders (3 of them required the CPAP treatment). In 4 patients during REM sleep hypoxia of central origin were found, 3 patients had mixed type of respiratory disorders. Other parameters such as BMI, daytime sleepiness, and neck circumference did not correlate with the occurrence of sleep-disordered breathing.
Myotonic dystrophy (DM) is the most common neuromuscular disease in the adult population (Rowland, 2005). During sleep, individuals with DM may develop hypopneas and apneas, obstructive, central and mixed (Finnimore, 1994; Kiyan, 2009). These disorders occur in about half of patients with DM (Labanowski, 1996; Kiyan, 2009). Polysomnographic studies show a reduction in the duration and sleep efficiency, increased number of nocturnal arousals and time of light sleep (NREM1) and decrease in the time of REM sleep (Bourke, 2002). During the day, the rhythm of breathing in patients with myotonic dystrophy is irregular while awake, as well as during light sleep. The main problems are observed in the REM phase of sleep (Finnimore, 1994). Usually, symptoms of sleep-disordered breathing in patients with myotonic dystrophy are far before of signs of respiratory distress during the day (Bourke, 2002). Daytime sleepiness in patients with DM (assessed with the Epworth sleepiness scale > 10) is felt by about 50% of patients (Laberge, 2009). Objective tests of daytime sleepiness (MSLT test) show excessive daytime sleepiness in 69% of the respondents (Laberge, 2009). Excessive sleepiness correlates with the degeneration of serotonergic neurons in the raphe nuclei and central superior nucleus of the reticular formation (Ono, 1998). Authors describe the decrease of orexin concentration in the cerebrospinal fluid, which indicates a similarity in the pathomechanism of sleepiness in narcolepsy and DM (Martinez-Rodriguez, 2003). Due to the progressive nature of the disease and mixed character of breathing disorders, respiratory treatment should be implemented only in specialized centers. Sometimes it is necessary to apply a positive pressure with a variable values (BiPAP, Auto-CP AP) or additional oxygen therapy. In the treatment of excessive sleepiness psychostimulants - metylfenidad and modafinil are used.
Disorders of neuromuscular transmission in the course of myasthenia gravis may cause sleep-disordered breathing of central type, especially during REM sleep accompanied by declines in blood oxygen saturation (Quera-Salva, 1992; Manni, 1995). The nature of respiratory disorders is similar as in other neuromuscular diseases. The severity of respiratory distress is associated with disease severity. Sleep-disordered breathing in patients with myasthenia gravis is particularly pronounced before the occurrence of myasthenic crisis and precede symptoms of respiratory failure due to exhaustion of the respiratory muscles during the night. At that time hypercapnia is the most characteristic symptom. Hypoxia and hypercapnia occurring during sleep are often the case of morning headaches and progressive fatigue associated with underlying disease. Implementation of treatment reduces sleep-disordered breathing (Amino, 1998). There is no clear data to evaluate the incidence of SDB in patients with well-controlled myasthenia gravis. Some authors have shown an increased incidence of obstructive type of sleep-disordered breathing in patients with myasthenia gravis (36% compared to 15-20% expected in the population (Nicolle, 2006). Other authors (Prudlo, 2007) found no correlation between the occurrence of myasthenia gravis and the occurrence of obstructive breathing disorder during sleep. Most studies on the prevalence of SDB in myasthenia gravis was conducted on small groups (up to 30 patients). These results should therefore be carefully analyzed. Currently it seems that the periods of worsening of the disease are associated with increased risk of respiratory distress, while the periods of remission during medical treatment are not associated with an increased risk of respiratory disorders during sleep (Prudlo, 2007).
Pompe disease is a chronic, progressive metabolic myopathy associated with deficiency or reduced activity of the acid alpha-glucosidase enzyme. As a result, glycogen storage occurs in tissues and impairs their functioning. Depending on the degree of enzyme defficiency clinical course of disease may be different. The infantile form is associated with a complete lack of the enzyme. Symptoms begin within the first few months of life. The usual presenting features are cardiomyopathy and hepatomegaly leading to progressive heart failure and respiratory distress. Juvenile and adult forms are due to partial enzyme deficiency. Symptoms appear later and the disease has a chronic progressive course (Lewandowska, 2008). Adult -onset type of Pompe disease is associated with progressive respiratory failure resulting from progressive respiratory muscle weakness (Wierzba-Bobrowicz, 2007). Patients with adult-onset type of Pompe disease often have sleep-disordered breathing (Bembi, 2008; Mellies, 2001). These problems usually occur before the total respiratory failure. Sleep-disordered breathing is usually present in the REM sleep phase in forms of central apneas or hypopneas (Mellies, 2001). Since Pompe is a rare disease, few studies have been published regarding the prevalence of SDB in this disease. In one study performed in 27 patients with juvenile and adult form, sleep-disordered breathing was found in 13 patients, 12 of which had diaphragm weakness (Mellies, 2001). Respiratory disorders: hypopneas and apneas, occurred primarily during REM sleep and correlated with decreased tidal volumes, as measured by spirometry during the day. In some patient overnight non-invasive mechanical ventilation were initiated (Mellies, 2001). Recommendations of treatment and diagnosis of Pompe disease suggest control polysomnography study and initiation of respiratory treatment as early as possible in patients with significant SDB (Bembi, 2008).
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