Relationship between abnormal respiratory control and perinatal brainstem and cerebellar infarctions

Clinical and neuropathologic studies were performed in 5 infants who had brainstem or cerebellar infarction and respiratory control abnormalities during early infancy. The anatomic distribution of brainstem infarction was closely related to the failure of neural respiratory control as was unilateral cerebral hemorrhagic infarction to sudden death. Brainstem and cerebellar lesions may be important in the pathogenetic mechanism of sleep apnea and sudden infant death syndrome due to brainstem tegmental gliosis and cerebellar respiratory control disturbance.     

Characteristics of breathing abnormality in Leigh and its overlap syndromes

In this report we describe the respiratory patterns of six patients with Leigh syndrome, including two individual cases with accompanying clinical phenotypes of Alpers disease and mitochondrial encephalopathy with ragged red fibers. In five cases where sleep apnea was monitored, each one showed isolated or post-sigh central apnea, hiccup, apneusis-like breathing and obstructive apnea in various combinations. The remaining patient with Alpers/Leigh overlap syndrome showed an apneusis-like pattern of dyspnea. The sleep structure was examined in three patients.Two patients with brainstem lesions showed a decrease in the deep sleep stages and an absence of REM sleep. Medullary lesions were found in four patients by magnetic resonance imaging or at autopsy and involved predominantly the dorsal respiratory group (DRG) of medullary neurons. The role of DRG lesions in the pathophysiology of respiratory symptoms in Leigh syndrome is discussed.     

Autonomic regulation during sleep and wakefulness: a review with implications for defining the pathophysiology of neurological disorders

Cardiovascular and respiratory parameters change during sleep and wakefulness. This observation underscores an important, albeit incompletely understood, role for the central nervous system in the differential regulation of autonomic functions. Understanding sleep/wake-dependent sympathetic modulations provides insights into diseases involving autonomic dysfunction. The purpose of this review was to define the central nervous system nuclei regulating sleep and cardiovascular function and to identify reciprocal networks that may underlie autonomic symptoms of disorders such as insomnia, sleep apnea, restless leg syndrome, rapid eye movement sleep behavior disorder, and narcolepsy/cataplexy. In this review, we examine the functional and anatomical significance of hypothalamic, pontine, and medullary networks on sleep, cardiovascular function, and breathing.     

Prenatal and postnatal maturation of medullary 'respiratory centers'

During infancy respiratory patterns change with maturation. However, there is no documentation of the development of the neurons thought to be related to respiratory control. Relevant neurons in the medulla oblongata were examined using Golgi impregnation methods. Dendritic spines increased prenatally and decreased postnatally in the medullary respiratory centers (i.e., dorsal vagal nucleus, nucleus tractus solitarii and reticular formation). The prenatal neuronal maturation is earlier in the reticular formation than the vagal nucleus. These changes in neuronal dendrites may be related to the development of central respiratory control and the occurrence of primary apnea in prematurity and sleep apnea in sudden infant death syndrome.     

Acute failure of automatic respirations secondary to a unilateral brainstem infarct

A case of failure of automatic respiration with sleep apnea is described in a patient with a unilateral lateral medullary tegmental lesion. This case is the first known with autopsy confirmation in which a unilateral lesion has caused this syndrome.     

Sleep apnea in well-controlled myasthenia gravis

Polygraphic monitoring of the respiratory status during sleep provides a definitive test for the presence of the sleep apnea syndrome. This syndrome has been recognized in various kinds of neurological disorders. However, as far as we know, there have been no reports of describing the sleep apnea syndrome in myasthenia gravis (MG). We conducted overnight polygraphic sleep studies of 10 patients of clinically well-controlled MG. Patients: We examined 10 patients of MG (4 men and 6 women). The subtypes of MG were IIA(1), IIB(8) and V(1) according to Osserman's criteria. Results: Six patients, with an average age of 47.8 and the average duration of 6.2 years, had polysomnographically obstructive and central types of sleep apnea, appearing longer than 10 seconds and more than 30 times in one night. Their mean Apnea Index (AI) was 14.6. The duration of mean apnea was 23.4 seconds and 99.0 times the average frequency. On the other hand, in four patients of MG, averaged age at 30.8 and for a 0.9-year duration, the sleep apnea syndrome was never seen. Therefore, the longest duration of MG tended to have the sleep apnea syndrome. Discussion: Six out of the 10 patients of MG had obstructive and central types of the sleep apnea syndrome. Since their respiratory functions examined in a daytime were normal and the physical findings concerned with MG were well controlled by medications, our findings of nocturnal sleep apnea might be indicative of a central cholinergic system disturbance in MG during sleep.     

Snoring and the risk of ischemic brain infarction

To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers.     

Respiratory disturbances in rett syndrome: don't forget to evaluate upper airway obstruction

Rett syndrome is characterized by loss of motor and social functions, development of stereotypic hand movements, seizures, and breathing disturbances. This study evaluates the presence of overnight respiratory disturbances. Polysomnography in combination with a questionnaire (the Sleep Disturbance Scale for Children) was performed in 12 Dutch patients with Rett. Respiratory disturbances were present in all, clinically relevant in 10 (apnea hypopnea per hour 1.0-14.5). In 8 children, central apneas were present during the day often with obstructive apneas at night. In 6, obstructive sleep apnea syndrome was diagnosed, in 3 severe, with frequent oxygen desaturations. Significant respiratory complaints were present in 3 patients, all had obstructive sleep apnea syndrome. Of the 12 patients with Rett, 8 (67%) snored, and in 5 obstructive sleep apnea syndrome was present. In children, hypertrophied tonsils and adenoids are a common cause of obstructive sleep apnea syndrome, which may benefit from therapeutic intervention. We recommend performing polysomnography in patients with Rett syndrome and respiratory complaints.     

Paroxysmal apnea and vasomotor instability following medullary infarction

BACKGROUND: Central hypoventilation and paroxysmal hypertension are uncommon complications of medullary infarction. To our knowledge, the combination of these autonomic complications of medullary stroke has not previously been reported. OBJECTIVE: To describe a patient who experienced life-threatening paroxysmal attacks of central apnea and vasomotor instability 3 months after medullary infarction, a combination of symptoms that is unusual. PATIENT, METHODS, AND RESULTS: Following a right lateral medullary infarction, an otherwise stable 70-year-old woman developed recurrent episodes of apnea (PCO2), > 100 mm Hg), blood pressure instability (systolic blood pressure, > 200 to < 100 mm Hg), and mental status changes (from agitation to coma) within hours of removal from mechanical ventilation. These attacks occurred repeatedly after removal from mechanical ventilation and were prevented by diaphragm pacing with a phrenic nerve pacemaker and nocturnal mechanical ventilation via a tracheostomy. CONCLUSIONS: A syndrome of life-threatening central hypoventilation and vasomotor instability can occur after medullary infarction. Placement of a phrenic nerve pacemaker can prevent these complications, without the functional limitations imposed by continuous mechanical ventilation.     

Obstructive sleep apnea syndrome or abnormal upper airway resistance during sleep?

Obstructive sleep apnea syndrome is well known by now, but, at both extremes of age, increased upper airway resistance may lead to clinical symptoms without complete apnea. Abnormal craniofacial features appear to be responsible for the very early appearance during childhood of increased upper airway resistance. In adults, snoring, often related to partial upper airway obstruction located in the pharynx, may be associated with changes in respiratory timing and intermittent arousal. Many treatments are currently available to deal with obstructive sleep apnea syndrome. It is important to recognize the location(s) of the upper airway obstruction before considering treatment and to evaluate the associated risk factors. Early recognition of factors involved in increased upper airway resistance may allow prevention, a more efficacious approach than treatment of an already developed syndrome.     

Sleep in women

The timing and continuity of sleep in healthy individuals is regulated by the synchronous function of the sleep homeostasis and the endogenous circadian rhythms. Multiple factors affect these two processes and the way they interact. Sleep disorders may manifest differently in men and women and these differences are particularly notable during pregnancy, lactation, and menopause. Insomnia may occur relatively commonly during pregnancy and in the postpartum, and may be the result of either a primary sleep disorder, such as obstructive sleep apnea (OSA), movement disorders such as restless legs syndrome (RLS), or sometimes depression, especially in the postpartum period. Obstructive sleep apnea may contribute to a higher risk of hypertension during pregnancy and doubles the risk for preeclampsia and preterm birth. Snoring, a frequent symptom of OSA, increases in frequency during pregnancy. Restless legs syndrome is more common in pregnant women, is more frequent in the third trimester of pregnancy, and tends to improve dramatically after delivery. Factors associated with increased RLS in pregnancy may be related to iron and folate metabolism. Risk for OSA increases after menopause and presentation with insomnia can delay the diagnosis of OSA. Various treatment options for sleep disorders in women are discussed.     

Central type of sleep apnea syndrome caused by unilateral lateral medullary infarction]

We reported here a 64-year-old man with a central apnea resulted from unilateral medullary infarction. He was admitted because of cerebellar ataxia, dysarthria and dysphasia of abrupt onset. After the injection of diazepam for alcohol forbidden syndrome, he induced complete apnea and required the endotracheal intubation. At the spontaneous respiration under room air, his arterial blood gas showed hypercapnea without hypoxemia, and he fell into severe hypoventilation when hypnotic drug was injected. Respisomnogram revealed the frequent presence of central apnea both while he was awake and asleep. MRI demonstrated an abnormal high intensity area on T2 weighted image at the right lateral medulla just below the ponto-medullary junction. At autopsy, areas of the infarction were limited within the right lateral medulla, including lateral portion of the medullary reticular formation, the ambigual nucleus, one part of the solitary nuclear complex, the inferior cerebellar peduncle and the spinal trigeminal nucleus. However, the dorsomotor nucleus of vagus was completely free from the infarct lesion. There was no other lesion within central nervous system. Such a distribution seemed the minimal extent of the lesion responsible for central, apnea compared to the previous reports. We suggest that central apnea occurs not infrequently in the cases of Wallenberg's syndrome.     

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.     

A 13-year-old-girl with Pickwickian syndrome and Asperger syndrome

We reported a 13-year-old girl with Pickwickian syndrome and Asperger syndrome. The chief complaint on admission was apnea attacks during sleep. She had severe obesity. Whole night polysomnography showed that the apnea attacks occurred during light and REM sleep, and that slow wave sleep and REM sleep volumes were decreased. These findings were the same as those on adult cases. Weight control was very difficult because of Asperger syndrome.     

Therapy of obstructive sleep apnea syndrome

Symptomatology and sequelae, as well as diagnosis and therapy of the obstructive sleep apnea syndrome are discussed. The Esmarch prosthesis, which we developed for the prosthetic treatment of obstructive sleep apnea syndrome, was tested in 7 patients. Patients were polysomnographically recorded during two sequential nights with and without Esmarch prosthesis. All apnea parameters improved significantly (apnea time by 78%, apnea index by 67% of baseline values). The mean duration of the remaining apnea phases diminished by 31%. Improvement of O2 saturation of haemoglobin and O2 partial pressure in the tissue paralleled that of the apnea parameters. The severely disturbed sleep profile of the patients showed a clear tendency towards normalization. The Esmarch prosthesis is an efficient method for the treatment of the obstructive sleep apnea syndrome.     

A case of sleep choking syndrome improved by the Kampo extract of Hange-koboku-to

A case of sleep choking syndrome with typical symptoms is presented. A 44-year-old Japanese male suffered from multiple episodes of choking, which suddenly appeared with fear of impending death about 30 min after falling asleep almost every night. Overnight polysomnography showed an apnea index of 0.92 events/h, an apnea-hypopnea index of 2.77 events/h, and normal respiration during sleep with the exception of the episodes of apnea and hypopnea. No choking episode occurred in the sleep laboratory. The administration of 500 mg of acetazolamide was ineffective, but the choking episode improved after the administration of Kampo extract of Hange-koboku-to (Ban-xia-hou-pu-tang). Hange-koboku-to may be effective in treating choking sensation during sleep as well as during wakefulness.     

Sleep apnea in patients with postpolio syndrome

We studied sleep architecture and sleep apnea pattern in patients with postpolio syndrome (PPS). Ten patients with clinical signs of PPS underwent polysomnographic recording for two consecutive nights. Although sleep efficiency and proportions of sleep stages were within the normal range, sleep architecture was disrupted owing to sleep apnea. Patients with bulbar involvement had more frequent sleep apnea (mean sleep apnea index, 11.09) than patients without (apnea index, 5.88). The former also had significantly more central apnea, which occurred more commonly during non-rapid-eye-movement (NREM) than rapid-eye-movement (REM) sleep, than those without bulbar signs. This finding suggests reduction in forebrain control of compromised bulbar respiratory centers during NREM sleep in PPS.     

The impact of sleep disruption on executive function in Down syndrome

The high prevalence of sleep disorders, particularly obstructive sleep apnea, is well established in children with Down syndrome. However, only a few studies have focused on older children and young adults in this population. Given the presence of sleep disorders and the early emergence of Alzheimer's disease, more work is needed to examine the relationship between sleep and cognition in Down syndrome. Twenty-nine adolescents and young adults with Down syndrome participated in the present study. Parents reported on their sleep difficulties using a well-validated measure of sleep problems in intellectual disabilities. Based on theoretical models linking obstructive sleep apnea to prefrontal cortex dysfunction, we tested components of executive functions that have been shown to be impaired in previous studies of Down syndrome. First, results indicate that participants with Down syndrome with higher body mass index also had increased caregiver reports of sleep apnea symptoms. Individuals with high ratings of sleep disruption also showed greater difficulties with executive function. These results suggest that sleep disruption may place this set of functions at risk in young adults. Future work should examine if this risk may result in earlier onset of dementia or steeper decline with Alzheimer's disease. Further, additional studies are needed to investigate the effect of exercise interventions and weight reduction on sleep disorders in this population.     

Upper airway resistance syndrome in children: A clinical review

Upper airway resistant syndrome (UARS) is more common in children than is obstructive sleep apnea syndrome (OSAS). Age will color the symptoms associated with the syndrome. UARS must be looked for in families with adult sleep-disordered breathing. Polygraphic recording during sleep will show flow limitation with usage of nasal cannula/pressure transducer system, but the abnormal breathing during sleep may be indicated also by burst of tachypnea without saturation drops. Esophageal pressure monitoring may be the only way to confirm a suspected diagnosis. A mild developmental anomaly of the craniofacial skeleton is often seen in these children even in the presence of enlarged tonsils and adenoids. Children with sleep-disordered breathing should have a maxillomandibular examination to assess the need for orthodontic treatment to expand the oral cavity.     

Polysomnographic and urodynamic changes in a case of obstructive sleep apnea syndrome with enuresis

A 53-year-old female patient with obstructive sleep apnea syndrome was reported. She had complained of enuresis as well as a 15-year history of snoring, but she had no complaint of sleep and awake disturbance. Polysomnographic study showed repeated obstructive apnea and hypopnea with an apnea/hypopnea index of 52.6, and severe oxygen desaturation during sleep. On cystometography during sleep, the changing amplitude of the spike wave corresponds to the changes of respiratory efforts against a closed upper airway. The patient was treated successfully with imipramine and acetazolamide for the obstructive sleep apnea and enuresis. Apnea/hypopnea index, nocturnal oxygen desaturation, and sleep architecture were improved, and enuresis completely disappeared. Cystometrography during sleep showed that the average amplitude of the spike wave tended to be low. Percentage urinary volume during sleep compared with 24 h volume was significantly reduced. We considered that the enuresis was mainly related to increased intra-abdominal pressure produced by respiratory efforts and enhanced nocturnal urine production.