Neuroimaging of sleep and sleep disorders

Herein are presented the results of research in the area of sleep neuroimaging over the past year. Significant work has been performed to clarify the basic mechanisms of sleep in humans. New studies also extend prior observations regarding altered brain activation in response to sleep deprivation by adding information regarding vulnerability to sleep deprivation and regarding the influence of task difficulty on aberrant responses. Studies in sleep disorder medicine have yielded significant findings in insomnia, depression, and restless legs syndrome. Extensive advances have been made in the area of sleep apnea where physiologic challenges have been used to probe brain activity in the pathophysiology of sleep apnea syndrome.     

Functional neuroimaging of sleep

Sleep and sleep disorders have traditionally been viewed from a polysomnographic perspective. Although these methods provide information on the timing of various stages of sleep and wakefulness, they do not provide information regarding function in brain structures that have been implicated in the generation of sleep and that may be abnormal in different sleep disorders. Functional neuroimaging methods provide information regarding changes in brain function across the sleep-wake cycle that provides information for models of sleep dysregulation in a variety of sleep disorders. Early studies show reliable increases in function in limbic and anterior paralimbic cortex in rapid eye movement (REM) sleep and decreases in function in higher-order cortical regions in known thalamocortical networks during non-REM sleep. Although most of the early work in this area has been devoted to the study of normal sleep mechanisms, a collection of studies in diverse sleep disorders such as sleep deprivation, depression, insomnia, dyssomnias, narcolepsy, and sleep apnea suggest that functional neuroimaging methods have the potential to clarify the pathophysiology of sleep disorders and to guide treatment strategies.     

Update on disorders of sleep and the sleep--wake cycle.

Wakefulness and sleep are antagonistic states competing for the domain of brain activity. Non-REM sleep and REM sleep are different states of being, sustained by activity in brainstem nuclei, hypothalamus, basal forebrain, and thalamus. Such complex phenomenology is subject to many alterations grouped in the new International Classification of Sleep Disorders. The insomnias are the result of interacting psychosocial, psychophysiologic, neurodevelopmental, and medical factors. Proper perspective of each factor provides the clinical strategies to approach medically the symptom-complex of insomnia. The most common cause of daytime hypersomnia is chronic sleep deprivation. Obstructive sleep apnea responds to nasal CPAP, but the failure rate approaches 30%. In intolerant patients BiPAP and surgical remedies should be considered. Motor and behavioral abnormalities of sleep may be linked to REM sleep as in the REM sleep behavior disorder. Paroxysmal nocturnal dystonia and nocturnal wanderings may be associated with epilepsy. Intrusions of one state of being (wakefulness, non-REM sleep, and REM sleep) into another result in mixed, poorly defined, or only partially developed states. Dissociation of states may be responsible for confusional arousals, hallucinations, and cateplexy. Senile degeneration of the suprachiasmatic nuclei may underlie the circadian rhythm changes in old age and the "sundown" syndrome in demented patients. Misalignment of the hypothalamic pacemaker causes dysregulation of sleep-related physiologic and behavioral variables. Exposure to bright light retrains the pacemaker in night-shift workers, transmeridian travelers, and in patients with seasonal affective syndrome. Benzodiazepine compounds are very effective hypnotics, but should be used sparingly in the elderly to avoid falls, memory lapses, and aggravation of a preexisting sleep apnea syndrome. Sleep laboratory evaluations are indicated in patients with hypersomnia, suspected sleep apnea syndrome, motor-behavioral disorders of sleep, and in many individuals complaining of insomnia.     

Probable causal link between epilepsy and sleep apnea: case report

Patients with epilepsy were reported to have concomitant sleep apnea, but it has been rarely linked to the epilepsy itself. We present a case of a 28-year-old, obese man with secondary medically resistant partial complex epilepsy due to a brain trauma, with progressive snoring, and sleep agitation, apneas, and important daytime somnolence. It was noticed in the polysomnographic study that he had several sleep respiratory events, probably due both to the epileptic seizures and the sleep apnea syndrome as a co-morbidity. Apnea and epilepsy will be discussed. A careful video-EEG-polysomnography study is important in evaluating refractory epileptic patients and/or epileptic patients with snoring.     

Obstructive sleep apnea and its controversial effects on cognition

Obstructive sleep apnea syndrome is a sleep disorder that may affect many brain functions. We are interested in the cognitive consequences of the condition with regard to the quality of life of individuals with this disorder. A debate is still underway as to whether cognitive difficulties caused by obstructive sleep apnea actually induce a “pseudodementia” pattern. This work provides a brief overview of the main controversies currently surrounding this issue. We report findings and opinions on structural and cognitive brain changes in individuals affected by obstructive sleep apnea by highlighting the involvement of executive functions and the possible reversibility of signs following-treatment with continuous positive airway pressure. Much research has been done on this issue but, to the best of our knowledge, a review of the present state of the literature evaluating different points of view has not yet been carried out.     

Neurocognitive consequences of sleep deprivation

Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.     

Clinical effects of sleep fragmentation versus sleep deprivation

Common symptoms associated with sleep fragmentation and sleep deprivation include increased objective sleepiness (as measured by the Multiple Sleep Latency Test); decreased psychomotor performance on a number of tasks including tasks involving short term memory, reaction time, or vigilance; and degraded mood. Differences in degree of sleepiness are more related to the degree of sleep loss or fragmentation rather than to the type of sleep disturbance. Both sleep fragmentation and sleep deprivation can exacerbate sleep pathology by increasing the length and pathophysiology of sleep apnea. The incidence of both fragmenting sleep disorders and chronic partial sleep deprivation is very high in our society, and clinicians must be able to recognize and treat Insufficient Sleep Syndrome even when present with other sleep disorders.     

颅内肿瘤和睡眠呼吸暂停低通气综合征

目的 评估颅内肿瘤病人呼吸暂停低通气的类型以及肿瘤切除术在改善呼吸紊乱方面起的作用.方法 对30例颅内肿瘤病人(22例幕上,8例幕下)术前、术后进行睡眠呼吸检测.结果 术前平均呼吸暂停低通气指数为23.3,18例病人存在阻塞性呼吸暂停,3例病人存在阻塞性和中枢性呼吸暂停.术后平均呼吸暂停低通气指数降为9.6(P＜0.0...     

Different effect of sleep on working memory and skill learning: cognitive function in obstructive sleep apnea

In obstructive sleep apnea syndrome (OSAS) hypoxia and sleep deprivation lead to neuropsychological impairments. Our goal in this study to evaluate working memory and skill learning to get a complex picture about cortical and sub-cortical function in patients with sleep apnea. Twenty-one OSAS patients and 21 healthy controls participated in the study. We analyzed verbal-, vizuo-spatial, complex working memory, general skill learning and sequence specific learning separately. Our data show that complex working memory was impaired in OSAS patients, in contrary OSAS patients represented better achievement in the vizuo-spatial task compared to the control group. We found that OSAS patients showed general skill learning and implicit learning of probabilistic sequences similar to that of controls. Taken together, we found dissociation between working memory and implicit sequence learning in OSAS. These findings suggest that sleep has less influence on the functions related to sub-cortical structures like cortical functions.     

A case of multiple sclerosis with intractable hiccups and sleep apnea syndrome]

A 48-year-old female with multiple sclerosis (MS) accompanied by intractable hiccups of over one month' duration and the sleep apnea syndrome was reported. This MS patient had been well controlled until September 16, 1991 when she experienced nausea, vomiting and hiccups. The patient was admitted to Kawasaki Medical School Hospital on October 9, 1991. A physical examination revealed intractable hiccups. T1-weighted MRI showed a low and T2-weighted image disclosed a high signal intensity area in the tegmentum of the medulla oblongata. The intractable hiccups and vomiting improved with intravenous high dose methylprednisolone injection therapy. The following day, she complained of insomnia and her family observed severe snoring and apnea during the night. These symptoms and the results of a breathing monitor were compatible with the sleep apnea syndrome. These symptoms disappeared following the administration of amitriptyline. There have been few reports of the combination of intractable hiccups and the sleep apnea syndrome in MS. The MRI findings suggest that the causative lesion of these symptoms is in the tegmentum of the medulla oblongata.     

Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP)

Abstract

The obstructive sleep apnea syndrome is characterized by nocturnal sleep disturbance, excessive daytime sleepiness and neuropsychological deficits in the areas of memory, attention, and executive tasks. In the present study, these clinical manifestations were assessed in apneic patients before and 6 months after treatment with nasally applied continuous positive airway pressure (CPAP). CPAP treatment was found to restore normal respiration during sleep and to normalize sleep organization. Daytime vigilance greatly improved with treatment but some degree of somnolence as compared to normal controls persisted. Similarly, most neuropsychological deficits normalized with treatment. The exception was for planning abilities and manual dexterity, two neuropsychological deficits that have been found to be highly correlated with the severity of nocturnal hypoxemia. These results raise the possibility that anoxic brain damage is a pathogenic factor in severe obstructive sleep apnea syndrome.     

间歇缺氧及睡眠剥夺大鼠血管内皮细胞相关指标的变化***☆

背景：血管内皮功能损坏是睡眠呼吸暂停的病理基础。 目的：观察间歇缺氧、睡眠剥夺对SD大鼠有创动脉收缩压及血浆一氧化氮、内皮素、降钙素基因相关肽水平的影响。 方法：将3月龄雄性SD大鼠16只随机等分为2组，模型组大鼠每天置入睡眠剥夺合并间歇性缺氧条件10 h (22：00-08：00)，单纯睡眠剥夺条件12 h(08：00-20：00)，剩余时间置大鼠笼饲养。对照组无睡眠剥夺、无缺氧条件饲养。 结果与结论：造模8周后，与对照组比较，模型组大鼠有创动脉压明显升高(P < 0.01)，血浆一氧化氮、降钙素基因相关肽水平显著降低(P < 0.01)，血浆内皮素水平显著升高(P < 0.01)。说明间歇性缺氧、睡眠剥夺可以引起SD大鼠血压增高，血管内皮功能受损。     

Neuroimaging and sleep medicine

In sleep medicine, patients with sleep disorders are evaluated and treated. The primary assessment tool of the field has traditionally been polysomnography. While polysomnography has been helpful in the evaluation of some sleep disorders, such as sleep apnea syndrome and periodic limb movement disorder, it has been less helpful in others, such as the insomnias, or sleep disorders secondary to mental disorders. These disorders are presumed to stem from some alteration in brain function that disrupts sleep. The development of functional neuroimaging methods provides a means to understand brain function in patients with sleep disorders in a manner not accessible to polysomnography. This paper summarizes functional neuroimaging findings during healthy sleep, then, reviews available studies in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: (1) clarification of pathophysiology; (2) aid in differential diagnosis; (3) assessment of treatment response; (4) guiding new drug development; and (5) monitoring treatment response.     

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.     

Functional neuroimaging insights into how sleep and sleep deprivation affect memory and cognition

PURPOSE OF REVIEW: The review summarizes current knowledge about what fMRI has revealed regarding the neurobehavioral correlates of sleep deprivation and sleep-dependent memory consolidation. RECENT FINDINGS: Functional imaging studies of sleep deprivation have characterized its effects on a number of cognitive domains, the best studied of these being working memory. There is a growing appreciation that it is important to consider interindividual differences in vulnerability to sleep deprivation, task and task difficulty when interpreting imaging results. Our understanding of the role of sleep and the dynamic evolution of offline memory consolidation has benefited greatly from human imaging studies. Both hippocampal-dependent and hippocampal-independent memory systems have been studied. SUMMARY: Functional imaging studies contrasting sleep-deprived and well-rested brains provide substantial evidence that sleep is highly important for optimal cognitive function and learning. The experimental paradigms developed to date merit evaluation in clinical settings to determine the impact of sleep disruption in sleep disorders.     

The eye and sleep apnea

Several eye disorders have been found in association with obstructive sleep apnea (OSA). This paper reviews the current state of knowledge of eye disorders associated with OSA. OSA is associated with a number of eye disorders including floppy eyelid syndrome (FES), optic neuropathy, glaucoma, non-arteritic anterior ischemic optic neuropathy and papilledema secondary to raised intracranial pressure. FES patients have a very high incidence of OSA and a causal relationship may exist, but amongst patients with OSA, FES is uncommon but commoner than in the general population. Treatment of OSA may help floppy eyelid syndrome, halt progression of associated glaucoma or optic neuropathy, and reduce intracranial pressure in patients with associated papilledema. Sleep apnea patients should be asked about ocular symptoms and appropriately examined or referred for assessment as some of the associated eye disorders may permanently impair vision. Ophthalmologists should be aware of the association of sleep apnea with these eye disorders and consider referral to a sleep physician for investigation and possible treatment.     

Impact of sleep apnea on economics

Obstructive sleep apnea syndrome (OSA) alters sleep quality and is associated with sleepiness and decreased cognitive functioning. It has therefore always been recognized as a major public health issue with potential societal consequences: accidents, increased morbidity, and cognitive deficits impairing work efficiency. The number of patients diagnosed and treated for OSA has increased drastically in the last few years. In response to this epidemic, health authorities have encouraged studies investigating how patients cope with OSA and also its diagnosis, comparing ambulatory to hospital-based polysomnography. Based on epidemiological knowledge, this review aims to carefully describe the possible links between sleep apnea and public health concerns along with identifying the certitudes and missing data concerning the consequences of sleep apnea on accidents, work, economics and health-related quality of life.     

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.     

Mitochondrial encephalomyopathy with sleep apnea

A rare case with mitochondrial encephalomyopathy, in association with cerebellar ataxia, peripheral neuropathy, mental retardation and alveolar hypoventilation syndrome with sleep apnea, as demonstrated by polysomnography, was encountered. This combination has not been described previously. From a prognostic point of view, alveolar hypoventilation syndrome with sleep apnea is an important clinical feature is this disease entity. Neither ataxia nor the abnormality of pyruvate metabolism was alleviated after 6 months of therapy with coenzyme Q10.