Prader-Willi syndrome

https://tud.qucosa.de/api/qucosa%3A26871/attachment/ATT-0/

Cost of disorders of the brain in Europe 2010

Principles and Practice of Sleep Medicine

/pdf/beck-depression-inventory-iinituitenoyi-kao-cha-3143h0pleh.pdf

Beck Depression Inventory-IIについての一考察

This paper, which has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association, provides the background for the Standards of Practice Committee's parameters for the practice of sleep medicine in North America. The intent of this paper is to provide an overview of the surgical treatment of obstructive sleep apnea syndrome, to provide the basis for the American Sleep Disorders Association's practice parameters on this subject and to share our findings of metanalysis of previously published studies regarding uvulopalatopharyngoplasty. We searched MEDLINE from January 1966 through April 1993, with an update in February 1995, to provide a review of the application of surgical modifications of the upper airway to treat adults with obstructive sleep apnea syndrome. Operations to treat obstructive sleep apnea syndrome include nasal septal reconstruction; uvulopalatopharyngoplasty; uvulopalatopharyngoglossoplasty; laser midline glossectomy; lingualplasty; inferior sagittal mandibular osteotomy and genioglossal advancement, with hyoid myotomy and suspension (the entire process is referred to as GAHM); maxillomandibular osteotomy and advancement, and tracheotomy. Papers included in metanalysis provided preoperative and postoperative polysomnographic data on at least nine patients treated with uvulopalatopharyngoplasty for their obstructive sleep apnea. Analysis of the uvulopalatopharyngoplasty papers revealed that this procedure is, at best, effective in treating less than 50% of patients with obstructive sleep apnea syndrome. The site of pharyngeal narrowing or collapse, although identified by different and unvalidated methods, has a marked effect on the probability of success of uvulopalatopharyngoplasty. Patients who achieve a favorable response with uvulopalatopharyngoplasty tend to have less severe obstructive sleep apnea than those who do not. For patients who demonstrate retrolingual narrowing or collapse, other surgical modifications have been described, such as lingualplasty, GAHM, and maxillomandibular osteotomy and advancement. The studies to support the use of the surgical treatment of obstructive sleep apnea syndrome contain biases related to small sample size, limited follow-up and patient selection.

The Efficacy of Surgical Modifications of the Upper Airway in Adults With Obstructive Sleep Apnea Syndrome

Background: Narcolepsy usually starts around adolescence; however, there is great variability in the clinical presentation of narcolepsy. Objective: To determine the age at onset in conjunction with severity of narcoleptic symptoms in two large populations of narcoleptic patients with a similar genetic background. Methods: Information on age at onset and severity of the condition was obtained in 317 patients with well-defined narcolepsy–cataplexy from Montpellier (France) and in 202 from Montreal (Canada). Results: The mean age at onset was 23.4 years in Montpellier and 24.4 in Montreal. The age at onset was bimodal in two independent patient populations: a first peak occurring at 14.7 years, and a second peak occurring at 35. Age at onset clearly differentiates patients with a positive family history of narcolepsy (early onset) from those without a family history. Other clinical and polygraphic findings may indicate that young age at onset is associated with increased severity of the condition (higher frequency of cataplexy and decreased mean sleep latency on the Multiple Sleep Latency Test). Conclusion: Bimodal distribution of age at onset of narcolepsy was found in two independent patient populations. Our data suggest that age at onset is genetically determined.

Age at onset of narcolepsy in two large populations of patients in France and Quebec

Objective: To determine the role of CSF hypocretin-1 in narcolepsy with and without cataplexy, Kleine-Levin syndrome (KLS), idiopathic and other hypersomnias, and several neurological conditions. Patients: 26 narcoleptic patients with cataplexy, 9 narcoleptic patients without cataplexy, 2 patients with abnormal REM-sleep-associated hypersomnia, 7 patients with idiopathic hypersomnia, 2 patients with post-traumatic hypersomnia, 4 patients with KLS, and 88 patients with other neurological disorders. Results: 23 patients with narcolepsy-cataplexy had low CSF hypocretin-1 levels, while one patient had a normal hypocretin level (HLA-DQB1*0602 negative) and the other two had intermediate levels (familial forms). One narcoleptic patient without cataplexy had a low hypocretin level. One patient affected with post-traumatic hypersomnia had intermediate hypocretin levels. The KLS patients had normal hypocretin levels while asymptomatic, but one KLS patient (also affected with Prader-Willi syndrome) showed a twofold decrease in hypocretin levels during a symptomatic episode. Among the patients without hypersomnia, two patients with normal pressure hydrocephalus and one with unclear central vertigo had intermediate levels. Conclusion: Low CSF hypocretin-1 is highly specific (99.1%) and sensitive (88.5%) for narcolepsy with cataplexy. Hypocretin ligand deficiency appears not to be the major cause for other hypersomnias, with a possible continuum in the pathophysiology of narcolepsy without cataplexy and idiopathic hypersomnia. However, partial hypocretin lesions without low CSF hypocretin-1 consequences cannot be definitely excluded in those disorders. The existence of normal hypocretin levels in narcoleptic patients and intermediate levels in other rare aetiologies needs further investigation, especially for KLS, to establish the functional significance of hypocretin neurotransmission alterations.

https://jnnp.bmj.com/content/jnnp/74/12/1667.full.pdf

CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions

Background: Kleine-Levin syndrome (KLS) is a rare disorder of unknown etiology. Pathophysiologic hypotheses include a hypothalamic dysfunction and abnormalities in the central serotonin and dopamine metabolism. Several clinical symptoms also suggest an underlying autoimmune process. Objective: To systematically investigate patients with KLS with reference to the available hypotheses. Methods: The authors collected clinical, polysomnographic, CSF, CT, and MRI records and analyzed gene polymorphisms of HLA-DQB1, tryptophan hydroxylase (TpH), and catechol-O-methyltransferase (COMT) in 30 unrelated patients with KLS and their families. The genotype data were contrasted with data from a normal control population. Results: Only human leukocyte antigen (HLA)-DQB1*0201 allele frequency was significantly increased in patients with KLS. Three patients with KLS but none of the control subjects were DQB1*0201 homozygous. Two affected subjects from the same family were DQB1*0201 homozygous. In 17 DQB1*0201 heterozygous parents, 11 (64.7%) had transmitted this allele, suggesting a preferential transmission. Conclusion: These findings, together with the young age at onset, the recurrence of symptoms, and the frequent infectious precipitating factors, suggest an autoimmune etiology for Kleine-Levin syndrome.

Kleine-Levin syndrome An autoimmune hypothesis based on clinical and genetic analyses

Sleep architecture, slow wave activity, and sleep spindles in adult patients with sleepwalking and sleep terrors

Modafinil is a central putative alpha-1 postsynaptic agonist with vigilance-promoting properties. Fifty narcoleptics (33 male and 17 female) participated in a multicentric study aimed at assessing the effects of the compound on night sleep, feeling on awakening, excessive daytime sleepiness and cataplexy. Modafinil was administered in a double-blind cross-over design at a daily dosage of 300 mg versus placebo. The duration of the study was 12 weeks, including a 2-week "run in" period with placebo, a first 4-week treatment period with either modafinil or placebo, a 2-week wash-out period with placebo and a second 4-week treatment period with either placebo or modafinil. Daily evaluation was based on a sleep log, visual analog scales, a sleep questionnaire and a clinical global index. Sleep laboratory evaluation took place on nights 1, 28, 42 and 70. It included 1 night of polysomnography preceded by a questionnaire on therapeutic and side effects, and a maintenance of wakefulness test (MWT). Sleep logs did not show any modification of night sleep, but a reduction of daytime sleepiness and sleep. Feeling on awakening was not modified. An overall benefit was noted by physicians as well as by patients. MWT disclosed a positive effect of modafinil on excessive daytime sleepiness. Cataplexy was not modified.

/pdf/modafinil-a-double-blind-multicentric-study-2xhyigsfi9.pdf

Michel Billiard

Papers

Age at onset of narcolepsy in two large populations of patients in France and Quebec

CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions

Kleine-Levin syndrome An autoimmune hypothesis based on clinical and genetic analyses

Sleep architecture, slow wave activity, and sleep spindles in adult patients with sleepwalking and sleep terrors

Modafinil : a double-blind multicentric study