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Y Dauvilliers

Publications and source records attributed to Y Dauvilliers.

At least 19 recordsLinked to original sources
PubMed2006

EFNS guidelines on management of narcolepsy.

Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.

Advisory Committees↗
PubMed2005

Genetics of normal and pathological sleep in humans.

The complexity of sleep-wake regulation, in addition to the many environmental influences, includes genetic predisposing factors, which begin to be discovered. Most of the current progress in the study of sleep genetics comes from animal models (dogs, mice, and drosophila). Multiple approaches using both animal models and different genetic techniques are needed to follow the segregation and ultimately to identify 'sleep genes' and molecular bases of sleep disorders. Recent progress in molecular genetics and the development of detailed human genome map have already led to the identification of genetic factors in several complex disorders. Only a few genes are known for which a mutation causes a sleep disorder. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental factors, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep and suggest a few future perspectives.

Brain↗
PubMed2005

Aerobic and functional capacities in a selected active population of European octogenarians.

Master athletes are often considered to represent the ideal rate of decline of aerobic function; however, most of the studies interested in active elderly people are often limited to people younger than 75. We aimed to determine the physiological adaptations and aerobic fitness in a selected European population of active octogenarians during maximal and submaximal exercise tests. Aerobic capacity was measured during maximal incremental tests on treadmill (TR) and cycle-ergometer (CE) and functional capacity during a 6-minute walk test (6-MWT) in 17 subjects aged 81.2 +/- 0.8 years. Pulmonary gas exchange and heart rate (HR) were continuously measured during the different exercise tests. Maximal oxygen consumption (V.O (2max)) on TR and CE was significantly higher than predicted values (TR: 28.7 +/- 1.2 vs. 17 +/- 0.5 ml . kg (-1) . min (-1); CE: 23 +/- 1.2 vs. 16 +/- 0.6 ml . kg (-1) . min (-1) for measured and predicted values respectively). V.O (2max) and HR (max), as well as V.O (2) and HR at the ventilatory threshold (V.O (2)T (V.E) and HR T (V.E)) were significantly higher on TR than on CE (HR (max): 144 +/- 4 vs. 138 +/- 4 bpm; V.O (2)T (V.E): 22.5 +/- 0.8 vs. 17.7 +/- 0.9 ml . kg (-1) . min (-1) for TR and CE respectively). V.O (2)T (V.E) and HR T (V.E) on TR were equivalent to V.O (2) and HR measured during the 6-MWT. HR T (V.E) on TR and mean HR during the 6-MWT were strongly correlated (R = 0.82, p < 0.01). Maintenance of regular physical activity provides high aerobic fitness, in octogenarians, as was shown by the higher values of our subjects in comparison to predicted values. Moreover, the close relation between the intensity developed at T (V.E) on TR and 6-MWT could support the idea that a walk test is a submaximal test performed at high intensity that could provide a basis for exercise prescription in an individualized manner in active elderly people.

Adaptation, Physiological↗
PubMed2004

Dissociation in circadian rhythms in a pseudohypersomnia form of fatal familial insomnia.

The authors present clinical, sleep, and neuroendocrine features of a patient with genetically confirmed fatal familial insomnia (D178N mutation with heterozygosity at codon 129 of the prion protein gene). The patient exhibited pseudohypersomnia behavior instead of insomnia. There was profound alteration in the sleep-wake cycle with a clear dissociation in the disappearance of circadian and neuroendocrine rhythms, findings unrelated to abnormalities in the hypocretinergic system.

Adrenocorticotropic Hormone↗
PubMed2004

Effect of age on MSLT results in patients with narcolepsy-cataplexy.

OBJECTIVE: To measure the effect of age on Multiple Sleep Latency Test (MSLT)characteristics, sleep latency, and number of sleep-onset REM periods (SOREMP) in two large populations of narcoleptic patients with similar genetic backgrounds. METHODS: Clinical and polygraphic information on the severity of the condition was obtained on 236 well-defined narcolepsy-cataplexy-human leukocyte antigen DR2-positive patients from Montpellier (France) and on 147 similar patients from Montreal (Canada). RESULTS: The results show a progressive decrease in the number of SOREMP with age and a progressive increase in the mean sleep latency on the MSLT as a function of age. This finding is also related to the severity of cataplexy as assessed from the clinical history with a progressive decrease in the frequency of cataplexy attacks with age. These results may reflect the progressive increase in sleep latency seen in normal aging and suggest that clinical improvement might be due to changes in the neural mechanisms responsible for SOREMP, which may weaken with age. CONCLUSIONS: The progressive decrease in the number of SOREMP and increase in the mean sleep latency on the MSLT as a function of age suggest that the current criteria used for diagnosis may be too stringent in older patients. The major influence of age on MSLT results should therefore be taken into account when diagnosing a narcoleptic patient.

Adolescent↗
PubMed2003

Sleep architecture, slow wave activity and sleep spindles in mild sleep disordered breathing.

OBJECTIVE: A high degree of sleep fragmentation by arousals related to respiratory events would result in an abnormal distribution of slow wave activity (SWA) and a decrease in sleep spindle density in sleep disordered breathing (SDB) patients when compared to controls. METHODS: Eighteen mild SDB subjects (6 females and 12 males), aged 18-56 years with (5<respiratory disturbance index (RDI)<30/h) were compared to 18 controls (11 female and 7 male) aged 18-52 years. The sleep EEG power density was performed using fast Fourier transform (FFT) analysis and sleep spindle density integrated digital filtering analysis (IDFA). Esophageal pressure monitoring was performed on the third night. RESULTS: Sleep analysis showed a significant higher number of awakenings <1 min and arousal indexes in total sleep time, in non-REM (NREM) sleep and in slow wave sleep (SWS) than in controls. SWA and theta band decreased significantly from the first to the fourth cycle in both subjects. Theta and sigma bands were significantly lower in patients than in controls, in each sleep cycle and during the whole night. Moreover, the temporal course of SWA showed an exponential decay in both patients and controls but the time constant of the curve was significantly slower in patients than in controls. Furthermore, in both groups, the sleep spindle index was significantly lower in both SWS and stage 2 in patients than in controls. CONCLUSIONS: Sleep architecture in mild SDB subjects is characterized by a high degree of sleep fragmentation resulting in a different time course of SWA and a decreased sleep spindle index when compared to controls.

Adolescent↗
PubMed2003

HLA and genetic susceptibility to sleepwalking.

HLA-DQB1 typing was performed in 60 Caucasian subjects with sleepwalking (SW) disorder and their families and 60 ethnically matched subjects without any diagnosed sleep disorder. A total of 21 sleepwalkers (35.0%) were DQB1*0501 positive vs eight (13.3%) controls (P = 0.0056; odds ratio = 3.5, 95% CI = 1.4-8.7). The family data for all HLA subtypes were further assessed for allelic association with SW using the transmission-disequilibrium test. A significant excess transmission was observed for DQB1*05 and *04 alleles in familial cases, strongly suggesting that a DQB1 polymorphic amino acid might be more tightly associated than any single allele. Sequence screening revealed that Ser74 in the second exon shared by all DQB1*05 and *04 was 20 times transmitted against 4 times non-transmitted (P = 0.001) in familial cases of SW. Thus, together with narcolepsy and REM sleep behavior disorder, these findings suggest that specific DQB1 genes are implicated in disorders of motor control during sleep.

Adolescent↗
PubMed2003

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

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.

Adolescent↗
PubMed2003

[Neurodegenerative, autoimmune and genetic processes of human and animal narcolepsy].

Narcolepsy is a rare disabling sleep disorder whose main features are excessive daytime sleepiness and cataplexy. Human narcolepsy is most frequently a sporadic disorder with both genetic and environmental factors playing a role in its pathophysiology. Implication of the hypocretin system is well-established: as mutations in both canine and murine narcolepsies and as a consistent reduction in hypocretin neuron in human narcolepsy. The cause of human narcolepsy remains unknown. However degenerative, autoimmune and/or genetic processes are the most probable causes of the hypocretin neurons loss. Acting on a specific genetic background, an autoimmune process with hypocretin neuron degeneration, in response to environmental factors, is the most probable hypothesis for most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest association with a specific HLA antigen (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. Monoaminergic, immune (TNF alpha) and hypocretinergic systems seem to be involved and may interfere with the phenotype. Treatment has not evolved significantly over the last few years. However, new drugs, such as hypocretin agonists, are currently being developed.

Animals↗
PubMed2002

Kleine-Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses.

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.

Adolescent↗
PubMed2002

Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil.

The gene for catechol-O-methyltransferase (COMT) plays a key modulatory role in dopaminergic and noradrenergic neurotransmission. Recent evidence suggests that modafinil, like other stimulants, might act through the dopaminergic system. We have reported a sexual dimorphism and a strong effect of the COMT genotype on narcolepsy symptoms and hypothesized that response to modafinil treatment may be associated with the COMT genotype. Here we confirm that COMT genotype distribution between men and women narcoleptics is associated with response to modafinil. In addition, the optimal daily dose of modafinil is approximately 100 mg lower in women narcoleptics and lower in all narcoleptics with low activity COMT genotype. Our results suggest that a sexual dimorphism in COMT activity affects the response to modafinil and probably to other dopaminergic stimulants.

Adolescent↗
PubMed2001

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

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.

Adolescent↗
PubMed2001

[Sleep in fibromyalgia: review of clinical and polysomnographic data].

Fibromyalgia syndrome is a common chronic pain syndrome that is often associated with sleep disturbances characterized by subjective experience of non-restorative sleep. The complaints of sleep disturbances are correlated with polysomnographic features showing clear abnormalities in the continuity of sleep as well as in the sleep architecture. Sleep-recording abnormalities are characterized by a reduced sleep efficiency with increased number of awakenings, a reduced amount of slow wave sleep and an abnormal alpha wave intrusion in non rapid eye movement, termed alpha-delta sleep. These data were confirmed by spectral analysis of sleep showing an increased EEG power density in the higher frequency band and a reduced EEG power density in the lower frequency bands. Moreover, other microstructural aspects of sleep were modified with high frequency of arousals and alpha-K complex reported, both indicators of fragmented sleep. The fibromyalgia symptoms may relate to a non-restorative sleep disorder associated with the alpha-EEG sleep anomalies. However, alpha-EEG sleep anomaly is non-specific for fibrositis, also seen in normal controls during stage 4 sleep deprivation. Moreover, fibromyalgia patients may also experience primary sleep disorder such as sleep apnea or periodic leg movements. The etiology of this common condition is incompletely understood and the existence of a specific entity of fibromyalgia is still a matter of debate. However, several studies have found abnormal brain metabolism of substances such as serotonin implicated in sleep arousal and pain mechanisms and administration of tricyclic antidepressants and selective serotonin reuptake inhibitors may be useful in fibromyalgia. Pain, poor sleep quality and anxiety may contribute to the clinical picture. Several factors such as psychological, environmental, genetic factor, altered serotonin metabolism and altered sleep physiology are involved in the pathogenesis of fibromyalgia.

Adult↗
PubMed2001

MAO-A and COMT polymorphisms and gene effects in narcolepsy.

Narcolepsy presents one of the tightest associations with a specific HLA antigen (DQB1*0602) but there is strong evidence that non-HLA genes also confer susceptibility. Recent observations have implicated the hypocretin/orexin system in narcolepsy in both humans and animals. In addition, the implication of monoaminergic systems in the pathophysiology of narcolepsy is well established and a significant association between the monoamine oxydase-A (MAO-A) gene and human narcolepsy has recently provided a possible genetic link. We investigated polymorphisms of MAO-A and catechol-O-methyltransferase (COMT) in 97 Caucasians with well-defined narcolepsy-cataplexy and sought for genotypic effects on disease symptoms. No evidence of association between genotype or allele frequencies of both MAO-A or COMT gene and narcolepsy was found. However, a sexual dimorphism and a strong effect of COMT genotype on disease severity were found. Women narcoleptics with high COMT activity fell asleep twice as fast as those with low COMT activity during the multiple sleep latency test (MSLT) while the opposite was true for men. COMT genotype also strongly affected the presence of sleep paralysis and the number of REM sleep onsets during the MSLT. In agreement with well-documented pharmacological results in canine narcolepsy, this study reports the first genetic evidence for the critical involvement of the dopaminergic and/or noradrenergic systems in human narcolepsy.

Cataplexy↗
PubMed2001

Idiopathic Hypersomnia.

In contrast to narcolepsy and the Kleine-Levin syndrome, idiopathic hypersomnia is a recently described sleep disorder. Absence of associated clinical features such as cataplexy or megaphagia and characteristic polysomnographic features such as sleep-onset REM episodes render positive diagnosis more uncertain in idiopathic hypersomnia than in the fwo former conditions. Consequently there has been an unfortunate tendency to label all difficult to classify cases of excessive daytime sleepiness as idiopathic hypersomnia. At present due to the description of new disorders such as upper airway resistance syndrome, narcolepsy without cataplexy, delayed sleep phase syndrome, all of which were formerly confused with idiopathic hypersomnia and the clear identification of a "polysymptomatic" or "classic" form of idiopathic hypersomnia, the limits of the disorder become more precise. Still there are a number of cases of isolated excessive daytime sleepiness with no prolonged night sleep, no difficulty waking up, which lay between narcolepsy and genuine idiopathic hypersomnia. Thus there is a definite need to further develop laboratory investigations to help identify and classify these cases. Moreover pathophysiology and pathogenesis are still in their infancy and efforts have to be pursued in this direction. Treatment has not made consistent progress except for the use of a new wake promoting compound, modafinil, which has not yet been evaluated in controlled studies.

Journal Article↗