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Biomedical subjects

M Billiard

Publications and source records attributed to M Billiard.

At least 19 recordsLinked to original sources
PubMed2006

EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep.

In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short-term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.

Advisory Committees↗
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↗
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

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↗
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

[Staphylococcal toxic syndrome, atypical presentation of Kawasaki syndrome or staphylococcal skin syndrome?].

CASE REPORT: A three-year-old girl was admitted for persistent fever, erythermatous rash with subsequent desquamation, stomatitis, cheleitis and cervical lymphadenopathy following development of a buttock abscess secondary to an insect bite. A TSS-positive Staphylococcus aureus strain was isolated from the abscess. COMMENTS: Both clinical and bacteriological features led to discuss a "toxic shock syndrome without shock", an atypical form of Kawasaki syndrome without thrombocytosis and coronary arteritis or a staphylococcal skin syndrome. An early treatment with antibiotics could have limited the toxin production explaining both symptomatology and favourable course of the disease.

Abscess↗
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

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↗
PubMed2001

[Disorders of awakening. Second part: secondary disorders].

Secondary disorders of awakening should be distinguished from primary disorders, narcolepsy, idiopathic hypersomnia, recurrent hypersomnia, the causes of which are still unknown despite regular progress in the knowledge of the pathophysiology of narcolepsy. By definition secondary disorders of awakening are due to clearly identified causes of various origins. Two main types of secondary disorders of awakening have been distinguished: those depending on more or less voluntary sleep curtailment or on psychotropic or non psychotropic medications and those consecutive to different disorders, respiratory, neurologic, traumatic, psychotropic, infectious, metabolic, endocrinologic, and insomnia. Some of these disorders, frequent or very frequent, are polysomnographically investigated, night and day, enabling to assess in each case the type and severity of sleepiness. Others are only clinically evaluated. Disorders of awakening secondary to neurologic conditions and to a lesser extent to infectious conditions offer a special opportunity to study the anatomical basis of these disorders. They are granted more space.

Alzheimer Disease↗
PubMed2001

[Physiopathology of idiopathic hypersomnia. Current studies and new orientations].

In 1976 Bedrich Roth coined the term "idiopathic hypersomnia" and described two forms of the disease, one monosymptomatic, manifested only by excessive daytime sleepiness, and one polysymptomatic, characterized by excessive daytime sleepiness, nocturnal sleep of abnormally long duration and signs of "sleep drunkenness" on awakening. In comparison with that of narcolepsy, the pathophysiology of idiopathic hypersomnia remains poorly known. There are two main reasons for that: the absence of clinical and polysomnographic criteria pathognomonic or at least characteristic of the condition, as the cataplexies and the sleep onset REM periods of narcolepsy, and also the absence of a natural animal model comparable with the canine model of narcolepsy. The first investigations have stressed the frequent familial pattern of idiopathic hypersomnia. Later on biochemical assays have been performed in the CSF with results in favour of a dysfunction of noradrenergic systems. In the light of the two process model of sleep regulation in which sleep propensity is determined by a homeostatic process S and a circadian process C and of the later three-process model of regulation in which sleepiness/alertness are simulated by the combined action of a homeostatic process, a circadian process and sleep inertia, we suggest that idiopathic hypersomnia is not a pathological entity in itself, but rather the consequence of chronic sleep deprivation in very long sleepers.

Arousal↗