Biomedical subjects

Jacques Montplaisir

Publications and source records attributed to Jacques Montplaisir.

At least 37 records · Page 2Linked to original sources

PubMed2005

Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.

BACKGROUND: Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder. OBJECTIVES: To replicate and to further characterize our previously reported chromosome 12q linkage results. DESIGN: Family linkage study. SETTING AND PARTICIPANTS: A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on chromosome 12q. RESULTS: Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at theta = 0.10; for marker D12S1636; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304. Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families. CONCLUSIONS: These results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.

Chromosome Mapping↗

PubMed2005

Slow-wave sleep and delta power in rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss of normal muscle atonia during REM sleep, leading to an increase of phasic muscle activity and complex motor behaviors during the night. There is some evidence that RBD patients have more of slow-wave sleep (SWS) than healthy elderly subjects. No study has looked at quantitative electroencephalogram analysis during non-REM sleep in either primary or secondary RBD. The aim of this study was to assess the increase of SWS and to analyze different electroencephalographic frequency ranges during non-REM sleep in 28 idiopathic RBD patients compared with 28 age- and sex-matched healthy volunteers. Idiopathic RBD patients spent more time in SWS (men: 1.4%; women: 5.9%) than control subjects (men: 0.4%; women: 0.6%; p = 0.004). Spectral analyses demonstrated that idiopathic RBD patients had increased all-night delta power in comparison with control subjects (p = 002). This study shows an increase of SWS and power in the delta band during non-REM sleep in idiopathic RBD patients compared with control subjects. Results are discussed about the possible nigrostriatal dopaminergic impairment in RBD patients and the association between RBD and neurodegenerative disorders.

Aged↗

PubMed2005

Effects of periodic leg movements during sleep in middle-aged subjects without sleep complaints.

Recent reports have called into question the relevance of periodic leg movements during sleep disorder (PLMSD) as a specific clinical entity. Because periodic leg movement in sleep index (PLMSI) increases with age, it has become an important exclusion criterion in research on aging. However, it is unknown if PLMSI is related to sleep quality in middle-aged subjects without sleep complaints. The sleep of 70 healthy, middle-aged subjects (age 40 to 60 years) without sleep complaints was evaluated. Subjects were divided into two groups according to their PLMSI severity: (1) 43 subjects (28 women, 15 men) were in the low PLMSI group (<5) and (2) 22 subjects (9 women, 13 men) were in the high PLMSI group (>10). A significantly higher proportion of men than women showed PLMSI greater than 5. There was no significant effect of PLMSI severity group for polysomnographic sleep parameters. PLMSI exerted a small but significant effect on subjective sleep quality, especially in middle-aged men. These results raise questions about the relevance of PLMSI as a pathological index for middle-aged subjects without sleep complaints and support the notion that an increase in PLMSI may be part of the normal process of aging associated with the loss of dopaminergic function.

Adult↗

PubMed2005

Circadian variation of the effects of immobility on symptoms of restless legs syndrome.

STUDY OBJECTIVES: It is now well established that symptoms of restless legs syndrome (RLS) are worsened by immobility and that their severity fluctuates according to a circadian pattern with a maximum occurring in the late evening or during the night. However, no study has ever attempted to dissociate these two effects. The objective of this study was to evaluate the nycthemeral variations in the effects of duration of immobility on symptoms of RLS. DESIGN: A 28-hour modified constant routine protocol. SETTING: Sleep Disorders Center, Montreal Sacré-Coeur Hospital. PARTICIPANTS: Seven patients with primary RLS (3 men, 4 women; mean age: 43.9 years) and seven controls matched for age (42.4 years) and gender. INTERVENTION: None. MEASUREMENTS AND RESULTS: A 40-minute Suggested Immobilization Test (SIT) was repeated every 2 hours during the 28-hour protocol in order to quantify both subjective leg discomfort and periodic leg movements (PLM). Regarding leg discomfort, a two-way ANOVA performed on patients' data revealed a significant interaction (p = 0.037) between Time within the SIT and Time of day. Simple effect analyses performed to decompose the interaction showed that the increase in leg discomfort with duration of immobility was found only on SIT 7, 8, 9, 10 and 12, which corresponds to the period between 21:20 and 08:00. In addition, in patients, a significant circadian variation (p < 0.01) was found for the 28-hour profiles of leg discomfort progression during the SIT. No interaction or Time within the SIT effect was found for controls. CONCLUSIONS: These results show that worsening of RLS symptoms by immobility is closely linked to their intrinsic circadian variation.

Adult↗

PubMed2004

A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy.

STUDY OBJECTIVES: To measure the effect of nocturnal sodium oxybate administration on sleep architecture in patients with narcolepsy. DESIGN: Open-label study. SETTING: Four accredited sleep clinics. PARTICIPANTS: 25 adult patients with narcolepsy-cataplexy. INTERVENTIONS: Patients were weaned from previously used anticataplectic medications and administered increasing nightly doses of sodium oxybate over a 10-week period: 4.5 g for 4 weeks, 6 g for 2 weeks, 7.5 g for 2 weeks, and 9 g for 2 weeks. The effect of sodium oxybate was measured using nocturnal polysomnograms, the Epworth Sleepiness Scale, the Maintenance of Wakefulness Test, and a narcolepsy symptoms questionnaire. RESULTS: The nightly administration of sodium oxybate produced dose-related increases in slow-wave sleep and delta power, rapid eye movement sleep increased initially and then decreased in a dose-related manner, nocturnal awakenings decreased, and daytime sleep latency increased. Significant improvements in daytime symptoms were measured by the Maintenance of Wakefulness Test, the Epworth Sleepiness Scale, and the narcolepsy symptom questionnaire. CONCLUSIONS: Nocturnal administration of sodium oxybate in patients with narcolepsy produces significant improvements in sleep architecture, which coincide with significant improvements in daytime functioning.

Adjuvants, Anesthesia↗

PubMed2004

Circadian rhythm of restless legs syndrome: relationship with biological markers.

Recently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28-hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night.

Adult↗

PubMed2004

Mutational analysis of neurotensin in familial restless legs syndrome.

A susceptibility locus for restless legs syndrome (RLS) has been identified recently on chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in chromosome 12-linked families.

5' Untranslated Regions↗

PubMed2004

Sleep and quantitative EEG in neurodegenerative disorders.

This paper reviews current knowledge on sleep problems, sleep architecture changes and quantitative EEG alteration brought on by various neurodegenerative diseases, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), REM sleep behavior disorder (RBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy MSA, Huntington's disease and Creutzfeldt-Jakob disease, in comparison to normal aging. The study of sleep variables and that of the spectral composition of the EEG can provide valuable information for understanding the pathophysiology and for assisting the diagnosis of neurodegenerative diseases.

Aged↗

PubMed2004

Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study.

OBJECTIVES: To assess the frequency, impact, and medical response to the restless legs syndrome (RLS) in a large multi-national primary care population. METHOD: Questionnaire surveys of matched patients and primary care physicians (PCPs) in five modern industrialized western countries. RESULTS: An RLS screening questionnaire was completed by 23,052 patients: 2223 (9.6%) reported weekly RLS symptoms; 1557 of these patients had medical follow-up questionnaires completed both by themselves and by their physician. An RLS sufferer subgroup (n=551) likely warranting treatment was defined as reporting at least twice weekly symptoms with appreciable negative impact on quality of life. A total of 88.4% of RLS sufferers reported at least one sleep-related symptom. Most reported impaired sleep consistent with a diagnosis of insomnia. Out of 551 sufferers, 357 (64.8%) reported consulting a physician about their RLS symptoms, but only 46 of these 357 (12.9%) reported having been given a diagnosis. PCPs reported that 209 (37.9%) RLS sufferers consulted them about RLS symptoms, but only 52 (24.9%) were given an RLS diagnosis. In most countries, sufferers, regardless of diagnosis, were prescribed therapies not known to be effective in RLS. CONCLUSIONS: RLS significantly impairs patients' lives, often by severely disrupting sleep. The marked under-diagnosis and inappropriate treatment of RLS indicates that PCPs need better education about this condition. Recognizing how often disrupted sleep results from RLS should improve diagnosis.

Drug Therapy↗

PubMed2004

Abnormal motor behavior during sleep.

Abnormal motor behaviors during sleep can be classified into four categories, ranging from myoclonic jerks to complex and integrated motor behaviors There have been recent developments in several of these conditions, in particular restless legs syndrome (RLS) and rapid-eye-movement sleep behavior disorder (RBD). RLS is one of the major causes of insomnia. Familial aggregation of RLS has been demonstrated by several groups, and molecular genetics studies have suggested the presence of susceptibility genes on chromosomes 12q and 14q. Pharmacologic and brain imaging studies suggest the involvement of dopaminergic mechanisms in RLS, but recent work has focused on brain iron metabolism. Studies indicate that RBD patients may eventually develop Parkinson's disease (PD). Conversely, RBD has been found in patients already diagnosed with PD. Single-photon emission computed tomography and positron emission tomography studies have shown a decrease in binding to presynaptic dopamine transporter in both idiopathic RBD and PD. Patients with RBD (associated or unassociated with PD) also have neuropsychological deficits. RBD may therefore represent the prodrome of a neurodegenerative disease leading to multiple system atrophy and Lewy body dementia. Understanding the underlying pathophysiology of abnormal sleep motor behaviors may prove useful in the management of insomnia.

Brain↗

PubMed2004

Sleep complaints in patients with myotonic dystrophy.

The aim of this study was to document the clinical picture of excessive daytime sleepiness (EDS) and of other sleep disturbances, and to study the relationship of daytime sleepiness to anthropometric data, muscular impairment, and CTG trinucleotide repeat expansion in myotonic dystrophy type 1 (DM1). A total of 157 DM1 patients were surveyed using a modified version of the Sleep Questionnaire and Assessment of Wakefulness. Other measurements included muscular impairment rating and the size of the trinucleotide repeat. Factor analysis and reliability estimates were used to produce a daytime sleepiness scale with five items of the questionnaire. Thirty-eight healthy family members were studied as control subjects. It was found that EDS was present in 33.1% of DM1 patients. Severity of daytime sleepiness correlated with the degree of muscular impairment but not with age, gender, body mass index, age at onset of symptoms, duration of illness, and CTG repeat. DM1 patients reported a longer sleep period, a less restorative sleep, and more difficulty falling asleep, being alert in the morning and staying awake after meals than controls, but a similar incidence of narcolepsy auxiliary symptoms. Compared with DM1 patients without EDS, those with EDS reported greater hypnagogic hallucinations, and greater pain associated with nocturnal awakenings and in their legs upon morning awakenings. In sum, both DM1 patients with and without EDS exhibit characteristics of sleep duration and sleepiness comparable with those found in idiopathic hypersomnia. The severity of daytime sleepiness is weakly related to the extent of muscular impairment but not to CTG repeat.

Adult↗

PubMed2004

Analysis of postarousal EEG activity during somnambulistic episodes.

Early studies found that electroencephalographic (EEG) recordings during somnambulistic episodes were characterized by a combination of alpha, theta, and delta frequencies, without evidence of clear wakefulness. Three postarousal EEG patterns associated with slow-wave sleep (SWS) arousals were recently identified in adults with sleepwalking and sleep terrors. The goal of the present study was to evaluate the distribution of these postarousal EEG patterns in 10 somnambulistic patients (three males, seven females, mean age: 25.1, SD: 4.1) evaluated at baseline and following 38 h of sleep deprivation. A total of 44 behavioral arousals were recorded in the laboratory; seven episodes at baseline (five from SWS, two from stage 2 sleep) and 37 episodes during recovery sleep (30 from SWS, seven from stage 2 sleep). There was no significant difference in the distribution of postarousal EEG patterns identified during baseline and recovery sleep. One pattern, comprised of diffuse rhythmic and synchronous delta activity, was preferentially associated with relatively simple behavioral episodes but did not occur during episodes from stage 2 sleep. Overall, delta activity was detected in 48% of the behavioral episodes from SWS and in 22% of those from stage 2. There was no evidence of complete awakening during any of the episodes. The results support the view of somnambulism as a disorder of arousal and suggest that sleepwalkers' atypical arousal reactions can manifest themselves in stage 2 sleep in addition to SWS.

Adult↗

PubMed2003

Analysis of CAG repeat expansions in restless legs syndrome.

STUDY OBJECTIVES: A relatively high prevalence of restless legs syndrome symptoms has been recently reported in a substantial proportion of patients affected with spinocerebellar ataxia type 3. Our aim was to investigate whether there is a common genetic etiology between restless legs syndrome and spinocerebellar ataxia type 3. DESIGN: Systematic differences in the number of spinocerebellar ataxia type 3 trinucleotide repeat were investigated by means of an association study. The relationship between the size of the expanded alleles and several clinical features was also considered. PARTICIPANTS AND SETTING: 125 extensively characterized restless legs syndrome patients compared with 188 healthy controls matched for ethnic background. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No CAG repeat expansions in the pathologic or intermediate range were detected in any of the examined subjects, including patients and controls. A similar allelic distribution was observed in both groups (Mann-Whitney U test = 78406; P = 0.99). Moreover, stratification analyses of the patients' samples according to different clinical and polysomnographic variables disclosed no significant differences. CONCLUSIONS: These results do not provide evidence toward an involvement of large CAG trinucleotide expansions at the spinocerebellar ataxia type 3 locus in idiopathic restless legs syndrome.

Female↗

PubMed2003

Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene.

BACKGROUND: Infantile and juvenile forms of Alexander disease are well characterized and are caused by de novo mutations in the glial fibrillary acid protein (GFAP) gene. In contrast, the adult form of the disease has been rarely described, and the etiology of this variant remains unknown. OBJECTIVE: To characterize the clinical phenotype and identify the gene causing an autosomal dominant form of adult Alexander disease. METHODS: We identified a large kindred segregating clinical features compatible with adult Alexander disease in an autosomal dominant fashion. A neurological examination was performed on all affected members of this family. Most of these patients also underwent magnetic resonance imaging of the brain and a polysomnographic study. The diagnosis was confirmed pathologically in 2 individuals. We screened all coding regions of the GFAP gene in affected individuals by means of direct sequencing and single-stranded conformational polymorphisms analysis. RESULTS: We found a novel D78E mutation in GFAP in all affected individuals. This mutation was not detected in more than 100 control subjects. Clinical and radiological features of affected individuals were clearly different from those of patients with the infantile and juvenile forms of the disease. The most consistent finding was the presence of bulbar signs. In addition, sleep disturbance (mainly sleep apnea), symptoms of dysautonomia, and dysmorphism were found in all affected individuals. In younger patients, magnetic resonance imaging showed T2 signal abnormalities in the medulla compatible with an area of demyelination. In contrast, in older patients, we found marked atrophy of the medulla without signal abnormalities. None of the affected individuals exhibit signs of demyelination of the cerebral white matter. CONCLUSIONS: The present study is the first demonstration of a mutation in GFAP that causes an autosomal dominant form of Alexander disease and establishes the existence of the adult variant. Clinical evaluation in individuals carrying mutation in the GFAP gene allowed a better definition of this heterogeneous clinical syndrome and will help increase its recognition in neurological practice.

Adult↗

PubMed2003

Slowing of electroencephalogram in rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a loss of atonia and an increase in phasic muscle activity during REM sleep, leading to complex nocturnal motor behaviors. Brainstem structures responsible for the pathogenesis of RBD are also implicated in cortical activation. To verify the hypothesis that electroencephalogram (EEG) activation will be impaired in RBD, we performed quantitative analyses of waking and REM sleep EEG in 15 idiopathic RBD patients and 15 age- and gender-matched healthy subjects. During wakefulness, RBD patients showed a considerably higher theta power in frontal, temporal, and occipital regions with a lower beta power in the occipital region. The dominant occipital frequency was significantly lower in RBD. During REM sleep, beta power in the occipital region was lower in RBD. This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls. EEG slowing in these patients may represent an early sign of central nervous system dysfunction, perhaps paralleled by subclinical cognitive deficits. The topographical distribution of EEG slowing and possible pathophysiological mechanisms are discussed in light of the known association between RBD and neurodegenerative disorders.

Aged↗

PubMed2003

Clinical aspects and pathophysiology of narcolepsy.

UNLABELLED: Narcolepsy is a chronic debilitating sleep disorder first described in the late 19th century. It is characterized by two major symptoms, excessive daytime sleepiness and cataplexy, and two so-called auxiliary symptoms, hypnagogic hallucinations and sleep paralysis. The final diagnosis relies on polysomnography showing the presence of sleep onset rapid eye movement periods (SOREMPs) during the multiple sleep latency test. The presence of HLA DQA1*0102-DQB1*0602 is supportive of the diagnosis. The pathophysiology of the disorder is still unknown but an imbalance between monoamines and acetylcholine is generally accepted. Recent findings in narcoleptic dogs, a natural model of narcolepsy, and in knockout mice revealed that a mutation of type 2 hypocretin receptor plays a major role in the etiology of narcolepsy. Up to now, no mutation has been found in humans except a case of early onset and atypical narcolepsy. However, a marked reduction of hypocretin type 1 has been found in the cerebrospinal fluid (CSF) of a majority of patients and a global loss of hypocretins was noted in post-mortem brain tissue of narcoleptic subjects. Conversely, no hypocretin neuron degeneration has been observed in the genetic form of narcolepsy in dogs but no trace of hypocretin was seen in the brain or the CSF in cases of sporadic canine narcolepsy. This suggests that different hypocretinergic mechanisms are involved in sporadic and genetic forms of canine narcolepsy. Treatment has not evolved significantly over the last few years. However, new drugs, such as hypocretin agonists, are currently being developed. SIGNIFICANCE: After the discovery of the type 2 hypocretin receptor mutation in canine narcolepsy and the finding of a CSF hypocretin-1 deficiency in human narcolepsy, the major stream of research has involved the hypocretinergic system. However, other lines of research deserve to be pursued simultaneously, in view of comprehensive advancements in the understanding of narcolepsy.

Animals↗

PubMed2003

Month of birth as a risk factor for narcolepsy.

STUDY OBJECTIVES: A loss of hypocretin neurons has been observed in human narcolepsy; however, the cause of this disorder is still unknown. While family history and genetic factors are important individual risk factors for narcolepsy, environmental factors also contribute to the pathogenesis of the disease. The aim of the study was to find out whether there is a seasonality of month of birth in narcoleptic patients. DESIGN: Diagnosis of narcolepsy with cataplexy was based on International Classification of Sleep Disorders criteria with clinical, standard polysomnographic, and Multiple Sleep Latency Test features. PATIENTS AND SETTING: The birth dates of 886 patients with a clear-cut diagnosis of narcolepsy with cataplexy from 3 large narcolepsy databases (352 from Montpellier-France, 157 from Montreal-Canada, and 377 from Stanford-United States of America) were compared with those of 35,160,522 subjects from the general population. MEASUREMENTS AND RESULTS: Patients with narcolepsy had a significantly different seasonality of month of birth compared to that of the general population. The monthly distribution of birth yielded a peak in March with a maximal odds ratio at 1.45 and a trough in September with a minimal odds ratio at 0.63. No gender or country of origin differences were observed. CONCLUSIONS: A birth seasonality in the development of narcolepsy suggests the presence of environmental factors acting in combination with genetic factors during the fetal or perinatal period, in terms of an autoimmune process targeting the hypocretin system.

Birth Rate↗

PubMed2002

Procedural skill learning in obstructive sleep apnea syndrome.

STUDY OBJECTIVES: To better characterize the cognitive deficits observed in obstructive sleep apnea syndrome (OSAS) by examining procedural skill learning abilities. DESIGN: Procedural skill learning was assessed using Mirror Tracing and Rotary Pursuit skill learning tasks. Subjects also completed a comprehensive neuropsychological test battery. SETTING: Cognitive testing was performed during the day following the second of two consecutive nights during which sleep and respiratory variables were recorded. PARTICIPANTS: Two groups (28 OSAS patients and 18 normal controls) with equivalent mean age and education levels. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No significant differences in learning rates were observed between the groups on the Rotary Pursuit Task. On the Mirror Tracing Task, overall learning of the skill and transfer to a new figure or to the reverse tracing direction was similar in the OSAS and NC groups. However, there was a subgroup of OSAS subjects (n=11) who showed marked difficulties in the initial acquisition of the Mirror Tracing Task. This subgroup's performance was no longer significantly different from that of controls and OSAS subjects without initial adaptation difficulty in the subsequent trials. Performance of subjects who had difficulty with initial adaptation on the Mirror Tracing was also significantly lower on tests of frontal executive function, but not on episodic memory tests. Sleep and respiratory variables did not distinguish between the two subgroups of OSAS patients. However, none of the young OSAS subjects (<40 years) presented this deficit. CONCLUSION: Results indicate that contrary to this study's hypothesis, OSAS patients did not show procedural skill learning deficits. A subgroup of OSAS patients, however, did show deficits in initial skill adaptation and difficulties on other neuropsychological tests. Frontal dysfunction and decrement in psychomotor efficiency and vigilance appeared to be the most consistent explanation for characterizing the profile of neuropsychological test results among the OSAS patients.

Adult↗