Biomedical subjects
Publications and source records attributed to M Billiard.
A meningoencephalitis Behçet's disease revealing is reported. Magnetic resonance imaging is more sensitive than computerized tomography in detecting encephalitic lesions. However, no specific pattern may be retained. This exploration is non invasive and can be used to monitor the evolution after treatment.
Since the discovery of an almost 100% association of HLA-DR2 with narcolepsy-cataplexy, many efforts have been made to demonstrate the intervention of immune factors in the pathogeny of the disease. Some epidemiological features could support this hypothesis: age of onset around 25, triggering factors, association with multiple sclerosis. Molecular studies at the DNA level have, up to now, failed to uncover an abnormal gene in the HLA system, which would imply that the DR2 antigen acts through its role in the immune response. However, results have been largely inconclusive as far as classical features of autoimmunity in blood and CSF are concerned. In canine narcolepsy, a linkage with a human immunoglobulin-related gene has recently been shown, and may constitute a counterpart of the HLA association in man. Thus, the hypothesis of a transient and discrete autoimmune aggression may be ruled out.
CNS stimulants are the most widely used drugs to treat narcolepsy which is characterized by the excessive daytime sleepiness and typically associated with cataplexy. However, a number of side effects may often arise with this therapeutic approach. Thus, investigating new drugs which are efficient but well tolerated is of utmost importance in the treatment of narcolepsy. Although modafinil, an alpha-1 adreno-receptor agonist, has been reported to bring substantial awakening properties in animals, the studies performed in man, particularly in narcoleptic subjects, are few. In the present study, we evaluated the effects of a 300 mg daily dose of modafinil on sleepiness and psychomotor performance of 16 narcoleptic subjects. The major effect of modafinil in narcoleptic subjects was a decrease of daytime sleepiness and corresponding improvement of performances involving attentive functions. However, the learning effect in psychomotor tests may mask the drug effect.
The upper airway cross-sectional areas were studied with pharyngeal computed tomography (CT) at the nasopharyngeal, velopharyngeal, tongue base and hyoid bone levels in 119 consecutively investigated patients with a snoring complaint. According to their findings in an all-night static charge sensitive bed (SCSB) recording, the subjects were divided into four equally sized groups with increasing severity of nocturnal breathing disturbance. The body mass index (BMI) increased and the minimal cross-sectional area at the velopharyngeal level decreased consistently as a function of the severity of nocturnal breathing disturbance. The minimal cross-sectional area at the hyoid bone level showed a biphasic trend, with an initial decrease but a final increase, as the degree of nocturnal breathing disturbance aggravated. The results contradict the idea of gradually increasing anatomical narrowing of the upper airways in general as the nocturnal breathing disturbance exacerbates and support the concept of two anatomically determined entities of partial and complete upper airway obstruction during sleep.
Data from the literature about plasma and CSF amino acid (AA) levels in amyotrophic lateral sclerosis (ALS) remain controversial. To refine such analyses we used HPLC, and report a study of plasma and CSF AA concentrations in patients with ALS, the type of the disease (spinal and bulbar onset) being precisely determined. In ALS, there is a decrease in the plasma levels of the large neutral amino acids (LNAA) alanine, isoleucine, leucine, methionine and tyrosine which was particularly striking in the bulbar type (p < 0.05). Plasma glutamate levels do not differ between ALS and controls, but are significantly increased in ALS with spinal onset and decreased in the bulbar type (p < 0.05 vs controls, p < 0.001 bulbar vs spinal). In CSF, the analysis of the whole ALS group shows no difference from controls. However, there is an increase of CSF serine, glutamine and alanine in ALS with spinal onset (p < 0.05). Our results do not support an abnormal profile of excitatory AA concentrations in ALS. The heterogeneous changes we observed, mainly concerning LNAAs, may be explained by a blood-CSF barrier disturbance in the disease. As AA levels clearly differ between ALS types, with low concentrations in bulbar ALS, this dual profile probably explains some of the discrepancies between previous studies.
Polygraphic exploration during sleep using cystomanometry was performed in 20 patients aged 7-17 years with primary (17) or secondary (3) enuresis. In this group of patients, 9 presented with isolated nocturnal enuresis while 11 patients had associated diurnal micturition troubles. During this study we documented 24 episodes of enuresis. There was no disturbance in sleep architecture or correlation between the uncontrolled micturition and any particular state or stage of sleep. Most episodes of enuresis occurred in a unique pattern in which a sudden or progressive intravesical increased pressure was associated with an awakening reaction. From a physiopathologic point of view, our findings are in favor of immaturity of the central system of inhibition of micturition reflex during sleep.
The comparison of 24 hours polysomnographic recordings of middle-aged narcoleptic subjects (39-51 years, group A) with 11 twenty four hours and 3 nighttime recordings of elderly narcoleptic subjects (aged 60-72 years, group B) using T test for non paired values was made. No difference was found in parameters of nighttime registrations: total sleep time (A:510.4 +/- 71.2 min., B: 475.9 +/- 92.4 min), intrasleep wakefulness (A: 107.5 +/- 75.3 min., B: 112.3 +/- 65.3 min), latencies of sleep stages (1NREM-A: 3.4 +/- 2.8 min, B: 4.3 +/- 3.7 min, 2NREM-A: 7.4 +/- 7.6 min, B: 6.6 +/- 12.7 min, 3NREM-A: 27.2 +/- 10.4 min, B: 51.6 +/- 62.6 min, REM-A: 62.2 +/- 59.5 min, B: 64.6 +/- 71.6 min), relative duration of each sleep stage (1NREM-A: 20.0 +/- 9.5%, B: 21.4 +/- 13.2%, 2NREM-A: 51.3 +/- 8.5%, B: 51.9 +/- 14.2%, 3 +/- 4NREM-A: 8.2 +/- 6.5%, B: 7.2 +/- 6.5%, REM-A: 20.4 +/- 4.5%, B: 19.1 +/- 5.7%), and sleep continuity index (A: 0.83 +/- 0.11, B: 0.81 +/- 0.11). Total sleep time in the daytime was similar (A: 160.5 +/- 53.8 min, B: 180.5 +/- 59.9 min), the number of sleep episodes during the day was in elderly patients higher (A: 3.4 +/- 1.2, B: 4.8 +/- 1.3, P < 0.05) and the number of sleep onset REM periods was in elderly subjects slightly higher (A: 1.9 +/- 1.1, B: 2.7 +/- 1.7). The authors conclude that the nocturnal sleep of both age groups of narcoleptic subjects is disturbed and the character and the intensity of this disturbance are similar. Elderly narcoleptic subjects displayed more daytime sleep periods.
The MRI exploration of a woman suspected, on clinical grounds, of having Hallervorden-Spatz disease (or rather syndrome) revealed, on T2-weighted sequences, the "tiger's eye" or "target" image of the pallidum described by previous authors: i.e. a high-intensity signal in the centre of a distinct low-intensity signal; it also showed an abnormal low-intensity signal of the substantia nigra. These changes are related to the iron deposits and neuro-axonal lesions which characterize the disease. The MRI semeiology of Hallervorden-Spatz disease has been analyzed in the literature. The images we obtained in this patient with the echo-gradient technique using T1-weighted sequences were unusual, showing a low-intensity signal of the globi pallidi surrounded by central and peripheral low-intensity signal areas, whereas the images obtained with spin-echo T1-weighted sequences were normal.
Explore the source record for details and available documents.
Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects.
1. In a double-blind cross-over study 8 athletes received during 2 sessions of 2 nights zopiclone (7.5 mg) or placebo. 2. Residual effects on subsequent daytime functions were evaluated both subjectively by visual analogue scales as well as objectively by a test battery measuring psychomotor and physical skills. 3. Zopiclone had some favourable effects on self-estimated sleep quality and daytime sleepiness. 4. Psychomotor and physical performance tests did not show any significant difference between zopiclone and placebo. 5. We conclude that zopiclone has useful hypnotic activity without significant adverse effects on athletic performance.
The relationships between severe developmental dysphasias and epilepsy were analysed in 32 patients with congenital dysphasias. The mean age was 8 years 2 months; 19 of 32 had never had seizures; 9 had had occasional seizures; 4 were epileptic. Twenty-two of 32 had normal repeated standard EEGs, but 10 (2 of which never had seizures) showed epileptic interictal discharges. During prolonged EEG after sleep deprivation, epileptic abnormalities were observed in 13 of the 32 cases (4 of which never had seizures). The overall night sleep recordings showed epileptic abnormalities in 30 of the 32 cases (17 of which had never had seizures). The epileptic interictal abnormalities varied considerably in intensity and aspect in the same patient from one examination to another. Developmentally aphasic children show a higher incidence of abnormal EEG than expected, particularly during overall night recordings. In most cases, the physiopathology of the language disturbance might be identical to that in Landau-Kleffner syndrome.
Sleep of 11 narcoleptic subjects was recorded on baseline and after 16 and 24 hours of prior wakefulness (16 and 24 hours sleep deprivation). Eleven sex- and age-matched control subjects were recorded for comparisons. All recordings in narcoleptic subjects were characterized by frequent sleep onset rapid eye movement (REM) episodes, increased amounts of wake time after sleep onset and low sleep efficiencies. Mean total sleep time (TST) was significantly decreased in narcoleptic subjects after sleep deprivation (SD). Recovery sleep after 24 hours SD showed reduced nonREM (NREM) sleep stage 2 percentage, whereas percentages of stage 4 and slow-wave sleep (SWS = stages 3 + 4) were significantly increased. The values of REM sleep percentage of TST were remarkably constant throughout and did not differ significantly as a function of experimental conditions, indicating a normal REM sleep pressure in narcolepsy. Sleep stage analysis per sleep cycles revealed significant differences between the two groups. Percentages of stage 4 and SWS were increased during the first cycle of recovery sleep in narcoleptic subjects. Stage 2 was decreased during the third cycle, and SWS decreased rapidly from cycle 1 to cycle 2 and slightly increased thereafter. These results indicate that sleep need is increased in narcolepsy, whereas its decrease over the first NREM-REM cycle is accelerated. We hypothesize that this could reflect an alteration of the homeostatic process of sleep regulation in narcolepsy.
Human narcolepsy is a genetically determined disorder of sleep strongly associated with the human leucocyte antigens (HLA) DR2 and DQw1. In black narcoleptic patients, susceptibility for narcolepsy is more closely related to a specific gene subtype of DQw1, DQB1-0602, than to DR2. About 30% of black narcoleptic patients are nonDR2, but all carry the HLA DQB1-0602 gene. In the present study, we have tested caucasian nonDR2 cataplectic patients (6 sporadic cases and 7 familial cases from 3 multiplex families) for the presence of the HLA DQB1-0602 and DQA1-0102 (DQw1) using a specific polymerase chain reaction (PCR)-oligotyping technique. None of the patients was DQB1-0602 or DQA1-0102 positive, thus proving that, in caucasians, DQB1-0602 and DQA1-0102 (DQw1) are not prerequisites for the diagnosis of narcolepsy. Further studies with more patients are warranted to exclude the possibility that a few caucasian patients carry rare haplotypes with DQB1-0602 independently of DR2.
Uvulopalatopharyngoplasty (UPPP) is the surgery most often performed for sleep apnea syndrome (SAS). However, good results with UPPP, demonstrated by polysomnography, have been reported in only 50% of cases. Failure of UPPP may be caused by: 1) bad management of the SAS, which is better treated in some patients with nasal CPAP than with surgery; and 2) an airway obstruction located not only at the palatopharynx (PP) level. Other surgical procedures to enlarge other sites of obstruction are described. Retro-tongue-base-pharynx (RTBP) surgery is emphasized, including mandibular advancement, hyoid bone suspension, and tongue base reduction. Maxillomandibular advancement is the most efficient technique but also the most complicated.
Thirty-two narcoleptic subjects with excessive daytime sleepiness and cataplexy were recorded for 33 continuous hours. The continuous polysomnographic recording (CPSG) was followed by a standard MSLT at 2-h intervals. There were 64 sleep onset REM episodes (SOREMs) vs 64 sleep onset nonREM episodes (SONREMs) during the CPSG, and 102 SOREMs vs 50 SONREMS during the MSLT. Both sleep onset types peaked at 13-15 h during the CPSG while sleep onsets were evenly distributed during the MSLT. In the latter procedure, the mean sleep latency was significantly shorter with SOREMs occurrence than with SONREMs occurrence. Two factors were extracted in each procedure by means of a Varimax Rotated Factor Analysis. During the CPSG, SOREMs were related to the preceding nocturnal sleep parameters in the first factor, and to the daytime total sleep time and the total number of sleep onsets in the second factor. During the MSLT, SOREMs were related only to the mean sleep latency and the total number of sleep onsets. It was concluded that the occurrence of SOREMs is primarily due to the residual somnolence in narcoleptic subjects. However, their occurrence during the MSLT is largely independent of the prior history of sleep and waking. Thus, we propose a nonREM-REM sleep dysregulation hypothesis to account for the appearance of SOREMs in narcolepsy.
The authors present their approach to the sleep factor in children with enuresis, based on a still on-going exploration of manometric changes in bladder activity. Twenty patients have already been examined by cystomanometry in day time and polygraphic sleep recording at night, combined with continuous measurement of bladder pressure. This method derives from the studies of Gastaut and Broughton, in 1963, but takes into account the concept of bladder immaturity. The patients studied fell into two homogeneous groups, depending on whether enuresis was obviously due to bladder immaturity (Group I) or was strictly isolated (Group II). No disorder of sleep organization has been found in none of these two groups, but both had apparently nonspecific irritant factors. The enuresis episode is described. It tends to occur frequently at the beginning of the night, is prepared by an increase in bladder pressure which is always very pronounced in Group I subjects, and is associated with insufficient awakening reaction due to an apparently exceedingly high awakening threshold. The physiopathological and therapeutic implications of these findings are discussed.
Patients with obstructive sleep apnea (OSA) and heavy snorers without apnea both show intrathoracic suction pressures during sleep that exceed their static upper airway closing pressures. Complete airway occlusion, however, occurs only in the former patient group. We hypothesized that the kinetic properties of the airflow would be different in these two types of patients because of differences in upper airway morphology. The pharyngeal computed tomography (CT) was used to measure the cross-sectional areas of the upper airways in 15 patients with OSA, 25 nonapneic heavy snorers, and 14 control subjects while they were awake. Nocturnal breathing was monitored with the static charge-sensitive bed (SCSB). The patients with OSA had a narrower airspace at the velopharyngeal (VP) level than the controls (p less than 0.01); the nonapneic snorers did not differ from the other groups. At the tongue base (TB) and the hyoid bone (HB) levels there was no difference between the OSA and the control groups, but the nonapneic snorers had narrower airways at both of these levels compared with control subjects (p less than 0.01) and at the hyoid bone level compared with the OSA group (p less than 0.05). The VP/HB ratio was the parameter that best distinguished the patients with OSA from the nonapneic snorers (lower in the OSA group, p less than 0.001). We suggest that airway collapse during sleep is favored by a narrow velopharynx associated with large hypopharynx. Some heavy snorers may not have an oropharyngeal collapse because the peak inspiratory suction pressure could already be damped down at the level of the relatively narrow hypopharyngeal airways.