Sleep disorders and multiple sclerosis: a clinical and polysomnography study.

BACKGROUND: Patients with multiple sclerosis (MS) report sleep disturbances (SD) and excessive daytime sleepiness (EDS) more frequently than the general population. Our objectives were to evaluate SD and EDS in MS patients and to test the reliability of subjective sleep questionnaires. METHODS: Demographic and clinical characteristics of unselected consecutive patients with MS were collected. Different questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, anxiety, depression and quality of life (QoL). Nocturnal polysomnography and Multiple Sleep Latency Test (MSLT) were performed in 25 selected MS patients with fatigue and with or without EDS. RESULTS: 205 MS patients were enrolled. More than half of the MS patients were classified as 'poor sleepers'. In multivariate analysis, SD were correlated with disability, fatigue, depression, QoL, and pain, but not with EDS. Subjective sleepiness evaluated with the Epworth Sleepiness Scale and SD with the Pittsburgh Sleep Quality Index were not correlated with the results of the objective assessments of vigilance (MSLT) and sleep. CONCLUSIONS: SD and EDS are frequent among MS patients. Objective assessment of vigilance and sleep can be challenging but MS patients who are poor sleepers should receive immediate assessment and treatment in order to improve QoL.

Restless legs syndrome and pregnancy: follow-up of pregnant women before and after delivery.

AIMS: To describe the frequency of restless legs syndrome (RLS) in a French population of randomly selected women during their third trimester of pregnancy and its evolution up to 3 months after delivery and to identify potential factors associated with the improvement of RLS after delivery. METHODS: A cross-sectional questionnaire survey. RESULTS: 186 pregnant women living in a French town were included. 32% of women were affected by RLS during the third trimester of their pregnancy. Multiple pregnancies and iron intake during pregnancy were significantly associated with RLS during the third trimester. RLS disappeared after delivery among 64.8% of the women, and by less than 2 weeks after delivery in half of them. This improvement after delivery was not associated with the number of previous pregnancies, the RLS severity and iron intake during pregnancy, peridural anaesthesia, caesarean section, delivery complications, newborn weight, breastfeeding, dopaminergic agent intake after delivery, and with the absence of RLS before pregnancy. CONCLUSIONS: RLS affects one third of pregnant women during their third trimester and usually improves after delivery. Although there is no allowed treatment, most of the time only counselling and iron status assessment should be provided.

Restless legs syndrome and pregnancy: a questionnaire study in the Poitiers District, France.

AIMS: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy in a European country. METHODS: A cross-sectional questionnaire survey. The questionnaire was distributed by the medical staff in different outpatient waiting rooms (obstetrics and gynecology department of the university hospital, obstetrics and gynecology department of a private clinic, private midwives, private obstetrician-gynecologists, radiological centers before fetal ultrasound examination and general practitioners) in a French town and its surrounding area (200,000 inhabitants): A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. RESULTS: 1,022 pregnant women living in a French town were included. 24% of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and had a significant impact on sleep leading to severe nocturnal and diurnal consequences with a high consumption of sleep medication. CONCLUSIONS: RLS affects one quarter of pregnant women, essentially during the third trimester and represents an important public health issue with sleep medication intake.

[Physiology of normal sleep]. / Physiologie du sommeil normal.

Normal sleep of a young adult is composed of around 4 to 6 cycles of 90 minutes each. Two states of sleep have been established, REM sleep and Non REM sleep. REM sleep is mainly characterized by a complete atonia which creates a physiological paralysis. Slow wave sleep is characterized by an increase of more than 20% of EEG delta waves. Sleep could be represented by a two process model. The first one, the homeostatic component, represents the propensity to sleep, the second one, the circadian component, symbolizes 24th light-dark cycle of the rotation of the earth. The homeostatic component is probably linked to the accumulation of a metabolic molecule, adenosine which concentration increases progressively during the day in human brain tissue, especially in the hypothalamus facilitating the onset of sleep. The sleep-wake cycle is under the control of a biological clock located in the supra-chiasmatic nuclei (SCN) of the hypothalamus. The internal period of the SCN is roughly 24.5 hours setting to 24 hours by the light-obscurity cycle and the melatonin secretion by the pineal gland. The biological clock is regulated by complex mechanisms involving the production of specific proteins inhibiting their own genes by a negative feedback control.

Simultaneous central nervous system distribution and pharmacokinetic-pharmacodynamic modelling of the electroencephalogram effect of norfloxacin administered at a convulsant dose in rats.

The objective of this study was to investigate the contribution of norfloxacin blood-brain barrier (BBB) transport to its delayed electroencephalogram (EEG) effect in rats. Norfloxacin was injected as a bolus dose of 150 mg kg(-1). Blood samples were collected for total norfloxacin plasma concentration measurements. The corresponding unbound levels were determined in brain extracellular fluid (ECF) using microdialysis. Quantitative EEG recording was conducted during 9 h post-dose. Brain ECF norfloxacin concentrations were much lower than plasma levels (AUC ratio=9.7+/-2.8%) but peaked very early, and concentration versus time profiles were parallel in both biological fluids. The best pharmacokinetic (PK) modelling was obtained by considering that ECF concentrations were part of the central compartment, with a proportionality factor. The peak of EEG effect was delayed and the effect versus plasma concentration curves exhibited a dramatic hysteresis. A PK-pharmacodynamic (PD) effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site successfully described the data. Comparisons of PK-PD parameters estimated from plasma and ECF concentrations show that most of the delayed norfloxacin EEG effect is not due to BBB transport, but also that PD parameters derived from plasma data must be carefully interpreted when drug distribution at the effect site is restricted, as may often be the case for centrally acting drugs.

Stroke and sleep apnoea: cause or consequence?

The relationships between obstructive sleep apnoea syndrome (OSAS) and stroke are still under discussion, but increasing evidence demonstrates that the OSAS is an independent risk factor for stroke. However, in rare cases, OSAS could be a consequence of strokes, especially if located in the brainstem. Many recent studies have found a 70 to 95% frequency of OSAS (defined by an apnoea/hypopnoea index >10) in patients with acute stroke. Age, body mass index, diabetes, and severity of stroke have been identified as independent predictors of stroke. Furthermore, the presence of OSAS in stroke patients could lead to a poor outcome. The potential mechanisms linking OSAS and stroke are probably multiple (arterial hypertension, cardiac arrhythmia, increased atherogenesis, coagulation disorders, and cerebral haemodynamic changes). Despite numerous uncertainties, OSAS should be systematically screened at the moment it is clinically suspected in patients with acute stroke. However, the optimal timing (early or differed) for treatment with nasal continuous positive airway pressure remains to be determined.

Short sleep in young adults: Insomnia or sleep debt? Prevalence and clinical description of short sleep in a representative sample of 1004 young adults from France.

BACKGROUND: Increasing evidence suggests an association between short sleep with adverse health outcomes: obesity, type 2 diabetes and hypertension. But there are few or no data on "who these short sleepers are" in the general population. OBJECTIVES: To describe short sleepers and the associated sleep disorders in young adults. METHODS: Cross-sectional telephone survey in a representative sample of 1004 French young adults (25-45 years old). Total sleep time (TST), insomnia, snoring, sleepiness and daytime consequences were assessed using subjective validated tools. Short sleepers were defined as sleeping <6h a weekday (sleep+nap+pauses). Sleep debt was defined as those who "sleep 90 min less than the sleep they need to be in good shape." RESULTS: Prevalence of short sleep was 18%, insomnia 12%, and sleep debt 20% in the total group. Among short sleepers, 16% had insomnia, 45% sleep debt, and 39% neither. Short sleepers were significantly mostly males, blue collar workers and more overweight and obese compared to nonshort sleepers. Working >10h per day, smoking and drinking coffee after 5p.m. were also significantly associated with short sleep. Short sleepers had higher Epworth sleepiness scale ESS scores (7.8 vs 6.7; p = 0.0058) and more sleepiness while driving (11.5% vs 2.9%; p < 0.0001). CONCLUSION: Short sleep is highly prevalent in young adults but is not an homogeneous group, including both insomniacs and subjects with or without sleep debt. Short sleep has to be defined more precisely in order to better understand its impact on public health.

Functional brain imaging by EEG graph-matching.

Our goal is to image the brain activation and function by the mean of electroencephalogram signals. The work's originality is that we build a data structure, a graph, that sums up the brain activity in the spatial, temporal and frequency domain. This graph is formed from the information included in the EEG time-frequency map. Contrary to methods trying to reproduce or analyze the whole complexity of the signal, our method is based on a multi-scale approach. In this order the level of information extraction could be adapted. So as to obtain a pattern of activation or to compare different EEG signals, we use some techniques of graph-matching on our data structure. The developed algorithm is based on the A* algorithm that allows us to compare variations of the recorded EEG answer in term of latency, frequency, energy and activated areas. The first results of this new project show on the one hand that the graph is a good choice to sums up the cortical activity and on the another hand that the graph-matching offers some interesting perspectives in order to describe the functional brain activity.

Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of norfloxacin in rats.

A previously developed pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of norfloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of norfloxacin at a rate of 5 mg kg of body weight(-1) min(-1) over 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. An important delay was observed between concentrations of norfloxacin in plasma and the EEG effect. Indirect effect models failed to describe these data, which were successfully fitted by using an effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site, as previously observed with imipenem. The robustness of the PK-PD model was then assessed by keeping the dose constant but increasing the duration of infusion to 120 and 240 min. Although this was accompanied by PK modifications, PD parameters did not vary significantly, and the PK-PD model still applied. In conclusion, the successful PK-PD modeling of the norfloxacin EEG effect in rats should be considered to predict and reduce the epileptogenic risk associated with this antibiotic as a representative fluoroquinolone (E. Fuseau and L. B. Sheiner, Clin. Pharmacol. Ther. 35:733-741, 1984).

Norfloxacin-induced electroencephalogram alteration and seizures in rats are not triggered by enhanced levels of intracerebral glutamate.

Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram (EEG) effect was combined with intracerebral glutamate determinations using microdialysis for rats receiving norfloxacin intravenously (150 mg/kg of body weight). The EEG effect (accompanied by tremors and seizures) was consistently observed without glutamate level modifications. Therefore, norfloxacin-inducted seizures are not triggered by intracerebral glutamate level enhancement.