Effect of continuous positive airway pressure treatment on short-term memory performance over 24 h of sustained wakefulness in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Few studies have examined the impact of continuous positive airway pressure (CPAP) therapy on short-term memory (STM) over sustained wakefulness in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We have investigated if impaired STM can be reversed by CPAP treatment in a 24-h sustained wakefulness paradigm. METHODS: Our follow-up study was conducted with repeated-memory tasks within 12 OSAHS patients and 10 healthy controls who underwent three 32-h sessions, one before CPAP (T0) and the second (T3) and the third (T6), after 3 and 6 months of treatment, respectively, for OSAHS patients. Each session included one night of sleep followed by 24h of sustained wakefulness, during which both groups performed STM tasks including both digit span (DS) and Sternberg tasks. RESULTS: Untreated OSAHS patients had no deficit in the forward DS task measuring immediate memory but were impaired in STM, especially working memory assessed by the complex Sternberg task and the backward DS. However, only performance in the latter was improved after 6 months of CPAP treatment. CONCLUSIONS: Because the high level of memory scanning required high speed in information processing, persistent impairment on the complex Sternberg task may be attributable to working memory slowing, possibly enhanced by sustained wakefulness.

Floppy eyelid syndrome is associated with obstructive sleep apnoea: a prospective study on 127 patients.

A few investigations have raised the question of a possible relationship between obstructive sleep apnoea syndrome (OSAS) and floppy eyelid syndrome (FES). FES is an easily inverted floppy eyelid with papillary conjunctivis, and is a subset of the general pathology, lax eyelid syndrome. The aim of the current study is to determine whether OSAS severity is associated with FES. One hundred and 27 consecutive subjects (aged 25-75 years) referred to the Strasbourg University Sleep Clinic with suspicion of OSAS were included. All patients underwent overnight ambulatory respiratory polygraphy, comprehensive ophthalmological examination and completed standard sleep questionnaires. OSAS severity was defined based on the patient's obstructive apnoea-hypopnoea index (AHI). As expected, age, body mass index (BMI) and the proportion of males increased with OSAS severity. FES was observed in 15.8% of the subjects without OSAS, 25.8% of the total OSAS population and the frequency was significantly increased (40%) in patients with severe OSAS (AHI > 30 h(-1)). A significant correlation between OSAS severity and FES was found after adjustment for age, sex and BMI, using a principal component analysis (PCA). The multivariate analysis included clinical, polygraphic and comorbidity data and was followed by logistic regressions for the main components extracted from the PCA. In summary, our findings show an association between OSAS severity and FES and suggest that severe OSAS might be an independent risk factor for FES. These two disorders may share common biological determinants, such as tissue elasticity. Finally, clinicians should be aware of this association so that underlying OSAS or FES can be detected.

Short-term memory performances during sustained wakefulness in patients with obstructive sleep apnea-hypopnea syndrome.

Both working and immediate memories were assessed every 4h by specific short-term memory tasks over sustained wakefulness in 12 patients with obstructive sleep apnea and hypopnea syndrome (OSAHS) and 10 healthy controls. Results indicated that OSAHS patients exhibited lower working memory performances than controls on both backward digit span and complex Sternberg tasks. Speed and accuracy on Sternberg tasks were affected by memory load in both groups. However, immediate memory was not impaired in OSAHS patients. Diurnal and nocturnal SaO(2) were correlated with speed and accuracy high-speed memory scanning performance on Sternberg tasks in patients. These results suggest specific working memory deficits associated with OSAHS over sustained wakefulness with a possible deficiency in the central executive responsible for the higher information processing, in addition to a potentially insufficient storage capacity. Among OSAHS patients, working memory ability involved in high-speed memory scanning may be impaired by chronic hypoxemia.

Narcolepsy is strongly associated with the T-cell receptor alpha locus.

Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported. Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders; thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders.

Outcome of sleepiness and fatigue scores in obstructive sleep apnea syndrome patients with and without restless legs syndrome after nasal CPAP.

BACKGROUND & PURPOSE: The association of obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS) has been reported in the literature for many years. Both conditions may be responsible for fatigue and somnolence complaints secondary to nocturnal sleep disruption. The primary concern of this study is to evaluate the outcome of fatigue and daytime sleepiness symptoms at baseline and after continuous positive air pressure (CPAP) treatment in OSAS patients with and without RLS. METHOD: A prospective and comparative study between a group of 13 patients with OSAS and a group of 17 patients with OSAS+RLS. Laboratory blood tests and polysomnography were performed at baseline. The Epworth Sleepiness Scale (ESS) and the Pichots questionnaire of fatigue/depression (PIC) were applied before and after 3 months of CPAP treatment. Results were compared. RESULTS: No significant differences were found on PSG and laboratory results at baseline. Both groups had similar ESS and PIC scores at baseline (p=0.73 and 0.08, respectively). After n-CPAP, OSAS+RLS patients showed higher ESS and PIC scores (p=0.017 and 0.03, respectively). CONCLUSIONS: Despite a favorable general response, n-CPAP seemed less effective in treating fatigue and sleepiness in the OSAS+RLS group.

Outcome of sleepiness and fatigue scores in obstructive sleep apnea syndrome patients with and without restless legs syndrome after nasal CPAP

BACKGROUND & PURPOSE: The association of obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS) has been reported in the literature for many years. Both conditions may be responsible for fatigue and somnolence complaints secondary to nocturnal sleep disruption. The primary concern of this study is to evaluate the outcome of fatigue and daytime sleepiness symptoms at baseline and after continuous positive air pressure (CPAP) treatment in OSAS patients with and without RLS. METHOD: A prospective and comparative study between a group of 13 patients with OSAS and a group of 17 patients with OSAS+RLS. Laboratory blood tests and polysomnography were performed at baseline. The Epworth Sleepiness Scale (ESS) and the PichotÆs questionnaire of fatigue/depression (PIC) were applied before and after 3 months of CPAP treatment. Results were compared. RESULTS: No significant differences were found on PSG and laboratory results at baseline. Both groups had similar ESS and PIC scores at baseline (p=0.73 and 0.08, respectively). After n-CPAP, OSAS+RLS patients showed higher ESS and PIC scores (p=0.017 and 0.03, respectively). CONCLUSIONS: Despite a favorable general response, n-CPAP seemed less effective in treating fatigue and sleepiness in the OSAS+RLS group.

OBJETIVO: A associação síndrome de apnéia obstrutiva do sono / síndrome de pernas inquietas (SAOS-SPI) tem sido mencionada na literatura há muito. Ambas podem ser responsáveis por queixas de fadiga e sonolência secundárias à fragmentação do sono noturno. O objetivo deste estudo é avaliar a evolução dos sintomas de fadiga e sonolência diurna excessiva antes e após o tratamento com pressão aérea positiva contínua (CPAP) em pacientes portadores de SAOS, com e sem SPI. MÉTODO: Estudo prospectivo e comparativo entre um grupo de 13 pacientes com SAOS e um grupo de 17 com SAOS +SPI. Exames laboratoriais e polissonografia (PSG) foram realizados no início do estudo. A escala de sonolência de Epworth (ESE) e o questionário de fadiga/depressão de Pichot (PIC) foram aplicados antes do tratamento com CPAP e 3 meses após. Os resultados foram comparados. RESULTADOS: No início do estudo não foram encontradas diferenças significativas na avaliação laboratorial e PSG. Ambos os grupos apresentavam inicialmente pontuação semelhante na avaliação da ESE e PIC (p=0,73 e 0,08, respectivamente). Após CPAP, os pacientes SAOS+SPI apresentaram maiores ESE e PIC (p=0,017 e 0,03, respectivamente). CONCLUSÃO: Apesar de resposta inicial favorável em ambos os grupos, o CPAP foi aparentemente menos eficaz na redução das queixas de fadiga e sonolência nos pacientes apnéicos com associação a SPI.

Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor.

The suprachiasmatic nuclei of the hypothalamus (SCN) are the site of the master circadian clock in mammals. The SCN clock is mainly entrained by the light-dark cycle. Light information is conveyed from the retina to the SCN through direct, retinohypothalamic fibres. The SCN also receive other projections, like cholinergic fibres from basal forebrain. To test whether cholinergic afferents are involved in photic resetting, lesions of cholinergic projections were performed in rats with intracerebroventricular (i.c.v.) injections or intra-SCN microinjections of 192 IgG-saporin. When injected in the SCN, this immunotoxin destroys the cholinergic projections and retinohypothalamic afferents that express p75 low-affinity nerve growth factor (p75(NGF)) receptors. The extent of lesions in the basal forebrain and SCN was assessed by acetylcholinesterase histochemistry, p75(NGF) receptor, choline acetyl-transferase, calbindin-D28K and VIP immunocytochemistry. The intra-SCN treatment reduced light-induced phase advances by 30%, and induced a complete loss of forebrain and retinal afferents expressing p75(NGF) receptors within the SCN and a decrease of forebrain cholinergic neurons, most likely those projecting to the SCN. The i.c.v. treatment reduced light-induced phase advances by 40%, increased phase delays and led to extensive damage of forebrain p75(NGF)-expressing neurons, while sparing half of the fibres expressing p75(NGF) receptors (retinal afferents?) in the SCN. Because the integrity of forebrain p75(NGF)-expressing neurons appears to be critical in mediating the effects on light-induced phase advances, we therefore suggest that anterior cholinergic projections expressing p75(NGF) receptors modulate the sensitivity of the SCN clock to the phase advancing effects of light.