Werner Cassel

Risk of traffic accidents in patients with sleep-disordered breathing: reduction with nasal CPAP

Sleepiness whilst driving constitutes a road safety risk. Sleep-related breathing disorders are the most frequent medical cause of daytime sleepiness, and untreated patients with this condition have been shown to be at a higher risk of having accidents while driving. This study addressed the question of the extent to which treatment of sleep-disordered breathing by nasal continuous positive airway pressure (nCPAP) is related to changes in patients accident risk. Seventy eight male patients requiring treatment of sleep-related breathing disorders with nCPAP were enrolled in the study. The protocol included a questionnaire dealing with alertness-related problems while driving, an 80 min vigilance test, and the Multiple Sleep Latency Test. These baseline evaluations were repeated after 1 year of treatment with nCPAP. Fifty nine patients completed the study. The accident rate was significantly decreased from 0.8 per 100,000 km (untreated) to 0.15 per 100,000 km with nCPAP treatment. Variables that were considered to be likely to increase accident risk (sleeping spells, fatigue, vigilance test reaction time, daytime sleep latency) also improved with treatment. We conclude that treatment of sleep-disordered breathing by nasal continuous positive airway pressure is related to reduction in patient motor vehicle accident rates, probably due to the reversal of excessive daytime sleepiness.

Predictors of sudden onset of sleep in Parkinson's disease.

With respect to the ongoing discussion of “sleep attacks” in Parkinsons disease (PD), we sought to estimate the prevalence of sudden onset of sleep (SOS) with and without preceding sleepiness in PD, to identify associated factors, and to define the role of antiparkinsonian medication in SOS. We sent a questionnaire about SOS, sleep behaviour, and medication to 12,000 PD patients. The response rate was 63%, from which 6,620 complete data sets could be analysed. A total of 42.9% of our population reported SOS, 10% of whom never experienced sleepiness before the appearance of SOS (4.3% of all), and we identified the administration of all dopaminergic drugs as a risk factor for SOS. However, SOS occurred earlier after introduction of nonergoline dopamine agonists (DA) and was more strongly associated with nonergoline DA in younger patients (below 70 years) with a shorter disease duration (up to 7 years) but, actually, medication was less efficient in predicting SOS than most other factors considered such as higher age, male sex, longer disease duration, and the report of sleep disturbances. This survey strongly suggests that SOS is a multifactorial phenomenon. Some subgroups are at particular risk of experiencing SOS under nonergoline DA, especially at the beginning of this therapy. Our results support the current notion that SOS, in part, can be attributed to PD‐specific pathology because disease duration and subjective disease severity have been shown to be predictors of SOS. We recommend the development of a standardised question to recognise SOS and to facilitate the comparison of prevalence estimates.

Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized, placebo-controlled polysomnographic study

OBJECTIVE To assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236). METHODS Sixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3mg/24h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings. RESULTS Mean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48,7.28], p<0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: -3.12 (95% CI [-5.36, -0.88], p=0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS=0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity. CONCLUSIONS Rotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances.

Sleep fragmentation and daytime vigilance in patients with OSA treated by surgical maxillomandibular advancement compared to CPAP therapy

Impaired vigilance is a frequent daytime complaint of patients with obstructive sleep apnoea (OSA). To date, continuous positive airway pressure (CPAP) is a well established therapy for OSA. Nevertheless, in patients with certain craniofacial characteristics, maxillomandibular advancement osteotomy (MMO) is a promising surgical treatment. Twenty‐four male patients with OSA (pretreatment respiratory disturbance index (RDI) 59.3 SD±24.1 events/h) participated in this investigation. The mean age was 42.7±10.7 years and the mean body mass index was 26.7±2.9 kg/m2. According to cephalometric evaluation, all patients had a narrow posterior airway space, more or less due to severe maxillary and mandibular retrognathia. All patients except two were treated first with CPAP for at least 3 months and afterwards by MMO. Two patients only tolerated a CPAP trial for 2 nights. Polysomnographic investigation and daytime vigilance were assessed before therapy, with CPAP therapy and 3 months after surgical treatment. Patients’ reports of impaired daytime performance were confirmed by a pretreatment vigilance test using a 90‐min, four‐choice reaction‐time test. The test was repeated with effective CPAP therapy and postoperatively. Daytime vigilance was increased with CPAP and after surgical treatment in a similar manner. Respiratory and polysomnographic patterns clearly improved, both with CPAP and after surgery, and showed significant changes compared to the pretreatment investigation. The RDI decreased significantly, both with CPAP (5.3±6.0) and postoperatively (5.6±9.6 events/h). The percentages of non‐rapid eye movement Stage 1 (NREM 1) sleep showed a marked decrease (with CPAP 8.2±3.6% and after MMO 8.2±4.4% vs. 13.3±7.4% before treatment), whereas percentages of slow wave sleep increased significantly from 8.0±6.1% before therapy to 18.2±12.8 with CPAP and 14.4±7.3% after MMO. The number of awakenings per hour time in bed (TIB) was significantly reduced after surgery (2.8±1.3), compared to both preoperative investigation (baseline 4.2±2.0 and CPAP 3.4±1.5). Brief arousals per hour TIB were reduced to half with CPAP (19.3±20.0) and after MMO (19.7±13.6), compared to baseline (54.3±20.0). We conclude that the treatment of OSA by MMO in carefully selected cases has positive effects on sleep, respiration and daytime vigilance, which are comparable to CPAP therapy.

Evaluation of sleep and driving performance in six patients with Parkinson's disease reporting sudden onset of sleep under dopaminergic medication: A pilot study

Six patients with Parkinsons disease (PD) reporting unusually fast or sudden onset of sleep under the addition of dopamine agonists to a previous levodopa‐containing therapy were examined using a sleep–wake diary, the Epworth sleepiness scale (ESS), polysomnography, multiple sleep latency tests (MSLT), a standardized vigilance test, and driving simulation. In all patients, ESS scores were increased and polysomnography showed disruption of the sleep pattern, a tendency towards poor sleep efficiency, and reduced proportions of slow‐ wave and rapid eye movement sleep. Pathological results in the MSLT or the vigilance test were obtained in five cases. For evaluation of driving performance, the standard deviation from the mean lane position during driving simulation was calculated. Three of five patients had clearly increased mean SDLP values. With respect to the measurement of daytime sleepiness (ESS, MSLT, vigilance test, and driving simulation), each patient had pathological results in at least two of these examinations. However, only a limited transfer of the routine vigilance assessment to driving performance was possible. In summary, this pilot study indicates that unusually fast or sudden onset of sleep in PD patients is a phenomenon of daytime sleepiness.

Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients

Cerebrospinal fluid (CSF) and blood obtained from 22 untreated or scarcely treated patients with moderate to severe restless legs syndrome (RLS; mean age, 58.6 ± 13 years) and 11 control subjects (mean age, 56.6 ± 12.9 years) were investigated for biogenic amines between 6:00 and 8:00 PM. We did not find any significant differences in the CSF concentrations of homovanillic acid, 3‐ortho‐ methyl‐dopa, levodopa, 5‐hydroxytryptophan, 5‐hydroxyindoleacetic acid, tetrahydrobiopterin, dihydrobiopterin, 5‐methyltetrahydrofolate, and neopterin. In addition, serotonin in whole blood and plasma activity of aromatic amino acid decarboxylase were all normal. Our results suggest that dopaminergic and serotonergic release is not substantially affected in RLS.

A Prospective Polysomnographic Study on the Evolution of Complex Sleep Apnoea

Complex sleep apnoea (CompSA) may be observed following continuous positive airway pressure (CPAP) treatment. In a prospective study, 675 obstructive sleep apnoea patients (mean age 55.9 yrs; 13.9% female) participated. Full-night polysomnography was performed at diagnosis, during the first night with stable CPAP and after 3 months of CPAP. 12.2% (82 out of 675 patients) had initial CompSA. 28 of those were lost to follow-up. Only 14 out of the remaining 54 patients continued to satisfy criteria for CompSA at follow-up. 16 out of 382 patients not initially diagnosed with CompSA exhibited novel CompSA after 3 months. 30 (6.9%) out of 436 patients had follow-up CompSA. Individuals with CompSA were 5 yrs older and 40% had coronary artery disease. At diagnosis, they had similar sleep quality but more central and mixed apnoeas. On the first CPAP night and at follow-up, sleep quality was impaired (more wakefulness after sleep onset) for patients with CompSA. Sleepiness was improved with CPAP, and was similar for patients with or without CompSA at diagnosis and follow-up. CompSA is not stable over time and is mainly observed in predisposed patients on nights with impaired sleep quality. It remains unclear to what extent sleep impairment is cause or effect of CompSA.

Does short‐term treatment with modafinil affect blood pressure in patients with obstructive sleep apnea?

To investigate the effects of modafinil, a central nonamphetamine awakening substance, on blood pressure and heart rate in hypersomnolent patients with obstructive sleep apnea.

CSF hypocretin-1 levels in restless legs syndrome.

CSF hypocretin-1 levels at 6 pm did not significantly differ between patients with restless legs syndrome (RLS) and control subjects as measured by direct radioimmunoassay and after acid extraction. The authors did not observe significant differences between early onset and late onset RLS. Hypocretin-1 levels did not correlate with RLS severity or polysomnographic measures. These results contrast with previous findings reporting significantly increased CSF hypocretin-1 in the late evening and mostly in early onset RLS.

Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order. Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45+/-2.42 cmH2O) compared to CPAP (9.96+/-2.7 cmH2O) (p=0.002). The mean minimal arterial oxygen saturation (Sa,O2) (82.8+/-6.5%) on the diagnostic night increased significantly (p<0.001) to an average Sa,O2 of 93.35+/-1.71% and 93.19+/-2.9% during CPAP and PPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (p<0.001), while sleep stage nonrapid eye movement (NREM) 1 and 2 decreased. Six patients preferred the PPAP titration night, four patients did not have a preference, and two patients preferred CPAP. The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.