These results demonstrate conservation of gene, protein and function for many established sedative hypnotic pathways. The results indicate feasibility of conducting large-scale pharmacogenomic screens to isolate novel proteins modulating susceptibility to hypnotic compounds in a vertebrate system.

on behalf of the HAROSA I Study Group * BACKGROUND: Excessive daytime sleepiness (EDS) in individuals with OSA syndrome persisting despite good adherence to CPAP is a disabling condition. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects.RESEARCH QUESTION: Is pitolisant effective and safe for reducing daytime sleepiness in individuals with moderate to severe OSA adhering to CPAP treatment but experiencing residual EDS? STUDY DESIGN AND METHODS: In a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was titrated individually at up to 20 mg/day and taken over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score in the intention-totreat population. Key secondary end points were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, Clinical Global Impressions scale of severity, the patient's global opinion, EuroQoL quality-of-life questionnaire score, Pichot fatigue questionnaire score, and safety.RESULTS: Two hundred forty-four OSA participants (82.8% men; mean age, 53.1 years; mean Apnea Hypopnea Index with CPAP, 4.2/h; baseline ESS score, 14.7) were randomized to pitolisant (n ¼ 183) or placebo (n ¼ 61). ESS significantly decreased with pitolisant compared with placebo (À2.6; 95% CI, -3.9 to À1.4; P < .001), and the rate of responders to therapy (ESS # 10 or change in ESS $ 3) was significantly higher with pitolisant (71.0% vs 54.1%; P ¼ .013). Adverse event occurrence (mainly headache and insomnia) was higher in the pitolisant group compared with the placebo group (47.0% and 32.8%, respectively; P ¼ .03). No cardiovascular or other significant safety concerns were reported.INTERPRETATION: Pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity.

1. The aim of the study was to assess the effect of ambulatory monitoring of blood pressure on sleep and on blood pressure in middle-aged patients. 2. Nine consecutive patients (seven men, two women; mean age 57 years) complaining of snoring and various degrees of excessive daytime somnolence were studied. Five patients were normotensive and four were being treated for hypertension. During one night standard laboratory polysomnography was performed with monitoring of blood pressure by a silent ambulatory monitor and continuous infrared blood pressure by photoplethysmography. 3. Ambulatory blood pressure significantly disturbs sleep architecture, causing EEG arousals in 64% of measurements, and induces a significant rise in blood pressure during systolic pressure measurement by the ambulatory monitor (rise in systolic pressure, 13.7 +/- 15.9 mmHg, P < 0.001; rise in diastolic pressure, 3.7 +/- 8.2 mmHg, P < 0.01). At the time of diastolic measurement, blood pressure had returned to the preinflation value. The rise in systolic blood pressure was higher when an arousal was associated with cuff inflation (P < 0.001). This rise in blood pressure is probably the consequence of sympathetic nervous system activation. 4. We conclude that ambulatory blood pressure recordings of systolic blood pressure during sleep should be interpreted with caution as systolic blood pressure may be significantly increased in patients suspected of suffering from sleep-disordered breathing.

The onset of restless legs syndrome (RLS) is usually progressive and the neural substrates underlying its pathophysiology remain to be identifi ed. Here we report on a patient presenting with acute-onset RLS that was symptomatic of a right anteromedial pontine infarction. This case is exceptional because RLS appeared several hours before the occurrence of a regressive dysarthria clumsy-hand syndrome. Additionally, millimetric MRI sections showed that the structures possibly involved in RLS pathogenesis were the corticospinal tract, the pontine nuclei, and the pontocerebellar fi bers. Although this is uncommon, clinicians should be aware that RLS characterized by a sudden onset can be a clinical manifestation related to stroke. Keywords: pontine stroke, pontine anteromedial infarction, restless legs syndrome, RLS, periodic limb movements, RLS C A S E R E P O R T SR estless legs syndrome (RLS) is a common neurological disorder whose symptoms develop progressively.1 The neural substrates underlying RLS pathophysiology remain to be identifi ed.1 Here, we report an exceptional case of a patient who presented with acute onset RLS as the fi rst clinical manifestation of a right anteromedial pontine infarction. Additionally, we analyzed, using millimetric MRI sections, the structures affected by the lesion. REPORT OF CASEA 64-year-old patient presented a severe RLS characterized by sudden onset. He complained, for the fi rst time ever, of an urge to move the legs with paresthesia, worsened during rest and as he lay down. The symptoms were relieved by mobilization, fulfi lled the criteria of the International study group for diagnosis of RLS, and caused unusual and severe sleep-onset insomnia. The following morning the patient presented additionally with dysarthria-clumsy hand syndrome. He was a former smoker and was previously diagnosed with hypertension. Upon admission, MRI scans revealed a recent right anteromedial pontine infarction.Investigations were otherwise unremarkable, and the stroke was presumed to be atherothrombotic. Treatment consisted of aspirin, atorvastatin and nebivolol. Ten days after RLS onset, the neurological examination was normal, yet RLS persisted and was evaluated as severe (24/ DISCUSSIONWe describe the case of a patient presenting with RLS and presumably PLMS whose onset was coincident with a classic lacunar stroke syndrome (i.e., clumsy-hand dysarthria syndrome). The neural substrate and the generator(s) responsible for RLS and PLMS remain unknown. Stroke-related RLS might emerge from interrupted fi bers of presumably descending "inhibitory" pathways causing a supraspinal disinhibition. How can lesions of the paramedian pons be responsible for RLS occurrence? Using MRI with millimetric sections, we analyzed, in reference to the Duvernoy brain atlas, the structures that might be involved. Firstly, the reticular formation located in the tegmentum was spared, in contrast to previously reported