IMPORTANCE Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα). RESULTS Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.

Setting Sleep centres and paediatric neurology centres in England.Participants Children and young people aged 4-18 with onset of narcolepsy from January 2008. Main outcome measuresThe odds of vaccination in those with narcolepsy compared with the age matched English population after adjustment for clinical conditions that were indications for vaccination. The incidence of narcolepsy within six months of vaccination compared with the incidence outside this period measured with the self controlled cases series method.Results Case notes for 245 children and young people were reviewed; 75 had narcolepsy (56 with cataplexy) and onset after 1 January 2008. Eleven had been vaccinated before onset; seven within six months. In those with a diagnosis by July 2011 the odds ratio was 14.4 (95% confidence interval 4.3 to 48.5) for vaccination at any time before onset and 16.2 (3.1 to 84.5) for vaccination within six months before onset. The relative incidence from the self controlled cases series analysis in those with a diagnosis by July 2011 with onset from October 2008 to December 2010 was 9.9 (2.1 to 47.9). The attributable risk was estimated as between 1 in 57 500 and 1 in 52 000 doses. ConclusionThe increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children. IntroductionNarcolepsy is a chronic disorder presenting with excessive daytime sleepiness, often accompanied by a transient loss of muscle tone triggered by strong emotion (cataplexy). Diagnosis is based on clinical criteria and can be confirmed by polysomnography followed by a multiple sleep latency test. 1 Estimates of prevalence generally range between 25 and 50 per 100 000, though might be less in some populations, possibly because of differences in genetic susceptibility or exposure to aetiological risk factors.2 Information on incidence is more limited. Onset can occur at any age 2 but is commonest in those aged 10-19, in whom an incidence of 3.84 per 100 000 person years has been reported. 3 The interval between onset and diagnosis can be long, with a median of 10.5 years in one study. 4 Diagnostic delay is less in those with cataplexy and in younger patients. 5 There is a strong association with human leucocyte antigen (HLA) DQB1*0602 and reported associations with environmental factors such as streptococcal infection, 6 seasonal influenza, 7 and more recently pandemic A/H1N1 2009 influenza. 8 In England, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix) was introduced in October 2009 during the second wave of infection, initially for people with high risk clinical conditions 9 10 and then in healthy 12 A second pandemic vaccine was used (Celvepan) but accounted for less than 1% of the total.In August 2010 concerns were raised in Finland and Sweden about a possible associat...

Patients and Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Measurements and Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.

Background-It has been suggested that cough eVectiveness can be improved by assisted techniques. The eVects of manually assisted cough and mechanical insufflation on cough flow physiology are reported in this study. Methods-The physiological actions and patient self-assessment of manually assisted cough and mechanical insuZation were investigated in 29 subjects (nine normal subjects, eight patients with chronic obstructive pulmonary disease (COPD), four subjects with respiratory muscle weakness (RMW) with scoliosis, and eight subjects with RMW without scoliosis). Results-The peak cough expiratory flow rate and cough expiratory volume were not improved by manually assisted cough and mechanical insuZation alone or in combination in normal subjects. The median increase in peak cough expiratory flow in subjects with RMW without scoliosis with manually assisted cough alone or in combination with mechanical insuZation of 84 l/min (95% confidence interval (CI) 19 to 122) and 144 l/min (95% CI 14 to 195), respectively, reflects improvement in the expulsive phase of coughing by these techniques. Manually assisted cough and mechanical insuZation in combination raised peak expiratory flow rate more than either technique alone in this group. The abnormal chest shape in scoliotic subjects and the fixed inspiratory pressure used made eVective manually assisted cough and mechanical insuZation diYcult in this group and no improvements were found. In patients with COPD manually assisted cough alone and in combination with mechanical insuZation decreased peak expiratory flow rate by 144 l/min (95% CI 25 to 259) and 135 l/min (95% CI 30 to 312), respectively. Conclusions-Manually assisted cough and mechanical insuZation should be considered to assist expectoration of secretions in patients with RMW without scoliosis but not in those with scoliosis. (Thorax 2001;56:438-444)

The pulmonary associations of inflammatory bowel disease (IBD) are poorly characterized. The clinical, physiological and high-resolution computed tomographic thorax characteristics of the lung disease in patients with IBD presenting with respiratory symptoms are described.Detailed clinical information was obtained and standard pulmonary physiological tests and thorax high-resolution computed tomography performed on 14 patients with ulcerative colitis (UC) and three with Crohn's disease (CD), 10 male, aged 38±83 yrs.Respiratory symptoms had been present for 2±50 yrs and extraintestinal manifestations were present in three (17.6%). Normal pulmonary physiology (six patients) was associated with the high resolution computed tomographic changes of bronchiectasis, mosaic perfusion and air trapping suggestive of obliterative bronchiolitis and a pattern of centrilobular nodules and branching linear opacities ("tree in bud" appearance) suggestive of either cellular bronchiolitis or bronchiolectasis with mucoid secretions. Bronchiectasis was found in 13 patients (11 UC, 2 CD), 11 had air trapping and five had a "tree in bud" appearance on computed tomography. One patient had a predominantly peripheral reticular pattern at the lung bases similar to that found in cryptogenic fibrosing alveolitis and one patient had a mixed reticular and groundglass pattern in the midzones with a patchy distribution in the central and peripheral portions of the lungs with air trapping. Eleven patients (three with alveolitis) exhibited a clinical and/or physiological response to steroids.Pulmonary abnormalities in ulcerative colitis and Crohn's disease can present years after the onset of the bowel disease and can affect any part of the lungs. Early recognition is important as they can be strikingly steroid-responsive. Eur Respir J 2000; 15: 41±18. The presence of subclinical disease in patients without respiratory symptoms was suggested in one study because result of abnormal pulmonary function found in 38% of UC patients and 54% of CD patients, significantly greater pro-portions than in a healthy control populations [27].Pul-monary function abnormalities include a decrease in gas transfer factor [28±30], an elevated functional residual capacity (FRC) and raised residual volume (RV) during periods of active bowel disease [30±32] and an increased frequency of bronchial hyperresponsiveness [33]. Further-more, alveolar lymphocytosis is evident in bronchoalveolar lavage fluid from CD patients without respiratory symptoms [34].The chest radiograph is often normal in patients with respiratory symptoms and inflammatory bowel disease (IBD) [6,8] and as a result the radiological characteristics remain poorly characterized. Two studies described the high resolution computed tomographic findings in seven patients (in each study) with IBD who presented with cough and sputum production. However, these reports did not correlate the computed tomographic appearances with symptoms or pulmonary physiology or evaluate air trapping with scans performe...