Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

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

Sleep deficits but no metabolic deficits in premanifest Huntington's disease.

OBJECTIVE: Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage. METHODS: We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain. RESULTS: Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations. INTERPRETATION: The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.The study was funded from a grant from CHDI Foundation, Inc.CHDI-RG50786. RAB received grants from NIHR BRC-RG64473. PS is funded by an MRC Programme grant (Physiological Modelling and Metabolic Risk: MC_UP_A090_1005).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/ana.2449

Digital clubbing in tuberculosis – relationship to HIV infection, extent of disease and hypoalbuminemia

BACKGROUND: Digital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed. METHODS: A cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done. RESULTS: Two hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB. CONCLUSION: Clubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia

Narcolepsy Associated with Duane's Syndrome

The best characterised disorder of REM sleep, narcolepsy has never previously been associated with Duane's syndrome, in which there is developmental failure of the abducens nerve and its nucleus. The major brain stem nuclei responsible for REM sleep generation are situated in the pons in close proximity to the abducens nerve nucleus. We report the novel combination of Duane's syndrome and narcolepsy, providing new insight into the pathogenesis of narcolepsy

Weaning from prolonged invasive ventilation in motor neurone disease: analysis of outcomes and survival

International audienceIntroduction: Non-invasive ventilation (NIV) improves prognosis in patients with Motor Neurone Disease (MND) in the absence of major bulbar involvement. However, some experience a rapid and unexpected decline in respiratory function and may undergo emergency tracheal intubation. Weaning from invasive ventilation can be difficult and reported independence from invasive ventilation is uncommon with poor prognosis. The outcomes of patients with MND referred to a specialist weaning service following emergency tracheal intubation were examined and compared with MND patients electively initiating NIV. Methods: A case note review was performed on all patients with MND invasively ventilated and referred to a specialist weaning service between 1992 and 2007. Outcomes were compared with those electively commenced on NIV during the same period. Results: Thirty patients were referred for weaning from invasive ventilation which was started in 17 before MND was diagnosed. Fourteen patients (47%) were weaned from invasive ventilation but still required NIV, 13 failed to wean and three died. Seventeen were discharged home from hospital. Median survival from tracheal intubation was 13.7 months (95% CI 0-30.8) for those previously diagnosed and 7.2 months (95% CI 5.1-9.4) for those not previously known to have MND. Comparison with patients initiated electively on NIV demonstrated similar survival estimates to that from emergency intubation (median 9.4 (95% CI 6.9 - 12.0) vs. 7.8 (95% CI 2.6 - 12.9) months respectively). Conclusion: The prognosis in MND following acute respiratory failure and intubation is not always complete ventilator dependence if patients are offered a comprehensive weaning programme