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Jennum P.J.,Danish Center for Sleep Medicine | Pedersen L.O.,Lundbeck | Bahl J.M.C.,Statens Serum Institute | Fog K.,Lundbeck
Sleep | Year: 2017

Objectives: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. Methods: Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1). Results: Levels of β-amyloid were lower in patients with type 1 narcolepsy (375.4-143.5 pg/mL) and type 2 narcolepsy (455.9-65.0 pg/mL) compared to controls (697.9-167.3 pg/mL, p < .05). Furthermore, in patients with type 1 narcolepsy, levels of T-tau (79.0-27.5 pg/mL) and P-tau181 (19.1-4.3 pg/mL) were lower than in controls (162.2-49.9 pg/mL and 33.8-9.2 pg/mL, p < .05). Levels of α-synuclein, NF-L, and CHI3L1 in CSF from narcolepsy patients were similar to those of healthy individuals. Conclusion: Six CSF biomarkers of neurodegeneration were decreased or normal in narcolepsy indicating that taupathy, synucleinopathy, and immunopathy are not prevalent in narcolepsy patients with a disease duration of 2-29 years. Lower CSF levels of β-amyloid, T-tau protein, and P-tau181 in narcolepsy may indicate that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in the central nervous system.

Wijnans L.,Erasmus Medical Center | Lecomte C.,Erasmus Medical Center | de Vries C.,University of Bath | Weibel D.,Erasmus Medical Center | And 28 more authors.
Vaccine | Year: 2013

Background: In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. Methods: We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. Results: Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women > men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. Conclusions: The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail. © 2012 Elsevier Ltd.

Barloese M.,Danish Headache Center | Jennum P.,Danish Center for Sleep Medicine | Knudsen S.,Glostrup University Hospital | Jensen R.,Danish Headache Center
Cephalalgia | Year: 2012

Purpose of review: Sleep and the chronobiological disease cluster headache are believed to be interconnected. Despite efforts, the precise nature of the relationship remains obscured. A better understanding of this relation may lead to more effective therapeutic regimes for patients suffering from this debilitating disease. This review aims to evaluate the existing literature on the subject of cluster headache and sleep.Latest findings: Several previous studies describe an association between episodic cluster headache and distinct macrostructural sleep phases. This association was not confirmed in a recent study of seven episodic cluster headache patients, but it was suggested that further studies into the correlation between cluster headache attacks and the microstructure of sleep are relevant. The connection between cluster headache and the hypocretins is currently under investigation.Summary: There is evidence in favour of an association between episodic cluster headache and REM sleep whereas no such relation to chronic cluster headache has been reported. Particular features in the microstructure of sleep and arousal mechanisms could play a role in the pathogenesis of cluster headache. Reports indicate that cluster headache and obstructive sleep apnoea are associated. Single cases show improvement upon treatment of sleep apnoea, but the causal relationship remains in question. © International Headache Society 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Jennum P.,Danish Center for Sleep Medicine | Ibsen R.,Itracks | Kjellberg J.,Danish National Institute for Local and Regional Government Research
Journal of Clinical Sleep Medicine | Year: 2013

Background: Sleep-disordered breathing (SDB) causes burden to the sufferer, the healthcare system and society. Most studies have focused on cardiovascular diseases (CVDs) after a diagnosis of obstructive sleep apnea (OSA) or obesity hypoventilation syndrome (OHS); however, the overall morbidity prior to an SDB diagnosis has not been evaluated. The aim of this study was to identify morbidity prior to a SDB diagnosis to identify patients at risk for having/developing SDB. Methods: Using data from the Danish National Patient Registry (1998-2006), we identified all patients nationwide given a diagnosis of OSA (19,438) or OHS (755) in all hospitals and clinics. For each patient, we randomly selected 4 citizens matched for age, sex, and socioeconomic status from the Danish Civil Registration System Statistics. Results: Patients with OSA or OHS presented with increased morbidity at least 3 years prior to their SDB diagnosis. The most common contacts with the health system (odds ratio [OR]/confidence interval [CI]) for OSA/OHS were due to musculoskeletal system (1.36[1.29-1.42]/1.35[1.05-1.74]); CVD (1.38[1.30-1.46]/1.80[1.38-2.34]); endocrine, nutritional, and metabolic diseases (1.62[1.50-1.76]/4.10[2.90-5.78]) ; diseases of the nervous system (1.62[1.0-1.76]/3.54[2.56-4.88]); respiratory system (1.84[1.73-1.96]/2.83[2.07-3.89]); skin and subcutaneous tissue (1.18[1.07-1.30]/2.12[1.33-3.38]); gastrointestinal (1.17[1.10-1.24]/NS); infections (1.20[1.08-1.33]/NS); genitourinary system (1.21[1.13-1.30]/NS); and ear, nose, and throat (1.44[1.32-1.56]/NS). Conclusions: Patients with SDB show significant morbidities several years prior to a diagnosis of OSA or OHS. OSA should be considered in all medical specialties as an important comorbidity. In our study, evidence points to particular emphasis for considering this diagnosis in endocrinology and metabolic specialties.

PubMed | Danish Center for Sleep Medicine
Type: Journal Article | Journal: Thorax | Year: 2013

Little is known about the diagnostic patterns of obstructive sleep apnoea (OSA) in children. A study was undertaken to evaluate morbidity and mortality in childhood OSA.2998 patients aged 0-19 years with a diagnosis of OSA were identified from the Danish National Patient Registry. For each patient we randomly selected four citizens matched for age, sex and socioeconomic status, thus providing 11 974 controls.Patients with OSA had greater morbidity at least 3 years before their diagnosis. The most common contacts with the health system arose from infections (OR 1.19, 95% CI 1.01 to 1.40); endocrine, nutritional and metabolic diseases (OR 1.30, 95% CI 0.94 to 1.80); nervous conditions (OR 2.12, 95% CI 1.65 to 2.73); eye conditions (OR 1.43, 95% CI 1.07 to 1.90); ear, nose and throat (ENT) diseases (OR 1.61, 95% CI 1.33 to 1.94); respiratory system diseases (OR 1.78, 95% CI 1.60 to 1.98); gastrointestinal diseases (OR 1.34, 95% CI 1.09 to 1.66); skin conditions (OR 1.32, 95% CI 1.02 to 1.71); congenital malformations (OR 1.56, 95% CI 1.31 to 1.85); abnormal clinical or laboratory findings (OR 1.21, 95% CI 1.06 to 1.39); and other factors influencing health status (OR 1.29, 95% CI 1.16 to 1.43). After diagnosis, OSA was associated with incidences of endocrine, nutritional and metabolic diseases (OR 1.78, 95% CI 1.29 to 2.45), nervous conditions (OR 3.16, 95% CI 2.58 to 3.89), ENT diseases (OR 1.45, 95% CI 1.14 to 1.84), respiratory system diseases (OR 1.94, 95% CI 1.70 to 2.22), skin conditions (OR 1.42, 95% CI 1.06 to 1.89), musculoskeletal diseases (OR 1.29, 95% CI 1.01 to 1.64), congenital malformations (OR 1.83, 95% CI 1.51 to 2.22), abnormal clinical or laboratory findings (OR 1.16, 95% CI 1.06 to 1.27) and other factors influencing health status (OR 1.35, 95% CI 1.20 to 1.51). The 5-year death rate was 70 per 10 000 for patients and 11 per 10 000 for controls. The HR for cases compared with controls was 6.58 (95% CI 3.39 to 12.79; p<0.001).Children with OSA have significant morbidities several years before and after their diagnosis.

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