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      Comorbidity of Narcolepsy Type 1 With Autoimmune Diseases and Other Immunopathological Disorders: A Case-Control Study

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          Abstract

          Background

          Several evidences suggest that autoimmune diseases (ADs) tend to co-occur in an individual and within the same family. Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a selective loss of hypocretin-producing neurons due to a mechanism of neural destruction that indicates an autoimmune pathogenesis, although no evidence is available. We report on the comorbidity of ADs and other immunopathological diseases (including allergy diseases) in narcolepsy.

          Methods

          We studied 158 Caucasian NT1 patients (60.7% male; mean age 49.4 ± 19.7 years), in whom the diagnosis was confirmed by polysomnography followed by a multiple sleep latency test, or by hypocretin-1 levels measurements.

          Results

          Thirty out of 158 patients (18.99%; 53.3% female; 29 sporadic and one familial cases) had one or more immunopathological diseases associated. A control group of 151 subjects were matched by gender and age with the narcolepsy patients. Results demonstrated that there was a higher frequency of ADs in our series of narcolepsy patients compared to the sample of general population (odds ratio: 3.17; 95% confidence interval: 1.01 - 10.07; P = 0.040). A temporal relationship with the age at onset of the diseases was found.

          Conclusions

          Cataplexy was significantly more severe in NT1 patients with immunopathological diseases, and immunopathological diseases are a risk factor for severe forms of cataplexy in our series (odds ratio: 23.6; 95% confidence interval: 5.5 - 100.1).

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          Most cited references65

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          The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

          We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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            Hypocretin (orexin) deficiency in human narcolepsy.

            Alterations in the hypocretin receptor 2 and preprohypocretin genes produce narcolepsy in animal models. Hypocretin was undetectable in seven out of nine people with narcolepsy, indicating abnormal hypocretin transmission.
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              AS03 Adjuvanted AH1N1 Vaccine Associated with an Abrupt Increase in the Incidence of Childhood Narcolepsy in Finland

              Background Narcolepsy is a chronic sleep disorder with strong genetic predisposition causing excessive daytime sleepiness and cataplexy. A sudden increase in childhood narcolepsy was observed in Finland soon after pandemic influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase was observed in other age groups. Methods Retrospective cohort study. From January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of all children living in Finland and born from January 1991 through December 2005. Vaccination data of the whole population was obtained from primary health care databases. All new cases with assigned ICD-10 code of narcolepsy were identified and the medical records reviewed by two experts to classify the diagnosis of narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy was defined as the first documented contact to health care because of excessive daytime sleepiness. The primary follow-up period was restricted to August 15, 2010, the day before media attention on post-vaccination narcolepsy started. Findings Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1–30.8). The vaccine-attributable risk of developing narcolepsy was 1∶16,000 vaccinated 4 to 19-year-olds (95% confidence interval 1∶13,000–1∶21,000). Conclusions Pandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009–2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing conclusions about the use of adjuvanted pandemic vaccines in the future.
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                Author and article information

                Journal
                J Clin Med Res
                J Clin Med Res
                Elmer Press
                Journal of Clinical Medicine Research
                Elmer Press
                1918-3003
                1918-3011
                July 2016
                29 May 2016
                : 8
                : 7
                : 495-505
                Affiliations
                [a ]Sleep Unit, Clinical Neurophysiology Service, San Carlos University Hospital, Madrid, Spain
                [b ]Histocompatibility, Blood Center of the Community of Madrid, Madrid, Spain
                [c ]Neurology Service, Gregorio Maranon University Hospital, Madrid, Spain
                [d ]Immunology Service, San Carlos University Hospital, Madrid, Spain
                [e ]Sleep and Epilepsy Unit, Clinical Neurophysiology Service, Gregorio Maranon University Hospital, Madrid, Spain
                Author notes
                [f ]Corresponding Author: Rosa Peraita-Adrados, Sleep and Epilepsy Unit, Clinical Neurophysiology Service, Gregorio Maranon University Hospital, Complutense University of Madrid (UCM), C/ Dr. Esquerdo, 46, E-28007 Madrid, Spain. Email: rosa-peraita@ 123456telefonica.net
                Article
                10.14740/jocmr2569w
                4894018
                27298657
                195b61e4-b342-4292-9578-bbc5cf107610
                Copyright 2016, Martinez-Orozco et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 May 2016
                Categories
                Original Article

                Medicine
                autoimmune diseases,comorbidity,epidemiology,immunopathological diseases,narcolepsy with cataplexy,narcolepsy type 1

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