Browsing by Subject "Narcolepsy"

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  • Sarkanen, Tomi; Alakuijala, Anniina; Partinen, Markku (2016)
    Objective: To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccinerelated narcolepsy (pNT1). Methods: Twenty-six drug-naive confirmed pNT1 subjects completed Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), Swiss Narcolepsy Scale (SNS), Rimon's Brief Depression scale (RDS), and WHO-5 Well-being index questionnaires near the disease onset and in a follow-up a minimum of two years later. The number of cataplexies and body mass index (BMI) were recorded. The effects of hypocretin-1 levels and sleep recording results were analyzed. The findings at the follow-up visit were compared with 25 non-vaccine-related type 1 narcolepsy (NT1) subjects. Results: In pNT1, RDS score decreased significantly (mean 10.2, SD 4.7 vs mean 6.7, SD 4.5, p = 0.003). Median of BMI increased from 20.8 kg m(-2) to 23.4 kg m(-2), p <0.001. There were no significant differences in other sleep scores. However, deviation and range in questionnaire scores at the follow-up were wide. Subjects with very low or undetectable hypocretin-1 levels had worse scores in UNS (mean 26.4, SD 6.95 vs mean 19.1, SD 3.83, p = 0.006) and ESS (mean 17.9, SD = 4.29 vs mean 14.1, SD = 3.70, p = 0.047) than those with hypocretin-1 levels of 20-110 pg/mL. Most disabling symptoms were excessive daytime sleepiness and disturbed sleep. There were no significant differences between the scores in pNT1 and NT1. Conclusions: Clinical course of pNT1 is heterogeneous but the evolution of pNT1 seems similar to NT1. Lower hypocretin levels in pNT1 are associated with a more severe phenotype. (C) 2015 Elsevier B.V. All rights reserved.
  • Lammers, Gert Jan; Bassetti, Claudio L.A.; Dolenc-Groselj, Leja; Jennum, Poul J.; Kallweit, Ulf; Khatami, Ramin; Lecendreux, Michel; Manconi, Mauro; Mayer, Geert; Partinen, Markku; Plazzi, Giuseppe; Reading, Paul J.; Santamaria, Joan; Sonka, Karel; Dauvilliers, Yves (2020)
    Summary The aim of this European initiative is to facilitate a structured discussion to improve the next edition of the International Classification of Sleep Disorders (ICSD), particularly the chapter on central disorders of hypersomnolence. The ultimate goal for a sleep disorders classification is to be based on the underlying neurobiological causes of the disorders with clear implication for treatment or, ideally, prevention and or healing. The current ICSD classification, published in 2014, inevitably has important shortcomings, largely reflecting the lack of knowledge about the precise neurobiological mechanisms underlying the majority of sleep disorders we currently delineate. Despite a clear rationale for the present structure, there remain important limitations that make it difficult to apply in routine clinical practice. Moreover, there are indications that the current structure may even prevent us from gaining relevant new knowledge to better understand certain sleep disorders and their neurobiological causes. We suggest the creation of a new consistent, complaint driven, hierarchical classification for central disorders of hypersomnolence; containing levels of certainty, and giving diagnostic tests, particularly the MSLT, a weighting based on its specificity and sensitivity in the diagnostic context. We propose and define three diagnostic categories (with levels of certainty): 1/“Narcolepsy” 2/“Idiopathic hypersomnia”, 3/“Idiopathic excessive sleepiness” (with subtypes)
  • Sarkanen, Tomi O.; Alakuijala, Anniina P. E.; Dauvilliers, Yves A.; Partinen, Markku M. (2018)
    An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009-2010. The H1N1 vaccine - narcolepsy connection is based on observational studies that are prone to various biases, e.g., confounding by H1N1 infection, and ascertainment, recall and selection biases. A direct pathogenic link has, however, remained elusive. We conducted a systematic review and meta-analysis to analyze the magnitude of H1N1 vaccination related risk and to examine if there was any association with H1N1 infection itself. We searched all articles from PubMed, Web of Science and Scopus, and other relevant sources reporting the incidence and risk of post-vaccine narcolepsy. In our paper, we show that the risk appears to be limited to only one vaccine (Pandemrix (R)). During the first year after vaccination, the relative risk of narcolepsy was increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults. The vaccine attributable risk in children and adolescents was around 1 per 18,400 vaccine doses. Studies from Finland and Sweden also appear to demonstrate an extended risk of narcolepsy into the second year following vaccination, but such conclusions should be interpreted with a word of caution due to possible biases. Benefits of immunization outweigh the risk of vaccination-associated narcolepsy, which remains a rare disease. (C) 2017 Elsevier Ltd. All rights reserved.
  • Nevalainen, Päivi; Ilveskoski, Ismo; Vanhatalo, Sampsa; Lauronen, Leena (2019)
    Kliinisen neurofysiologian menetelmillä selvitetään keskus- ja ääreishermoston sekä lihaksiston sairauksia. Lapsilla yleisin tutkimus on aivosähkökäyrä eli EEG, jolla selvitetään erityisesti kohtausoireiden taustaa. Tavallisia ovat myös uni- ja vireystilatutkimukset, elektroneuromyografia ja herätevastetutkimukset. Erityistilanteissa tarvitaan akuuttihoidon aivomonitorointia, leikkauksenaikaista neuromonitorointia sekä aivotoimintojen paikantamista.
  • Sarkanen, Tomi; Alakuijala, Anniina; Partinen, Markku (2017)
    •Liikaunisuus tarkoittaa poikkeavaa päiväaikaista väsymystä, johon yhdistyy pakonomainen nukahtamistarve. •Tavallisin päiväväsymyksen syy on riittämätön tai rikkonainen ja virkistämätön yöuni. Keskushermostoperäiset liikaunisuussairaudet sen sijaan ovat harvinaisia. •Liikaunisuuden syy tulee selvittää ja hoito kohdentaa siihen aina kun mahdollista. •Lääkkeettömistä hoitomuodoista on hyötyä taustasyystä riippumatta. •Keskushermostoperäisissä liikaunisuussairauksissa vireyttä parantava lääkehoito on usein tarpeen, mutta tilanne on aina arvioitava yksilöllisesti. Lääkehoitovaihtoehtojen keskeinen ongelma on näytön puute.
  • Sarkanen, Tomi; Alakuijala, Anniina; Julkunen, Ilkka; Partinen, Markku (2018)
    After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix and narcolepsy was recognized in 2010, research on narcolepsy has been more intensive than ever before. The purpose of this review is to provide the reader with current concepts and recent findings on the Pandemrix-associated narcolepsy. After the Pandemrix vaccination campaign in 2009-2010, the risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults. According to observational studies, the risk of narcolepsy was elevated for 2 years after the Pandemrix vaccination. Some confounding factors and potential diagnostic biases may influence the observed narcolepsy risk in some studies, but it is unlikely that they would explain the clearly increased incidence in all the countries where Pandemrix was used. An increased risk of narcolepsy after natural H1N1 infection was reported from China, where pandemic influenza vaccination was not used. There is more and more evidence that narcolepsy is an autoimmune disease. All Pandemrix-associated narcolepsy cases have been positive for HLA class II DQB1*06:02 and novel predisposing genetic factors directly linking to the immune system have been identified. Even though recent studies have identified autoantibodies against multiple neuronal structures and other host proteins and peptides, no specific autoantigens that would explain the disease mechanism in narcolepsy have been identified thus far. There was a marked increase in the incidence of narcolepsy after Pandemrix vaccination, especially in adolescents, but also in young adults and younger children. All vaccine-related cases were of narcolepsy type 1 characterized by hypocretin deficiency in the central nervous system. The disease phenotype and the severity of symptoms varied considerably in children and adolescents suffering from Pandemrix-associated narcolepsy, but they were indistinguishable from the symptoms of idiopathic narcolepsy. Narcolepsy type 1 is most likely an autoimmune disease, but the mechanisms have remained elusive.
  • Partinen, Markku; Alakuijala, Anniina; Sarkanen, Tomi; Sved, Gabriele (2018)
  • Melén, Krister; Jalkanen, Pinja; Kukkonen, Jyrki P.; Partinen, Markku; Nohynek, Hanna; Vuorela, Arja; Vaarala, O.; Freitag, Tobias L.; Meri, Seppo; Julkunen, Ilkka (2020)
    Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX2 orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX1 or OX2 receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX1 and OX2 receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX2. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors. © 2020 The Authors
  • Sieminski, Mariusz; Szypenbejl, Jacek; Partinen, Eemil (2018)
    The aim of this review was to summarize collected data on the role of orexin and orexin neurons in the control of sleep and blood pressure. Although orexins (hypocretins) have been known for only 20 years, an impressive amount of data is now available regarding their physiological role. Hypothalamic orexin neurons are responsible for the control of food intake and energy expenditure, motivation, circadian rhythm of sleep and wake, memory, cognitive functions, and the cardiovascular system. Multiple studies show that orexinergic stimulation results in increased blood pressure and heart rate and that this effect may be efficiently attenuated by orexinergic antagonism. Increased activity of orexinergic neurons is also observed in animal models of hypertension. Pharmacological intervention in the orexinergic system is now one of the therapeutic possibilities in insomnia. Although the role of orexin in the control of blood pressure is well described, we are still lacking clinical evidence that this is a possibility for a new approach in the treatment of cardiovascular diseases.
  • Peltola, Hanna (Helsingfors universitet, 2016)
    This report aims to describe the video assessment of the hypotonic and active motor phenomena in childhood narcolepsy with cataplexy performed for two articles specified in the additional information as well as to briefly present the other results of those articles. The video recordings for subjects with narcolepsy with cataplexy and their control groups were assessed for negative and positive cataplectic motor phenomena in two settings: 1st drug-naïve narcolepsy patients compared to healthy controls and evaluated at disease onset and after a follow-up and 2nd post-H1N1 Pandemrix® vaccinated narcolepsy patients compared to sporadic cases. In the first setting the cataplexy severity reflected by hypotonic and active motor phenomena decreased over time and the clinical picture evolved into resembling the classical cataplexy phenotype without spontaneous hypotonia. In the second setting the two groups were similar but subjects with sporadic narcolepsy onset were found to have more active movements of the facial muscles.