Vitalmed Research Center

Helsinki, Finland

Vitalmed Research Center

Helsinki, Finland
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Sarkanen T.O.,Central Finland Central Hospital | Sarkanen T.O.,University of Helsinki | Alakuijala A.P.E.,University of Helsinki | Dauvilliers Y.A.,Montpellier University Hospital Center | And 3 more authors.
Sleep Medicine Reviews | Year: 2017

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®). 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. © 2017 Elsevier Ltd.

Sieminski M.,Medical University of Gdańsk | Losy J.,Polish Academy of Sciences | Partinen M.,Vitalmed Research Center | Partinen M.,University of Helsinki
Sleep Medicine Reviews | Year: 2015

Restless legs syndrome (RLS) is a sleep-related sensory-motor disorder characterized by an irresistible urge to move the legs accompanied by unpleasant sensations in the lower extremities. According to many recent studies patients with multiple sclerosis (MS) suffer frequently from symptoms of RLS. The prevalence of RLS in MS patients varies 13.3%-65.1%, which is higher than the prevalence of RLS in people of the same age in the general population. MS patients with RLS have higher scores in the Expanded Disability Status Scale compared to MS patients without RLS. Presence of RLS has a negative impact on sleep quality and fatigue of MS patients. Iron deficiency and chronic inflammation may be factors contributing to development of RLS in MS. The relationship between the course and treatment of MS and RLS requires further prospective studies. © 2014 Elsevier Ltd.

Julkunen I.,University of Turku | Partinen M.,VitalMed Research Center
Nature Reviews Neurology | Year: 2014

A pandemic influenza vaccine with a specific type of vaccine antigen has been linked to an increased incidence of narcolepsy in children from 2009-2010. However, the recent retraction of an article that reported a putative autoantigen means that the search for the mechanisms behind the vaccine-narcolepsy connection continues. © 2014 Macmillan Publishers Limited. All rights reserved.

Partinen M.,Vitalmed Research Center | Partinen M.,University of Helsinki | Kornum B.R.,Glostrup Hospital | Plazzi G.,University of Bologna | And 5 more authors.
The Lancet Neurology | Year: 2014

Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger. © 2014 Elsevier Ltd.

Nohynek H.,Finnish National Institute for Health and Welfare | Jokinen J.,Finnish National Institute for Health and Welfare | Partinen M.,Vitalmed Research Center | Vaarala O.,Finnish National Institute for Health and Welfare | And 8 more authors.
PLoS ONE | Year: 2012

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. © 2012 Nohynek et al.

Hublin C.,Finnish Institute of Occupational Health | Hublin C.,University of Helsinki | Partinen M.,University of Helsinki | Partinen M.,Vitalmed Research Center | And 3 more authors.
Journal of Sleep Research | Year: 2013

Genetic factors affect many aspects of sleep, such as sleep length. We investigated the contribution of genetic factors to stability and change of sleep length among adults over a 15-year period. In this representative follow-up study we used the Finnish Twin Cohort as the study population. Questionnaire surveys were performed in 1975 (response rate 89%, 11 041 twin pairs; age ≥18 years), 1981 (84%, 9323; ≥24 years) and 1990 (77%, 4507; 33-60 years). Sleep was categorized as short (<7 h), average or long (>8 h). Pairwise similarity in monozygotic and dizygotic pairs was examined at each survey by age group and sex. Quantitative genetic modelling was used to estimate cross-sectional and longitudinal genetic effects. The proportion of variance in sleep length at one point in time that was accounted for by genetic effects was very stable over the study period, being 0.31 in 1975, 0.32 in 1981 and 0.30 in 1990. Longitudinal genetic modelling indicated that the correlations of genetic effects between the three measurement points were high: 0.85 between 1975 and 1981; 0.93 between 1981 and 1990; and 0.76 between 1975 and 1990. Despite a high contribution of environmental effects, their correlations over time were modest: 0.31 between 1975 and 1981; 0.33 between 1981 and 1990; and 0.18 between 1975 and 1990. In conclusion, genetic factors have a modest but stable effect on the evolution of sleep length over a long time span in adults. Multiple measures are a more robust basis for genetic analyses than a single cross-sectional measure. © 2013 European Sleep Research Society.

Hublin C.,Finnish Institute of Occupational Health | Hublin C.,University of Helsinki | Partinen M.,Vitalmed Research Center | Partinen M.,University of Helsinki | And 3 more authors.
Sleep | Year: 2011

Study Objectives: Our aim was to estimate heritability in phenotypic insomnia and the association between insomnia and mortality. Design: Representative follow-up study. Participants: 1990 survey of the Finnish Twin Cohort (N = 12502 adults; 1554 monozygotic and 2991 dizygotic twin pairs). Measurements: Current insomnia-related symptoms (insomnia in general, difficulty in initiating sleep, sleep latency, nocturnal awakening, early morning awakening, and non-restorative sleep assessed in the morning and during the day) were asked. Latent class analysis was used to classify subjects into different sleep quality classes. Quantitative genetic modelling was used to estimate heritability. Mortality data was obtained from national registers until end of April 2009. Results: The heritability estimates of each symptom were similar in both genders varying from 34% (early morning awakening) to 45% (nocturnal awakening). The most parsimonious latent class analysis produced 3 classes: good sleepers (48%), average sleepers (up to weekly symptoms, 40%), and poor sleepers (symptoms daily or almost daily, 12%). The heritability estimate for the cluster was 46% (95% confidence interval 41% to 50%). In a model adjusted for smoking, BMI, and depressive symptoms, the all-cause mortality of poor sleepers was elevated (excess mortality 55% in men and 51% in women). Further adjustment for sleep length, use of sleep promoting medications, and sleep apnea-related symptoms did not change the results. Conclusions: Insomnia-related symptoms were common in both genders. The symptoms and their clusters showed moderate heritability estimates. A significant association was found between poor sleep and risk of mortality, especially in those with somatic disease.

Ylikoski A.,Vitalmed Research Center | Ylikoski A.,Hospital of Laakso | Martikainen K.,Finnish Parkinson Foundation | Partinen M.,Vitalmed Research Center | Partinen M.,University of Helsinki
Journal of the Neurological Sciences | Year: 2014

Results The prevalence of REM sleep behavior disorder (RBD) evaluated by the RBDSQ ≥ 6 was 39.0%. The occurrences of other parasomnias (≥ 1/week) in patients with PD were: nightmares 17.2%, night terrors 3.9%, sleepwalking 1.8%, enuresis 21.0%, and hallucinations 15.3%. Occurrences (≥ 1/week) of the isolated sleep symptoms were: nocturnal sweating 28.8%, bruxism 4.7%, and sleep talking 21.7%. Association of RBD with sleepwalking (parasomnia overlap disorder) was found in 1.7% of all PD patients. Adjusted logistic regression analysis showed that weekly nightmares (OR 12.5; 95% CI 5.3 to 29.7), hallucinations (OR 5.1; 2.1 to 12.4), sleep talking (OR 11.6; 5.9 to 22.8), male gender (OR 1.9; 1.1 to 3.1), and restless legs syndrome (OR 4.7; 1.7 to 13.2) associated with the presence of RBD.Conclusion Parkinson patients with RBD have often also other parasomnias and/or isolated sleep symptoms.Background Sleep disorders are among the most common non-motor symptoms in Parkinson's disease.Method The prevalence of parasomnias and their association with other symptoms were studied in a questionnaire study among 1447 randomly selected Parkinson patients, aged 43 to 89 years. The response rate was 59.0% and of these 77% had answered to all questions that were used in the analyses (N = 661). © 2014 Elsevier B.V. All rights reserved.

Alakuijala A.,University of Helsinki | Alakuijala A.,Vitalmed Research Center | Sarkanen T.,University of Helsinki | Sarkanen T.,Vitalmed Research Center | And 3 more authors.
Sleep Medicine | Year: 2015

Objective: After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and early 2010, the incidence of narcolepsy increased in many European countries. This incidence mainly increased in children and adolescents and, to a lesser degree, in adults. Patients/Methods: 125 unmedicated patients, aged 4 to 61 years, were included in this case-series study. Of these, 69 were diagnosed to have an H1N1-vaccine-related narcolepsy and 57 had sporadic narcolepsy. Most of these patients had: an actigraphy recording of 1-2 weeks, polysomnography, a Multiple Sleep Latency Test (MSLT), and cerebrospinal fluid hypocretin-1 concentration analysis. Results: Patients with H1N1-vaccine-related narcolepsy had shorter diagnostic delays, lower periodic leg movement index during sleep, earlier sleep-wake rhythm, and were younger in age at diagnosis, compared with sporadic cases. They also had shorter sleep latency and more sleep onset REM periods in MSLT, but these results were strongly age-dependent. Actigraphy showed quantitatively less sleep and more sleep fragmentation than polysomnography. Conclusion: Regarding polysomnographic and actigraphic characteristics, there were no dramatic deviations between H1N1-vaccine-related and sporadic narcolepsy. Circadian rhythms indicated some interesting new findings with respect to the H1N1-vaccine-related disease. An actigraphy recording of 1-2 weeks is useful when studying the nocturnal aspects of narcolepsy and sleep-wake rhythms of narcoleptic patients. © 2014 Elsevier B.V.

Pizza F.,University of Bologna | Pizza F.,CNR Institute of Neurological Sciences | Peltola H.,Vitalmed Research Center | Sarkanen T.,Vitalmed Research Center | And 5 more authors.
Sleep Medicine | Year: 2014

Objectives: We aimed to compare post-Pandemrix® vaccination (postvaccine) childhood narcolepsy with cataplexy (NC) vs sporadic pre-H1N1 pandemic (pre-H1N1) cases. Methods: Clinical, anthropometric, polysomnographic, and cerebrospinal hypocretin 1 (hcrt-1) measurements were collected together with the video recordings of cataplexy in 27 Finnish patients with NC onset after H1N1 Pandemrix® vaccination (mean age, 12 ± 4. years; 52% boys) and 42 Italian NC patients with NC onset before the H1N1 pandemic (mean age, 11 ± 3. years; 48% boys). All subjects carried the HLA-DQB1*0602 allele. Results: Postvaccine subjects were older at NC onset (12 ± 3 vs 9 ± 3. years; P= .008) and displayed a shorter mean sleep latency in multiple sleep latency tests (MSLT) (2.3 ± 2.2 vs 3.7 ± 2.9 min; P= .026) compared to pre-H1N1 cases. Anthropometric, clinical (core NC symptoms), hcrt-1 deficiency, and polysomnographic data did not differ among groups, but higher disrupted nocturnal sleep was observed in postvaccine subjects. Comparison of cataplexy features at video assessment showed an overlapping picture with the exception for hyperkinetic movements which appeared to be more evident in pre-H1N1 subjects. Conclusions: The clinical picture of childhood NC was similar in postvaccine and pre-H1N1 children. © 2013 Elsevier B.V.

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