Tomi Sarkanen - Academia.edu (original) (raw)
Papers by Tomi Sarkanen
Journal of Clinical Sleep Medicine
Erikoislääkäri 3/2021 • 31 vsk 84 LUE LISÄÄ brintellix.fi Brintellix on tehokas masennuksen hoido... more Erikoislääkäri 3/2021 • 31 vsk 84 LUE LISÄÄ brintellix.fi Brintellix on tehokas masennuksen hoidossa 1-6 Brintellix on hyvin siedetty 1-5 Mahdollisuus yksilölliseen annosteluun vasteen mukaan FI-BRIN-0154 (08/2021) 10 mg 5 mg 20 mg 15 mg PE RU S-JA ER ITY ISK OR VA TT AV A (11 2) MA SE NN US LÄ ÄK E Brintellix ® 5 mg, 10 mg, 15 mg ja 20 mg kalvopäällysteiset tabletit Käyttöaiheet: Brintellix on tarkoitettu vakavien masennustilojen hoitoon aikuisille. Annostus ja antotapa: Aloitusannos ja suositeltu annos Brintellixvalmistetta alle 65-vuotiaille aikuisille on 10 mg kerran päivässä, aterian yhteydessä tai ilman ateriaa. Annosta voi potilaan yksilöllisen hoitovasteen mukaan suurentaa tai pienentää. Enimmäisannos on 20 mg vortioksetiinia kerran vuorokaudessa ja vähimmäisannos 5 mg vortioksetiinia kerran vuorokaudessa. 65 vuotta täyttäneillä aloitusannos on 5 mg kerran vuorokaudessa. Hoidon lopettaminen: Vortioksetiinihoitoa saavat voivat lopettaa lääkevalmisteen käytön äkillisesti, vähentämättä annosta vähitellen. Vasta-aiheet: Yliherkkyys vaikuttavalle aineelle/apuaineille. Samanaikainen käyttö epäselektiivisten monoamiinioksidaasin estäjien (MAO-estäjien) tai selektiivisten MAO-A:n estäjien kanssa. Varoitukset ja käyttöön liittyvät varotoimet: Masennukseen liittyy lisääntynyt alttius itsemurha-ajatuksiin, itsensä vahingoittamiseen ja itsemurhiin (itsemurhaan liittyvät tapahtumat). Tämä alttius säilyy, kunnes itse taudissa tapahtuu merkittävää paranemista. Koska paranemista ei ehkä tapahdu ensimmäisten hoitoviikkojen aikana, potilaita tulee seurata tarkoin siihen saakka, että paranemista tapahtuu. Kliinisen kokemuksen perusteella tiedetään, että itsemurha-alttius saattaa kasvaa toipumisen alkuvaiheessa. Vortioksetiinin käyttö on aloitettava varovasti, jos potilaalla on ollut aiemmin kouristuskohtauksia tai jos hän sairastaa epästabiilia epilepsiaa. Serotoniinioireyhtymän ja neuroleptioireyhtymän mahdollisia oireita on seurattava vortioksetiinihoidon aikana. Vortioksetiinia on käytettävä varoen, jos potilaalla on ollut mania tai hypomania, ja sen käyttö on lopetettava, jos potilaalle tulee maaninen vaihe. Masennuslääkkeillä, kuten vortioksetiinilla, hoidetuilla potilailla voi myös ilmetä aggression, vihan, agitaation ja ärtyisyyden tunteita. Potilaan tilaa ja taudin tilaa on tarkkailtava tarkasti. Verenvuotohäiriöitä ja verenvuototapahtumia on ilmoitettu esiintyneen harvoin käytettäessä serotonergisiä masennuslääkkeitä, mukaan lukien vortioksetiinia. Hyponatremiaa on todettu joskus harvoin serotonergisiä masennuslääkkeitä (SSRI, SNRI) käyttävillä. Mydriaasivaikutus voi mahdollisesti kaventaa kammiokulmaa, mikä johtaa silmänpaineen kohoamiseen ja ahdaskulmaglaukoomaan. Maksan tai munuaisten vajaatoimintaa sairastavilla potilailla on noudatettava varovaisuutta. Yhteisvaikutukset: Vortioksetiini metaboloituu suurelta osin maksassa, pääasiassa hapettumalla CYP2D6:n ja vähäisessä määrin CYP3A4/5:n ja CYP2C9:n katalysoimana. Varo vaisuutta suositellaan noudattamaan, kun lääkettä käytetään yhdessä MAO-estäjien, serotonergisten lääkkeiden, kouristuskynnystä alentavien lääkkeiden, litiumin, tryptofaanin, oraalisten antikoagulanttien ja verihiutaleiden estäjien kanssa. Vortioksetiiniannoksen sovittamista voidaan harkita yhdistettäessä sitä voimakkaisiin sytokromi P450 induktoreihin tai inhibiittoreihin. Katso tarkemmat tiedot valmisteyhteenvedosta. Raskaus ja imetys: Brintellix-valmistetta saa antaa raskaana oleville naisille vain, jos odotettavissa olevat hyödyt katsotaan sikiöön kohdistuvaa riskiä suuremmiksi. Suurentunut synnytyksenjälkeisen verenvuodon riski on mahdollinen. Vortioksetiinin oletetaan erittyvän rintamaitoon. Imeväiseen kohdistuvia riskejä ei voida poissulkea. On pohdittava lääkehoidon hyödyt suhteessa haittoihin. Vaikutus ajokykyyn ja koneiden käyttökykyyn:
Journal of Stroke and Cerebrovascular Diseases, 2022
OBJECTIVES We examined the association between obesity and early-onset cryptogenic ischemic strok... more OBJECTIVES We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.
Frontiers in Neurology, 2021
Actigraphy provides longitudinal sleep data over multiple nights. It is a less expensive and less... more Actigraphy provides longitudinal sleep data over multiple nights. It is a less expensive and less cumbersome method for measuring sleep than polysomnography. Studies assessing accuracy of actigraphy compared to ambulatory polysomnography in different sleep-disordered patients are rare. We aimed to compare the concordance between these methods in clinical setting. We included 290 clinical measurements of 281 sleep laboratory patients (mean age 37.9 years, 182 female). Concomitant ambulatory polysomnography and actigraphy were analyzed to determine the agreement in patients with obstructive sleep apnea, narcolepsy, periodic leg movement disorder, hypersomnia, other rarer sleep disorders, or no organic sleep disorder. Bland-Altman plots showed excellent accuracy, but poor precision in single night results between the two methods in the measurement of sleep time, sleep efficiency, and sleep latency. On average, actigraphy tended to overestimate sleep time by a negligible amount, −0.13 m...
Narkolepsian moninainen oirekuva ja käypä diagnostiikka Narkolepsia on keskushermostoperäinen uni... more Narkolepsian moninainen oirekuva ja käypä diagnostiikka Narkolepsia on keskushermostoperäinen unihäiriö, jonka keskeisiä oireita ovat poikkeava päiväaikainen väsymys, tahaton nukahtelu, katapleksia ja rikkonainen yöuni. Muita narkolepsian klassisia oireita ovat nukahtamis-ja heräämisvaiheen aistiharhat ja unihalvaukset. Narkolepsia jaetaan kahteen alamuotoon. Tyypin 1 narkolepsiassa aivo-selkäydinnesteen oreksiinipitoisuus on poikkeavan pieni. Huomattavasti harvinaisemmassa tyypin 2 narkolepsiassa ei esiinny katapleksiaa ja oreksiinipitoisuus on viitealueella. Diagnostiikassa suljetaan pois muut päiväaikaista väsymystä aiheuttavat syyt, kuten unen puute, unijakson viivästyminen, uniapnea, krooninen väsymysoireyhtymä, aktiivisuuden ja tarkkaavuuden häiriö (ADHD), jaksottainen liikaunisuus sekä elimelliset (esimerkiksi diabetes, hypotyreoosi) ja psykiatriset syyt. Sekundaarisen narkolepsian syitä ovat muun muassa aivovammat, aivokasvaimet ja harvinaiset perinnölliset sairaudet. Narkolepsian oireet Klassisen vuonna 1960 julkaistun "narkolepsiatetradin" oireita ovat tahaton nukahtelu, katapleksia, hypnagogiset (nukahtamisvaiheen) aistiharhat ja unihalvaukset (12). Täydellinen narkolepsiatetradi todetaan vain noin kolmasosalla narkolepsiapotilaista. Narkolepsian yleisimmät oireet ovat tahaton nukahtelu, katapleksia ja huonolaatuinen yöuni. Poikkeava päiväaikainen väsymys, tahaton nukahtelu ja rikkonainen yöuni. Tervekin ihminen voi helposti torkahtaa esimerkiksi brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Helsingin yliopiston digitaalinen arkisto
Objectives: After the 2009-2010 pandemic H1N1 vaccination campaign, a large number of new narcole... more Objectives: After the 2009-2010 pandemic H1N1 vaccination campaign, a large number of new narcolepsy cases suddenly appeared in countries where the AS03adjuvanted Pandemrix vaccination was used. An increased incidence of narcolepsy after the 2009/2010 H1N1 influenza season was observed also in China, where vaccine coverage was very low. However, epidemiological studies are prone to various biases and confounders. Furthermore, there is evidence from animal studies that H1N1 virus infection per se might be able to manifest a narcolepsy-like phenotype. Therefore, some controversy exists in the association between vaccination and narcolepsy. Our first aim was to systematically analyze the magnitude of the risk of narcolepsy after Pandemrix vaccination and to examine whether an increased association emerged with any other vaccine or H1N1 virus infection (Study I). H1N-vaccine-associated narcolepsy (pNC) cases had very abrupt onset, short diagnostic delay, and common psychiatric comorbidity, which warranted thorough analysis of the phenotype and characteristics of the disease. In Studies II and III, we aimed to determine whether differences were present in clinical, polysomnographic (PSG), or actigraphic (ACT) characteristics between pNC and sporadic narcolepsy (sNC). Moreover, clinical evolution of pNC was analyzed. Diagnosis of narcolepsy can be challenging since neurophysiological sleep studies are not 100% accurate for narcolepsy. Furthermore, lumbar puncture to measure hypocretin level (HCRT) is an invasive procedure that some patients refuse to undergo. Patient-reported outcomes or questionnaires to measure narcolepsy symptoms or tools to help in diagnostics remain scarce. The Ullanlinna Narcolepsy Scale (UNS) was developed for population screening for narcolepsy, but the structure of the questionnaire could allow its use in the clinical population as well. In Study IV, we wanted to validate the UNS in diagnostics of narcolepsy. Methods: Study I is a comprehensive systematic review and meta-analysis of the risk of pNC. In Study II, PSG and ACT characteristics of 69 pNC and 57 sNC subjects were analyzed. In Study III, 26 pNC patients completed the modified Basic Nordic Sleep Questionnaire near onset of the disease and at the follow-up at least two years later. We specifically analyzed the results from UNS, Epworth Sleepiness Scale (ESS), Rimon's Brief Depression Scale (RDS), and WHO-5 Well-Being Index. Follow-up results were compared with 25 subjects with sNC. In Study IV, we reviewed sleep questionnaires of 89 patients with narcolepsy type 1 (NT1), 10 with narcolepsy type 2 (NT2), 37 with sleep apnea, 56 with restless legs syndrome or periodic limb movement disorder, 51 with other sleep-related disorders, and 24 with other hypersomnias (Kleine-Levin syndrome, idiopathic hypersomnia, or hypersomnia not otherwise specified). v Results: The relative risk of narcolepsy was increased 5-to 14-fold in children and adolescents and 2-to 7-fold in adults in the countries where Pandemrix vaccine was used widely (Finland, Sweden, Norway, France, England, Ireland) or in certain age groups (< 5 years, in the Netherlands). The vaccine-attributable risk in children and adolescents was 1 per 18,400 vaccines. Studies from Finland and Sweden suggest that the risk was increased two years after the vaccination, but this result needs to be interpreted with caution because of possible biases. Patients with pNC had shorter diagnostic delays, were diagnosed younger, had lower periodic limb movement index during sleep, and had earlier sleep-wake rhythm than sNC patients, but otherwise there were no significant differences in ACT and PSG parameters between the patient groups. In pNC patients in Study III, RDS points decreased significantly, indicating less symptoms of depression (mean (M) difference-3.5, 95% confidence interval (CI) [-5.5,-1.3], P = .003). At follow-up, the median of body mass index increased from 20.8 kgm-2 to 23.4 kgm-2 (P < .001). There were no significant differences in other sleep scores. However, variation in questionnaire scores at follow-up was wide. pNC subjects with very low or undetectable HCRT had higher scores in UNS and ESS than those with HCRT between 20 and 110 pg/mL (UNS
PLOS ONE, 2017
Study objective Narcolepsy type 1 (NT1) is caused by a deficiency or absence of the neurotransmit... more Study objective Narcolepsy type 1 (NT1) is caused by a deficiency or absence of the neurotransmitter orexin. NT1 is also associated with a reduced nocturnal "dipping" of blood pressure (BP). The study objective was to analyze whether nocturnal BP values differed in patients depleted of orexin, versus those in whom production was preserved. Methods We performed a retrospective analysis of the polysomnographic recordings, orexin levels, and BP values of patients with NT1. Data was collected from a total of 21 patients, divided into two groups as follows: those with a complete depletion of orexin (n = 11) (Group1), and those with a remaining, limited presence of orexin (n = 10) (Group 2). Results The groups did not differ in terms of the clinical features of NT1 or sleep characteristics, with an exception of increased number of cataplexy episodes and increased percentage of sleep stage 2 in the Group 1. Daytime and nocturnal BP did not differ between the groups. Most patients, regardless of group, had a non-dipping blood pressure pattern, and no difference in dipping prevalence was observed between groups. The amplitude of the daytime to nighttime change in BP did not differ between the groups. Conclusions Non-dipping BP patterns are frequent among patients with narcolepsy type 1, but we saw no evidence that they depended on whether orexin levels were above or below the assay detection threshold. Therefore, our results do not support the hypothesis that in patients with narcolepsy type 1 residual orexin levels play a role in the control of nocturnal BP dipping.
Current Neurology and Neuroscience Reports, 2018
Purpose of Review After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix an... more Purpose of Review 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. Recent Findings 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 Pandemrixassociated 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. Summary 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.
Sleep, 2018
Study objectives: To validate Ullanlinna Narcolepsy Scale (UNS) as a screening tool for narcoleps... more Study objectives: To validate Ullanlinna Narcolepsy Scale (UNS) as a screening tool for narcolepsy in a clinical population and to compare it with Swiss Narcolepsy Scale (SNS) and Epworth Sleepiness Scale (ESS). Methods: UNS questionnaires of 267 participants visiting Helsinki Sleep Clinic were analyzed. The diagnoses of the participants were narcolepsy type 1 (NT1, n = 89), narcolepsy type 2 (NT2, n = 10), other hypersomnias (n = 24), sleep apnea (n = 37), restless legs syndrome or periodic limb movement disorder (n = 56), and other sleep-related disorders (n = 51). In addition, ESS and SNS scores in a subset of sample (total N = 167) were analyzed and compared to UNS. Results: Mean UNS score in NT1 was 22.0 (95% confidence interval [CI] = 20.4 to 23.6, range 9-43), which was significantly higher than in other disorders, including NT2 (mean 13.7, 95% CI = 10.3 to 17.1, range 7-21, p = .0013). Sensitivity and specificity of UNS in separating NT1 from other disorders were 83.5% and 84.1%, respectively. Positive and negative predictive values were 82.5% and 85.1%, respectively. Sensitivities of SNS and ESS in NT1 were 77.2% and 88.6%, and specificities 88.6% and 45.5%, respectively. There were no differences in receiver operating characteristic curves between UNS and SNS. UNS had moderate negative correlation with hypocretin-1 levels (r s =-.564, p < .001), and mean sleep latency in multiple sleep latency test (r s =-.608, p < .001). Conclusions: UNS has high specificity and sensitivity for NT1 in a sleep clinic setting. UNS scores below 9 strongly suggest against the diagnosis of narcolepsy.
Sleep Medicine Reviews, 2017
An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza... more An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009e2010. The H1N1 vaccine e 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.
The neurologist, 2016
Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing ... more Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing neurons in hypothalamus. In addition to daytime sleepiness, the spectrum and severity of symptoms are very variable. Psychiatric comorbidity and phenomena resembling psychotic symptoms are also common. Current treatment options for narcolepsy are symptomatic but there are few case reports of positive effect of immunotherapy. We report a very severely affected young boy treated with rituximab (RXB). A 12-year-old boy developed narcolepsy after Pandemrix H1N1 vaccination in 2010. He started to express severe psychiatric symptoms shortly after the onset. Cataplexy and sleepiness were devastatingly disabling. Conventional treatments did not have any effect on symptoms so we decided to try RXB, chimeric human monoclonal antibody against CD20 expressed in B lymphocytes. After the first treatment his condition ameliorated dramatically. Unfortunately, the effect lasted only for 2 months. Followi...
Sleep Medicine, 2015
Introduction: To explore the co-occurrence of narcolepsy and attention deficit hyperactivity diso... more Introduction: To explore the co-occurrence of narcolepsy and attention deficit hyperactivity disorder (ADHD) symptoms and compare the damage of cognitive function and improvement after treatment of methylphenidate hydrochloride for 8-16weeks between narcolepsy with and without ADHD.
Sleep Medicine, 2016
To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccinerelated na... more To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccinerelated narcolepsy (pNT1). Methods: Twenty-six drug-naïve 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.
SLEEP, 2016
Study Objectives: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy... more Study Objectives: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. Methods: Actigraphy recording of 1−2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31−79 pg/mL. Results: According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. Conclusions: Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep.
Duodecim; lääketieteellinen aikakauskirja, 2015
Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature ... more Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.
Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are ... more Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.
Sleep Medicine, 2015
After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and ... more 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. 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. 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. 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.
Journal of Clinical Sleep Medicine
Erikoislääkäri 3/2021 • 31 vsk 84 LUE LISÄÄ brintellix.fi Brintellix on tehokas masennuksen hoido... more Erikoislääkäri 3/2021 • 31 vsk 84 LUE LISÄÄ brintellix.fi Brintellix on tehokas masennuksen hoidossa 1-6 Brintellix on hyvin siedetty 1-5 Mahdollisuus yksilölliseen annosteluun vasteen mukaan FI-BRIN-0154 (08/2021) 10 mg 5 mg 20 mg 15 mg PE RU S-JA ER ITY ISK OR VA TT AV A (11 2) MA SE NN US LÄ ÄK E Brintellix ® 5 mg, 10 mg, 15 mg ja 20 mg kalvopäällysteiset tabletit Käyttöaiheet: Brintellix on tarkoitettu vakavien masennustilojen hoitoon aikuisille. Annostus ja antotapa: Aloitusannos ja suositeltu annos Brintellixvalmistetta alle 65-vuotiaille aikuisille on 10 mg kerran päivässä, aterian yhteydessä tai ilman ateriaa. Annosta voi potilaan yksilöllisen hoitovasteen mukaan suurentaa tai pienentää. Enimmäisannos on 20 mg vortioksetiinia kerran vuorokaudessa ja vähimmäisannos 5 mg vortioksetiinia kerran vuorokaudessa. 65 vuotta täyttäneillä aloitusannos on 5 mg kerran vuorokaudessa. Hoidon lopettaminen: Vortioksetiinihoitoa saavat voivat lopettaa lääkevalmisteen käytön äkillisesti, vähentämättä annosta vähitellen. Vasta-aiheet: Yliherkkyys vaikuttavalle aineelle/apuaineille. Samanaikainen käyttö epäselektiivisten monoamiinioksidaasin estäjien (MAO-estäjien) tai selektiivisten MAO-A:n estäjien kanssa. Varoitukset ja käyttöön liittyvät varotoimet: Masennukseen liittyy lisääntynyt alttius itsemurha-ajatuksiin, itsensä vahingoittamiseen ja itsemurhiin (itsemurhaan liittyvät tapahtumat). Tämä alttius säilyy, kunnes itse taudissa tapahtuu merkittävää paranemista. Koska paranemista ei ehkä tapahdu ensimmäisten hoitoviikkojen aikana, potilaita tulee seurata tarkoin siihen saakka, että paranemista tapahtuu. Kliinisen kokemuksen perusteella tiedetään, että itsemurha-alttius saattaa kasvaa toipumisen alkuvaiheessa. Vortioksetiinin käyttö on aloitettava varovasti, jos potilaalla on ollut aiemmin kouristuskohtauksia tai jos hän sairastaa epästabiilia epilepsiaa. Serotoniinioireyhtymän ja neuroleptioireyhtymän mahdollisia oireita on seurattava vortioksetiinihoidon aikana. Vortioksetiinia on käytettävä varoen, jos potilaalla on ollut mania tai hypomania, ja sen käyttö on lopetettava, jos potilaalle tulee maaninen vaihe. Masennuslääkkeillä, kuten vortioksetiinilla, hoidetuilla potilailla voi myös ilmetä aggression, vihan, agitaation ja ärtyisyyden tunteita. Potilaan tilaa ja taudin tilaa on tarkkailtava tarkasti. Verenvuotohäiriöitä ja verenvuototapahtumia on ilmoitettu esiintyneen harvoin käytettäessä serotonergisiä masennuslääkkeitä, mukaan lukien vortioksetiinia. Hyponatremiaa on todettu joskus harvoin serotonergisiä masennuslääkkeitä (SSRI, SNRI) käyttävillä. Mydriaasivaikutus voi mahdollisesti kaventaa kammiokulmaa, mikä johtaa silmänpaineen kohoamiseen ja ahdaskulmaglaukoomaan. Maksan tai munuaisten vajaatoimintaa sairastavilla potilailla on noudatettava varovaisuutta. Yhteisvaikutukset: Vortioksetiini metaboloituu suurelta osin maksassa, pääasiassa hapettumalla CYP2D6:n ja vähäisessä määrin CYP3A4/5:n ja CYP2C9:n katalysoimana. Varo vaisuutta suositellaan noudattamaan, kun lääkettä käytetään yhdessä MAO-estäjien, serotonergisten lääkkeiden, kouristuskynnystä alentavien lääkkeiden, litiumin, tryptofaanin, oraalisten antikoagulanttien ja verihiutaleiden estäjien kanssa. Vortioksetiiniannoksen sovittamista voidaan harkita yhdistettäessä sitä voimakkaisiin sytokromi P450 induktoreihin tai inhibiittoreihin. Katso tarkemmat tiedot valmisteyhteenvedosta. Raskaus ja imetys: Brintellix-valmistetta saa antaa raskaana oleville naisille vain, jos odotettavissa olevat hyödyt katsotaan sikiöön kohdistuvaa riskiä suuremmiksi. Suurentunut synnytyksenjälkeisen verenvuodon riski on mahdollinen. Vortioksetiinin oletetaan erittyvän rintamaitoon. Imeväiseen kohdistuvia riskejä ei voida poissulkea. On pohdittava lääkehoidon hyödyt suhteessa haittoihin. Vaikutus ajokykyyn ja koneiden käyttökykyyn:
Journal of Stroke and Cerebrovascular Diseases, 2022
OBJECTIVES We examined the association between obesity and early-onset cryptogenic ischemic strok... more OBJECTIVES We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.
Frontiers in Neurology, 2021
Actigraphy provides longitudinal sleep data over multiple nights. It is a less expensive and less... more Actigraphy provides longitudinal sleep data over multiple nights. It is a less expensive and less cumbersome method for measuring sleep than polysomnography. Studies assessing accuracy of actigraphy compared to ambulatory polysomnography in different sleep-disordered patients are rare. We aimed to compare the concordance between these methods in clinical setting. We included 290 clinical measurements of 281 sleep laboratory patients (mean age 37.9 years, 182 female). Concomitant ambulatory polysomnography and actigraphy were analyzed to determine the agreement in patients with obstructive sleep apnea, narcolepsy, periodic leg movement disorder, hypersomnia, other rarer sleep disorders, or no organic sleep disorder. Bland-Altman plots showed excellent accuracy, but poor precision in single night results between the two methods in the measurement of sleep time, sleep efficiency, and sleep latency. On average, actigraphy tended to overestimate sleep time by a negligible amount, −0.13 m...
Narkolepsian moninainen oirekuva ja käypä diagnostiikka Narkolepsia on keskushermostoperäinen uni... more Narkolepsian moninainen oirekuva ja käypä diagnostiikka Narkolepsia on keskushermostoperäinen unihäiriö, jonka keskeisiä oireita ovat poikkeava päiväaikainen väsymys, tahaton nukahtelu, katapleksia ja rikkonainen yöuni. Muita narkolepsian klassisia oireita ovat nukahtamis-ja heräämisvaiheen aistiharhat ja unihalvaukset. Narkolepsia jaetaan kahteen alamuotoon. Tyypin 1 narkolepsiassa aivo-selkäydinnesteen oreksiinipitoisuus on poikkeavan pieni. Huomattavasti harvinaisemmassa tyypin 2 narkolepsiassa ei esiinny katapleksiaa ja oreksiinipitoisuus on viitealueella. Diagnostiikassa suljetaan pois muut päiväaikaista väsymystä aiheuttavat syyt, kuten unen puute, unijakson viivästyminen, uniapnea, krooninen väsymysoireyhtymä, aktiivisuuden ja tarkkaavuuden häiriö (ADHD), jaksottainen liikaunisuus sekä elimelliset (esimerkiksi diabetes, hypotyreoosi) ja psykiatriset syyt. Sekundaarisen narkolepsian syitä ovat muun muassa aivovammat, aivokasvaimet ja harvinaiset perinnölliset sairaudet. Narkolepsian oireet Klassisen vuonna 1960 julkaistun "narkolepsiatetradin" oireita ovat tahaton nukahtelu, katapleksia, hypnagogiset (nukahtamisvaiheen) aistiharhat ja unihalvaukset (12). Täydellinen narkolepsiatetradi todetaan vain noin kolmasosalla narkolepsiapotilaista. Narkolepsian yleisimmät oireet ovat tahaton nukahtelu, katapleksia ja huonolaatuinen yöuni. Poikkeava päiväaikainen väsymys, tahaton nukahtelu ja rikkonainen yöuni. Tervekin ihminen voi helposti torkahtaa esimerkiksi brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Helsingin yliopiston digitaalinen arkisto
Objectives: After the 2009-2010 pandemic H1N1 vaccination campaign, a large number of new narcole... more Objectives: After the 2009-2010 pandemic H1N1 vaccination campaign, a large number of new narcolepsy cases suddenly appeared in countries where the AS03adjuvanted Pandemrix vaccination was used. An increased incidence of narcolepsy after the 2009/2010 H1N1 influenza season was observed also in China, where vaccine coverage was very low. However, epidemiological studies are prone to various biases and confounders. Furthermore, there is evidence from animal studies that H1N1 virus infection per se might be able to manifest a narcolepsy-like phenotype. Therefore, some controversy exists in the association between vaccination and narcolepsy. Our first aim was to systematically analyze the magnitude of the risk of narcolepsy after Pandemrix vaccination and to examine whether an increased association emerged with any other vaccine or H1N1 virus infection (Study I). H1N-vaccine-associated narcolepsy (pNC) cases had very abrupt onset, short diagnostic delay, and common psychiatric comorbidity, which warranted thorough analysis of the phenotype and characteristics of the disease. In Studies II and III, we aimed to determine whether differences were present in clinical, polysomnographic (PSG), or actigraphic (ACT) characteristics between pNC and sporadic narcolepsy (sNC). Moreover, clinical evolution of pNC was analyzed. Diagnosis of narcolepsy can be challenging since neurophysiological sleep studies are not 100% accurate for narcolepsy. Furthermore, lumbar puncture to measure hypocretin level (HCRT) is an invasive procedure that some patients refuse to undergo. Patient-reported outcomes or questionnaires to measure narcolepsy symptoms or tools to help in diagnostics remain scarce. The Ullanlinna Narcolepsy Scale (UNS) was developed for population screening for narcolepsy, but the structure of the questionnaire could allow its use in the clinical population as well. In Study IV, we wanted to validate the UNS in diagnostics of narcolepsy. Methods: Study I is a comprehensive systematic review and meta-analysis of the risk of pNC. In Study II, PSG and ACT characteristics of 69 pNC and 57 sNC subjects were analyzed. In Study III, 26 pNC patients completed the modified Basic Nordic Sleep Questionnaire near onset of the disease and at the follow-up at least two years later. We specifically analyzed the results from UNS, Epworth Sleepiness Scale (ESS), Rimon's Brief Depression Scale (RDS), and WHO-5 Well-Being Index. Follow-up results were compared with 25 subjects with sNC. In Study IV, we reviewed sleep questionnaires of 89 patients with narcolepsy type 1 (NT1), 10 with narcolepsy type 2 (NT2), 37 with sleep apnea, 56 with restless legs syndrome or periodic limb movement disorder, 51 with other sleep-related disorders, and 24 with other hypersomnias (Kleine-Levin syndrome, idiopathic hypersomnia, or hypersomnia not otherwise specified). v Results: The relative risk of narcolepsy was increased 5-to 14-fold in children and adolescents and 2-to 7-fold in adults in the countries where Pandemrix vaccine was used widely (Finland, Sweden, Norway, France, England, Ireland) or in certain age groups (< 5 years, in the Netherlands). The vaccine-attributable risk in children and adolescents was 1 per 18,400 vaccines. Studies from Finland and Sweden suggest that the risk was increased two years after the vaccination, but this result needs to be interpreted with caution because of possible biases. Patients with pNC had shorter diagnostic delays, were diagnosed younger, had lower periodic limb movement index during sleep, and had earlier sleep-wake rhythm than sNC patients, but otherwise there were no significant differences in ACT and PSG parameters between the patient groups. In pNC patients in Study III, RDS points decreased significantly, indicating less symptoms of depression (mean (M) difference-3.5, 95% confidence interval (CI) [-5.5,-1.3], P = .003). At follow-up, the median of body mass index increased from 20.8 kgm-2 to 23.4 kgm-2 (P < .001). There were no significant differences in other sleep scores. However, variation in questionnaire scores at follow-up was wide. pNC subjects with very low or undetectable HCRT had higher scores in UNS and ESS than those with HCRT between 20 and 110 pg/mL (UNS
PLOS ONE, 2017
Study objective Narcolepsy type 1 (NT1) is caused by a deficiency or absence of the neurotransmit... more Study objective Narcolepsy type 1 (NT1) is caused by a deficiency or absence of the neurotransmitter orexin. NT1 is also associated with a reduced nocturnal "dipping" of blood pressure (BP). The study objective was to analyze whether nocturnal BP values differed in patients depleted of orexin, versus those in whom production was preserved. Methods We performed a retrospective analysis of the polysomnographic recordings, orexin levels, and BP values of patients with NT1. Data was collected from a total of 21 patients, divided into two groups as follows: those with a complete depletion of orexin (n = 11) (Group1), and those with a remaining, limited presence of orexin (n = 10) (Group 2). Results The groups did not differ in terms of the clinical features of NT1 or sleep characteristics, with an exception of increased number of cataplexy episodes and increased percentage of sleep stage 2 in the Group 1. Daytime and nocturnal BP did not differ between the groups. Most patients, regardless of group, had a non-dipping blood pressure pattern, and no difference in dipping prevalence was observed between groups. The amplitude of the daytime to nighttime change in BP did not differ between the groups. Conclusions Non-dipping BP patterns are frequent among patients with narcolepsy type 1, but we saw no evidence that they depended on whether orexin levels were above or below the assay detection threshold. Therefore, our results do not support the hypothesis that in patients with narcolepsy type 1 residual orexin levels play a role in the control of nocturnal BP dipping.
Current Neurology and Neuroscience Reports, 2018
Purpose of Review After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix an... more Purpose of Review 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. Recent Findings 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 Pandemrixassociated 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. Summary 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.
Sleep, 2018
Study objectives: To validate Ullanlinna Narcolepsy Scale (UNS) as a screening tool for narcoleps... more Study objectives: To validate Ullanlinna Narcolepsy Scale (UNS) as a screening tool for narcolepsy in a clinical population and to compare it with Swiss Narcolepsy Scale (SNS) and Epworth Sleepiness Scale (ESS). Methods: UNS questionnaires of 267 participants visiting Helsinki Sleep Clinic were analyzed. The diagnoses of the participants were narcolepsy type 1 (NT1, n = 89), narcolepsy type 2 (NT2, n = 10), other hypersomnias (n = 24), sleep apnea (n = 37), restless legs syndrome or periodic limb movement disorder (n = 56), and other sleep-related disorders (n = 51). In addition, ESS and SNS scores in a subset of sample (total N = 167) were analyzed and compared to UNS. Results: Mean UNS score in NT1 was 22.0 (95% confidence interval [CI] = 20.4 to 23.6, range 9-43), which was significantly higher than in other disorders, including NT2 (mean 13.7, 95% CI = 10.3 to 17.1, range 7-21, p = .0013). Sensitivity and specificity of UNS in separating NT1 from other disorders were 83.5% and 84.1%, respectively. Positive and negative predictive values were 82.5% and 85.1%, respectively. Sensitivities of SNS and ESS in NT1 were 77.2% and 88.6%, and specificities 88.6% and 45.5%, respectively. There were no differences in receiver operating characteristic curves between UNS and SNS. UNS had moderate negative correlation with hypocretin-1 levels (r s =-.564, p < .001), and mean sleep latency in multiple sleep latency test (r s =-.608, p < .001). Conclusions: UNS has high specificity and sensitivity for NT1 in a sleep clinic setting. UNS scores below 9 strongly suggest against the diagnosis of narcolepsy.
Sleep Medicine Reviews, 2017
An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza... more An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009e2010. The H1N1 vaccine e 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.
The neurologist, 2016
Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing ... more Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing neurons in hypothalamus. In addition to daytime sleepiness, the spectrum and severity of symptoms are very variable. Psychiatric comorbidity and phenomena resembling psychotic symptoms are also common. Current treatment options for narcolepsy are symptomatic but there are few case reports of positive effect of immunotherapy. We report a very severely affected young boy treated with rituximab (RXB). A 12-year-old boy developed narcolepsy after Pandemrix H1N1 vaccination in 2010. He started to express severe psychiatric symptoms shortly after the onset. Cataplexy and sleepiness were devastatingly disabling. Conventional treatments did not have any effect on symptoms so we decided to try RXB, chimeric human monoclonal antibody against CD20 expressed in B lymphocytes. After the first treatment his condition ameliorated dramatically. Unfortunately, the effect lasted only for 2 months. Followi...
Sleep Medicine, 2015
Introduction: To explore the co-occurrence of narcolepsy and attention deficit hyperactivity diso... more Introduction: To explore the co-occurrence of narcolepsy and attention deficit hyperactivity disorder (ADHD) symptoms and compare the damage of cognitive function and improvement after treatment of methylphenidate hydrochloride for 8-16weeks between narcolepsy with and without ADHD.
Sleep Medicine, 2016
To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccinerelated na... more To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccinerelated narcolepsy (pNT1). Methods: Twenty-six drug-naïve 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.
SLEEP, 2016
Study Objectives: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy... more Study Objectives: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. Methods: Actigraphy recording of 1−2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31−79 pg/mL. Results: According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. Conclusions: Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep.
Duodecim; lääketieteellinen aikakauskirja, 2015
Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature ... more Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.
Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are ... more Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.
Sleep Medicine, 2015
After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and ... more 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. 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. 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. 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.