Accuracy of Actigraphy Compared to Concomitant Ambulatory Polysomnography in Narcolepsy and Other Sleep Disorders

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 min, 95% confidence interval [-5.9, 5.6] min in the whole sample. Overestimation was largest, -12.8 [-25.1, -0.9] min, in patients with obstructive sleep apnea. By contrast, in patients with narcolepsy, actigraphy tended to underestimate sleep time by 24.3 [12.4, 36.1] min. As for sleep efficiency, actigraphy underestimated it by 0.18 [-0.99, 1.35] % and sleep latency by 11.0 [8.5, 13.6] min compared to polysomnography. We conclude that, in measuring sleep time, actigraphy is reasonably reliable and helpful to be used for a week or two to exclude insufficient sleep in patients with the suspicion of narcolepsy. However, the effectiveness of actigraphy in determining sleep seems to decrease in subjects with low sleep efficiencies.Peer reviewe

Narkolepsia : kliininen oirekuva, diagnostiikka ja yhteys H1N1 rokotteeseen

After the 2009-2010 pandemic H1N1 vaccination campaign the incidence of narcolepsy increased sharply in countries where the Pandemrix vaccination was used. An increased incidence was observed also in China, where vaccine coverage was very low. Moreover, epidemiological studies are prone to biases, and animal studies suggest 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. pNC cases had severe onset and common psychiatric comorbidity, which warranted thorough analysis of the pNC phenotype. Tools to measure narcolepsy symptoms or to help in diagnostics remain scarce. Our first aim was to systematically analyze the magnitude of the risk of H1N-vaccine-associated narcolepsy (pNC) and to examine whether an increased association emerged with any other vaccine or H1N1 virus infection. 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). In study IV we aimed to validate the Ullanlinna Narcolepsy Scale (UNS), a population screening tool for narcolepsy published in 1994, in clinical population. Based on the meta-analysis in Study I, 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). The vaccine-attributable risk in children and adolescents was 1 per 18,400 vaccines. The risk seems to have increased for two years and was not associated with any other vaccine. In study II we analyzed PSG and ACT characteristics of 69 pNC and 57 sNC subjects and in study III sleep questionnaires of 26 pNC and 25 sNC subjects. We found that pNC patients had shorter diagnostic delays, were diagnosed younger, had less periodic limb movements in sleep, and had earlier sleep-wake rhythm than sNC patients. The clinical course was highly variable in a two-year follow-up. There were no significant differences between pNC and sNC questionnaire scores. In study IV we analyzed questionnaire scores of patients with narcolepsy type 1 (n = 89), narcolepsy type 2 (n = 10), sleep apnea (n = 37), restless legs syndrome or periodic limb movement disorder (n = 56), other sleep-related disorders (n = 56), or other hypersomnias (n = 24). Sensitivity and specificity of the UNS in separating NT1 from other disorders were 83.5-85.4% and 84.1-87.6%, respectively. The UNS had a strong negative correlation with hypocretin-1 levels and mean sleep latency in MSLT.Tyypin 1 narkolepsia on aivoperäinen liikaunisuussairaus, joka aiheutuu oreksiinia tuottavien hermosolujen tuhoutumisesta. Narkolepsian ilmaantuvuuden huomattiin lisääntyneen huomattavasti H1N1-pandemiarokotekampanjan jälkeen niissä maissa, joissa käytettiin Pandemrix-rokotetta. Toisaalta samaan aikaan Pekingin seudulla Kiinassa, jossa rokotekattavuus oli hyvin matala, todettiin myös noin kolminkertainen määrä narkolepsiatapauksia tavanomaiseen nähden. Eläinkokeissa on myös todettu tietyissä olosuhteissa H1N1-viruksen itsessään kykenevän aiheuttamaan narkolepsian kaltaista oirekuvaa. H1N1-rokotteeseen liittyvän narkolepsian alku oli monilla sairastuneilla hyvin äkillinen ja voimakas. Tutkimuksiin hakeuduttiin nopeasti, jo ennen kuin tietoisuus sairaudesta oli lisääntynyt. Aiemmin viive narkolepsiadiagnoosin on ollut hyvin pitkä. Niinpä heräsi kysymys siitä, eroaako rokotenarkolepsia jollain tavoin tavanomaisesta narkolepsiasta. Tämä väitöskirja koostuu neljästä osatyöstä. Ensimmäisessä toteutimme systemaattisen katsauksen ja meta-analyysin tutkien narkolepsian ilmaantuvuutta H1N1-rokotekampanjan jälkeen ja selvitimme, liittyykö lisääntynyttä riskiä mihinkään muuhun kuin Pandemrix-rokotteeseen. Toisessa ja kolmannessa osatyössä analysoimme rokotenarkolepsian oirekuvaa ja neurofysiologisten tutkimustulosten löydöksiä ja vertasimme niitä tavanomaiseen narkolepsiaan. Neljännessä osatyössä tutkimme Ullanlinnan narkolepsia-asteikon (UNS) soveltuvuutta kliinisessä työssä narkolepsian tunnistamiseen. Totesimme narkolepsian riskin lisääntyneen lapsilla ja nuorilla 5-14-kertaiseksi ja aikuisilla 2-7-kertaiseksi H1N1-rokotekampanjan jälkeen. Yhtä rokoteannosta kohden riski oli 1 per 18 000 ja riski vaikuttaa olleen koholla kahden vuoden ajan rokottamisesta. Mihinkään muuhun kuin Pandemrix-rokotteeseen ei liity lisääntynyttä riskiä eikä H1N1-virukseen liittyvää riskiä todettu missään muualla kuin Kiinassa. Pääosin neurofysiologisten tutkimusten tulokset olivat samansuuntaisia tavanomaisessa ja rokotenarkolepsiassa. Diagnostinen viive oli lyhyempi ja diagnoosi-ikä varhaisempi rokotenarkolepsiassa. Rokotenarkolepsiassa unenaikaisia jaksottaisia raajaliikkeitä oli vähemmän ja vuorokausirytmi oli aikaisempi. Kliinisessä oirekuvassa ei ollut suurta eroa sairauksien välillä. Toisaalta rokotenarkolepsiaa sairastavien oirekuva on hyvin vaihteleva. UNS vaikuttaa tunnistavan narkolepsian hyvin ja erottavan sen muista unihäiriöistä katkaisupistemäärällä 14. Jos pistemäärä on alle 9, narkolepsia on hyvin epätodennäköinen. Asteikolla on myös kohtalainen negatiivinen korrelaatio aivoselkäydinnesteen oreksiinipitoisuuden kanssa

Ullanlinna Narcolepsy Scale in diagnosis of narcolepsy

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.Peer reviewe

Narcolepsy Associated with Pandemrix Vaccine

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.Peer reviewe

Liikaunisuuden kelpo hoito

•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.Peer reviewe

Incidence of narcolepsy after H1N1 influenza and vaccinations : Systematic review and meta-analysis

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.Peer reviewe

Narkolepsian moninainen oirekuva ja käypä diagnostiikka

English summaryPeer reviewe

Misdiagnosis of narcolepsy caused by a false-positive orexin-A/hypocretin-1 enzyme immune assay

The diagnosis of narcolepsy is based on clinical history, sleep studies, and, in some cases, cerebrospinal fluid orexin-A/hypocretin-1 measurement. The gold standard for orexin measurement is the radioimmunoassay but other commercial kits are also available, such as the enzyme immune assay (EIA). The specificity of orexin EIA in humans is unknown. We report four cases where orexin levels were measured by EIA and resulted in false positives and the misdiagnosis of narcolepsy. Therefore, orexin EIA measurement should be strongly discouraged in a clinical setting. CITATION: Sarkanen T, Sved G, Juujärvi M, Alakuijala A, Partinen M. Misdiagnosis of narcolepsy caused by a false-positive orexin-A/hypocretin-1 enzyme immune assay. J Clin Sleep Med. 2022;18(8):2075-2078.acceptedVersionPeer reviewe

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults

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.Peer reviewe