Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

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.

Narcolepsy Associated with Pandemrix Vaccine.

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 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.

Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns.

Narcolepsy is a chronic sleep disorder, likely with an autoimmune component. During 2009 and 2010, a link between A(H1N1)pdm09 Pandemrix vaccination and onset of narcolepsy was suggested in Scandinavia. In this study, we searched for autoantibodies related to narcolepsy using a neuroanatomical array: rat brain sections were processed for immunohistochemistry/double labeling using patient sera/cerebrospinal fluid as primary antibodies. Sera from 89 narcoleptic patients, 52 patients with other sleep-related disorders (OSRDs), and 137 healthy controls were examined. Three distinct patterns of immunoreactivity were of particular interest: pattern A, hypothalamic melanin-concentrating hormone and proopiomelanocortin but not hypocretin/orexin neurons; pattern B, GABAergic cortical interneurons; and pattern C, mainly globus pallidus neurons. Altogether, 24 of 89 (27%) narcoleptics exhibited pattern A or B or C. None of the patterns were exclusive for narcolepsy but were also detected in the OSRD group at significantly lower numbers. Also, some healthy controls exhibited these patterns. The antigen of pattern A autoantibodies was identified as the common C-terminal epitope of neuropeptide glutamic acid-isoleucine/α-melanocyte-stimulating hormone (NEI/αMSH) peptides. Passive transfer experiments on rat showed significant effects of pattern A human IgGs on rapid eye movement and slow-wave sleep time parameters in the inactive phase and EEG θ-power in the active phase. We suggest that NEI/αMSH autoantibodies may interfere with the fine regulation of sleep, contributing to the complex pathogenesis of narcolepsy and OSRDs. Also, patterns B and C are potentially interesting, because recent data suggest a relevance of those brain regions/neuron populations in the regulation of sleep/arousal.

[Narcolepsy as an autoimmune disease]. / Narkolepsia autoimmuunisairautena.

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.

Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults.

BACKGROUND: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. PATIENTS AND METHODS: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. RESULTS: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. CONCLUSIONS: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Association between hypersomnolence and the COVID-19 pandemic: The International COVID-19 Sleep Study (ICOSS).

BACKGROUND: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear. METHODS: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and excessive quantity of sleep (EQS), as well as sociodemographic factors, sleep patterns, psychological symptoms, and quality of life was distributed in 15 countries across the world from May to September in 2020. RESULTS: Altogether responses from 18,785 survey participants (65% women, median age 39 years) were available for analysis. Only 2.8% reported having had COVID-19. Compared to before the pandemic, the prevalence of EDS, EQS, and fatigue increased from 17.9% to 25.5%, 1.6%-4.9%, and 19.4%-28.3% amid the pandemic, respectively. In univariate logistic regression models, reports of having a COVID-19 were associated with EQS (OR 5.3; 95%-CI 3.6-8.0), EDS (2.6; 2.0-3.4), and fatigue (2.8; 2.1-3.6). In adjusted multivariate logistic regression, sleep duration shorter than desired (3.9; 3.2-4.7), depressive symptoms (3.1; 2.7-3.5), use of hypnotics (2.3; 1.9-2.8), and having reported COVID-19 (1.9; 1.3-2.6) remained strong predictors of EDS. Similar associations emerged for fatigue. In the multivariate model, depressive symptoms (4.1; 3.6-4.6) and reports of having COVID-19 (2.0; 1.4-2.8) remained associated with EQS. CONCLUSIONS: A large increase in EDS, EQS, and fatigue occurred due to the COVID-19 pandemic, and especially in self-reported cases of COVID-19. These findings warrant a thorough understanding of their pathophysiology to target prevention and treatment strategies for long COVID condition.

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.

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.

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 (rs = -.564, p < .001), and mean sleep latency in multiple sleep latency test (rs= -.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.

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®). 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 relationship between orexin levels and blood pressure changes in patients with narcolepsy.

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.

Hypocretin-1 Levels Associate with Fragmented Sleep in Patients with Narcolepsy Type 1.

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.

Clinical course of H1N1-vaccine-related narcolepsy.

OBJECTIVE: To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccine-related 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.

Transient Impact of Rituximab in H1N1 Vaccination-associated Narcolepsy With Severe Psychiatric Symptoms.

INTRODUCTION: 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). CASE REPORT: 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. Following attempts did not show any effect. CONCLUSIONS: Effect of RXB on narcolepsy has not been reported before. Remarkable but short-lasting effect of RXB in narcolepsy is intriguing as it could imply that there is still ongoing B cell-mediated autoimmune response possible contributing to symptoms in narcolepsy.

Polysomnographic and actigraphic characteristics of patients with H1N1-vaccine-related and sporadic narcolepsy.

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.

Parkinson's disease and narcolepsy-like symptoms.

OBJECTIVE: Various sleep-related problems, for example, insomnia and symptoms of rapid eye movement behavior disorder (RBD), are common in patients with Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy (NARC), hallucinations, and RBD and their association with other symptoms. METHODS: Altogether, 1447 randomly selected patients with PD, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, RBD, and other issues were included. RESULTS: The response rate was 59.0%; of these patients, 73% had answered to all questions that were used in the analyses (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale ≥ 14 and Epworth Sleepiness Scale ≥ 11) was observed in 9.3% of the subjects (PD with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire ≥ 6) in 39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In patients with PD, hallucinations before going to bed in the evening occurred in 5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of subjects with PD and NARC. In a logistic regression analysis, PD with NARC was associated with RBD, all types of hallucinations, daytime sleepiness, fatigue, insomnia, and intense dreaming also when adjusted for age, sex, disease duration, and levodopa. CONCLUSIONS: Narcolepsy-like symptoms may be present in patients with PD. Symptoms of RBD were associated with symptoms of narcolepsy including symptoms of cataplexy.

Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate.

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. METHOD: We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia. RESULTS: Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone) alleviated psychotic symptoms in two cases. CONCLUSION: Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia; however, the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.

Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases.

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.