School Problems and School Support for Children with Narcolepsy: Parent, Teacher, and Child Reports.

OBJECTIVE: To assess problems faced by children with type 1 narcolepsy (NT1) at school and obtain insight into potential interventions for these problems. METHODS: We recruited children and adolescents with NT1 from three Dutch sleep-wake centers. Children, parents, and teachers completed questionnaires about school functioning, interventions in the classroom, global functioning (DISABKIDS), and depressive symptoms (CDI). RESULTS: Eighteen children (7-12 years) and thirty-seven adolescents (13-19 years) with NT1 were recruited. Teachers' most frequently reported school problems were concentration problems and fatigue (reported by about 60% in both children and adolescents). The most common arrangements at school were, for children, discussing school excursions (68%) and taking a nap at school (50%) and, for adolescents, a place to nap at school (75%) and discussing school excursions (71%). Regular naps at home on the weekend (children 71% and adolescents 73%) were more common than regular naps at school (children 24% and adolescents 59%). Only a minority of individuals used other interventions. School support by specialized school workers was associated with significantly more classroom interventions (3.5 versus 1.0 in children and 5.2 versus 4.1 in adolescents) and napping at school, but not with better global functioning, lower depressive symptom levels, or napping during the weekends. CONCLUSIONS: Children with NT1 have various problems at school, even after medical treatment. Interventions to help children with NT1 within the classroom do not seem to be fully implemented. School support was associated with the higher implementation of these interventions. Longitudinal studies are warranted to examine how interventions can be better implemented within the school.

Psychomotor Vigilance Performance in Participants with Excessive Daytime Sleepiness in Obstructive Sleep Apnea or Narcolepsy Compared with SAFTE-FAST Model Predictions.

INTRODUCTION: Excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) can impair vigilance/attention. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved to treat EDS associated with narcolepsy (75-150 mg/day) or OSA (37.5-150 mg/day). The analysis reported here explored the use of the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) model (used in transport industries to model performance based on accumulated sleep and circadian variability) as a substitute for healthy controls using psychomotor vigilance task (PVT) data collected during clinical studies. METHODS: Data were analyzed from two phase 2 studies of solriamfetol in adults with OSA (NCT02806895, EudraCT 2015-003930-28) or narcolepsy (NCT02806908, EudraCT 2015-003931-36). Participants were randomly assigned 1:1 to solriamfetol 150 mg/day (3 days) followed by 300 mg/day (4 days), or placebo (7 days), then crossed over to the other treatment. Actual task effectiveness scores were calculated from average PVT inverse reaction time (pre-dose; 2 h post-dose; 6 h post-dose). Actigraphy-derived sleep intervals were used in SAFTE to determine modeled healthy control task effectiveness scores. RESULTS: In participants with OSA (N = 31) on placebo or solriamfetol, actual and modeled healthy control task effectiveness did not differ at any time point. In participants with narcolepsy (N = 20) on placebo, actual task effectiveness at 2 h post-dose was lower than modeled healthy control task effectiveness (nominal P = 0.03), a difference not present with solriamfetol. There was no main effect of solriamfetol on actual or modeled healthy control task effectiveness across time points. CONCLUSION: This study represents a novel application of the SAFTE biomathematical model to approximate healthy controls in sleep disorder research and provides valuable lessons that may optimize future research. Future studies should perform a priori power analyses for model-tested outcomes and use sleep measures that capture sleep fragmentation characteristic of sleep disorders for sleep input (e.g., total sleep time rather than time in bed). TRIAL REGISTRATION: NCT02806895, EudraCT 2015-003930-28: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Obstructive Sleep Apnea. NCT02806908, EudraCT 2015-003931-36: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Narcolepsy.

Multimodal nocturnal seizure detection: Do we need to adapt algorithms for children?

OBJECTIVE: To assess the performance of a multimodal seizure detection device, first tested in adults (sensitivity 86%, PPV 49%), in a pediatric cohort living at home or residential care. METHODS: In this multicenter, prospective, video-controlled cohort-study, nocturnal seizures were detected by heartrate and movement changes in children with epilepsy and intellectual disability. Participants with a history of >1 monthly major motor seizure wore Nightwatch bracelet at night for 3 months. Major seizures were defined as tonic-clonic, generalized tonic >30 s, hyperkinetic, or clusters (>30 min) of short myoclonic or tonic seizures. The video of all events (alarms and nurse diaries) and about 10% of whole nights were reviewed to classify major seizures, and minor or no seizures. RESULTS: Twenty-three participants with focal or generalized epilepsy and nightly motor seizures were evaluated during 1511 nights, with 1710 major seizures. First 1014 nights, 4189 alarms occurred with average of 1.44/h, showing average sensitivity of 79.9% (median 75.4%) with mean PPV of 26.7% (median 11.1%) and false alarm rate of 0.2/hour. Over 90% of false alarms in children was due to heart rate (HR) part of the detection algorithm. To improve this rate, an adaptation was made such that the alarm was only triggered when the wearer was in horizontal position. For the remaining 497 nights, this was tested prospectively, 384 major seizures occurred. This resulted in mean PPV of 55.5% (median 58.1%) and a false alarm rate 0.08/h while maintaining a comparable mean sensitivity of 79.4% (median 93.2%). SIGNIFICANCE: Seizure detection devices that are used in bed which depend on heartrate and movement show similar sensitivity in children and adults. However, children do show general higher false alarm rate, mostly triggered while awake. By correcting for body position, the false alarms can be limited to a level that comes close to that in adults.

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA). METHODS: Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm. On Day 7 of each period, standardised on-road driving tests occurred (2 and 6 hours postdose). Standard deviation of lateral position (SDLP) was the primary endpoint. RESULTS: Solriamfetol significantly reduced SDLP at 2 (n = 34; least squares mean difference, -1.1 cm; 95% CI, -1.85, -0.32; p = 0.006) and 6 hours postdose (n = 32; least squares mean difference, -0.8 cm; 95% CI, -1.58, -0.03; p = 0.043). Two hours postdose, 4 placebo-treated and 1 solriamfetol-treated participants had incomplete driving tests; 6 hours postdose, 7 and 3 participants, respectively, had incomplete tests. Common treatment-emergent adverse events included headache, nausea, and insomnia. CONCLUSIONS: Solriamfetol 300 mg/day significantly improved on-the-road driving performance in participants with EDS associated with OSA.

HLA associations in narcolepsy type 1 persist after the 2009 H1N1 pandemic.

We aimed to compare HLA-DQB1-associations in narcolepsy type 1 (NT1) patients with disease onset before and after the 2009 H1N1 pandemic in a large Dutch cohort. 525 NT1 patients and 1272 HLA-DQB1*06:02-positive healthy controls were included. Because of the discussion that has arisen on the existence of sporadic and post-H1N1 NT1, HLA-DQB1-associations in pre- and post-H1N1 NT1 patients were compared. The associations between HLA-DQB1 alleles and NT1 were not significantly different between pre- and post-H1N1 NT1 patients. Both HLA-DQB1-associations with pre- and -post H1N1 NT1 reported in recent smaller studies were replicated. Our findings combine the results of studies in pre- and post-H1N1 NT1 and argue against considering post-H1N1 NT1 as a different entity.

Decreased body mass index during treatment with sodium oxybate in narcolepsy type 1.

Narcolepsy type 1 is characterised by an increase in body weight after disease onset, frequently leading to obesity. It was suggested that this weight gain may be counteracted by treatment with sodium oxybate. We here provide longitudinal body mass index data of patients with narcolepsy type 1 after starting treatment with sodium oxybate, compared with patients in whom treatment with modafinil was initiated. Eighty-one individuals with narcolepsy type 1 fulfilled the entry criteria for this retrospective study: 59 had newly started treatment with sodium oxybate and 22 had newly started modafinil. Gender-specific differences between both treatment groups were compared using Student's t tests and mixed effect modeling. Patients using sodium oxybate lost weight, with a mean body mass index decrease of 2.56 kg/m2 between the first and last measurement (women; p = .001) and 0.84 kg/m2 (men; p = .006). Patients using modafinil, however, gained weight, with a mean body mass index increase of 0.57 kg/m2 (women; p = .033) and 0.67 kg/m2 (men; p = .122). Medication (p = .006) and baseline body mass index (p = .032) were predictors for body mass index decrease. In conclusion, treatment with sodium oxybate is associated with a body mass index reduction in narcolepsy type 1, whereas modafinil treatment is not. This effect is most pronounced in those who already have a higher baseline body mass index.

Chronic sleep reduction is associated with academic achievement and study concentration in higher education students.

Inadequate sleep impairs cognitive function and has been associated with worse academic achievement in higher education students; however, studies that control for relevant background factors and include knowledge on sleep hygiene are scarce. This study examined the association of chronic sleep reduction (i.e. symptoms of chronic sleep reduction such as shortness of sleep, sleepiness and irritation), subjective sleep quality and sleep hygiene knowledge with academic achievement (grades and study credits) and study concentration among 1378 higher education students (71% female, mean age 21.73 years, SD = 3.22) in the Netherlands. Demographic, health, lifestyle and study behaviour characteristics were included as covariates in hierarchical regression analyses. After controlling for significant covariates, only chronic sleep reduction remained a significant predictor of lower grades (last exam, average in current academic year). Better sleep quality and sleep hygiene knowledge were associated with better academic achievement, but significance was lost after controlling for covariates, except for a remaining positive association between sleep hygiene beliefs and grades in the current academic year. Moreover, better sleep quality and lower scores on chronic sleep reduction were associated with better study concentration after controlling for significant covariates. To conclude, chronic sleep reduction is associated with academic achievement and study concentration in higher education students. Inadequate sleep hygiene knowledge is moderately associated with worse academic achievement. Future research should investigate whether sleep hygiene interventions improve academic achievement in students of higher education.

Core Body and Skin Temperature in Type 1 Narcolepsy in Daily Life; Effects of Sodium Oxybate and Prediction of Sleep Attacks.

STUDY OBJECTIVES: Previous laboratory studies in narcolepsy patients showed altered core body and skin temperatures, which are hypothesised to be related to a disturbed sleep wake regulation. In this ambulatory study we assessed temperature profiles in normal daily life, and whether sleep attacks are heralded by changes in skin temperature. Furthermore, the effects of three months of treatment with sodium oxybate (SXB) were investigated. METHODS: Twenty-five narcolepsy patients and 15 healthy controls were included. Core body, proximal and distal skin temperatures, and sleep-wake state were measured simultaneously for 24 hours in ambulatory patients. This procedure was repeated in 16 narcolepsy patients after at least 3 months of stable treatment with SXB. RESULTS: Increases in distal skin temperature and distal-to-proximal temperature gradient (DPG) strongly predicted daytime sleep attacks (P < 0.001). As compared to controls, patients had a higher proximal and distal skin temperature in the morning, and a lower distal skin temperature during the night (all P < 0.05). Furthermore, they had a higher core body temperature during the first part of the night (P < 0.05), which SXB decreased (F = 4.99, df = 1, P = 0.03) to a level similar to controls. SXB did not affect skin temperature. CONCLUSIONS: This ambulatory study demonstrates that daytime sleep attacks were preceded by clear changes in distal skin temperature and DPG. Furthermore, changes in core body and skin temperature in narcolepsy, previously only studied in laboratory settings, were partially confirmed. Treatment with SXB resulted in a normalisation of the core body temperature profile. Future studies should explore whether predictive temperature changes can be used to signal or even prevent sleep attacks.

The effects of sodium oxybate on core body and skin temperature regulation in narcolepsy.

Patients suffering from narcolepsy type 1 show altered skin temperatures, resembling the profile that is related to sleep onset in healthy controls. The aim of the present study is to investigate the effects of sodium oxybate, a widely used drug to treat narcolepsy, on the 24-h profiles of temperature and sleep-wakefulness in patients with narcolepsy and controls. Eight hypocretin-deficient male narcolepsy type 1 patients and eight healthy matched controls underwent temperature measurement of core body and proximal and distal skin twice, and the sleep-wake state for 24 h. After the baseline assessment, 2 × 3 g of sodium oxybate was administered for 5 nights, immediately followed by the second assessment. At baseline, daytime core body temperature and proximal skin temperature were significantly lower in patients with narcolepsy (core: 36.8 ± 0.05 °C versus 37.0 ± 0.05 °C, F = 8.31, P = 0.01; proximal: 33.4 ± 0.26 °C versus 34.3 ± 0.26 °C, F = 5.66, P = 0.03). In patients, sodium oxybate administration increased proximal skin temperature during the day (F = 6.46, P = 0.04) to a level similar as in controls, but did not affect core body temperature, distal temperature or distal-proximal temperature gradient. Sodium oxybate administration normalised the predictive value of distal skin temperature and distal-proximal temperature gradient for the onset of daytime naps (P < 0.01). In conclusion, sodium oxybate administration resulted in a partial normalisation of the skin temperature profile, by increasing daytime proximal skin temperature, and by strengthening the known relationship between skin temperature and daytime sleep propensity. These changes seem to be related to the clinical improvement induced by sodium oxybate treatment. A causal relationship is not proven.

Glucose and fat metabolism in narcolepsy and the effect of sodium oxybate: a hyperinsulinemic-euglycemic clamp study.

INTRODUCTION: Narcolepsy is associated with obesity though it is uncertain whether this is caused by changes in glucose and fat metabolism. Therefore, we performed a detailed analysis of systemic energy homeostasis in narcolepsy patients, and additionally, investigated whether it was affected by three months of sodium oxybate (SXB) treatment. METHODS: Nine hypocretin deficient patients with narcolepsy-cataplexy, and nine healthy sex, age, and BMI matched controls were enrolled. A hyperinsulinemic-euglycemic clamp combined with stable isotopes ([6,6-(2)H2]-glucose and [(2)H5]- glycerol) was performed at baseline. In seven patients a second study was performed after three months of SXB treatment. RESULTS: Glucose disposal rate (GDR) per unit serum insulin was significantly higher in narcolepsy patients compared to matched controls (1.6 ± 0.2 vs. 1.1 ± 0.3 µmol/kgFFM/min/mU×L; P = 0.024), whereas ß-cell function was similar (P = 0.50). Basal steady state glycerol appearance rate tended to be lower in narcolepsy patients (5.2 ± 0.4 vs. 7.5 ± 1.3 µmol/kgFM/min; P = 0.058), suggesting a lower rate of lipolysis. SXB treatment induced a trend in reduction of the GDR (1.4 ± 0.1 vs. 1.1 ± 0.2 µmol/kgFFM/min/mU×L; P = 0.063) and a reduction in endogenous glucose production (0.24 ± 0.03 vs. 0.16 ± 0.03 µmol/kgFFM/min/mU×L: P = 0.028) per unit serum insulin. After SXB treatment lipolysis increased (4.9 ± 0.4 vs. 6.5 ± 0.6 µmol/kgFM/min; P = 0.018), and body weight decreased in narcolepsy patients (99.2 ± 6.0 vs. 94.0 ± 5.4 kg; P = 0.044). CONCLUSION: We show that narcolepsy patients are more insulin sensitive and may have a lower rate of lipolysis than matched controls. SXB stimulated lipolysis in narcolepsy patients, possibly accounting for the weight loss after treatment. While sodium oxybate tended to decrease systemic insulin sensitivity, it increased hepatic insulin sensitivity, suggesting tissue-specific effects.

Delusional confusion of dreaming and reality in narcolepsy.

STUDY OBJECTIVES: We investigated a generally unappreciated feature of the sleep disorder narcolepsy, in which patients mistake the memory of a dream for a real experience and form sustained delusions about significant events. DESIGN: We interviewed patients with narcolepsy and healthy controls to establish the prevalence of this complaint and identify its predictors. SETTING: Academic medical centers in Boston, Massachusetts and Leiden, The Netherlands. PARTICIPANTS: Patients (n = 46) with a diagnosis of narcolepsy with cataplexy, and age-matched healthy healthy controls (n = 41). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: "Dream delusions" were surprisingly common in narcolepsy and were often striking in their severity. As opposed to fleeting hypnagogic and hypnopompic hallucinations of the sleep/wake transition, dream delusions were false memories induced by the experience of a vivid dream, which led to false beliefs that could persist for days or weeks. CONCLUSIONS: The delusional confusion of dreamed events with reality is a prominent feature of narcolepsy, and suggests the possibility of source memory deficits in this disorder that have not yet been fully characterized.

DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.

STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: basal concentrations and response to sodium oxybate.

STUDY OBJECTIVES: Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxybate, alter the levels of these hormones. METHODS: Eight male, medication free, hypocretin deficient, narcolepsy with cataplexy patients, and 8 healthy controls matched for age, sex, body mass index (BMI), waisttohip ratio, and body fat percentage were assessed. Blood samples of total ghrelin and leptin were collected over 24 hours at 60 and 20-min intervals, respectively, during 2 study occasions: baseline, and during the last night of 5 consecutive nights of sodium oxybate administration (2 × 3.0 g/night). RESULTS: At baseline, mean 24-h total ghrelin (936 ± 142 vs. 949 ± 175 pg/mL, p = 0.873) and leptin (115 ± 5.0 vs. 79.0 ± 32 mg/L, p = 0.18) levels were not different between hypocretin deficient narcolepsy patients and controls. Furthermore, sodium oxybate did not significantly affect the plasma concentration of either one of these hormones. CONCLUSIONS: The increased BMI of narcolepsy patients is unlikely to be mediated by hypocretin deficiency-mediated alterations in total ghrelin or leptin levels. Thus, the effects of these hormones on hypocretin neurons may be mainly unidirectional. Although sodium oxybate may influence body weight, the underlying mechanism is unlikely to involve changes in total ghrelin or leptin secretion.

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study.

Narcolepsy with cataplexy is a sleep disorder characterized by excessive daytime sleepiness, irresistible sleep episodes, and sudden loss of muscle tone (cataplexy) mostly triggered by emotions. Narcolepsy with cataplexy is a disabling lifelong disorder frequently arising during childhood. Pediatric narcolepsy often results in severe learning and social impairment. Improving awareness about this condition increases early diagnosis and may allow patients to rapidly access adequate treatments, including pharmacotherapy and/or non-medication-based approaches. Even though children currently undergo pharmacotherapy, data about safety and efficacy in the pediatric population are scarce. Lacking international guidelines as well as drugs registered for childhood narcolepsy with cataplexy, physicians have no other alternative but to prescribe in an off-label manner medications identical to those recommended for adults. We retrospectively evaluated 27 children ranging from 6 to 16 years old, suffering from narcolepsy with cataplexy, who had been treated with off-label sodium oxybate and had been followed in a clinical setting. Throughout a semi-structured interview, we documented the good efficacy and tolerability of sodium oxybate in the majority of the patients. This study constitutes a preliminary step towards a further randomized controlled trial in childhood narcolepsy with cataplexy.

Altered circadian rhythm of melatonin concentrations in hypocretin-deficient men.

Hypocretin deficiency causes narcolepsy. It is unknown whether melatonin secretion is affected in this sleep disorder. Therefore, in both narcolepsy patients and matched controls, the authors measured plasma melatonin levels hourly for 24 h before and after 5 days of sodium oxybate (SXB) administration. Although mean melatonin concentrations were similar between patients and controls, in narcoleptics the percentage of 24-h melatonin secreted during the daytime was significantly higher, and melatonin secretion exhibited a weaker coupling to sleep. SXB did not affect melatonin secretion. These findings suggest that hypocretin deficiency might disturb both the circadian control of melatonin release and its temporal association with sleep.

Month of birth is not a risk factor for narcolepsy with cataplexy in the Netherlands.

The month of birth has been proposed as a risk factor for narcolepsy, suggesting a harmful influence during early development. Several authors have described an excess of births in March in those developing narcolepsy later. Analysis methods in published studies varied, but no study corrected completely for possible changes in seasonal birth pattern over time in the appropriate population. The present study describes changes in seasonal birth pattern of the entire Dutch population over a 79-year span and compared the monthly birth pattern of Dutch narcoleptics with the population data. Month and year of birth were noted for 307 patients with non-familial narcolepsy with cataplexy, born in the Netherlands between 1923 and 2001. The numbers of live births per month and per year from the entire Dutch population for the same period were used to calculate a virtual data set of expected births per month with exactly the number of cataplexy cases, but with the birth pattern of the Dutch population. Observed and expected numbers per month were compared using the chi-square test. In the 1970s the peak of births shifted from spring to autumn, confirming the need to correct for changing seasonal patterns. There was no significant difference between observed and expected birth numbers per month. An effect of birth month on the occurrence of narcolepsy with cataplexy was not found in a study of 307 cases after adjusting for changing birth patterns in the general population.

Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls.

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.