Guardians of Rest? Investigating the gut microbiota in central hypersomnolence disorders.

In recent years, there has been an increased interest in elucidating the influence of the gut microbiota on sleep physiology. The gut microbiota affects the central nervous system by modulating neuronal pathways through the neuroendocrine and immune system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways. The gut microbiota can also influence circadian rhythms. In this study, we observed the gut microbiota composition of patients suffering from narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. We did not observe any changes in the alpha diversity of the gut microbiota among patient groups and healthy controls. We observed changes in beta diversity in accordance with Jaccard dissimilarities between the control group and groups of patients suffering from narcolepsy type 1 and idiopathic hypersomnia. Our results indicate that both these patient groups differ from controls relative to the presence of rare bacterial taxa. However, after adjustment for various confounding factors such as BMI, age, and gender, there were no statistical differences among the groups. This indicates that the divergence in beta diversity in the narcolepsy type 1 and idiopathic hypersomnia groups did not arise due to sleep disturbances. This study implies that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders might prove beneficial.

Idiopathic hypersomnia years after the diagnosis.

Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

Investigation of anti-neuronal antibodies and disparity in central hypersomnias.

STUDY OBJECTIVES: Microbial antigens can elicit an immune response leading to the production of autoantibodies cross-reacting with autoantigens. Still, their clinical significance in human sera in the context of brain diseases is unclear. Therefore, assessment of natural autoantibodies reacting with their neuropeptides may elucidate the autoimmune etiology of central hypersomnias. The study aims to determine whether serum autoantibody levels differ in patients with different types of central hypersomnias (narcolepsy type 1 and 2, NT1 and NT2; idiopathic hypersomnia, IH) and healthy controls and if the differences could suggest the participation of autoantibodies in disease pathogenesis. METHODS: Sera from 91 patients with NT1, 27 with NT2, 46 with IH, and 50 healthy controls were examined for autoantibodies against assorted neuropeptides. Participants were screened using questionnaires related to sleep disorders, quality of life, and mental health conditions. In addition, serum biochemical parameters and biomarkers of microbial penetration through the intestinal wall were determined. RESULTS: A higher prevalence of autoantibodies against neuropeptides was observed only for alpha-melanocytes-stimulating hormone (α-MSH) and neuropeptide glutamic acid-isoleucine (NEI), which differed slightly among diagnoses. Patients with both types of narcolepsy exhibited signs of microbial translocation through the gut barrier. According to the questionnaires, patients diagnosed with NT2 or IH had subjectively worse life quality than patients with NT1. Patients displayed significantly lower levels of bilirubin and creatinine and slightly higher alkaline phosphatase values than healthy controls. CONCLUSIONS: Overall, serum anti-neuronal antibodies prevalence is rare, suggesting that their participation in the pathophysiology of concerned sleep disorders is insignificant. Moreover, their levels vary slightly between diagnoses indicating no major diagnostic significance.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Central Disorders of Hypersomnolence: Association with Fatigue, Depression and Sleep Inertia Prevailing in Women.

Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women.

Idiopathic Hypersomnia-A Dynamic Simulation Model.

Aims of the study: Commonly used approach to illness assessment focuses on the patient's actual state supplemented by binary records of past events and conditions. This research project was designed to explain subjective experience in idiopathic hypersomnia (IH) patients influenced by their clinical symptoms and comorbidities. Material and Methods: Forty-three IH patients of both sexes (female 60.5%, male 39.5%) were assessed using a detailed structured examination. The interview covered neurologic, psychiatric, and internal medicine anamnesis, medication past and current, substance abuse, work impairment, detailed sleep-related data, specific sleep medication, and a full-length set of questionnaires including depression, quality of life, sleepiness, anxiety, fatigue, insomnia, and sleep inertia. The data were digitized and imported into statistical software (SPSS by IBM), and dynamic simulation software (Vensim by Ventana Systems Inc.) was used to build a causal loop diagram and stocks and flows diagram as a simulation structure. Results: The overall raw data and simulation-based patterns fit at 76.1%. The simulation results also identified the parameters that contribute the most to patients' subjective experience. These included sleep inertia, the refreshing potential of naps, the quality of nocturnal sleep, and the social aspects of the patient's life. Psychiatric disorders influence the overall pattern at a surprisingly low level. The influence of medication has been studied in detail. Although its contribution to the dynamics looks marginal at first sight, it significantly influences the contribution of other variables to the overall patient experience of the disease. Conclusion: Even the simplified dynamic structure designed by the research team reflects the real-life events in patients with IH at the acceptable level of 76.1% and suggests that a similar structure plays an important role in the course of the disease. Therapeutic focus on the parameters identified by the model should enhance the patients' subjective experience throughout illness duration and might even turn the progress from negative into positive. Further research is needed to understand the dynamics of idiopathic hypersomnia in greater detail to better understand the causes and design therapeutic approaches to improve patients' quality of life.

Delayed Sleep-Wake Phase Disorder: Can Polysomnography Be Useful?

BACKGROUND: Delayed sleep-wake phase disorder (DSWPD) is a chronic condition with a multifactorial etiology that primarily affects adolescents, significantly influencing their quality of life. In clinical practice, the contribution of intrinsic and behavioral factors is difficult to determine. The aim of our study was to compare data from clinical interviews, sleep diaries, actigraphy, and nocturnal polysomnography (PSG) in a cohort of adolescents with DSWPD and to assess psychiatric/neurodevelopmental comorbidity. METHODS: Thirty-one patients (22 male; mean age 15.4 ± 2.2 years, range 12 to 19 years) with a diagnosis of DSWPD based on detailed history, sleep diary, and actigraphy underwent nocturnal polysomnography (PSG) and neurological, psychological, and psychiatric examination. RESULTS: Attention-deficit/hyperactivity disorder (ADHD) was present in 14 cases (45%), specific learning difficulties in nine (29%), and mood disorder (anxiety/depression) in 16 patients (52%). PSG revealed sleep-onset delay in only 12 (38%) cases. No differences in clinical data or psychiatric comorbidity between the group with sleep delay and the group with normal sleep onset were detected. Decreased total sleep time, sleep efficiency, rapid eye movement (REM) sleep, and prolonged REM sleep latency were observed in patients with delayed sleep onset. CONCLUSIONS: PSG showed delayed sleep timing in only 38% of patients with a diagnosis of DSWPD based on diagnostic criteria of the International Classification of Sleep Disorders. We suggest that PSG can provide useful information regarding the prevailing etiology (biological versus behavioral) if dim light melatonin onset testing is not available.

2018 worldwide survey of health-care providers caring for patients with narcolepsy: WSS narcolepsy task force.

BACKGROUND: There are limited data available on regional differences in the diagnosis and management of narcolepsy. In order to better understand worldwide trends in clinical assessment and management of narcolepsy, a survey of health-care providers was conducted by the World Sleep Society Narcolepsy task force. METHODS: A total of 146 surveys that included items on the diagnosis and management of narcolepsy were completed by practitioners representing 37 countries. RESULTS: Most of the participants were from Europe, North America, Oceania, Asia and Latin America. A consistent approach to applying the diagnostic criteria of Narcolepsy was documented with the exception of measurement of CSF hypocretin-1, which has limited availability. While the majority of practitioners (58%) reported not using the test, 1% indicated always evaluating CSF hypocretin-1 levels. There was much variability in the availability of currently recommended medications such as sodium oxybate and pitolisant; modafinil and antidepressants were the most commonly used medications. Amphetamines were unavailable in some countries. CONCLUSION: The results of the study highlight clinical and therapeutic realities confronted by worldwide physicians in the management of narcolepsy. While the diagnostic criteria of narcolepsy rely in part on the quantification of CSF hypocretin-1, few physicians reported having incorporated this test into their routine assessment of the condition. Regional differences in the management of narcolepsy appeared to be related to geographic availability and expense of the therapeutic agents.

Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

Idiopathic hypersomnia: a homogeneous or heterogeneous disease?

INTRODUCTION: Idiopathic hypersomnia (IH) is a rare orphan disease characterized by excessive daytime sleepiness, frequently accompanied by prolonged nocturnal sleep and difficulties awakening, termed sleep inertia or sleep drunkenness. Severe sleepiness usually causes a greater handicap than manifestations of narcolepsy. METHODS: Forty-three IH patients (17 male, mean age 42.8 ± SD 12.2 years, range 20-67), diagnosed in the past 20 years according to ICSD-2 or ICSD-3 criteria were invited for clinical examination to evaluate the course, manifestations and severity of the disease, as well as clinical comorbidities. The patients completed a set of questionnaires scoring sleepiness, sleep inertia, fatigue, depression, anxiety, circadian preference, and quality of life. RESULTS: IH patients were divided according to the duration of nocturnal sleep at the time of their diagnosis into two cohorts: (1) with normal sleep duration (n = 25, 58.1%) and (2) with long sleep duration (n = 18, 41.9%). The mean duration of ad libitum sleep per 22 h in the second cohort was 732.0 ± 115.4 min (range 603-1100), and women markedly prevailed (n = 14, 77.8%). Age at disease onset was younger in the group with long sleep duration (21.2 ± 11.4 years versus 28.1 ± 13.6 years, p = 0.028), their MSLT latency was longer (7.2 ± 3.7 min versus 5.1 ± 1.7 min, p = 0.005), a history of sleep inertia prevailed (p = 0.005), and daily naps were mostly non-refreshing (p = 0.014). Additionally, questionnaires in the group with long sleep duration showed more severe sleep inertia (p = 0.007), fatigue (p = 0.004), and a tendency towards evening chronotype (p = 0.001). CONCLUSIONS: IH patients with long sleep duration differ clinically as well as by objective measures at the time of diagnosis and in long-term follow up from IH patients without long 24-h sleep time. In our opinion they represent an independent clinical entity to be considered in the revised ICSD-3 criteria.

Developmental Language Disorder: Wake and Sleep Epileptiform Discharges and Co-morbid Neurodevelopmental Disorders.

Developmental language disorder (DLD) is frequently associated with other developmental diseases and may lead to a handicap through adolescence or adulthood. The aim of our retrospective study was to characterize DLD subgroups, their etiological factors and clinical comorbidities, and the role of epileptiform discharges in wake and sleep recordings. Fifty-five children (42 male, mean age 6.2 ± 1.4 years, range 4-9 years) were included in the present study and underwent phoniatric, psychologic, neurologic, as well as wake and nocturnal electroencephalography (EEG) or polysomnography (PSG) examinations. A receptive form of DLD was determined in 34 children (63.0%), and an expressive form was found in 20 children (37.0%). Poor cooperation in one child did not permit exact classification. DLD children with the receptive form had significantly lower mean phonemic hearing (79.1% ± 10.9) in comparison with those with the expressive form (89.7% ± 6.2, p < 0.001). A high amount of perinatal risk factors was found in both groups (50.9%) as well as comorbid developmental diseases. Developmental motor coordination disorder was diagnosed in 33 children (61.1%), and attention deficit or hyperactivity disorder was diagnosed in 39 children (70.9%). Almost one half of DLD children (49.1%) showed abnormalities on the wake EEG; epileptiform discharges were found in 20 children (36.4%). Nocturnal EEG and PSG recordings showed enhanced epileptiform discharges, and they were found in 30 children (55.6%, p = 0.01). The wake EEG showed focal discharges predominantly in the temporal or temporo-parieto-occipital regions bilaterally, while in the sleep recordings, focal activity was shifted to the fronto-temporo-central areas (p < 0.001). Almost all epileptiform discharges appeared in non-rapid eye movement (NREM) sleep. A close connection was found between DLD and perinatal risk factors, as well as neurodevelopmental disorders. Epileptiform discharges showed an enhancement in nocturnal sleep, and the distribution of focal discharges changed.

Sleep-related rhythmic movements and rhythmic movement disorder beyond early childhood.

INTRODUCTION: Sleep-related rhythmic movements (SRRMs) are common in young children and become less prevalent with increasing age. When SRRMs significantly interfere with sleep and/or affect daytime functioning, potentially resulting in injury, rhythmic movement disorder (SRRMD) is diagnosed. OBJECTIVE: The aim of our study was to assess clinical comorbidities, types of SRRMs, sleep stage/wakefulness distribution during night, and age-dependence of these parameters. MATERIAL AND METHODS: In sum, 45 patients (age range 1-26 years, mean age 10.56 ± 6.4 years, 29 men) were clinically examined for SRRMs or SRRMD. Nocturnal polysomnography (PSG) was recorded in 38 patients. To evaluate clinical and sleep comorbidity, the cohort of 38 patients was divided according to age into four groups: (1) younger than 5 years (N = 7), (2) 5-9 years (N = 12), (3) 10-14 years (N = 11), and (4) ≥ 15 years (N = 8). RESULTS: A clear relationship between perinatal risk factors and developmental disorders (attention deficit hyperactivity disorder - ADHD, specific learning disability) was found which extended population prevalence at least five times. A total of 62 recordings were evaluated in 38 patients; SRRMs were found in PSG in 31 of 38 patients (82%). No age-dependent correlation between type of SRRMs and sleep stage/wakefulness distribution during the night was observed. However, when all recordings were correlated together, rolling stereotypes occurred more frequently in REM sleep, and rocking stereotypes in superficial NREM sleep. CONCLUSION: Developmental disorders and perinatal risk factors were connected with SRRMs and SRRMD in children and young adults. Rolling movements were significantly associated with REM stage and rocking stereotypes with superficial NREM sleep, independent of age.

Relapsing encephalopathy with cerebellar ataxia are caused by variants involving p.Arg756 in ATP1A3.

Mutations in ATP1A3 lead to different phenotypes having in common acute neurological decompensation episodes triggered by a specific circumstance and followed by sequelae. Alongside Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, Sensorineural hearing loss syndrome (CAPOS), a new Relapsing Encephalopathy with Cerebellar Ataxia (RECA) phenotype was published in 2015. We describe herein eight new pediatric cases. Most of them had no specific history when the first neurological decompensation episode occurred, before the age of 5 years, triggered by fever with severe paralytic hypotonia followed by ataxia with or without abnormal movements. Neurological sequelae with ataxia as the predominant symptom were present after the first episode in three cases and after at least one subsequent relapse in five cases. Five of the eight cases had a familial involvement with one of the two parents affected. The phenotype-genotype correlation is unequivocal with the causal substitution always located at position 756. The pathophysiology of the dysfunctions of the mutated ATPase pump, triggered by fever is unknown. Severe recurrent neurological decompensation episodes triggered by fever, without any metabolic cause, should lead to the sequencing of ATP1A3.

Sleep and sleep-related disorders in women.

There are sex differences in sleep from a very early age till adulthood and older age. The changing hormone profile across the reproductive life of a woman, from puberty through the reproductive period to the postmenopausal years, has a significant influence on sleep. Female hormones may lead to sleep disruption however, multiple factors play a role in insomnia during pregnancy as well as during menopause. Some sleep disorders, such as obstructive apnea and restless leg syndrome, are influenced by menstrual cycle, pregnancy and menopause.

Childhood narcolepsy and autism spectrum disorders: four case reports.

BACKGROUND: Childhood narcolepsy is associated with various emotional, behavioural and cognitive dysfunctions as well as with psychiatric and neurodevelopmental disorders: anxiety, depression, attention deficit hyperactivity disorder and psychosis. A relationship between these conditions is unclear - comorbidity or similar pathophysiological mechanisms can be suggested. OBJECTIVE: We reported four children with narcolepsy type 1 (NT1) and autism spectrum disorder (ASD) - Asperger syndrome (AS). RESULTS AND CONCLUSION: To the best of our knowledge co-occurrence of NT1 and AS has not been described in the literature as noted in this report.

Modafinil Reduces Parasympathetic Activity but Does Not Influence Autonomic Reactivity to Orthostatic Load in Narcolepsy Type 1.

INTRODUCTION: Modafinil may affect autonomic functions in healthy subjects. The aim of the study was to assess the long-term modafinil administration influence on the cardiac autonomic reactivity to orthostatic load in patients with narcolepsy type 1. METHODS: In 15 patients (4 male; 11 female; median age, 47 years; range, 18-70 years) with narcolepsy type 1 treated with modafinil in daily dose of 100 to 300 mg, the short-term spectral analysis of heart rate variability (HRV) in supine-standing-supine test was performed before and after 72 hours of modafinil discontinuation. RESULTS: The sympathovagal reactivity to orthostatic load was not modified by modafinil treatment; nevertheless, the parasympathetic activity expressed by length of R-R interval and high-frequency component of HRV is reduced in supine position in patients taking modafinil. CONCLUSIONS: We conclude that long-term use of modafinil does not influence the cardiac autonomic reactivity to orthostatic load expressed by the HRV changes in supine-standing-supine test in narcolepsy type 1 patients, but the parasympathetic cardiac activity may be reduced in quiet supine position in patients with narcolepsy taking modafinil.

The MSLT is Repeatable in Narcolepsy Type 1 But Not Narcolepsy Type 2: A Retrospective Patient Study.

STUDY OBJECTIVES: To examine repeatability of Multiple Sleep Latency Test (MSLT) results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3). METHODS: Repeatability of the MSLT was retrospectively evaluated in NT1 (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had documented HLA-DQB1*06:02 status and/or hypocretin-1 levels from cerebrospinal fluid. All subjects had undergone 2 MSLTs (≥ 1 meeting ICSD-3 criteria for narcolepsy). Repeatability was explored in children versus adults and in those on versus not on medication(s). Subsample and multivariate analysis were performed. RESULTS: Both MSLTs in unmedicated patients were positive for narcolepsy in 78%, 18%, and 7% of NT1, NT2, and controls, respectively. NT2 cases changed to idiopathic hypersomnia or to a negative MSLT 26% and 57% of the time, respectively. Although NT1 cases were 10 to 14 times more likely to demonstrate a second positive MSLT compared to NT2 cases (P < 10-5) and controls (P < 10-4), respectively, NT2 cases were not significantly different from controls (P = .64). Medication use (P = .009) but not adult versus children status (P = .85) significantly decreased the likelihood of a repeat positive MSLT. CONCLUSIONS: In a clinical setting, a positive MSLT for narcolepsy is a more reproducible and stable feature in NT1 than NT2. The retrospective design of this study hinders interpretation of these data, as there are many different, and possibly opposing, reasons to repeat a MSLT in NT1 versus NT2 (ie, ascertainment bias). Additional systematic MSLT repeatability studies independent of confounds are ideally needed to confirm these findings.

Cardiovascular fitness in narcolepsy is inversely related to sleepiness and the number of cataplexy episodes.

OBJECTIVE: Cardiopulmonary fitness depends on daily energy expenditure or the amount of daily exercise. Patients with narcolepsy spent more time being sleepy or asleep than controls; thus we may speculate that they have a lower quantity and quality of physical activity. The aim of the present study was thus to test the hypothesis that exercise tolerance in narcolepsy negatively depends on sleepiness. PATIENTS AND METHODS: The cross-sectional study included 32 patients with narcolepsy with cataplexy, 10 patients with narcolepsy without cataplexy, and 36 age- and gender-matched control subjects, in whom a symptom-limited exercise stress test with expired gas analysis was performed. A linear regression analysis with multivariate models was used with stepwise variable selection. RESULTS: In narcolepsy patients, maximal oxygen uptake (VO2peak) was 30.1 ± 7.5 mL/kg/min, which was lower than 36.0 ± 7.8 mL/kg/min, p = 0.001, in controls and corresponded to 86.4% ± 20.0% of the population norm (VO2peak%) and to a standard deviation (VO2peakSD) of -1.08 ± 1.63 mL/kg/min of the population norm. VO2peak depended primarily on gender (p = 0.007) and on sleepiness (p = 0.046). VO2peak% depended on sleepiness (p = 0.028) and on age (p = 0.039). VO2peakSD depended on the number of cataplexy episodes per month (p = 0.015) and on age (p = 0.030). CONCLUSIONS: Cardiopulmonary fitness in narcolepsy and in narcolepsy without cataplexy is inversely related to the degree of sleepiness and cataplexy episode frequency.