OBJECTIVE: Idiopathic hypersomnia (IH) is a disorder of central hypersomnolence that results in excessive daytime sleepiness in the absence of another identifying cause. Case studies from sleep clinic patients may not be a fair representation of the wider IH population. This study aims to better characterize patients diagnosed with IH in Australia and New Zealand using online patient-driven survey data.
METHODS: A retrospective analysis of 686 participants from the Hypersomnolence Australia Patient Data Registry diagnosed with either IH (n = 554), narcolepsy type 1 (NT1, n = 54) or narcolepsy type 2 (NT2, n = 78) between January 2013 and October 2022 was performed.
RESULTS: Participants with IH reported additional sleep disorders such as OSA (16.4%) and restless legs syndrome (7.9%) and notable comorbidities included depression (46.2%) and anxiety (50%). There was a mean delay in diagnosis of 10 years in participants with IH, when compared to symptom onset. IH presents with unique but also overlapping symptomatology with NT2, with similar reporting of long daytime naps, unrefreshed sleep and automatic behavior. Modafinil was the most common medication (45.5%) used by participants with IH followed by dexamphetamine (44.2%). Most participants with IH reported receiving physician advice regarding positive lifestyle changes but recommend that newly diagnosed patients be given more advice about medication use.
CONCLUSIONS: This study demonstrates a delay in IH diagnosis when compared to symptom onset and overlapping features of IH and NT2. It also highlights the heterogeneous presentation of IH and the value of large patient registries in future research.

OBJECTIVE: Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1; NT1) and patients with narcolepsy without cataplexy (narcolepsy type 2; NT2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the DQB1*06:02 allele.
METHODS: This case control study included 21 patients with NT1 (56.8%), 16 patients with NT2 (43.2%), and 100 controls. Sequence-based typing identified HLA-DRB1 alleles, and HLA-DQB1 typing was done using PCR-Sequence-Specific Oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants.
RESULTS: In the NT1 group, only one allele had a significantly higher frequency than in the NT2 group: DQB1*06:02 (61.9% vs. 18.8%;). Compared to controls, DQB1*06:02 (61.9% vs. 18.0% in controls) and DRB1*15:01(47.6% vs. 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. PSG was identified in DQB1*06:02 positive subgroup REM sleep latency (REML) ≤ 15 minutes, and all patients had two or more sleep-onset REM periods (SOREMPs) at MSLT.
CONCLUSIONS: This study showed a strong association between HLA DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter REMLs at PSG. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening.

OBJECTIVE: The Multiple Sleep Latency Test (MSLT) is a key diagnostic component in the diagnosis of central disorders of hypersomnolence. Due to time constraints, it is common practice to wake patients at a standard time from overnight polysomnography (PSG) prior to the MSLT. This has the potential to influence MSLT results due to sleep deprivation. We describe the impact of allowing ad libitum sleep on the night prior to the MSLT in patients being assessed for hypersomnolence.
METHODS: 580 consecutive patients undergoing PSG/MSLT for assessment of hypersomnolence were analyzed: 290 either side of a change in laboratory protocol which allowed patients ad libitum sleep during the PSG, rather than being woken at a pre-specified time. Baseline characteristics, PSG and MSLT results were compared between the groups.
RESULTS: Groups were similar at baseline, other than there being more females in the ad libitum group. After adjusting for confounding variables, ad libitum patients had later sleep offset time (+58.7 minutes; p<0.001), longer PSG total sleep time (+47.8 minutes; p<0.001), longer MSLT mean sleep latency (+1.3 minutes; p=0.002) and 23% fewer MSLT with mean sleep latency less than 8 minutes (p=0.004) when compared with patients who were woken at a standard time.
CONCLUSIONS: The common practice of waking patients from their PSG at a standard time has the potential to curtail sleep and impact MSLT results by reducing mean sleep latency. Patients being assessed for hypersomnolence should be allowed ad libitum sleep during the PSG on the night prior to their MSLT.

There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these chronic hypersomnia conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH, and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control, or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

UNASSIGNED: Sleeping disorders were reported in many patients who took vaccines during previous pandemics. We aim to investigate the relationship between coronavirus disease 2019 (COVID-19) vaccines and the incidence of narcolepsy symptoms in the Jordanian population.
UNASSIGNED: We used a descriptive, cross-sectional, online self-administered survey conducted between December 2022 and May 2023. The survey targeted males and females above the age of 18 years who took any type of COVID-19 vaccine, had no chronic diseases, and had no sleep disorders prior to taking the vaccine. The survey was distributed via social media platforms.
UNASSIGNED: A total of 873 participants were included in this study, consisting of 44.4% males and 55.6% females, with the majority being in the 18-29 age group. Most participants (79.8%) received two vaccine doses, with the Pfizer vaccine being the most common. Nearly half of the participants reported excessive daytime sleepiness. Sleep paralysis and hypnagogic hallucinations were reported by a notable proportion of participants, but no significant differences were found among the vaccine types. Sleep attacks and fragmented nighttime sleep were associated with the number of vaccine doses received, suggesting a possible influence of the dose count on these symptoms. The presence of excessive daytime sleepiness, sudden loss of muscle tone, sleep paralysis, and hypnagogic hallucinations showed no significant association with the number of doses taken.
UNASSIGNED: We hypothesize a possible link between COVID-19 vaccination and the emergence of narcolepsy symptoms in Jordanian individuals. Additional investigations and continuous monitoring to determine the extent of the risk and uncover potential mechanisms behind this connection should be performed.

Alteration of motor control during REM sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 is not associated with alpha-synucleinopathies. To determine whether the chronic absence of ORX neuropeptides is sufficient to induce RBD symptoms, we analyzed during REM sleep the EMG signal of the prepro-hypocretin knockout mice (ORX-/-), a recognized mouse model of NT1. Then, we evaluated the severity of motor alterations by comparing EMG data of ORX-/- mice to those of mice with a targeted suppression of the sublaterodorsal glutamatergic neurotransmission, a recognized rodent model of iRBD. We found a significant alteration of tonic and phasic components of EMG during REM sleep in ORX-/- mice, with more phasic events and more REM sleep episodes without atonia compared to the control wild-type mice. However, these phasic events were fewer, shorter and less complex in ORX-/- mice compared to the RBD-like ORX-/- mice. We thus show that ORX-deficiency, as seen in NT1, is sufficient to impair muscle atonia during REM sleep with a moderate severity of alteration as compared to isolated RBD mice. As described in NT1 patients, we report a major inter-individual variability in the severity and the frequency of RBD symptoms in ORX-deficient mice.

BACKGROUND: Observational and retrospective studies suggest that people with narcolepsy may have an increased prevalence of cardiovascular and cardiometabolic comorbidities and may be at greater risk for future cardiovascular events. An expert consensus panel was formed to establish agreement on the risk of hypertension and cardiovascular/cardiometabolic disease in people with narcolepsy and to develop strategies to mitigate these risks.
RESULTS: Experts in sleep medicine and cardiology were selected to participate in the panel. After reviewing the relevant literature, the experts identified key elements, drafted recommendation statements, and developed discussion points to provide supporting evidence for the recommendations. The draft and final recommendations were rated on a scale from 0 (not at all agree) to 4 (very much agree). All experts had an agreement rating of 4.0 for all 14 revised recommendation statements for patients with narcolepsy. These statements comprised 3 themes: (1) recognize the risk of hypertension and cardiovascular/cardiometabolic disease, (2) reduce the risk of hypertension and cardiovascular/cardiometabolic disease, and (3) reduce sodium intake to lower the risk of hypertension and cardiovascular disease.
CONCLUSIONS: These consensus recommendations are intended to increase awareness of potential cardiovascular/cardiometabolic risks in patients with narcolepsy for all clinicians. Early monitoring for, and prevention of, cardiovascular risks in this population are of great importance, especially as narcolepsy usually develops in adolescents and young adults, who will be exposed to adverse effects of the disease for decades. Prospective systematic studies are needed to determine association and causation of narcolepsy with cardiovascular/cardiometabolic disorders.

UNASSIGNED: This is a plain language summary of a published article in the journal Sleep. Narcolepsy is a sleep condition that has 2 different subtypes: narcolepsy type 1 and narcolepsy type 2. These are called NT1 and NT2 for short. Sodium oxybate (SXB) is approved to treat excessive daytime sleepiness (EDS) and cataplexy. People with NT1 and NT2 both have EDS, but cataplexy is only present in people with NT1. Limited information is available about how SXB works in people with NT2. This is because previous trials have included only people with NT1 or people with unspecified narcolepsy. For more than 20 years, the only available formulation of this medicine had to be given twice during the night. Many people with narcolepsy find that chronically waking up in the middle of the night for a second dose of SXB is disruptive to themselves or others in their household. People have also reported sleeping through alarm clocks, missing their second dose, and feeling worse the next day. Some people have accidentally taken the second dose too early, putting them at risk for serious adverse effects. These adverse effects may include slow breathing, low blood pressure, or sedation. The US Food and Drug Administration (FDA) approved a medicine called LUMRYZ™ (sodium oxybate) for extended-release oral suspension in May 2023. LUMRYZ is a once-nightly formulation of SXB (ON-SXB for short) and is taken as a single dose before bedtime. This medicine treats EDS and muscle weakness (also known as cataplexy) in people with narcolepsy. A clinical trial called REST-ON studied ON-SXB to find out if it was better at treating narcolepsy symptoms than a medicine with no active ingredients (placebo). This summary describes a study that tested whether ON-SXB was better than placebo at treating narcolepsy symptoms in people with NT1 or NT2.
UNASSIGNED: This study showed that compared to people who took placebo, people who took ON-SXB were able to stay awake longer during the day, felt less sleepy during the daytime, had less cataplexy, and had more improvements in their symptoms overall than people who took placebo.
UNASSIGNED: ON-SXB has been proven effective for people with NT1 or NT2. Unlike prior formulations of SXB, ON-SXB is taken once at bedtime, without requiring waking up in the middle of the night for a second dose.

BACKGROUND: Recent studies suggest the existence of a physiologic basis for bone rarefaction and increased risk for fractures. This study aimed to address anthropometric differences between patients with narcolepsy type 1 (NT1) and type 2 (NT2) and discrepancies in bone mineral content (BMC) as a function of hypocretin-1 (Hcrt-1) measured in cerebrospinal fluid (CSF).
METHODS: We have evaluated 31 adult patients (aged 18-65 years) with NT1 and 18 patients with NT2, comparing the groups in terms of anthropometric variables - body mass index (BMI) and waist-to-hip ratio (WHR) - and percentage of bone mineral content (%BMC), measured by bioelectrical impedance analysis (BIA). Statistical analysis assessed the effects of Hcrt-1 levels on CSF, dietary intake, and medication use over these variables. Statistical significance was achieved with a confidence interval of 95 % and p < 0.05.
RESULTS: Patients with NT1 presented with higher BMI (32.04 ± 6.95 vs. 25.38 ± 4.26 kg/m2; p < 0.01) and WHR (0.89 ± 0.09 vs. 0.83 ± 0.09; p = 0.02) compared to NT2, in detriment of %BMC, which was lower for NT1 (4.1 ± 1.02 vs. 4.89 ± 0.59; p < 0.01). Hcrt-1 in CSF showed a positive correlation with %BMC (r = +0.48, p < 0.01) and a negative correlation with anthropometric features (BMI: r = -0.54, p < 0.01; WHR: r = -0.37, p = 0.01). There was a correlation between WHR and diary caloric intake (r = +0.42, p < 0.01).
CONCLUSIONS: The evaluation of patients with narcolepsy presupposes a syndromic approach comprising symptoms that go far beyond excessive daytime sleepiness. The integrated follow-up, including nutritional profile and anthropometric features, should add value in reducing morbidity in this population.

BACKGROUND: Symptoms of depression and anxiety are common complications of narcolepsy. Earlier studies have shown that narcolepsy type 1 (NT1) is an autoimmune inflammatory disease and symptoms of depression and anxiety are closely related to fluctuations in inflammatory cytokines. The objective of the current research was to investigate the potential correlation between cytokines and symptoms of depression and anxiety in patients with NT1.
METHODS: We collected demographic and clinical data and information on cytokine levels from 50 patients with NT1 and used Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) to assess the severity of depression and anxiety symptoms. Patients with SDS scores ≥ 53 points were defined as depressive narcolepsy type 1 (D-NT1) and those with SDS scores < 53 points as non-depressive narcolepsy type 1 (ND-NT1). Patients with SAS scores ≥ 50 points were defined as anxious narcolepsy type 1 (A-NT1) and those with SAS scores < 50 points as non-anxious narcolepsy type 1 (NA-NT1). A binary logistic regression model was employed to identify the influencing factors of depressive and anxiety symptoms.
RESULTS: Levels of IL-10 (p = 0.02), IL-4 (p = 0.049) and disease duration (p = 0.049) were decreased, while SAS scores (p < 0.001) and total sleep duration (p = 0.03) were increased in D-NT1 relative to ND-NT1 patients. A-NT1 patients had higher SDS scores (p < 0.001) compared to NA-NT1 patients. Binary logistic regression analysis revealed associations of longer disease duration (OR=0.83; 95 % CI: 0.70-0.97) and increased IL-10 (OR=0.40; 95 % CI: 0.17-0.90) with reduced risk of depression and worsening anxiety (SAS score; OR=1.17; 95 % CI: 1.06-1.30) with increased risk of depression in patients with NT1. Consistently, worsening depression (SDS score; OR=1.22; 95 % CI: 1.07-1.39) was correlated with increased risk of anxiety in the NT1 group.
CONCLUSIONS: Our finding that higher IL-10 levels correlate with a lower risk of depression in NT1 patients provides a reference for further exploration of the pathophysiological mechanisms of depressive symptoms in NT1 patients.