Treatment Of Narcolepsy Research Articles

Treatment of Narcolepsy Type 1 With Orexin: A Systematic Review.

Narcolepsy is a rare, chronic neurological disorder characterized by excessive daytime sleepiness (EDS). Narcolepsy type 1 is probably caused by an autoimmune-mediated loss of orexin-producing neurons. Type 2 patients retain the physiological functioning of orexigenic neurons. The basis for treating narcolepsy type 1 with orexin-A is that if narcolepsy develops because of a loss of orexigenic neurons, then administering orexin should be able to eliminate, reduce, or prevent the impact of this loss. The aim of this review was to capture and analyze studies to elucidate the efficacy of orexin-A in the treatment of narcolepsy type 1 in humans. The search strategy included the following descriptors: "narcolepsy," "orexin," and "treatment," with filters for randomized clinical trials (RCT) and human studies. A total of 70 publications were retrieved from the databases. Duplicate records were removed before screening (n = 13), and 54 were then excluded for the following reasons: off-topic (n = 18), reviews (n = 14), use of a different intervention other than orexin (n = 14), non-human studies (n = 4), out-of-population selection criteria (n = 2), and case report (n = 2). Thus, the studies included in the review were three. Treatment of narcolepsy with orexin decreases the number of wake-REM (rapid eye movement) transitions and total time of REM sleep, although it does not increase wake time. The failure of orexin to alleviate daytime sleepiness suggests that orexin deficiency is not the only factor involved in the pathophysiology of type I narcolepsy.

Bibliometric and visual study of narcolepsy from 2000 to 2023.

More studies explored the prevalence, causes, associated conditions, and therapeutic strategies of narcolepsy. With an increasing focus on understanding narcolepsy's prevalence, associated conditions, and therapeutic strategies, there's a notable absence of bibliometric analyses summarizing trends in research and identifying emerging areas of focus within this field. To conduct a bibliometric analysis to investigate the current status and frontiers of narcolepsy. The documents related to narcolepsy are obtained from the Web of Science Core Collection database (WoSCC) from January 1, 2000, to December 31, 2023, and VOS viewer 1.6.16, and the WoSCC's literature analysis wire were used to conduct the bibliometric analysis. A total of 4672 publications related to narcolepsy were included, and 16182 authors across 4397 institutions and 96 countries/regions contributed to these documents in 1131 different journals. The most productive author, institution, country and journal were Yves Dauvilliers, Stanford University, United States, and Sleep Medicine, respectively. The first high-cited document was published in Nature in 2005 by Saper et al, and this research underscores the role of certain neurons in ensuring the stability of sleep-wake transitions, offering insights into narcolepsy's pathophysiology. In conclusion, the main research hotspots and frontiers in the field of narcolepsy are the diagnosis of narcolepsy, pathological mechanism of narcolepsy and the treatment of narcolepsy. More studies are needed to explore effective strategies for the diagnosis and treatment of narcolepsy.

Evaluation of pitolisant, sodium oxybate, solriamfetol, and modafinil for the management of narcolepsy: a retrospective analysis of the FAERS database.

Narcolepsy, a rare neurological disorder believed to have an autoimmune etiology, necessitates lifelong management. This study aimed to provide evidence supporting the safety of pharmacological treatment for narcolepsy. Five-year data on pitolisant, sodium oxybate, solriamfetol, and modafinil were extracted from the FDA Adverse Event Reporting System (FAERS) self-reporting database for the period spanning from 2019 to 2023. Various statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network analysis (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to quantify the signals. Finally, a comparative analysis was conducted between demographic data, outcomes, and inherent associations among the medications and the signals. After data analysis, we obtained 50 signals (a cumulative count of 762 cases) for pitolisant, 640 signals (corresponding to 46,962 cases) for sodium oxybate, 40 signals (equivalent to 1,228 cases) for solriamfetol, and finally, 72 signals (representing 632 cases) for modafinil. The majority of these patients were female. Psychiatric and nervous system disorders were identified as the predominant adverse drug events (ADEs). For sodium oxybate, it is crucial to consider psychiatric disorders (such as suicidal ideation), respiratory disorders (including sleep apnea syndrome and respiratory depression), and signs of pregnancy and congenital familial diseases. For solriamfetol, noteworthy new ADEs include drug inefficacy, suicidal ideation, restless legs syndrome, and somnambulism. Furthermore, a relationship has been observed between modafinil use and restricted fetal growth, spontaneous abortion, cognitive disorders, and drug inefficacy and abuse. The majority of observed adverse reactions in this study were consistent with those listed in the product instructions. However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy.

Development and characterization of solriamfetol-loaded PVA/PLGA electrospun nanofiber membranes: A promising approach for sustained narcolepsy treatment

Narcolepsy presents challenges in medication adherence and delivery, with traditional oral medications not always suitable for patients experiencing unexpected sleep episodes or difficulty in swallowing pills. This study focused on developing a solriamfetol (SF) loaded nanofiber membrane using a polymer blend of polyvinyl alcohol (PVA) and polylactic-co-glycolic acid (PLGA) for the management of narcoleptic patients with non-oral dosage options. The design required synthesis, optimization, characterization, and evaluation of these nanofibers for transdermal drug delivery. Using a Box-Behnken design, the nanofibers were produced via the electrospinning technique, achieving a high drug content of 96.31 ± 1.21 % and entrapment efficiency of 96.18 ± 1.42 %. The in vitro drug release studies demonstrated a prolonged release profile of SF over 24 h, with 97 % ± 2 % of the drug released. The SEM analysis revealed that the surface morphology of the nanofibers was smooth and homogenous, and the average diameter of the SF/PVA/PLGA nanofibers was found to be 150.23 ± 2.50 nm. X-ray diffraction results confirmed the amorphous structure of the nanofibers. The zebrafish embryonic toxicological study did not reveal any signs of toxicity or morphological abnormalities in the developing embryos, indicating that the nanofibers are safe. The results point to the applicability of SF nanofiber membranes in personalized narcolepsy therapy, which improves patients’ quality of life and the efficacy of their treatment. These nanofibers can be given in the form of a transdermal patch to patients for sustained drug delivery, even when they fall asleep or when they cannot take medicines orally.

Captagon: A comprehensive bibliometric analysis (1962–2024) of its global impact, health and mortality risks

Captagon is a synthetic stimulant combining amphetamine and theophylline. Initially introduced in 1961 as a treatment for hyperactivity, depression, and narcolepsy, Captagon was later classified as a Schedule 1 controlled substance due to its addictive and hallucinogenic properties. Despite its global prohibition in 1986, the trade of counterfeit products is widespread, especially in south-east Europe and far-east Asia, with its production being on the rise in Middle Eastern regions. This paper presents a quantitative data-driven bibliometric analysis of the existing literature on Captagon up to July 2024. It aims to delineate the structure and development of knowledge surrounding the substance, including key contributing countries, authors, prominent sources, and recurring thematic keywords. The quantitative and data-driven results were then used to guide the narrative discussion on Captagon. Findings indicate that current research predominantly focuses on Captagon’s use and impact in conflict zones, often exploring its interaction with other substances used by civilians and militias. Results also show a growing trend in Captagon research, with Saudi Arabia, Jordan, and Iraq emerging as main contributors to the literature. Despite the attention in specific regions, a considerable gap remains in understanding the mechanisms of action of Captagon (particularly regarding its metabolism, toxicology, mortality risk), and in developing protocols for its discontinuation. Additionally, the drug’s inconsistent composition requires further analyses to better predict risks and establish effective management strategies. Addressing these gaps will be crucial for the development of novel interventions and policies to mitigate the adverse effects of Captagon and improve public health systems worldwide.

Development and Validation of an Analytical Method to Identify and Quantitate Novel Modafinil Analogs in Products Marketed as Dietary Supplements

Modafinil (brand name Provigil®) is a Schedule IV (U.S.) drug used for the treatment of narcolepsy and sleep disorders. It is also known to be used recreationally. Analogs of modafinil, including adrafinil, remain unapproved and/or unscheduled. The lack of scheduling has made these analogs a popular target for recreational use and inclusion in dietary supplements. However, the use of controlled substances (or their analogs) without the care of a physician presents a public health risk. Preliminary nontargeted analyses in our laboratory revealed the presence of adrafinil in several dietary supplements, highlighting the need for an analytical method to identify modafinil analogs in supplements. A liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated to quantitate modafinil, plus four novel unscheduled modafinil analogs: adrafinil, CRL-40,940, CRL-40,941, and N-methyl-4,4-difluoromodafinil. This method was then applied to four samples of products marketed as dietary supplements collected via undercover purchase. These four products were marketed as nootropics or cognitive enhancers and labeled to contain adrafinil. Adrafinil was found in all four samples. The identification of modafinil analogs in this context is important so that consumers are not, knowingly or unknowingly, consuming these active pharmaceutical ingredients in products marketed as dietary supplements.

Measures of stimulant medications: A population-based study in Alberta, Canada

ObjectivesStimulants are a class of drugs approved for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. However, they are also often used “off-label” as adjunct therapies for the treatment of obesity and depression. The objective of this study is to summarize how stimulant use is globally measured in the literature and to explore rates of stimulant use in Alberta, Canada. MethodsA traditional narrative literature review was conducted to summarize global methods of stimulant assessment. Then using definitions guided by the literature and current regulatory bodies in Alberta, we conducted a series of descriptive analyses to assess how frequent stimulant use was in Alberta patients from 2019 to 2021: 1) number of dispenses by year; 2) average days of drug supply; 3) proportion of days covered (PDC); and 4) defined daily dose (DDDs). ResultsIn the literature review, the most frequently used measures of stimulant drug use were trends over time (prevalence), types of drug use, and dispensations of prescriptions. In all, there is a global trend of increased use of stimulants among both adults and children. In Alberta, 173,789 patients were prescribed stimulant medication in 2019–2021, representing approximately 4 % of the entire Alberta population. Overall, 61.1 % were between the ages of 10–34 and 46.8 % were female. The number of dispensations rose from 713,896 in 2019 to 973,930 in 2021 – with up to 43 % being lisdexamfetamine stimulant dispenses. ConclusionsAlthough stimulant use in AB was measured using similar trend estimates as the literature, there is a lack of research to support whether these measures are accurate and effective at the population-level. Future steps to standardize both medical and nonmedical use of prescription stimulants are warranted in efforts to fully quantify both benefits and risks associated with stimulant use.

Weight Loss With Once-nightly Sodium Oxybate for the Treatment of Narcolepsy: Analysis From the Phase III Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) Trial

Individuals with narcolepsy are more likely to be obese than the general population. Changes in weight-related measures with extended-release, once-nightly sodium oxybate (ON-SXB) and characteristics of participants with ≥5% weight loss were assessed in a Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) trial post hoc analysis. REST-ON (NCT02720744) was a Phase III, double-blind, placebo-controlled, multicenter, randomized clinical trial. Participants aged ≥16 years with narcolepsy type 1 (NT1) or NT2 received ON-SXB or placebo for 13 weeks (week 1, 4.5 g; weeks 2-3, 6 g; weeks 4-8, 7.5 g; and weeks 9-13, 9 g). Weight and body mass index were measured at baseline and study end. Weights were similar between groups at baseline (mean [SD]; ON-SXB, 81.2 [20.8] kg; N = 107 [NT1, n = 80; NT2, n = 27]; placebo, 82.1 [22.5] kg; N = 105 [NT1, n = 82; NT2, n = 23]). At week 13 (9 g), mean (SD) weight decreased 1.3 (3.6) kg with ON-SXB and increased 0.2 (2.6) kg with placebo; 17.8% (19/107; NT1, n = 14; NT2, n = 5) of participants receiving ON-SXB had ≥5% weight loss versus 3.8% receiving placebo (4/105; NT1, n = 3; NT2, n = 1; P = 0.001). At week 13, least squares mean (SE) body mass index change from baseline was ‒0.51 (0.13) kg/m2 with ON-SXB and 0.08 (0.13) kg/m2 with placebo (least squares mean difference [95% CI], -0.59 [-0.95 to -0.23] kg/m2; P = 0.001). Excessive daytime sleepiness improved for both groups with ON-SXB, the ≥5% weight-loss subgroup exhibited larger improvement in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale versus the other subgroup (weight loss <5%, no change, or weight gain) (Maintenance of Wakefulness Test, P = 0.019; Epworth Sleepiness Scale score, P < 0.001). Narcolepsy is often associated with obesity, which may increase cardiometabolic risks. ON-SXB, an effective treatment for excessive daytime sleepiness and cataplexy, may be preferred in overweight or obese individuals to provide a more tailored treatment approach. NCT02720744.

Development of a mindfulness-based intervention for narcolepsy: a feasibility study.

Mindfulness-based interventions (MBI) have been shown to improve psychosocial functioning in medical populations but have not been studied in narcolepsy. This study examined the feasibility and acceptability of an MBI that was adapted for narcolepsy, including three variations in program length. Adults with narcolepsy (N = 60) were randomized to MBI groups of varying durations: brief (4 weeks), standard (8 weeks), or extended (12 weeks). Participants completed assessments at baseline, 4, 8, and 12 weeks. To assess feasibility and acceptability, primary outcomes included attendance, meditation practice, and data completeness. Additionally, participants completed measures of mindfulness, self-compassion, mood, sleep, psychosocial functioning, and cognition. An effect size of Cohen's d ≥ 0.5 was used as the prespecified benchmark for a minimal clinically important difference (MCID). The attendance, meditation, and data completeness benchmarks were met by 71.7%, 61.7%, and 78.3% of participants, respectively. Higher proportions of the brief and extended groups met these benchmarks compared to the standard group. All groups met the MCID for mindfulness, self-compassion, self-efficacy for managing emotions, positive psychosocial impact, global mental health, and fatigue. Standard and extended groups met the MCID for anxiety and depression, and extended groups met the MCID for additional measures including social and cognitive functioning, daytime sleepiness, hypersomnia symptoms, and hypersomnia-related functioning. Results suggest that the remote delivery and data collection methods are feasible to employ in future clinical trials, and it appears that the extended MBI provides the most favorable clinical impact while maintaining attendance and engagement in meditation practice. Awareness and Self-Compassion Enhancing Narcolepsy Treatment (ASCENT), NCT04306952, https://clinicaltrials.gov/ct2/show/NCT04306952.

Amphetamine and methylphenidate potential on the recovery from stroke and traumatic brain injury: a review.

The prevalence of stroke and traumatic brain injury is increasing worldwide. However, current treatments do not fully cure or stop their progression, acting mostly on symptoms. Amphetamine and methylphenidate are stimulants already approved for attention deficit hyperactivity disorder and narcolepsy treatment, with neuroprotective potential and benefits when used in appropriate doses. This review aimed to summarize pre-clinical and clinical trials testing either amphetamine or methylphenidate for the treatment of stroke and traumatic brain injury. We used PubMed as a database and included the following keywords ((methylphenidate) OR (Ritalin) OR (Concerta) OR (Biphentin) OR (amphetamine) OR (Adderall)) AND ((stroke) OR (brain injury) OR (neuroplasticity)). Overall, studies provided inconsistent results regarding cognitive and motor function. Neurite outgrowth, synaptic proteins, dendritic complexity, and synaptic plasticity increases were reported in pre-clinical studies along with function improvement. Clinical trials have demonstrated that, depending on the brain region, there is an increase in motor activity, attention, and memory due to the stimulation of the functionally depressed catecholamine system and the activation of neuronal remodeling proteins. Nevertheless, more clinical trials and pre-clinical studies are needed to understand the drugs' full potential for their use in these brain diseases namely, to ascertain the treatment time window, ideal dosage, long-term effects, and mechanisms, while avoiding their addictive potential.

PCR46 A Qualitative Exploration of Patient and Healthcare Provider Perspectives on Oxybate Treatments for Narcolepsy

PCR46 A Qualitative Exploration of Patient and Healthcare Provider Perspectives on Oxybate Treatments for Narcolepsy

Dosing Optimization of Low-Sodium Oxybate in Narcolepsy and Idiopathic Hypersomnia in Adults: Consensus Recommendations.

Low-sodium oxybate (LXB) is approved for treatment of narcolepsy in patients aged 7years and older and treatment of idiopathic hypersomnia in adults. LXB contains the same active moiety with 92% less sodium than sodium oxybate (SXB). As the indication for oxybate treatment in patients with idiopathic hypersomnia is new and allows for individualized dosing optimization, guidance for beginning LXB treatment is needed. In particular, clinicians may benefit from guidance regarding treatment initiation, dosing/regimen options, potential challenges, and treatment expectations. Additionally, pharmacokinetic profiles differ slightly between both treatments, and further guidance on transitioning from SXB to LXB in patients with narcolepsy may aid clinicians. An expert panel of five sleep specialists was convened to obtain consensus on recommendations for these topics using a modified Delphi process. Across two virtual meetings, the panel agreed on 31 recommendations with a high degree of consensus that fell into four overarching topics: (1) introducing LXB to patients; (2) initiating LXB for adult narcolepsy and idiopathic hypersomnia; (3) addressing challenges in using LXB; and (4) transitioning from SXB to LXB. The panel recommended that clinicians provide a clear overview of how LXB works for treating symptoms in narcolepsy or idiopathic hypersomnia, as appropriate for their patients, explain safety aspects, and set expectations prior to initiating LXB treatment. Strategies for initial dosing and regimen are provided. Strategies for adjusting the dose, regimen, timing, and consideration of individual factors were developed for specific instances in which patients may have trouble staying asleep or waking up, as well as guidance for addressing potential adverse events, such as nausea, dizziness, anxiety, and depression. Discussion points based on existing literature and clinical experience were included as relevant for each statement. Clinicians may use this resource to guide LXB dosing optimization with patients.

0642 Real-world Experience Switching from Twice Nightly to Once Nightly Oxybate Therapy in the Treatment of Narcolepsy

0642 Real-world Experience Switching from Twice Nightly to Once Nightly Oxybate Therapy in the Treatment of Narcolepsy

Narcolepsy: an interface among neurology, immunology, sleep, and genetics.

Narcolepsy is a primary disorder of the central nervous system resulting from genetic, environmental, and immunological interactions defined as excessive daytime sleepiness plus cataplexy, hallucinations, sleep paralysis, and sleep fragmentation. The pathophysiology is not entirely known, but the interaction among genetic predisposition, environmental exposition, and immune component with consequent hypocretin-1 deficiency is the model to explain narcolepsy type I. The mechanism of narcolepsy type II is less understood. There is a delay of over ten years for the diagnosis of narcolepsy around the world. Patients with narcolepsy have many comorbidities with a negative impact on quality of life. The treatment of narcolepsy must contain an educational approach for the family, coworkers, and patients. Scheduled naps and sleep hygiene are essential to minimize the dose of medications. Much progress has been seen in the pharmacological treatment of narcolepsy with new stimulants, different presentations of oxybate, and recent studies with orexin agonists. Narcolepsy is a rare disease that needs to be more understood and highlighted to avoid delayed diagnosis and severe disabilities in patients.

A Review of Current and Future Pharmacologic Treatments for Narcolepsy

IntroductionNarcolepsy is a rare but disabling neurological disorder involving disruption of the sleep-wake cycle that is often under- or misdiagnosed (Barateau L, et al. J Sleep Res. 2022;31(4):e13631). It is characterized by a classical tetrad of excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Narcolepsy is divided into 3 types: Narcolepsy Type 1 (NT1); Narcolepsy Type 2 (NT2); and Secondary Narcolepsy. The pathophysiology remains unclear but is primarily associated with loss of hypocretin (orexin) neurons involving autoimmune and genetic risk factors, particularly for NT1.ObjectivesTo review the currently available therapies for the treatment of narcolepsy.MethodsThe extant literature was reviewed and discussed in the context of clinical relevance.ResultsTreatment historically has included medications developed for the treatment of other conditions such as psychostimulants (methylphenidate, modafinil/armodafinil, pemoline) and antidepressants (SSRIs,TCAs). These agents are also associated with limiting side effects in practice. In more recent years a variety of specific treatments have been approved that act on diverse pathways. Pitolisant, a histamine H3 receptor inverse agonist, is approved for the treatment of EDS or cataplexy in adult patients with narcolepsy (and children&gt; 6 years in European Union) (Keam SJ.Paediatr Drugs. 2023;25(4):483-488). Solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI) is indicated to improve wakefulness in adult patients with EDS associated with narcolepsy or obstructive sleep apnea (OSA) (Winter Y, et al. Sleep Med. 2023;103:138-143). Sodium oxybate (SXB), a GABAB receptor agonist, is approved for the treatment of cataplexy associated with narcolepsy and (EDS) in patients 7 years or older (Bogan RK, et al. CNS Drugs. 2023;37(4):323-335). Current research focuses on on-peptide hypocretin receptor-2 agonists (Saitoh T, Sakurai T. Peptides. 2023;167:171051).ConclusionsDespite limited understanding of the pathophysiology of narcolepsy there have been substantial advances in the pharmacotherapy, including medications now approved for children. Early diagnosis and treatment are associated with better outcomes. In view of the chronic and disabling morbidity associated with narcolepsy further research and better access to appopriate medications is necessary.Disclosure of InterestNone Declared

Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data.

The purpose of this study was to characterize the incidence of pediatric narcolepsy diagnosis, subsequent care, and potential sociodemographic disparities in a large US claims database. Merative MarketScan insurance claims (n = 12,394,902) were used to identify youth (6-17 years of age) newly diagnosed with narcolepsy (International Classification of Diseases, 10th revision codes). Narcolepsy diagnosis and care 1 year postdiagnosis included polysomnography with Multiple Sleep Latency Test, pharmacological care, and clinical visits. Potential disparities were examined by insurance coverage and child race and ethnicity (Medicaid-insured only). The incidence of narcolepsy diagnosis was 10:100,000, primarily type 2 (69.9%). Most diagnoses occurred in adolescents with no sex differences, but higher rates in Black vs White youth with Medicaid. Two thirds had a prior sleep disorder diagnosis and 21-36% had other co-occurring diagnoses. Only half (46.6%) had polysomnography with Multiple Sleep Latency Test (± 1 year postdiagnosis). Specialty care (18.9% pulmonary, 26.9% neurology) and behavioral health visits were rare (34.4%), although half were prescribed stimulant medications (51.0%). Medicaid-insured were 86% less likely than commercially insured youth to have any clinical care and 33% less likely to have polysomnography with Multiple Sleep Latency Test. Narcolepsy diagnoses occurred in 0.01% of youth, primarily during adolescence, and at higher rates for Black vs White children with Medicaid. Only half overall had evidence of a diagnostically required polysomnography with Multiple Sleep Latency Test, underscoring potential misdiagnosis. Many patients had co-occurring conditions, but specialty and behavioral health care were limited. Results suggest misdiagnosis, underdiagnosis, and limited narcolepsy treatment, as well as possible disparities. Results highlight the need to identify determinants of evidence-based pediatric narcolepsy diagnosis and management. Tang SH, Min J, Zhang X, etal. Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data. J Clin Sleep Med. 2024;20(7):1141-1151.

Association between vitamin B12 deficiency and risk of Paediatric narcolepsy: Evidence from cross-sectional study and Mendelian randomization analysis

BackgroundNarcolepsy, a chronic neurologic sleep disorder, has sparked growing interest in the potential role of vitamin B12 in its pathogenic mechanism. However, research on this association has predominantly focused on adults. Our objective was to delineate the phenotypic and genetic connections between serum vitamin B12 levels and paediatric narcolepsy. MethodsTo investigate the causal relationship between vitamin B12 and paediatric narcolepsy, we conducted a retrospective analysis involving 60 narcolepsy patients and a matched control group. Univariate and multivariate logistic regression models were employed to identify independent factors influencing paediatric narcolepsy. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to assess the causal connection between serum vitamin B12 levels and narcolepsy. ResultsPaediatric narcolepsy patients showed significantly lower serum levels of vitamin B12 and folate compared to the control group (P < 0.05). Multivariate logistic regression analysis identified serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy (P < 0.001; OR = 0.96; 95%CI: 0.94–0.98). Additionally, IVW model results provided compelling evidence supporting a potential causal association between serum vitamin B12 levels and paediatric narcolepsy (OR: 0.958, 95% CI = 0.946–0.969, P = 0.001). ConclusionThis study establishes connections at both phenotypic and genetic levels, associating vitamin B12 deficiency with an increased risk of paediatric narcolepsy. These findings provide innovative perspectives for clinical strategies in the prevention and treatment of narcolepsy.

Treatment of narcolepsy by means of vagus nerve stimulation

Treatment of narcolepsy by means of vagus nerve stimulation

Vagus nerve stimulation for the treatment of narcolepsy

Background and objectiveNo study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. MethodsIn our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. ResultsCompared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. ConclusionIn this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

The nature and magnitude of cognitive impairment in narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia: a meta-analysis.

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies conducted from January 2000 to October 2022. We classified cognitive tests assessing memory, executive function, and attention by cognitive domain. Between-group differences were analyzed as standardized mean differences (Cohen's d), and Cohen's d for individual tests were integrated according to cognitive domain and clinical disease group. Eighty-seven studies were screened for inclusion; 39 satisfied inclusion criteria, yielding 73 comparisons (k): NT1, k = 60; NT2, k = 8; IH, k = 5. Attention showed large impairment in people with NT1 (d = -0.90) and IH (d = -0.97), and moderate impairment in NT2 (d = -0.60). Executive function was moderately impaired in NT1 (d = -0.30) and NT2 (d = -0.38), and memory showed small impairments in NT1 (d = -0.33). A secondary meta-analysis identified sustained attention as the most impaired domain in NT1, NT2, and IH (d ≈ -0.5 to -1). These meta-analyses confirm that cognitive impairments are present in NT1, NT2, and IH, and provide quantitative confirmation of reports of cognitive difficulties made by patients and clinicians. These findings provide a basis for the future design of studies to determine whether cognitive impairments can improve with pharmacologic and nonpharmacologic treatments for narcolepsy and IH.