RESUMO
STUDY OBJECTIVES: The purpose of this study was to investigate the effects of neck myoclonus (NM) on sleep quality and daytime sleepiness in patients with narcolepsy (NT) and to further explore possible underlying mechanisms. METHODS: We included 72 patients with narcolepsy type 1 (NT1), 34 patients with narcolepsy type 2 (NT2) and 33 healthy controls. Patients underwent questionnaires, lumbar puncture procedure, polysomnography, and multiple sleep latency test (MSLT). Healthy controls underwent polysomnography and questionnaires. Orexin-A levels in the cerebrospinal fluid (CSF) were analyzed by radioimmunoassay. Three catecholamines, including dopamine, norepinephrine and epinephrine, in the CSF were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: Both the NT1 and NT2 groups displayed a higher level of NM incidence rate and index compared to the control group in PSG. NT1 displayed greater MSLT REM--NM incidence rate and index than NT2. NM were often associated with arousal or awakening and body movements, which had a prominent influence on sleep quality in both narcoleptic patients and controls. There was a positive correlation between the NM index and the Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale (SSS) and Ullanlinna Narcolepsy Scale (UNS) scores in NT1 patients. In MSLT of NT1 patients, REM-NM index were positively correlated with the CSF dopamine levels, and there were elevated dopamine levels but reduced orexin-A levels in patients with REM-NM. CONCLUSION: NM incidence rate and index were high in patients with narcolepsy, which had a huge effect on sleep quality and aggravated daytime sleepiness. NM should be considered pathological and viewed as a new sleep-related movement disorder. Orexin-A and dopamine may be involved in the development of NM.
Assuntos
Mioclonia , Narcolepsia , Orexinas , Polissonografia , Humanos , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/complicações , Narcolepsia/fisiopatologia , Masculino , Feminino , Adulto , Orexinas/líquido cefalorraquidiano , Mioclonia/líquido cefalorraquidiano , Mioclonia/fisiopatologia , Neuropeptídeos/líquido cefalorraquidiano , Pessoa de Meia-Idade , Qualidade do Sono , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Inquéritos e Questionários , Adulto Jovem , Dopamina/líquido cefalorraquidianoRESUMO
Narcolepsy type 1 (NT1) is associated with severe loss of orexin neurons and characterized by symptoms including excessive daytime sleepiness and cataplexy. Current medications indicated for NT1 often show limited efficacy, not addressing the full spectrum of symptoms, demonstrating a need for novel drugs. We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. However, danavorexton has limited oral availability and TAK-994 has a risk of off-target liver toxicity. To avoid off-target-based adverse events, a highly potent molecule with low effective dose is preferred. Here, we show that a novel OX2R-selective agonist, TAK-861 [N-{(2S,3R)-4,4-Difluoro-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3',5'-trifluoro[1,1'-biphenyl]-3-yl)methyl]pyrrolidin-3-yl}ethanesulfonamide], activates OX2R with a half-maximal effective concentration of 2.5 nM and promotes wakefulness at 1 mg/kg in mice and monkeys, suggesting ~ tenfold higher potency and lower effective dosage than TAK-994. Similar to TAK-994, TAK-861 substantially ameliorates wakefulness fragmentation and cataplexy-like episodes in orexin/ataxin-3 and orexin-tTA;TetO DTA mice (NT1 mouse models). Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile.
Assuntos
Modelos Animais de Doenças , Narcolepsia , Receptores de Orexina , Vigília , Animais , Narcolepsia/tratamento farmacológico , Receptores de Orexina/agonistas , Receptores de Orexina/metabolismo , Vigília/efeitos dos fármacos , Camundongos , Administração Oral , Fenótipo , Masculino , HumanosRESUMO
WHAT IS THIS SUMMARY ABOUT?: 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. WHAT WERE THE RESULTS?: 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. WHAT DO THE RESULTS MEAN?: 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.
Assuntos
Narcolepsia , Oxibato de Sódio , Humanos , Oxibato de Sódio/uso terapêutico , Oxibato de Sódio/administração & dosagem , Narcolepsia/tratamento farmacológico , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológicoRESUMO
BACKGROUND: The study seeks to assess serum neurofilament light chain (NfL) levels in paediatric narcolepsy-diagnosed patients. Moreover, it aims to explore the correlation between NfL levels and the severity of narcolepsy symptoms, sleep quality, and manifestations of anxiety and depression. METHODS: This retrospective analysis included 98 paediatric narcolepsy cases and 100 controls matched for age and gender. The study focused on comparing serum NfL levels across these groups. Severity of EDS in patients was measured with the Epworth Sleepiness Scale (ESS). Moreover, the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale-24 (HAMD-24), and Hamilton Anxiety Scale-14 (HAMA-14) were used to assess narcolepsy symptoms, sleep quality, and psychological conditions. RESULTS: Patients with paediatric narcolepsy had significantly higher serum NfL levels than controls (P < 0.05). Additionally, a positive correlation was found between serum NfL levels and ESS scores (P < 0.001). An independent link between serum NfL and paediatric narcolepsy was established via multiple logistic regression (OR = 0.943, 95 % CI = 0.921-0.993, P = 0.004). Moreover, serum NfL's diagnostic precision for paediatric narcolepsy was evident from the ROC curve area of 0.938 (95 % CI: 0.86-0.99, P < 0.001). CONCLUSION: The study implies a positive correlation between increased serum NfL levels and the severity of paediatric narcolepsy. Nevertheless, the causative link between serum NfL levels and paediatric narcolepsy remains uncertain, highlighting the need for larger sample sizes and well-structured cohort studies to offer more definitive.
Assuntos
Narcolepsia , Proteínas de Neurofilamentos , Humanos , Narcolepsia/sangue , Narcolepsia/diagnóstico , Feminino , Masculino , Criança , Proteínas de Neurofilamentos/sangue , Estudos Retrospectivos , Adolescente , Índice de Gravidade de Doença , Qualidade do Sono , Ansiedade/sangue , Depressão/sangue , Depressão/diagnóstico , Pré-EscolarRESUMO
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. METHODS AND 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.
Assuntos
Doenças Cardiovasculares , Consenso , Narcolepsia , Humanos , Narcolepsia/epidemiologia , Narcolepsia/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Medição de Risco , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Fatores de Risco de Doenças CardíacasRESUMO
Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.
Assuntos
Narcolepsia , Sono REM , Humanos , Narcolepsia/fisiopatologia , Narcolepsia/diagnóstico , Sono REM/fisiologia , Polissonografia , Transtorno do Comportamento do Sono REM/fisiopatologia , Cataplexia/fisiopatologiaRESUMO
Sleep is a physiological state that is essential for maintaining physical and mental health. Sleep disorders and sleep deprivation therefore have many adverse effects, including an increased risk of metabolic diseases and a decline in cognitive function that may be implicated in the long-term development of neurodegenerative diseases. There is increasing evidence that microglia, the resident immune cells of the central nervous system (CNS), are involved in regulating the sleep-wake cycle and the CNS response to sleep alteration and deprivation. In this chapter, we will discuss the involvement of microglia in various sleep disorders, including sleep-disordered breathing, insomnia, narcolepsy, myalgic encephalomyelitis/chronic fatigue syndrome, and idiopathic rapid-eye-movement sleep behavior disorder. We will also explore the impact of acute and chronic sleep deprivation on microglial functions. Moreover, we will look into the potential involvement of microglia in sleep disorders as a comorbidity to Alzheimer's disease and Parkinson's disease.
Assuntos
Microglia , Transtornos do Sono-Vigília , Humanos , Microglia/metabolismo , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/epidemiologia , Animais , Doença de Alzheimer/metabolismo , Privação do Sono/metabolismo , Doença de Parkinson , Narcolepsia/fisiopatologia , Narcolepsia/imunologia , Narcolepsia/metabolismo , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologiaRESUMO
BACKGROUND: DNA methylation may have a regulatory role in monogenic sensorineural hearing loss and complex, polygenic phenotypic forms of hearing loss, including age-related hearing impairment or Meniere disease. The purpose of this systematic review is to critically assess the evidence supporting a functional role of DNA methylation in phenotypes associated with hearing loss. RESULTS: The search strategy yielded a total of 661 articles. After quality assessment, 25 records were selected (12 human DNA methylation studies, 5 experimental animal studies and 8 studies reporting mutations in the DNMT1 gene). Although some methylation studies reported significant differences in CpG methylation in diverse gene promoters associated with complex hearing loss phenotypes (ARHI, otosclerosis, MD), only one study included a replication cohort that supported a regulatory role for CpG methylation in the genes TCF25 and POLE in ARHI. Conversely, several studies have independently confirmed pathogenic mutations within exon 21 of the DNMT1 gene, which encodes the DNA (cytosine-5)-methyltransferase 1 enzyme. This methylation enzyme is strongly associated with a rare disease defined by autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Of note, rare variants in DNMT1 and DNMT3A genes have also been reported in noise-induced hearing loss. CONCLUSIONS: Evidence supporting a functional role for DNA methylation in hearing loss is limited to few genes in complex disorders such as ARHI. Mutations in the DNMT1 gene are associated with ADCA-DN, suggesting the CpG methylation in hearing loss genes deserves further attention in hearing research.
Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Humanos , Metilação de DNA/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Animais , Ilhas de CpG/genética , Epigênese Genética/genética , Perda Auditiva/genética , Mutação , Fenótipo , Regiões Promotoras Genéticas , Perda Auditiva Neurossensorial/genética , Narcolepsia/genéticaRESUMO
Narcolepsy with cataplexy and myasthenia gravis are both chronic neurologic conditions causing symptoms of muscle weakness, often affecting facial muscles, and have both been attributed to an immune-mediated etiology. We report an adolescent girl diagnosed with both conditions and discuss possible shared mechanisms and the diagnostic challenges presented by her case to inform and aid clinicians managing children and young people with these rare conditions.
Assuntos
Miastenia Gravis , Narcolepsia , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/complicações , Narcolepsia/diagnóstico , Narcolepsia/complicações , Feminino , AdolescenteRESUMO
BACKGROUND: Optimal measurement tools for problematic sleep inertia, common in some central disorders of hypersomnolence (CDH), have not yet been determined. We evaluated the performance of the Sleep Inertia Questionnaire (SIQ) in CDH, and how well it distinguished hypersomnolent groups from controls, and IH (idiopathic hypersomnia) from narcolepsy type 1 (NT1). METHODS: This prospective, bi-centric study included 63 control, 84 IH, 16 NT1, 18 narcolepsy type 2 (NT2), and 88 subjective excessive daytime sleepiness (sEDS) participants, using ICSD-3 criteria. 126 (47.2 %) participants were on any medication at the time of SIQ completion. We assessed construct validity of SIQ scores, and sleep inertia duration (SID), and compared them across diagnoses, controlling for age and center. We derived cutpoints to distinguish hypersomnolent patients from controls and IH from NT1. Sensitivity analyses for depression, chronotype, and medication were performed. RESULTS: The SIQ sum and composite score were significantly lower in controls than in other groups (p < 0.0001), demonstrating outstanding ability to distinguish patients from controls (AUCs 0.92), without differences among hypersomnolent groups. SID (AUC 0.76) was significantly shorter in controls than in all hypersomnolent groups except NT1, and was shorter in NT1 than in IH or sEDS. Optimal SIQ sum cutpoint was 42 (J = 0.71) for patients versus controls. Optimal SID cutpoint in distinguishing IH from NT1 was 25 min (J = 0.39). CONCLUSION: The SIQ has excellent ability to distinguish hypersomnolent patients from healthy controls, after controlling for depression, eveningness, and medication. SID is best at distinguishing IH from NT1.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Humanos , Masculino , Feminino , Inquéritos e Questionários/normas , Adulto , Estudos Prospectivos , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Narcolepsia/diagnóstico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Hipersonia Idiopática/diagnósticoRESUMO
NT1 is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the hypocretin (HCRT)/orexin neuropeptides in the lateral hypothalamus. While the exact etiology of NT1 is still unknown, numerous studies have provided compelling evidence supporting its autoimmune origin. The prevailing hypothetical view on the pathogenesis of NT1 involves an immune-mediated loss of HCRT neurons that can be triggered by Pandemrix® vaccination and/or by infection in genetically susceptible patients, specifically carriers of the HLA-DQB1*06:02 MHC class II allele. The molecular mechanisms by which infection/vaccination can induce autoimmunity in the case of NT1 remain to be elucidated. In this review, evidence regarding the involvement of vaccination and infection and the potential mechanisms by which it could be linked to the pathogenesis of NT1 will be discussed in light of the existing findings in other autoimmune diseases.
Assuntos
Narcolepsia , Vacinação , Humanos , Narcolepsia/imunologia , Narcolepsia/induzido quimicamente , Narcolepsia/etiologia , Vacinação/efeitos adversos , Animais , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Orexinas/metabolismo , Cadeias beta de HLA-DQ/genética , Infecções/imunologiaRESUMO
ABSTRACT: Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness resulting from loss-of-function genetic variants in the WFS1 gene. Individuals with WS1 manifest a spectrum of neuropsychiatric disorders. Here, we report a pediatric case of WS1, which stemmed from a novel biallelic WFS1 loss-of-function genetic variant. The individual initially presented with obsessive-compulsive disorder, which was successfully managed by fluvoxamine. After 2 months, the child manifested excessive daytime sleepiness. Clinical evaluation and sleep recordings revealed a diagnosis of narcolepsy type 2. Excessive daytime sleepiness was improved with methylphenidate. To the best of our knowledge, this is the first report of narcolepsy in WS1, which possibly arose during a progressive neurodegenerative process. We emphasize the need for in-depth screening for neuropsychiatric phenotypes and sleep-related disorders in WS1, for clinical management, which significantly improves the quality of life.
Assuntos
Narcolepsia , Transtorno Obsessivo-Compulsivo , Síndrome de Wolfram , Humanos , Feminino , Síndrome de Wolfram/diagnóstico , Síndrome de Wolfram/genética , Síndrome de Wolfram/fisiopatologia , Síndrome de Wolfram/complicações , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Narcolepsia/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Criança , Proteínas de Membrana/genéticaRESUMO
BACKGROUND: Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans. The aim of this study was to identify the factors influencing TA in narcolepsy and to determine the most significant barriers to adherence. METHODS: An online survey was conducted during the pandemic, assessing demographic and clinical data, medication usage, and adverse effects of treatment. Various questionnaires, such as the Adherence Barriers Questionnaire (ABQ) and Epworth Sleepiness Scale (ESS), were utilized. The ABQ identified patient-specific barriers to medication adherence, while the Patient Health Questionnaire (PHQ-9) assessed depressive symptoms. RESULTS: We analyzed 243 narcolepsy patients (77 % female, mean age 35.7 ± 12.3 years) with 71 % having narcolepsy type 1 (NT1). The average ESS score was 16.4 (SD ± 3.7). Adherence barriers (AB) were identified in 89 % of patients (216/243) based on ABQ score. The most common barriers reported were "Forgetfulness" (77 %), "Depression" (57 %), and "Side effect-driven medication reduction/stopping behavior" (49 %). Approximately 72 % of patients reported side effects from their narcolepsy medication, leading to discontinuation in 78 % of cases. A moderate correlation was found between the severity of adherence barriers (ABQ score) and levels of depression (PHQ-9 score; rs = 0.412, p = 00.000), as well as ESS score (p = . 048). The results of this study may have been influenced by the pandemic situation. CONCLUSION: Adherence barriers are common (89 %) and diverse among people with narcolepsy. Many barriers are related to excessive daytime sleepiness (EDS), cognitive deficits or depressive symptoms, highlighting the importance of recognizing and addressing them for optimal TA. Medication side effects, especially occurring when polypharmacology is utilized, also significantly contribute to adherence challenges. Effective communication regarding therapy adherence and improved detection and management of EDS and depression are crucial for enhancing TA in narcolepsy patients.
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Adesão à Medicação , Narcolepsia , Humanos , Narcolepsia/tratamento farmacológico , Narcolepsia/psicologia , Feminino , Masculino , Adulto , Inquéritos e Questionários , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Depressão/tratamento farmacológicoRESUMO
Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep-wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive-compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament.
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Narcolepsia , Transtorno Obsessivo-Compulsivo , Humanos , Masculino , Adolescente , Narcolepsia/diagnóstico , Narcolepsia/complicações , Transtorno Obsessivo-Compulsivo/complicações , Doenças AutoimunesRESUMO
INTRODUCTION: 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). CONCLUSION: 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.
Assuntos
Índice de Massa Corporal , Densidade Óssea , Narcolepsia , Orexinas , Humanos , Masculino , Feminino , Adulto , Orexinas/líquido cefalorraquidiano , Estudos Transversais , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/fisiopatologia , Densidade Óssea/fisiologia , Pessoa de Meia-Idade , Adolescente , Relação Cintura-Quadril , Adulto Jovem , IdosoAssuntos
Narcolepsia , Antagonistas dos Receptores de Orexina , Distúrbios do Início e da Manutenção do Sono , Humanos , Antagonistas dos Receptores de Orexina/uso terapêutico , Antagonistas dos Receptores de Orexina/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Narcolepsia/tratamento farmacológico , Metanálise como AssuntoRESUMO
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. CONCLUSION: 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.
Assuntos
Ansiedade , Citocinas , Depressão , Narcolepsia , Humanos , Narcolepsia/psicologia , Narcolepsia/complicações , Masculino , Feminino , Adulto , Depressão/etiologia , Ansiedade/etiologia , Ansiedade/psicologia , Citocinas/sangue , Adulto Jovem , Adolescente , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Pessoa de Meia-IdadeRESUMO
ß-amyloid42 (Aß42) in Alzheimer's disease (AD) and orexin in narcolepsy are considered crucial biomarkers for diagnosis and therapeutic targets. Recently, orexin and Aß cerebral dynamics have been studied in both pathologies, but how they interact with each other remains further to be known. In this study, we investigated the reliability of using the correlation between orexin-A and Aß42 CSF levels as a candidate marker to explain the chain of events leading to narcolepsy or AD pathology. In order to test the correlation between these biomarkers, patients diagnosed with AD (n = 76), narcolepsy type 1 (NT1, n = 17), narcolepsy type 2 (NT2, n = 23) and healthy subjects (n = 91) were examined. Patients and healthy subjects underwent lumbar puncture between 8:00 and 10:00 am at the Neurology Unit of the University Hospital of Rome "Tor Vergata". CSF levels of Aß42, total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aß42 were significantly lower (p < 0.001) in AD (332.28 ± 237.36 pg/mL) compared to NT1 (569.88 ± 187.00 pg/mL), NT2 (691.00 ± 292.63 pg/mL) and healthy subjects (943.68 ± 198.12 pg/mL). CSF orexin-A levels were statistically different (p < 0.001) between AD (148.01 ± 29.49 pg/mL), NT1 (45.94 ± 13.63 pg/mL), NT2 (104.92 ± 25.55 pg/mL) and healthy subjects (145.18 ± 27.01 pg/mL). Moderate-severe AD patients (mini mental state examination < 21) showed the highest CSF orexin-A levels, whereas NT1 patients showed the lowest CSF orexin-A levels. Correlation between CSF levels of Aß42 and orexin-A was found only in healthy subjects (r = 0.26; p = 0.01), and not in narcolepsy or AD patients. This lack of correlation in both diseases may be explained by the pathology itself since the correlation between these two biomarkers is evident only in the healthy subjects. This study adds to the present literature by further documenting the interplay between orexinergic neurotransmission and cerebral Aß dynamics, possibly sustained by sleep.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Narcolepsia , Orexinas , Fragmentos de Peptídeos , Humanos , Orexinas/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Narcolepsia/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fragmentos de Peptídeos/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Adulto , Proteínas tau/líquido cefalorraquidianoRESUMO
Objective: To establish a prediction model for the identifying of cataplexy facial features based on clinical shooting videos by using a deep learning image recognition network ResNet-18. Methods: A cross-sectional study. Twenty-five narcolepsy type 1 patients who were first diagnosed and never received treatment and 25 healthy controls recruited by advertisement in the Second Affiliated Hospital of Nanchang University from 2020 to 2023.After image preprocessing, a total of 1 180 images were obtained, including 583 cataplexy faces and 597 normal faces.90% were selected as the training set and validation set, and then expanded the data by 5 times.80% of the expanded data set was extracted as the training set and 20% as the validation set, that is, the number of the training set was (583+597)×0.9×0.8×5=4 248, the number of the validation set was (583+597)×0.9×0.2×5=1 062. The data sets for training and validation were used train parameters to establish the model and were trained through the five-fold cross-validation method, to establish the ResNet-18 cataplexy face recognition model via transfer learning.10% (118 images) of the original non-amplified images were extracted as the test set. The test set data did not participate in data enhancement and model training, and was only used to evaluate the final performance of the model. Finally, ResNet-18 was compared with VGG-16, ResNet-34 and Inception V3 deep learning models, and the receiver operating characteristic curve was used to evaluate the value of ResNet-18 image recognition network in cataplexy face recognition. Results: Among 25 patients with narcolepsy type 1, 15 were males and 10 were females, aged [M (Q1, Q3)] of 14.0(11.0, 20.5) years.Among 25 healthy controls, 14 were males and 11 were females, with a median age of 16.0(14.4, 23.0) years.The overall accuracy of ResNet-18 image recognition network in the test set was 90.9%, the sensitivity was 96.4% and the specificity was 85.2%. The area under the ROC curve was 0.99(95%CI:0.96-1.00). The ResNet-18 model parameter amount was 11.69 M, the floating point operation amount was 1 824.03 M, and the single image recognition time was 5.9 ms. Conclusions: The cataplexy face prediction model built based on the deep learning image recognition network ResNet-18 has a high accuracy in identifying cataplexy faces.
Assuntos
Cataplexia , Aprendizado Profundo , Narcolepsia , Humanos , Narcolepsia/diagnóstico , Estudos Transversais , Cataplexia/diagnóstico , Face/anormalidades , Processamento de Imagem Assistida por Computador , Masculino , Feminino , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Numerous risk factors in paediatric narcolepsy may predispose them to obstructive sleep apnea (OSA). The concurrent presence of OSA in these patients might lead to underdiagnosing narcolepsy. This research investigates the prevalence and potential causality between OSA and paediatric narcolepsy. METHODS: A case-control study coupled with a two-sample Mendelian randomization (MR) analysis was employed to explore the prevalence and causal link between paediatric narcolepsy and OSA risk. RESULTS: The case-control study revealed that paediatric narcolepsy patients are at an increased risk of OSA, with an Odds ratio (OR) of 4.87 (95% CI: 2.20-10.71; P < 0.001). The inverse-variance weighted (IVW) model further suggests a potential causal link between narcolepsy and OSA (IVW OR: 4.671, 95% CI: 1.925-11.290; P < 0.001). Additionally, sensitivity analysis confirmed these findings' reliability. CONCLUSION: The findings highlight an elevated prevalence and genetic susceptibility to OSA among paediatric narcolepsy patients, underscoring the necessity for clinical screening of OSA. Continued research is essential to clarify the pathogenic mechanisms and develop potential treatments.