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2.
Anesth Analg ; 132(5): 1287-1295, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857970

RESUMO

Obstructive sleep apnea (OSA) has been shown to increase risk of adverse perioperative events. More recently, investigators have begun to examine other common sleep disorders to assess how they may be impacted by the perioperative environment, as well as influence postoperative outcomes. There are a number of mechanisms by which such common sleep disorders (eg, insomnia, restless legs syndrome, narcolepsy, and parasomnias) may have consequences in the perioperative setting, both related to the underlying pathophysiology of the diseases as well as their treatments. This review will highlight the current state of the literature and offer recommendations for management of these conditions during the perioperative journey.


Assuntos
Narcolepsia/terapia , Parassonias/terapia , Assistência Perioperatória , Síndrome das Pernas Inquietas/terapia , Distúrbios do Início e da Manutenção do Sono/terapia , Sono , Procedimentos Cirúrgicos Operatórios , Humanos , Narcolepsia/complicações , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Parassonias/complicações , Parassonias/diagnóstico , Parassonias/fisiopatologia , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/fisiopatologia , Medição de Risco , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento
3.
Ann Palliat Med ; 10(3): 3491-3494, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849131

RESUMO

Narcolepsy is a sleep disorder with the main manifestations of excessive daytime sleepiness, cataplexy, sleep paralysis, sleep hallucinations, and nighttime sleep disturbance. It is still not fully recognized by clinicians, and many patients are often misdiagnosed with epilepsy, syncope, or mental disorders. In the present study, we report the first case of narcolepsy diagnosed at the district, with a complete medical history, objective examinations, and cerebrospinal fluid and hematological tests, but no cataplexy. Mutiple sleep latentcy test (MSLT) showed that the average sleep latency was 3.1 min, and abnormal REM sleep episodes were detected in 4 naps. The average REM latency was 1.3 min. We review the knowledge and researches on this disease in Mainland China in the past 10 years. Data from China in 2014 showed a significant increase in the incidence of narcolepsy in 2011 after the H1N1 epidemic in China in 2009. Despite the low incidence rate, diagnosis of narcolepsy is still confusing and needs clinicians' attention. Whether the incidence of narcolepsy may increase after covid19 remains to be observed. So far, there is no clear evidence to support immunotherapy. In conclusion, further studies are needed to verify more treatments and improve the patient's life quality.


Assuntos
COVID-19 , Cataplexia , Vírus da Influenza A Subtipo H1N1 , Narcolepsia , China , Humanos , Narcolepsia/diagnóstico , SARS-CoV-2
4.
Fortschr Neurol Psychiatr ; 89(3): 103-113, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33339064

RESUMO

Narcolepsy is a hypersomnolence disorder of central origin that presents with a disturbance of the wake-sleep regulation. Lead symptoms consist of excessive daytime sleepiness and cataplexy. Nowadays, two types of narcolepsy are distinguished. Type 1 narcolepsy, formerly known as narcolepsy with cataplexy, is based on hypocretin deficiency. The cause of type 2 narcolepsy, formerly known as narcolepsy without cataplexy, remains mainly unknown. A multimodal approach is necessary for diagnosis. The mean latency between the onset of disease and diagnosis in Europe ranges 14 years. Narcolepsy has a major impact on workability and quality of life. The management of narcolepsy is usually life-long and includes non-pharmacological approaches and a symptomatic pharmacological treatment.


Assuntos
Cataplexia , Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Adulto , Cataplexia/diagnóstico , Cataplexia/terapia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Europa (Continente) , Humanos , Narcolepsia/diagnóstico , Narcolepsia/epidemiologia , Narcolepsia/terapia , Orexinas , Qualidade de Vida
5.
Actas esp. psiquiatr ; 48(6): 301-304, nov.-dic. 2020.
Artigo em Espanhol | IBECS | ID: ibc-200341

RESUMO

La narcolepsia es trastorno neurológico infrecuente, incluido dentro del catálogo de enfermedades raras. Pese a la existencia de criterios diagnósticos precisos, se encuentra infradiagnosticada. Se caracteriza por una excesiva somnolencia diurna asociada a cataplejías, y en algunos casos puede aparecer alucinaciones hipnagógicas e hipnopómpicas, alucinaciones auditivas y/o ideación delirante. La presencia de síntomas psicóticos dificulta enormemente el diagnóstico diferencial (narcolepsia, esquizofrenia o la concomitancia de ambas). Además, el manejo terapéutico puede resultar complejo, ya que el tratamiento de una patología puede empeorar la otra. El siguiente caso clínico corresponde a una paciente con esta infrecuente comorbilidad entre ambos trastornos, en el que quedan patentes las importantes dificultades tanto en el diagnóstico diferencial como en el manejo terapéutico, una vez alcanzado el diagnóstico de certeza


Narcolepsy is an infrequent neurological disorder, included in the catalog of rare diseases. Despite the existence of precise diagnostic criteria, this entity remains underdiagnosed. It is characterized by excessive daytime sleepiness associated with cataplexy; in some cases, hypnagogic or hypnopompic hallucinations, auditory hallucinations, and/or delusional ideation may appear. The occurrence of psychotic symptoms makes differential diagnosis extremely difficult (narcolepsy, schizophrenia, or both). Furthermore, therapeutic management may be complex, since the treatment of one of the disorders may worsen the other. Here we describe the case of a patient with this rare comorbidity, which illustrates the major difficulties associated to both differential diagnosis and therapeutic management once a definitive diagnosis has been reached


Assuntos
Humanos , Feminino , Adulto , Narcolepsia/complicações , Narcolepsia/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/complicações , Cataplexia/complicações , Transtornos Psicóticos Afetivos/complicações , Transtornos Psicóticos/diagnóstico , Doenças do Sistema Nervoso/complicações , Doenças Raras/classificação , Alucinações/complicações , Diagnóstico Diferencial
6.
J Clin Psychiatry ; 81(4)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32726523

RESUMO

Sleep disorders such as narcolepsy can cause excessive daytime sleepiness (EDS). However, the diagnosis of narcolepsy is often delayed by years in both children and adults, reducing their quality of life. Clinicians can improve the recognition of EDS and diagnosis of sleep disorders using screening tools such as the Epworth Sleepiness Scale, collecting sleep histories, and using sleep laboratory tests. By following up with patients who present with EDS and continuing to assess until a cause is found, clinicians can lessen the time to diagnosis and the negative impact of narcolepsy by initiating appropriate treatment.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Narcolepsia/diagnóstico , Humanos , Polissonografia
8.
Curr Psychiatry Rep ; 22(8): 36, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32514698

RESUMO

PURPOSE OF REVIEW: The complex nature of narcolepsy symptoms, along with the use of stimulants and anticataplectic medications, poses diagnostic difficulties in terms of underlying neuropsychiatric comorbidities. This study reviews recent evidence for the association between narcolepsy and neuropsychiatric disorders. We also critically analyze studies that have addressed the neuropsychiatric correlates of patients with narcolepsy, with a discussion of the possible pathophysiological mechanisms linking narcolepsy and neuropsychiatric disorders. RECENT FINDINGS: Neuropsychiatric manifestations are common among patients with narcolepsy as narcolepsy and some neuropsychiatric disorders share common clinical features. This may create challenges in making the correct diagnosis, and hence result in a delay in starting appropriate treatment. Comorbid neuropsychiatric manifestations in patients with narcolepsy include depression, anxiety, psychosis, rapid eye movement (REM) sleep behavior disorder, and cognitive impairment. Although hypocretin deficiency has been proposed as a pathophysiological mechanism underlying both narcolepsy and neuropsychiatric disorders, further research is necessary to identify the exact mechanisms. Narcolepsy patients often manifest comorbid neuropsychiatric symptoms, which makes the diagnosis difficult. Therefore, it is essential to address neuropsychiatric symptoms in the clinical care of patients with narcolepsy.


Assuntos
Estimulantes do Sistema Nervoso Central , Narcolepsia , Transtornos Psicóticos , Transtorno do Comportamento do Sono REM , Estimulantes do Sistema Nervoso Central/uso terapêutico , Comorbidade , Humanos , Narcolepsia/diagnóstico , Narcolepsia/epidemiologia
9.
BMC Neurol ; 20(1): 176, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393279

RESUMO

BACKGROUND: Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown. METHODS: TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm). DISCUSSION: TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise. TRIAL REGISTRATION: Number of the Tele-multidisciplinary care study NCT04316286. Registered 20 March 2020.


Assuntos
Narcolepsia/diagnóstico , Telemedicina , Adulto , Criança , Estudos Transversais , Diagnóstico Tardio , Estudos de Equivalência como Asunto , Humanos , Narcolepsia/terapia , Pacientes Ambulatoriais , Qualidade de Vida
11.
J Neuroimmunol ; 339: 577111, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756639

RESUMO

Narcolepsy-type 1 is a neurological sleep-disorder caused by a selective loss of hypothalamic orexin/hypocretin-producing neurons whose underlying mechanism is considered to be immune-mediated. We report the case of a 16 year-old girl with excessive daytime sleepiness, hypnagogic/hypnopompic hallucinations and cataplexy, fulfilling narcolepsy-type 1 diagnostic criteria. She was HLA-DQB1*06:02/DQA1*01:02 positive. CSF analysis demonstrated positive IgG oligoclonal bands, pleocytosis and hypocretin-1 below detection limit. Other autoimmune processes were excluded, including autoimmune encephalitis. After treatment with intravenous immunoglobulins sleep-related hallucinations transiently improved for a month. This case's CSF inflammatory findings support the role of neuroinflammation in narcolepsy-type 1 development in genetically predisposed patients.


Assuntos
Leucocitose/líquido cefalorraquidiano , Leucocitose/diagnóstico , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/diagnóstico , Bandas Oligoclonais/líquido cefalorraquidiano , Adolescente , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Leucocitose/tratamento farmacológico , Narcolepsia/tratamento farmacológico
12.
Sleep Med ; 65: 96-104, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739232

RESUMO

OBJECTIVE/BACKGROUND: To study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis. PATIENTS/METHODS: In sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS). RESULTS: No difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6-12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life. CONCLUSIONS: Educational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease. CLINICAL TRIAL REGISTRATION: Narcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.


Assuntos
Escolha da Profissão , Depressão/psicologia , Escolaridade , Narcolepsia/diagnóstico , Qualidade de Vida/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Narcolepsia/psicologia , Projetos Piloto , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários
13.
J Pediatr Psychol ; 45(1): 34-39, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670813

RESUMO

OBJECTIVE: Provide an overview of current research findings in pediatric central disorders of hypersomnolence (CDH) and propose a biopsychosocial model for clinical management, with a focus on interdisciplinary care and future directions for research and clinical practice. METHODS: Literature review drawing from pediatric and adult narcolepsy, as well as pediatric sleep and chronic pain research to develop an integrative biopsychosocial model for pediatric CDH. RESULTS: Youth with CDH are vulnerable to impairments in academics, emotional, and behavioral functioning, activity engagement and quality of life (QOL). There is a complex interrelationship between neurobiological features of disease, treatment-related factors, and psychological, sleep-related, and contextual factors across development. Research is limited largely to adults and pediatric narcolepsy type 1 and the mechanisms and evolution of morbidity remain poorly understood. CONCLUSIONS: In addition to first-line treatment (pharmacotherapy), routine screening of bio-behavioral and psychosocial functioning and QOL is needed to identify risk for compromised functioning warranting adjunctive interventions with behavioral health specialists.


Assuntos
Emoções , Hipersonia Idiopática/diagnóstico , Narcolepsia/diagnóstico , Qualidade de Vida/psicologia , Adolescente , Criança , Humanos , Hipersonia Idiopática/psicologia , Narcolepsia/psicologia , Sono/fisiologia
14.
Artigo em Russo | MEDLINE | ID: mdl-31626225

RESUMO

Based on own clinical experience in diagnostics and treatment of 4 patients, the authors describe main clinical presentations of narcolepsy. A case report of a 20-year female patient with psychogenic narcolepsy induced by a conflict in the family is described in details. According to polysomnography and Multiple Sleep Latency Test, a reduction in latency to sleep is 22 sec - 3 min 30 sec and the time of occurrence of REM sleep is 7 min 30 sec. The diagnosis is made on the basis of diagnostic criteria of narcolepsy. On average, it takes about 7-10 years to diagnose narcolepsy that reduces the quality of life of patients and leads to social and household maladaptation. Physicians should be wary of early identification of this disease for dynamic monitoring, the appointment of symptomatic therapy, prevention of anxiety and depression and the generation of behavior algorithm in the patient and his relatives in order to maximize social and household adaptation.


Assuntos
Narcolepsia , Polissonografia , Qualidade de Vida , Feminino , Humanos , Narcolepsia/diagnóstico , Narcolepsia/psicologia , Sono , Sono REM , Adulto Jovem
15.
Ir Med J ; 112(8): 991, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31650824

RESUMO

Presentation This is a case of a 31 year old gentleman who suffered an attack of status cataplecticus following abrupt withdrawal of clomipramine. Diagnosis Clomipramine was temporarily discontinued in order to confirm a suspected diagnosis of narcolepsy using Multiple Sleep Latency Testing. This precipitated an episode of status cataplecticus which resolved with re-introduction of therapy. A diagnosis of narcolepsy was later confirmed with undetectable levels of hypocretin/orexin in the CSF. Treatment Re-introduction of clomipramine led to resolution of status cataplecticus. The patient now remains stable with regards to his cataplexy on clomipramine 30mg. Discussion There have been a total of 4 case reports of status cataplecticus following withdrawal of antidepressant therapy. In all cases, reintroduction of anti-cataplectic therapy led to resolution of attacks. The abrupt discontinuation of an SSRI is believed to precipitate cataplexy attacks due to reduction in noradrenergic tone.


Assuntos
Cataplexia/fisiopatologia , Clomipramina/efeitos adversos , Inibidores de Captação de Serotonina/efeitos adversos , Síndrome de Abstinência a Substâncias/fisiopatologia , Adulto , Cataplexia/etiologia , Humanos , Masculino , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/diagnóstico , Orexinas/líquido cefalorraquidiano , Síndrome de Abstinência a Substâncias/etiologia
16.
Neurology ; 93(11): e1034-e1044, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405906

RESUMO

OBJECTIVE: To validate polysomnographic markers (sleep latency and sleep-onset REM periods [SOREMPs] at the Multiple Sleep Latency Test [MSLT] and nocturnal polysomnography [PSG]) for pediatric narcolepsy type 1 (NT1) against CSF hypocretin-1 (hcrt-1) deficiency and presence of cataplexy, as no criteria are currently validated in children. METHODS: Clinical, neurophysiologic, and, when available, biological data (HLA-DQB1*06:02 positivity, CSF hcrt-1 levels) of 357 consecutive children below 18 years of age evaluated for suspected narcolepsy were collected. Best MSLT cutoffs were obtained by receiver operating characteristic (ROC) curve analysis by contrasting among patients with available CSF hcrt-1 assay (n = 228) with vs without CSF hcrt-1 deficiency, and further validated in patients without available CSF hcrt-1 against cataplexy (n = 129). RESULTS: Patients with CSF hcrt-1 deficiency were best recognized using a mean MSLT sleep latency ≤8.2 minutes (area under the ROC curve of 0.985), or by at least 2 SOREMPs at the MSLT (area under the ROC curve of 0.975), or the combined PSG + MSLT (area under the ROC curve of 0.977). Although specificity and sensitivity of reference MSLT sleep latency ≤8 minutes and ≥2 SOREMPs (nocturnal SOREMP included) was 100% and 94.87%, the combination of MSLT sleep latency and SOREMP counts did not improve diagnostic accuracy. Age or sex also did not significantly influence these results in our pediatric population. CONCLUSIONS: At least 2 SOREMPs or a mean sleep latency ≤8.2 minutes at the MSLT are valid and reliable markers for pediatric NT1 diagnosis, a result contrasting with adult NT1 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children with suspected narcolepsy, polysomnographic and MSLT markers accurately identify those with narcolepsy type 1.


Assuntos
Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Polissonografia/normas , Latência do Sono/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino
17.
Sleep ; 42(12)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31418025

RESUMO

STUDY OBJECTIVES: (1) To compare the presence of autonomic symptoms using the validated SCOPA-AUT questionnaire in untreated patients with narcolepsy type 1 (NT1) to healthy controls, (2) to study the determinants of a high total SCOPA-AUT score in NT1, and (3) to evaluate the effect of drug intake on SCOPA-AUT results in NT1. METHODS: The SCOPA-AUT questionnaire that evaluates gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction was completed by 92 consecutive drug-free adult NT1 patients (59 men, 39.1 ± 15.6 years old) and 109 healthy controls (63 men, 42.6 ± 18.2 years old). A subgroup of 59 NT1 patients completed the questionnaire a second time, under medication (delay between two evaluations: 1.28 ± 1.14 years). RESULTS: Compared to controls, NT1 patients were more frequently obese, had more dyslipidemia, with no difference for age and gender. The SCOPA-AUT score of NT1 was higher than in controls in crude and adjusted models. Patients experienced more problems than controls in all subdomains. A higher score in NT1 was associated with older age, longer disease duration, altered quality of life and more depressive symptoms, but not with orexin levels and disease severity. Among patients evaluated twice, the SCOPA-AUT score total did not differ according to treatment status, neither did each subdomain. CONCLUSION: We captured a frequent and large spectrum of clinical autonomic dysfunction in NT1, with impairment in all SCOPA-AUT domains, without key impact of medication intake. This assessment may allow physicians to screen and treat various symptoms, often not spontaneously reported but associated with poor quality of life.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Adulto , Doenças do Sistema Nervoso Autônomo/psicologia , Depressão/diagnóstico , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Adulto Jovem
18.
Sleep ; 42(12)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31353416

RESUMO

STUDY OBJECTIVES: Arterial blood pressure (ABP) decreases during sleep compared with wakefulness and this change is blunted in mouse models of and adult patients with narcolepsy type 1 (NT1). We tested whether: (1) pediatric patients with NT1 have similar cardiovascular autonomic abnormalities during nocturnal sleep; and (2) these abnormalities can be linked to hypocretin-1 cerebrospinal fluid concentration (CSF HCRT-1), sleep architecture, or muscle activity. METHODS: Laboratory polysomnographic studies were performed in 27 consecutive drug-naïve NT1 children or adolescents and in 19 matched controls. Nocturnal sleep architecture and submentalis (SM), tibialis anterior (TA), and hand extensor (HE) electromyographic (EMG) activity were analyzed. Cardiovascular autonomic function was assessed through the analysis of pulse transit time (PTT) and heart period (HP). RESULTS: PTT showed reduced lengthening during total sleep and REM sleep compared with nocturnal wakefulness in NT1 patients than in controls, whereas HP did not. NT1 patients had altered sleep architecture, higher SM EMG during REM sleep, and higher TA and HE EMG during N1-N3 and REM sleep when compared with controls. PTT alterations found in NT1 patients were more severe in subjects with lower CSF HRCT-1, but did not cluster or correlate with sleep architecture alterations or muscle overactivity during sleep. CONCLUSION: Our results suggest that pediatric NT1 patients close to disease onset have impaired capability to modulate ABP as a function of nocturnal wake-sleep transitions, possibly as a direct consequence of hypocretin neuron loss. The relevance of this finding for cardiovascular risk later in life remains to be determined.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Músculo Esquelético/fisiopatologia , Narcolepsia/fisiopatologia , Fases do Sono/fisiologia , Adolescente , Biomarcadores/líquido cefalorraquidiano , Doenças Cardiovasculares/líquido cefalorraquidiano , Doenças Cardiovasculares/diagnóstico , Criança , Eletromiografia/métodos , Feminino , Humanos , Masculino , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/diagnóstico , Orexinas/líquido cefalorraquidiano , Polissonografia/métodos , Adulto Jovem
19.
Nat Rev Neurol ; 15(9): 519-539, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324898

RESUMO

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.


Assuntos
Encéfalo/fisiopatologia , Narcolepsia , Orexinas/fisiologia , Humanos , Hipotálamo/fisiopatologia , Narcolepsia/diagnóstico , Narcolepsia/etiologia , Narcolepsia/fisiopatologia , Narcolepsia/terapia
20.
Anal Chem ; 91(14): 9323-9329, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31260261

RESUMO

Low levels of hypocretin-1 (Hcrt1) in cerebrospinal fluid (CSF) are associated with narcolepsy type 1 (NT1). Although immunoassays are prone to antibody batch differences, detection methods and variation between laboratories, the standard method for Hcrt1 measurement is a radioimmunoassay (RIA). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is an antibody- and radioactive free alternative for precise measurement of Hcrt1. We developed an LC-MS/MS method for measurement of Hcrt1 in CSF with automated sample preparation by solid-phase extraction (SPE). The LC-MS/MS method was compared with the RIA method for Hcrt1 detection. CSF samples from healthy subjects and NT1 patients was obtained by lumbar puncture. NT1 patients were diagnosed according to the minimal criteria by the International Classification of Sleep Disorders (ICSD). The LC-MS/MS method showed linearity across the range of calibrators and had a limit of detection (LOD) of 2.5 pg/mL and a limit of quantitation (LOQ) of 3.6 pg/mL. Comparison of the LC-MS/MS method with RIA revealed a 19 times lower level in healthy controls and 22 times lower level in NT1 patients with the LC-MS/MS method than with RIA. Bland-Altman analysis demonstrated agreement between the methods. These results question what is detected by RIA and strongly suggest that the physiological concentrations of the peptide are much lower than previously believed. LC-MS/MS proves to be an alternative for detection of Hcrt1 for diagnosis of narcolepsy.


Assuntos
Cromatografia Líquida/métodos , Orexinas/líquido cefalorraquidiano , Espectrometria de Massas em Tandem/métodos , Adulto , Sequência de Aminoácidos , Humanos , Limite de Detecção , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/diagnóstico , Radioimunoensaio , Reprodutibilidade dos Testes , Extração em Fase Sólida
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