Health-related quality of life in patients with narcolepsy types 1 and 2 from a Sleep Center in Brazil / Qualidade de vida relacionada à saúde em pacientes com narcolepsia tipos 1 e 2 de um Centro de Sono no Brasil

ABSTRACT Introduction: Narcolepsy patients have higher prevalence of comorbidities, such as obesity, depression, and pain. Narcolepsy symptoms and concomitant medical conditions can impact the daily activities of patients. The objective of this study is to describe the quality of life in a sample of patients with narcolepsy, and the influence of the nutritional status in health domains. Methods: At Unifesp, two groups of 33 patients (narcolepsy types 1 and 2 meeting 2014 criteria, concerning hypocretin-1) and 33 controls without sleepiness, matched by age and sex, filled out the SF-36. Results: Narcolepsy groups, regardless of their nutritional status, had significantly lower scores in all domains, compared to controls, mainly in Role-physical, Role-emotional, and Energy/Fatigue. Role-physical score was lower in type 1 than in type 2 and controls (37.8±1.0 vs. 50.0±1.2 vs. 85.6±1.6; p<0.0001). Obese with type 2 narcolepsy scored lower than type 1 in physical scales. Conclusion: In a Sleep Center in São Paulo, Brazil, physical and mental health were impaired in narcolepsy types 1 and 2. The first report of the poor health status in Brazilians with narcolepsy type 2 suggests that obesity negatively affects physical domains.

RESUMO Introdução: Pacientes com narcolepsia têm maior prevalência de comorbidades, como obesidade, depressão e dor. Sintomas de narcolepsia e condições médicas concomitantes podem afetar as atividades diárias dos pacientes. O objetivo deste estudo é escrever a qualidade de vida em uma amostra de pacientes com narcolepsia e a influência do estado nutricional nos domínios de saúde. Métodos: Na Unifesp, dois grupos de 33 pacientes (narcolepsia tipos 1 e 2 compatível com os critérios de 2014, em relação a hipocretina-1) e 33 controles sem sonolência, pareados por idade e sexo, preencheram o SF-36. Resultados: Os grupos de narcolepsia, independentemente do estado nutricional, apresentaram pontuações significantemente menores em todos os domínios, comparados aos controles, principalmente nos quesitos físico, emocional e energia/fadiga. A pontuação do critério físico foi menor no tipo 1 do que no tipo 2 e nos controles (37,8±1,0 vs. 50,0±1,2 vs. 85,6±1,6; p<0,0001). Obesos com tipo 2 tiveram pontuação menor do que os com tipo 1 nas escalas físicas. Conclusão: Em um Centro de Sono de São Paulo, Brasil, as saúdes física e mental estavam comprometidas na narcolepsia tipos 1 e 2. O primeiro relato de estado de saúde ruim em brasileiros com narcolepsia tipo 2 sugere que a obesidade afeta negativamente os domínios físicos.

Autonomic disturbances in narcolepsy type 1 / 中华神经科杂志

The pathogenesis of narcolepsy type 1 is characterized by massive loss of hypocretin neurons in the lateral hypothalamus.Due to the extensive interaction between the hypocretin signalling pathway and the autonomic nerve centre of brain stem and spinal cord,narcolepsy type 1 patients often showed autonomic nervous dysfunctions,such as circadian rhythms/sleep abnormalities,energy metabolism and body temperature regulation disorder,pupil adjustment disorder,sexual dysfunction and autonomic fluctuations during cataplexy.We reviewed the autonomic dysfunction of the narcolepsy type 1 patients in general and during cataplexy,in order to strengthen the attention to autonomic nervous dysfunction in narcolepsy type 1.

Comparison of Health Related Quality of Life between Type I and Type II Narcolepsy Patients

OBJECTIVES: Narcolepsy with cataplexy is a rare chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations. The aims of the present study were comparing the health-related quality of life (HR-QOL) of patients with type I and type II narcolepy patients, and determining the factors that influence the HR-QOL in narcolepsy patients. METHODS: All patients performed night polysomnography (PSG) and multiple sleep latency test (MSLT). HR-QOL and the severity of subjective symptoms were evaluated using various questionnaires, including the Korean versions of the Medical Outcome Study Short Form-36, the Pittsburg Sleep Quality Index-Korean version, the Korean version Epworth Sleepiness Scale, and the Korean version Beck Depression Inventory-2. RESULTS: We enrolled 21 type I narcolepsy patients and 27 type II patients. Type I patients had short rapid eye movement (REM) latency on night PSG and more sleep onset REM periods on MSLT. The total score of HR-QOL was worse in patients with type I narcolepsy than in the type II narcolepsy patients. There was association between the severities of excessive daytime sleepiness, depression and the degree of worsening of QOL. CSF hypocretin level had no correlation with the scores of HR-QOL. CONCLUSIONS: These findings demonstrate that type I narcolepsy patients are sleepier, depressive, and have more burden on the HR-QOL. And the impairment in QOL of narcolepsy patients is related to the degree of excessive daytime and depressive mood.

Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre / Biomarcadores tradicionias em narcolepsia: experiência de um centro de sono brasileiro

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002). DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR) em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem da Hipocretina-1 são insuficientes para o diagnóstico da narcolepsia sem cataplexia.

Narcolepsy: Clinical features, co-morbidities & treatment.

Narcolepsy is a neurologic illness that typically begins in the second and third decades of life. It is chronic in nature and negatively impacts the quality of life of affected patients. The classic presentation is a tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. Some primary conditions that result in secondary narcolepsy include traumatic brain injury, congenital disorders, tumours, and strokes. Some medical and psychiatric disorders share characteristics of narcolepsy, at times leading to diagnostic inaccuracy. Other sleep disorders are commonly co-morbid. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioural modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Novel modalities are being examined to expand options for treatment.

Sistema hipocretinérgico y narcolepsia / Hypocretin system and narcolepsy

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) sleep periods. It is now identified as a neurodegenerative disease because there is a massive loss of specific neurons in the brain. These neurons contain the neuropeptides hypocretin-1 and hypocretin-2, which are also known as orexin-A and orexin-B. Cerebrospinal fluid hypocretin-1 measurements are diagnostic for primary narcolepsy. The cause of neural loss could be autoinmune since most patients have the HLA DQB1*0602 alíele that predisposes to the disorders. The discovery of hypocretin deficiency is redefining the clinical entity of narcolepsy and offering novel diagnostic procedures. This article reviews the current understanding of narcolepsy and discusses the implications of hypocretin discovery (Rev Méd Chile 2009; 137:1209-16).

HLA-DQB1 Allele and Hypocretin in Korean Narcoleptics with Cataplexy

Cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the frequency of the HLA-DQB1 allele and cerebrospinal fluid (CSF) hypocretin levels in Korean narcoleptics with cataplexy as compared with those who do not have cataplexy. Seventy-two narcoleptics were selected based on polysomnography and multiple sleep latency test as well as their history and clinical symptoms at Sleep Disorders Clinic. The patients were divided into a narcolepsy with cataplexy group (n=56) and a narcolepsy without cataplexy group (n=16). All patients were subjected to HLA typing to determine the frequency of DQB1 allele and to spinal tapping to measure the level of CSF hypocretin. In cataplexy-positive patients, as compared with cataplexy-negative patients, the frequency of HLA-DQB1*0602 was found to be significantly high (89.3% vs. 50.0%) (p=0.003). On the other hand, the frequency of HLA-DQB1*0601 was found to be significantly low (0% vs. 43.8%) (p<0.001). In 48 of 56 cataplexy-positive patients (85.7 %), hypocretin levels were decreased (< or =110 pg/mL). However, only 6 of 16 cataplexy-negative patients (37.5%) exhibited a decreased hyopcretin level (p<0.001). The high frequency of HLA-DQB1*0602, low frequency of HLA-DQB1*0601 and low hypocretin levels in cataplexy-positive groups suggest that cataplexy-positive narcolepsy might be an etiologically different disease entity from the cataplexy-negative.

CHANGES IN THE EXPRESSION OF OREXIN AND ITS RECEPTORS IN THE RAT HYPOTHALAMUS DURING PREGNANCY,PARTURITION AND LACTATION / 解剖学报

Objective To investigate the possible role of orexin in reproduction and examine the changes in the expression of orexin and its receptors(OX1R,OX2R) in the rat hypothalamus during pregnancy,parturition and lactation. Methods The expressions of prepro-orexin(prepro-OX),orexin-A,OX1R,and OX2R in the rat hypothalamus during pregnancy,parturition,and lactation were evaluated by competitive reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry assay. Results Orexin-A immunoreactive(ir) neurons and the OX1R subtype in neuronal cell bodies were mainly located in the lateral hypothalamic area(LHA) as well as in the magnocellular neurons of the paraventricular and supraoptic nuclei respectively in pregnant and lactating rats.The prepro-OX and OX1R mRNA levels on the 1st day of lactation were significantly higher than that during late pregnancy and lactation.No significant changes of OX2R expression were observed during the various reproductive phases.Conclusion Orexin might be involved in regulating reproductive function in early lactation through their binding sites in hypothalamic PVN and SON.

CHANGES OF OREXIN AND ITS RECEPTORS IN THE RAT HYPOTHALAMUS DURING ESTROUS CYCLE / 解剖学报

Objective To investigate a possible role of orexin in the regulation of estrous cycle by examining the expression of orexin and orexin receptors(OX1R,OX2R) in the rat hypothalamus during the estrous cycle. Methods The levels of prepro-orexin(prepro-OX),orexin-A,OX1R,and OX2R in the rat hypothalamus during the estrous cycle were evaluated by competitive reverse transcription-polymerase china reaction(RT-PCR) assay. Results Only expression OX1R mRNA during late proestrus was significantly higher than that at metestrus.No significant changes of prepro-OX and OX2R mRNA expression were observed during the various estrous cycle phases.Conclusion Orexin might regulate the secretion of GnRH and/or LH by binding OX1R,contributing to the occurrence of ovulation.