RESUMO
Narcolepsy has been studied as a possible autoimmune disease for many years, and recent findings lend more credence to this belief. Although recent and important advances have been done, no study has analyzed the role of the CD40L in patients with narcolepsy. The purpose of this study was to assess CD40L levels, CD3, TCD4, TCD8, CD19, and CD56 lymphocytes, as well as levels of tumor necrosis factor-α and interleukin-6 in narcoleptic patients. We quantified the levels of CD40L, different types of lymphocytes, and levels of tumor necrosis factor-α and interleukin-6 in narcoleptic patients and control subjects. Narcoleptic patients had lower levels of CD40L. Total lymphocytes; CD3, and TCD4 were lower than in the control group. Our findings highlight the important role of CD40L in narcolepsy.
Assuntos
Ligante de CD40/imunologia , Cadeias beta de HLA-DQ/análise , Linfopenia/imunologia , Narcolepsia/imunologia , Adulto , Brasil , Complexo CD3/análise , Complexo CD3/imunologia , Antígenos CD4/análise , Antígenos CD4/imunologia , Ligante de CD40/análise , Estudos de Casos e Controles , Feminino , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Contagem de Linfócitos , Linfócitos/citologia , Linfócitos/imunologia , Linfopenia/sangue , Linfopenia/complicações , Masculino , Pessoa de Meia-Idade , Narcolepsia/sangue , Narcolepsia/complicações , Neuropeptídeos/líquido cefalorraquidiano , Orexinas , Reação em Cadeia da Polimerase , Polissonografia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
UNLABELLED: 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 110 pg/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.
Assuntos
Antígenos HLA-DQ/genética , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Glicoproteínas de Membrana/genética , Narcolepsia/diagnóstico , Neuropeptídeos/líquido cefalorraquidiano , Adulto , Idoso , Alelos , Biomarcadores , Cataplexia/líquido cefalorraquidiano , Cataplexia/diagnóstico , Cataplexia/genética , Feminino , Cadeias beta de HLA-DQ , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/genética , Orexinas , Reação em Cadeia da Polimerase , Polissonografia , RadioimunoensaioRESUMO
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.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos HLA-DQ/genética , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Glicoproteínas de Membrana/genética , Narcolepsia/diagnóstico , Neuropeptídeos/líquido cefalorraquidiano , Alelos , Biomarcadores , Cataplexia/líquido cefalorraquidiano , Cataplexia/diagnóstico , Cataplexia/genética , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/genética , Reação em Cadeia da Polimerase , Polissonografia , RadioimunoensaioRESUMO
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 autoimmune since most patients have the HLA DQB1 0602 allele 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.
Assuntos
Narcolepsia , Neuropeptídeos , Humanos , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Neuropeptídeos/líquido cefalorraquidiano , Neuropeptídeos/deficiência , Neuropeptídeos/fisiologiaRESUMO
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).
Assuntos
Humanos , Narcolepsia , Neuropeptídeos , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Neuropeptídeos/líquido cefalorraquidiano , Neuropeptídeos/deficiência , Neuropeptídeos/fisiologiaRESUMO
Narcolepsy is a unique model for dysfunction in mechanisms that regulate sleep and wakefulness. The narcolepsy syndrome is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hypnagogic and/or hypnopompic hallucinations and sleep paralysis. The current hypothesis for the etiology of narcolepsy is that it is an autoimmune disorder because of its strong association with the human leukocyte antigen (HLA) system. HLA-DQ alleles are not particularly mutated in narcoleptic patients but they directly influence susceptibility to the disease. DQB10602 homozygote carriers have a two to four times higher risk of developing the disease than heterozygote carriers. In the present study we report a rare multiplex familial case of narcolepsy-cataplexy and show the strong effect of the HLA-DQB10602 allele upon the disease phenotype. In the family studied herein, both the proband and his brother are severely affected and homozygous DQB10602, whereas their sister does not carry the allele and is not affected at all. These data corroborate previous findings proposing DQB10602 homozygous subjects to be far more susceptible to narcolepsy. Insights into the DQB10602 positive family that include homozygous subjects may prove to be an important asset in the investigation of genetic vs. environmental factors predisposing to narcolepsy.
Assuntos
Suscetibilidade a Doenças , Saúde da Família , Antígenos HLA-DQ/genética , Glicoproteínas de Membrana/genética , Narcolepsia/genética , Adulto , Genótipo , Cadeias beta de HLA-DQ , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Masculino , Narcolepsia/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , OrexinasRESUMO
CSF hypocretin-1 measurements were performed during a period of hypersomnia and during an asymptomatic interval in a 14-year-old girl affected with severe Kleine-Levin syndrome. A twofold decrease in hypocretin-1 was evidenced during the period of hypersomnia in comparison with the asymptomatic interval. Together with previous data, this result is in favour of recurrent dysfunction at the hypothalamic level in Kleine-Levin syndrome.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Síndrome de Kleine-Levin/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Adolescente , Feminino , Humanos , Hipotálamo/fisiopatologia , OrexinasRESUMO
The hypocretins (orexins) are recently discovered neuropeptides initially associated with feeding behavior and sleep regulation. However, the normal function of these peptides is unclear and a number of studies have reported a role in energy homeostasis and locomotor activity. Exercise (or physical activity) is the most powerful way of challenging the internal homeostatic process. This study examines the circadian differences in response to forced activity and homeostatic challenges on hypocretin-1 (Hcrt-1) levels in the cerebrospinal fluid (CSF) of rats. Hcrt-1 levels were decreased after long-term immobilization at the end of active phase (zeigeber time-0, ZT-0) and increased after short-term forced swimming in the rest phase (ZT-8). Nevertheless, no effects were observed after short-term immobilization, total sleep deprivation or cold exposure. We concluded that despite the relation between hypocretins, stress and sleep regulation reported in the literature, short-term total sleep deprivation, immobilization and cold exposure did not induce increases in CSF Hcrt-1 levels at ZT-0 and ZT-8. On the other hand, the relationship between hypocretinergic system activation and motor activation is reinforced by decrease in Hcr-1 levels after long-term immobilization at ZT-0 and its increased levels after short-term forced swimming at ZT-8 in CSF of rats.
Assuntos
Proteínas de Transporte/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intracelular , Neuropeptídeos/líquido cefalorraquidiano , Natação/fisiologia , Animais , Masculino , Orexinas , Ratos , Ratos Wistar , Privação do Sono , Regulação para CimaRESUMO
Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or 96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8 after 24 h of REM sleep rebound. These results suggest that REM sleep deprivation activates and REM sleep rebound inhibits the hypocretin system. Increased hypocretin tone during REM deprivation may be important in mediating some of the effects of REM sleep deprivation such as antidepressant effects, hyperphagia and increased sympathetic activity.