Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.

• Keywords
• cytokines, glucose, immune system, metabolism, stress system,
• MeSH
• Adrenocorticotropic Hormone blood   MeSH
• Dexamethasone pharmacology   MeSH
• Adult MeSH
• Glucose Tolerance Test MeSH
• Corticotropin-Releasing Hormone pharmacology   MeSH
• Hydrocortisone blood   MeSH
• Body Mass Index MeSH
• Interleukin-6 metabolism   MeSH
• Cataplexy blood   complications   metabolism   MeSH
• Blood Glucose metabolism   MeSH
• Humans MeSH
• Narcolepsy blood   complications   metabolism   MeSH
• Case-Control Studies MeSH
• Pituitary-Adrenal System drug effects   metabolism   MeSH
• Hypothalamo-Hypophyseal System drug effects   metabolism   MeSH
• Tumor Necrosis Factor-alpha blood   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adrenocorticotropic Hormone MeSH
• Dexamethasone MeSH
• Corticotropin-Releasing Hormone MeSH
• Hydrocortisone MeSH
• Interleukin-6 MeSH
• Blood Glucose MeSH
• Tumor Necrosis Factor-alpha MeSH

Narcolepsy is characterized, beside other features, by excessive daytime sleepiness and disturbed sleep at night. The pineal hormone melatonin may affect the sleep characteristics. The aim of the study was to compare the circadian rhythm in salivary melatonin in narcoleptic patients with that in control healthy subjects; 18 patients and 21 age- and gender-matched controls were involved. Narcoleptic patients exhibited a nocturnal increase in salivary melatonin similar to the one in control subjects. The morning melatonin decline in the narcoleptic group, as opposed to the control group was, however, not significant, as 8 out of 18 patients exhibited elevated melatonin levels also during the day. In these patients, the mean daytime value of the multiple sleep latency test (MSLT) was decreased when compared with that in patients with undetectable daytime melatonin levels. The results suggest that in some narcoleptic patients the circadian rhythm might be disturbed.

• MeSH
• Biomarkers metabolism   MeSH
• Chronobiology Disorders etiology   metabolism   MeSH
• Circadian Rhythm physiology   MeSH
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Melatonin metabolism   MeSH
• Narcolepsy complications   metabolism   MeSH
• Saliva metabolism   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Melatonin MeSH

OBJECTIVES: Narcolepsy with cataplexy is associated with a loss of hypocretin. The question is, if there is an autoimmune or neurodegenerative process selectively killing the hypothalamic hypocretin-containing neurons or if these cells survive but fail to produce hypocretin. To support one of these hypothesis we aimed to detect structural changes in the hypothalamus of narcoletic patients. MATERIALS AND METHODS: Nineteen narcoleptic patients were compared to 16 healthy controls. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes to investigate hypothalamic region in this condition. RESULTS: Classical MRI protocol revealed no structural abnormalities, but using VBM we found significant reduction in hypothalamic gray matter volumes between patients and controls. CONCLUSIONS: VBM showed hypothalamic gray matter loss in narcolepsy with cataplexy. This suggest that functional abnormalities of hypocretin neurons in narcolepsy are associated with structural changes of hypothalamus.

• MeSH
• Atrophy MeSH
• Adult MeSH
• Hypothalamus pathology   MeSH
• Intracellular Signaling Peptides and Proteins metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging instrumentation   MeSH
• Narcolepsy metabolism   pathology   MeSH
• Neurons metabolism   pathology   MeSH
• Neuropeptides metabolism   MeSH
• Orexins MeSH
• Reference Values MeSH
• Case-Control Studies MeSH
• Organ Size MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Intracellular Signaling Peptides and Proteins MeSH
• Neuropeptides MeSH
• Orexins MeSH

• MeSH
• Circadian Rhythm physiology   MeSH
• Child MeSH
• Adult MeSH
• Hydrocortisone metabolism   MeSH
• Idiopathic Hypersomnia metabolism   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melatonin metabolism   MeSH
• Adolescent MeSH
• Narcolepsy metabolism   physiopathology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Hydrocortisone MeSH
• Melatonin MeSH

A mutation in the HCRT locus was proved in 18-yrs old male suffering from narcolepsy-cataplexy. He has demonstrated cataplectic attacks (brief spells of head dropping provoked by laughter) as well as imperative sleep in spells of several minutes up to one hour since the age of six months. He has suffered from severe bulimia since five years; later hypnagogic hallucinations, sleep paralysis and unquiet nocturnal sleep accompanied by periodic limb movements appeared. Symptoms are partially controlled with methylphenidate and either imipramine, clomipramine or fluoxetine. Periodic leg movements poorly responded to L-DOPA and clonazepam treatment. He is HLA-DQB1*0602 negative. Repeated MSLT (over 16 years followed-up period) showed extremely short latency with predominant SOREMPs and also nocturnal PSG recordings revealed fragmented sleep with SOREMPs. This case report demonstrates that hypocretin (orexin) mutations in human can produce the full narcolepsy phenotype and validates data recently reported in dog and mouse models suggesting a role for hypocretin (orexin) in the pathophysiology of narcolepsy and the regulation of REM sleep.

• MeSH
• Intracellular Signaling Peptides and Proteins * MeSH
• Cataplexy drug therapy   metabolism   MeSH
• Humans MeSH
• Adolescent MeSH
• Narcolepsy drug therapy   metabolism   MeSH
• Neuropeptides cerebrospinal fluid   deficiency   MeSH
• Neurotransmitter Agents cerebrospinal fluid   deficiency   MeSH
• Orexins MeSH
• Carrier Proteins cerebrospinal fluid   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Names of Substances
• Intracellular Signaling Peptides and Proteins * MeSH
• Neuropeptides MeSH
• Neurotransmitter Agents MeSH
• Orexins MeSH
• Carrier Proteins MeSH