Narcolepsy and cataplexy.

Stanford University School of Medicine, Stanford Sleep Research Center, Palo Alto, CA, USA.
Handbook of Clinical Neurology 01/2011; 99:783-814. DOI: 10.1016/B978-0-444-52007-4.00007-2
Source: PubMed

ABSTRACT The term "narcolepsy" was first coined by Gélineáu in 1880 with the complete description of a patient with excessive daytime sleepiness (EDS), sleep attacks, and episodes of muscle weakness triggered by emotions. In the current international classification, narcolepsy is characterized by "excessive daytime sleepiness that is typically associated with cataplexy and abnormal REM (rapid eye movement) sleep phenomena such as sleep paralysis and hypnagogic hallucinations". Narcolepsy is a chronic neurological condition, but is not a progressive disorder. The major pathophysiology of human narcolepsy has been elucidated recently based on the discovery of narcolepsy genes (hypocretin/orexin ligand and its receptor) in animals. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in many cases. This recent discovery is likely to lead to the development of new diagnostic tests and targeted treatments. As hypocretins are involved various hypothalamic functions, hypocretin-deficient narcolepsy appears now to be a more complex condition than just a simple sleep disorder. This chapter starts with an overview of the clinical aspects of narcolepsy, followed by an update on the pathophysiology. Finally, we discuss the expectations from future narcolepsy research.

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    ABSTRACT: Objective Our study was designed to assess symptomatology and occurrences of narcolepsy in Eastern China between 2003 and 2012. Herein we report the substantial changes in the occurrence and clinical features of narcolepsy over the last decade in China. Methods We performed a retrospective analysis of 162 Han Chinese patients with narcolepsy at Changzheng Hospital, Shanghai, China. Clinical histories and precipitating factors were recorded, in addition to narcolepsy and H1N1 winter flu pandemic(pH1N1) occurrences at Changzheng Hospital. The occurrences also were compared between the Changzheng Hospital and the People’s Hospital, Beijing, China. Results In our sample, narcolepsy occurred 1.73 times more frequently in men than in women. Most of the participants were children, which peaked to 91% in 2010. Excessive daytime sleepiness (EDS), disrupted nocturnal sleep, cataplexy, and weight gain were the 4 major symptoms. We found that 40% of patients had identifiable precipitating factors. The occurrence of narcolepsy in 2010 showed an approximate 3-fold difference from the baseline levels at the Changzheng Hospital, which showed positive relationships with occurrences of pH1N1 in Shanghai and the occurrence of narcolepsy at the People’s Hospital. Conclusions Our findings show the interactive effects of geography and H1N1 disease in relation to narcolepsy in Han Chinese populations and strengthen the theoretic hypothesis that immune and mental factors facilitate the onset of narcolepsy.
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    ABSTRACT: Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.
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    ABSTRACT: Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. Occurring spontaneously, cataplexy is typically triggered by strong positive emotions such as laughter and is often underdiagnosed owing to a variable disease course in terms of age of onset, presenting symptoms, triggers, frequency and intensity of attacks. This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin neurons. One pathogenetic mechanism that has been hypothesized for cataplexy is the activation, during wakefulness, of brainstem circuitry that normally induces muscle tone suppression in rapid eye movement sleep. Muscle weakness during cataplexy is caused by decreased excitation of noradrenergic neurons and increased inhibition of skeletal motor neurons by γ-aminobutyric acid-releasing or glycinergic neurons. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and γ-hydroxybutyrate being the most effective treatments. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies.
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