| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Introduction : Narcolepsy and other sleep disorders are underrecognized in children and the final diagnosis and initiation of treatment is often delayed.^1 This is partially due to the fact that the expression of the sleep-related symptoms in children is often different to adults. Hypersomnia is often expressed as a behavioral hyperactivity and/or deficient attention in children. Furthermore, polysomnography (PSG) is generally difficult to perform in children, and the interpretation of the results is often difficult (especially for diagnostic purposes).^2 Establishment of a specific diagnostic tool for sleep disorders in children is thus an urgent issue.^3 In this study, we describe the spectrum of the hypocretin deficiency syndrome by analysis of CSF hypocretin-1 (orexin-A) levels, and clinical, PSG, and human leukocyte antigen (HLA) data in 63 pediatric and teenage patients with various sleep disorders and 120 patients with neurological conditions.
Methods : Samples of CSF from 63 sub
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jects with various sleep disorders and 120 neurological controls under 20 years of age were provided from four hospitals in Japan. Informed consent for participation in this study was obtained from each subject or parent. Sleep disorders were diagnosed clinically and using sleep studies (nocturnal PSG and multiple sleep latency test ; MSLT).
Results : Diagnosis included narcolepsy with cataplexy (n = 24), narcolepsy without cataplexy (n = 10), idiopathic hypersomnia (n = 14), recurrent hypersomnia (n = 7), cataplectic attack (n = 6) and symptomatic hypocretin-deficient hypersomnia (n = 7). The hypocretin-1 levels of narcolepsy with cataplexy were significantly different from the neurological controls (P = 0.000 1). Further analysis was done among patients who had narcolepsy with cataplexy, narcolepsy without cataplexy and idiopathic hypersomnia. Twenty out of twenty four patients who had narcolepsy with cataplexy were HLA-DR2 positive and had low hypocretin-1 levels. Six out of ten patients with narcolepsy without cataplexy were HLA-DR2 positive and two of them had low hypocretin-1 levels. Five out of fourteen patients with idiopathic hypersomnia were HLA-DR2 positive but none of them had low hypocretin-1 levels.
Discussion : Recent CSF hypocretin-1 measurements and post-mortem studies in narcolepsy suggest that hypocretin deficiency is the major pathophysiology of the disease.^5 CSF hypocretin-1 in various neurological and sleep disorders in adults further demonstrated that a low hypocretin-1 level is highly specific to narcolepsy with cataplexy,^<3,6> and this measure is now being established as a new diagnostic tool.^<7,8> As well as those of adults, abnormally low hypocretin-1 levels are specific for narcolepsy with cataplexy in children and teenagers. The biological markers of pediatric narcolepsy and hypersomnia, such as HLA, MSLT and hypocretin-1, were also the same as those of adults. However, MSLT is difficult to perform in young children and it has not been standardized for people younger than 7 years of age.^2 In addition, the HLA test is not good at positive diagnosis of narcolepsy. The measurement of hypocretin-1 level is a useful diagnostic tool in pediatric narcolepsy, especially when other diagnostic measures (e.g.MSLT, nocturnal PSG and HLA) are not sufficient. Less
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