Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C.
Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C.
复制标题
C 型尼曼-匹克病的睡眠障碍和下丘脑分泌素缺乏。
DOI：
10.1093/sleep/26.4.427
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发表时间：
2003
期刊：
影响因子：
5.6
通讯作者：
Nevsimalova,Sona
中科院分区：
文献类型：
--
作者：
Vankova,Jitka;Stepanova,Iva;Jech,Robert;Elleder,Milan;Ling,Lig;Mignot,Emmanuel;Nishino,Seiji;Nevsimalova,Sona
设计和患者 据报道，患有 C 型尼曼-匹克病的受试者表现出嗜睡病样症状，包括猝倒。在这项研究中，使用夜间多导睡眠图、临床评估和多次睡眠潜伏期测试来评估 5 名青少年尼曼-匹克病患者的睡眠异常情况。还对 4 名患者进行了 HLA 分型和脑脊液下丘脑分泌素水平评估。所有病例的尼曼-匹克病诊断均通过生化检查和骨髓中泡沫细胞的存在得到证实。存在锥体、肌张力障碍和小脑特征；所有病例均观察到脾肿大。 1 名患者报告出现猝倒。夜间多导睡眠图显示所有患者的睡眠均受到干扰。与年龄匹配的对照组相比，总睡眠时间、睡眠效率、快速眼动睡眠和增量睡眠量均减少。睡眠模式的改变包括δ睡眠期间肌张力的突然增加、与快速眼球运动和肌肉无力相关的脑电图西格玛活动、非典型K复合体和纺锤体活动以及α-δ睡眠的存在。所有尼曼-匹克病病例均表现出碎片性肌阵挛。在多次睡眠潜伏期测试中，观察到 3 名患者的平均睡眠潜伏期缩短，但仅在猝倒病例中观察到入睡快速眼动期。该患者为 HLA DQB1*0602 阳性，而其他受试者为 HLA 阴性。 2 名患者（1 名患有猝倒症）的脑脊液下丘脑分泌素-1 水平降低，而另外 2 名患者的脑脊液下丘脑分泌素-1 水平处于正常值的较低范围。与对照组（265.8±48.8 pg/mL）相比，尼曼-匹克病组的下丘脑分泌素水平（204.8±39.3pg/mL）显着降低。结论研究结果表明，尼曼-匹克病患者的溶菌体储存异常可能会影响下丘脑，更具体地说，会影响含下丘脑分泌素的细胞。这些变化可能是尼曼-皮克病患者睡眠异常和猝倒的部分原因。
Design and PatientsSubjects with Niemann-Pick disease, type C have been reported to display narcolepsylike symptoms, including cataplexy. In this study, 5 patients with juvenile Niemann-Pick disease were evaluted for sleep abnormalities using nocturnal polysomnography, clinical evaluation, and the Multiple Sleep Latency Test. HLA typing and cerebrospinal fluid hypocretin levels were also evaluated in 4 patients. Niemann-Pick disease diagnosis was confirmed in all cases biochemically and by the presence of foam cells in the bone marrow.ResultsDeterioration of intellectual function; the presence of pyramidal, dystonic and cerebellar features; and splenomegaly were observed in all cases. Cataplexy was reported in 1 patient. Nocturnal polysomnography revealed disrupted sleep in all patients. Total sleep time, sleep efficiency, rapid eye movement sleep, and delta sleep amounts were decreased when compared to age-matched controls. Altered sleep patterns included sudden increases in muscle tone during delta sleep, electroencephalographic sigma activity connected with rapid eye movements and muscle atonia, atypical K-complexes and spindle activity, and the presence of alpha-delta sleep. All Niemann-Pick disease cases exhibited fragmentary myoclonus. Shortened mean sleep latencies were observed in 3 patients during the Multiple Sleep Latency Test, but sleep-onset rapid eye movement periods were observed only in the case with cataplexy. This patient was HLA DQB1*0602 positive, while the other subjects were HLA negative. Cerebrospinal fluid hypocretin-1 levels were reduced in 2 patients (1 with cataplexy) while in the 2 other patients, the levels were at the lower range of the normal values. Hypocretin levels in the Niemann-Pick disease group (204.8±39.3pg/mL) were significantly reduced when compared to controls (265.8±48.8 pg/mL).ConclusionsThe findings suggest that lysozomal storage abnormalities in Niemann-Pick disease patients may impact the hypothalamus and, more specifically, hypocretin-containing cells. These changes might be partially responsible for sleep abnormalities and cataplexy in patients with Niemann-Pick disease.