Low hypocretin levels depend on narcolepsy or hypersomnia?

我们进行了两个部分的研究：(1)嗜睡症患者的下丘脑泌素水平和(2)发作性睡病的自身免疫假说。(1)嗜睡症患者的下丘脑泌素水平。目前尚不清楚低水平的下丘脑肌素水平是否与发作性睡病或嗜睡有关。为了明确这一问题，我们测量了发作性睡病-猝倒(N/C)、发作性睡病无猝发(N/NOC)、原发性高睡眠(EHS)、特发性高睡眠(IHS)、睡眠呼吸暂停综合征(SAS)、Niemann-Pick C型(NPC)和神经功能障碍患者。5例N/C和DR2-患者正常。10例N/NOC患者中，4例N/NOC和DR2+为低水平，6例正常。EHS组(n=6)、IHS组(n=8)、SAS组(n=16)均正常。2例鼻咽癌患者中，1例为中度眩晕，1例为正常。在…中200多例神经系统疾病患者中，仅有少数格林-巴利综合征(GBS)患者存在低水平的甲状旁腺激素水平。低水平的下丘脑下丘脑与N/C和DR2+的疾病无关。另一方面，我们发现一些患者由于肿瘤或脱髓鞘疾病而出现过度睡眠和下丘脑损害。(2)发作性睡病的自身免疫假说。人类发作性睡病已被证明与一种特定的人类白细胞抗原密切相关。由于大多数与特定人类白细胞抗原相关的疾病本质上是自身免疫的，这一发现表明自身免疫参与了发作性睡病的病理生理学。然而，目前，所有证明人类发作性睡病是一种自身免疫性疾病的尝试都失败了。52例日本NID患者(GBS，n=28，Fisher综合征，n=12，CIDP，n=12)和48例非NID患者的脑脊液(CSF)水平与先前报道的健康对照组(280pg/ml)无差异。28例GBS患者中，7例为低水平，5例为中等水平。12例Fisher综合征患者中有5例和12例CIDP患者中有1例处于中等水平。7例低水平的GBS患者为临床重症患者(四肢瘫痪、呼吸困难)。大约25%的患者的血浆和脑脊液中可以看到抗神经节苷脂抗体。在接受测试的21名GBS受试者中，有16人有抗神经节苷脂抗体。此外，降克素-1水平与抗神经节苷脂抗体之间也没有相关性。GBS患者下丘脑功能低下的机制尚不清楚，但可能与免疫介导的下丘脑功能障碍有关。GBS和Fisher综合征的一个子集可能是研究发作性睡病患者下丘脑泌素系统可能的自身免疫损害的一个很好的模型。较少

We have conducted two parts of research (1)hypocretin levels with hypersomnia patients and (2)the autoimmune hypothesis of narcolepsy.(1)Hypocretin levels with hypersomnia patients.It is not clear whether the low hypocretin levels depend on narcolepsy or hypersomnia. In order to clear this question, we measured the samples of patients with narcolepsy-cataplexy (N/C), narcolepsy without cataplexy (N/noC), essential hypersomnia (EHS), idiopathic hypersomnia (IHS), sleep apnea syndrome (SAS), Niemann-pick type C (NPC) and neurological disorders.In 25 patients with N/C, 20 patients with N/C and DR2+ had low hypocretin levels. While 5 patients with N/C and DR2-had normal levels. In 10 patients with N/noC, 4 patients with N/noC and DR2+ had low levels and remaining 6 patients had normal levels. The patients with EHS (n=6), IHS (n=8) and SAS (n=16) had normal levels. In 2 patients with NPC, one patient with cataplexy had intermediate level and the other without cataplexy had normal level. In … More 200 patients with neurological disorders, only several patients with Guillain-Barre syndrome (GBS) had low levels.Low hypocretin levels only depends on the disease of N/C and DR2+, not the condition of hypersomnia On the other hand, we found some patients with hypersomnia and hypothalamic lesion due to tumor or demyelinating disorders.(2)The autoimmune hypothesis of narcolepsy.Human narcolepsy has been shown to be closely associated with a specific HLA. Because most diseases associated with a specific HLA are autoimmune in nature, the finding suggests that autoimmunity is involved in the pathophysiology of narcolepsy. However, at present, all attempts to demonstrate that human narcolepsy is an autoimmune disease have failed. Thus, it is important to know whether hypocretin changes are found in any definite neuroimmunological diseases (NID).Samples of CSF were obtained from 52 Japanese patients with NID (GBS, n=28, Fisher syndrome n=12, CIDP, n=12) and 48 patients with non-NID.Levels of CSF hypocretin-1 did not differ between the non-NID patients and the healthy controls previously reported (280pg/ml). In the 28 patients with GBS, 7 patients had lower levels and 5 patients had intermediate levels. Five out of 12 patients with Fisher syndrome and 1 out of 12 patients with CIDP had intermediate levels. Seven GBS patients with low hypocretin-1 levels were clinically severe cases (tetraplegia, dyspnea). Antibodies to gangliosides can be seen in the plasma and CSF of approximately 25% of patients. Sixteen of 21 GBS subjects tested had anti-ganglioside antibodies. There was also no correlation between hypocretin-1 levels and anti-ganglioside antibodies. The mechanism for low hypocretin-1 in GBS is unclear but may involve immune-mediated hypothalamic dysfunction. A subset of GBS and Fisher syndrome may be a good model for studying possible autoimmune damage to the hypocretin system in narcolepsy. Less