Low hypocretin levels depend on narcolepsy or hypersomnia?

我们进行了两个部分的研究（1）下丘脑泌素水平与嗜睡症患者和（2）自身免疫假说的发作性睡病。（1）下丘脑泌素水平与睡眠过度患者的关系：下丘脑泌素水平的降低是由嗜睡症还是由睡眠过度引起的尚不清楚。为了明确这一问题，我们检测了25例发作性睡病-癫痫（N/C）、无癫痫发作性睡病（N/noC）、原发性睡眠过度（EHS）、特发性睡眠过度（IHS）、睡眠呼吸暂停综合征（SAS）、C型尼曼匹克（NPC）和神经系统疾病患者的样本。5例N/C和DR 2-均正常。在10例N/noC患者中，4例N/noC和DR 2+患者的水平较低，其余6例患者的水平正常。EHS（n=6）、IHS（n=8）和SAS（n=16）患者的血清水平正常。2例鼻咽癌患者中，1例有症状者为中度水平，1例无症状者为正常水平。在 ...更多信息 200例神经系统疾病患者中，只有少数格林-巴利综合征（Guillain-Barre syndrome，GBS）患者的下丘脑泌素水平较低，其低水平仅取决于N/C和DR 2+的疾病，而不取决于睡眠过度的情况。（2）发作性睡病的自身免疫假说：人类发作性睡病与一种特定的HLA密切相关。由于大多数与特定HLA相关的疾病本质上是自身免疫性的，因此这一发现表明自身免疫性参与了发作性睡病的病理生理学。然而，目前，所有试图证明人类嗜睡症是一种自身免疫性疾病的尝试都失败了。从52例日本NID患者（GBS，n=28，Fisher综合征，n=12，CIDP，n=12）和48例非NID患者中获得CSF样品。在28例GBS患者中，7例患者为较低水平，5例患者为中等水平。12例Fisher综合征患者中有5例和12例CIDP患者中有1例为中等水平。7例下丘脑泌素-1水平低的GBS患者为临床严重病例（四肢瘫痪、呼吸困难）。在大约25%的患者的血浆和CSF中可以看到神经节苷脂抗体。21例GBS受试者中有16例有抗神经节苷脂抗体。下丘脑泌素-1水平和抗神经节苷脂抗体之间也没有相关性。GBS中下丘脑泌素-1水平降低的机制尚不清楚，但可能涉及免疫介导的下丘脑功能障碍。GBS和Fisher综合征的一个子集可能是一个很好的模型，用于研究可能的自身免疫性损伤发作性睡病的下丘脑泌素系统。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