Evaluation of etiology for symptomatic narcolepsy and CNS iron metabolism in narcolepsy with RLS

(1)嗜睡发生在各种神经系统疾病的过程中。最近的一项荟萃分析表明，116例有症状的发作性睡病患者中有10例与多发性硬化症（一种自身免疫性脱髓鞘疾病）有关。症状性发作性睡病例包括异质性疾病，但在这些发作性睡/EDS病例中，食欲素系统经常受损。自血清抗。水通道蛋白4 （AQP4=NMO）抗体滴度阳性，7例日本患者诊断为视神经脊髓炎（NMO）相关疾病。7例患者均伴有明显或中度食欲素缺乏的双侧及对称下丘脑病变。其中4例患者符合ICSD 2发作性睡症标准。由于AQP4在下丘脑脑室周围区域高表达，对AQP4的免疫攻击可能是与自身免疫性脱髓鞘疾病相关的发作性睡病/EDS双侧和下丘脑病变和食欲素缺乏的部分原因。进一步了解免疫介导的症状性发作性睡病的基本知识，不仅有助于选择最合适的治疗方法和预测疾病的预后，而且有助于了解发作性睡病的病因机制。(2)睡眠期间周期性腿动（PLMS）常与不宁腿综合征（RLS）相关。据报道，在PLMS/RLS受试者中，脑脊液中铁蛋白水平降低和转铁蛋白水平升高（铁水平正常或低）（作为低脑铁的指标）。据报道，发作性睡病患者的PLMS发病率要高得多（25-50% vs.一般人群的-5%）。由于两种疾病均提示多巴胺能神经递质改变，且铁是多巴胺合成（甲状腺氨酸羟化酶）的辅助因子，因此我们在研究中评估了食欲素缺乏性发作性睡患者的脑脊液铁蛋白、转铁蛋白和铁。与对照组相比，食欲素缺乏症发作性睡患者的脑脊液转铁蛋白和铁水平较高。两组脑脊液铁蛋白水平无差异。正如在睡眠倒睡症患者中所见，在发作性睡症患者中也观察到转铁蛋白的增加。然而，这些受试者的铁蛋白正常和铁水平升高可能表明发作性睡病患者铁的利用率较高或铁代谢产物失调。目前尚不清楚这些发现是否直接或间接（如多巴胺能合成代偿性增加）与食欲素缺乏有关，也不清楚这是否导致嗜睡症患者PLMS的高发。少

(1) Narcolepsy occurs during the course of various neurological conditions. A recent meta-analysis indicated that 10 out of 116 symptomatic cases of narcolepsy are associated with multiple sclerosis, a disease of autoimmune demyelination. Symptomatic narcoleptic cases consist of heterogeneous disease conditions, but the orexin systems are often impaired in these narcolepsy/EDS cases. Since, serum anti.aquaporin 4 (AQP4=NMO) antibody titer were positive, seven Japanese patients were diagnosed as neuromyelitis optica (NMO) related disorder. Bilateral and symmetrical hypothalamic lesions associated with marked or moderate orexin deficiency were found in all 7 cases. Four of these patients met the ICSD 2 narcolepsy criteria. Since AQP4 is highly expressed in the hypothalamic periventricular regions, an immune attack on AQP4 may be partially responsible for the bilateral and hypothalamic lesions and orexin deficiency in narcolepsy/EDS associated with autoimmune demyelinating diseases. Gaini … More ng the basic knowledge of symptomatic narcolepsy in immune mediated conditions will not be useful only for selecting the most appropriate treatment and predicting the prognosis of the disease but also for understanding the etiological mechanism of narcolepsy.(2) Periodic leg movements during sleep (PLMS) are often associated with restless legs syndrome (RLS). Reduced ferritin and elevated transferrin levels (with normal or low iron levels) in CSF (as indicators of low brain iron) are reported in PLMS/RLS subjects. A much higher incidence (25-50% vs.-5% in general population) of PLMS is reported in narcoleptic patients. Since altered dopaminergic neurotransmissions are suggested in both diseases and since iron is a co-factor for dopamine synthesis (thyrosine hydoroxylase), we evaluated CSF ferritin, transferrin and iron in patients with orexin deficient narcolepsy in the study. Patients with orexin deficient narcolepsy had higher CSF transferrin and iron levels compared to control subjects. There was no difference in CSF ferritin levels between the two groups. As seen in RLS subjects, an increase in transferrin was observed in narcoleptic subjects. However, normal ferritin and increased iron levels in these subjects may possibly suggest a higher utilization of iron or a dysregulation of iron metabolites in narcolepsy. It is not known if these findings are direct or indirect (such as a compensatory increase in dopaminergic synthesis) to orexin deficiency, and whether or not this contributes to the high incidence of PLMS in narcolepsy. Less