Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1)
Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1)
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DOI：
10.1093/brain/awn193
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发表时间：
2008-10-01
期刊：
影响因子：
14.5
通讯作者：
Hinze-Selch, Dunja
中科院分区：
文献类型：
--
作者：
Baier, Paul Christian;Weinhold, Sara Lena;Hinze-Selch, Dunja
直到最近，嗅觉功能障碍一直是嗜睡症的一个未知特征。食欲素A，也称为下丘脑分泌素-1，在发作性睡病患者的脑脊液中异常减少或检测不到。由于下丘脑含有食欲素的神经元分布于从嗅觉粘膜到嗅觉皮层的整个嗅觉通路，因此食欲素传递紊乱可能与发作性睡病患者的嗅觉功能受损有关。在我们的研究中，我们分析了发作性睡病猝倒患者（n = 10）以及年龄、性别、BMI和吸烟者/非吸烟者匹配的健康对照（n = 10）的嗅觉表现（阈值、辨别、识别和这些测量值的总和得分，TDI得分）。然后，我们采用双盲、随机、安慰剂对照交叉设计，对7名患者鼻内应用食欲素a，并测量2-苯基乙醇（PEA）单楼梯气味检测阈值。与对照组相比，患者嗅觉阈值（患者：中位数8.0，范围4.0-10.5；对照组：中位数9.4，范围7.5-13.3,P < 0.05）、鉴别（患者：中位数12.5，范围10-15；对照组：中位数15.0，范围12-16，P < 0.005）、鉴别（患者：中位数13.0，范围10-16；对照组：中位数14.0，范围13-16，P < 0.05）和TDI评分（患者：中位数33.4，范围30-36；对照组：中位数38.4，范围35-43，P < 0.0001）得分显著降低。在所有患者中，与安慰剂（中位数为7.75，范围6.25-11.25,P < 0.05）相比，给予食欲素A后PEA嗅觉阈值评分（中位数为11.5，范围6.5-13.25）均有所增加。我们的研究结果支持轻度嗅觉功能障碍是发作性睡病伴猝倒的内在症状的假设。鼻内食欲素A恢复嗅觉功能的观察结果支持这一假设。此外，我们的数据支持发作性睡病嗅觉功能障碍的病理生理机制是中枢神经系统食欲素的缺乏。
Until recently, olfactory dysfunction was an unknown feature of narcolepsy. Orexin A, also called hypocretin-1, is abnormally decreased or undetectable in the cerebrospinal fluid of narcoleptic patients with cataplexies. As hypothalamic orexin-containing neurons project throughout the entire olfactory pathway, from the olfactory mucosa to the olfactory cortex, disturbed orexinergic transmission may crucially be involved in impaired olfactory performance of narcolepsy patients. In our study we analysed the olfactory performance (threshold, discrimination, identification and sum score of these measurements, the TDI score) of narcoleptic patients with cataplexies (n = 10) and of age-, gender-, BMI- and smoker/non-smoker-matched healthy controls (n = 10). We then in a double-blind, randomized, placebo-controlled cross-over design applied orexin A intranasally to seven of the patients and measured 2-phenyl-ethyl alcohol (PEA) single-staircase odour detection thresholds. Compared to the controls, patients showed significantly lower scores for olfactory threshold (patients: median 8.0, range 4.0-10.5; controls: median 9.4, range 7.5-13.3; P < 0.05), discrimination (patients: median 12.5, range 10-15; controls: median 15.0, range 12-16; P < 0.005), identification (patients: median 13.0, range 10-16; controls: median 14.0, range 13-16; P < 0.05) and TDI score (patients: median 33.4, range 30-36; controls: median 38.4, range 35-43; P < 0.0001). In all patients, the PEA olfactory threshold score increased after administration of orexin A (median 11.5, range 6.5-13.25) compared to placebo (median 7.75, range 6.25-11.25; P < 0.05). Our results support the hypothesis that mild olfactory dysfunction is an intrinsic symptom of narcolepsy with cataplexies. The observation that intranasal orexin A restores olfactory function is in favour of this hypothesis. Furthermore, our data support that the pathophysiological mechanism underlying olfactory dysfunction in narcolepsy is the lack of CNS orexin.