Asai Hirohide, Hirano Makito, Furiya Yoshiko, Udaka Fukashi, Morikawa Masami, Kanbayashi Takashi, Shimizu Tetsuo, Ueno Satoshi
Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
Clin Neurol Neurosurg. 2009 May;111(4):341-4. doi: 10.1016/j.clineuro.2008.11.007. Epub 2008 Dec 20.
Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but clinically important because they significantly impair the daily lives of patients. Causes of SAs include long-term activation of dopaminergic (especially D3) receptors. Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain.
We measured levels of orexin in samples of spinal cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs, the selective dopamine D1/D2 agonist pergolide was substituted for the causative drugs with D3 stimulatory activity, and CSF-orexin levels were measured before and after switching treatment.
In the 25 patients with PD, including the 4 patients with SAs, lower CSF-orexin levels were associated with a longer disease duration, which has been linked to a higher incidence of SAs. Switching treatment to pergolide significantly increased CSF-orexin levels and completely resolved SAs in the four patients with PD.
Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs.
帕金森病（PD）中的睡眠发作（SA）较为罕见，但具有临床重要性，因为它们会显著损害患者的日常生活。SA的病因包括多巴胺能（尤其是D3）受体的长期激活。最近的研究表明，PD中的SA可能与下丘脑食欲素神经元受损有关，类似于发作性睡病。食欲素是否与多巴胺能受体的长期激活相关仍不确定。
我们测量了25例PD患者脊髓脑脊液（CSF）样本中的食欲素水平，其中包括9例白天过度嗜睡患者和4例有SA的患者。此外，在4例有SA的患者中，用选择性多巴胺D1/D2激动剂培高利特替代具有D3刺激活性的致病药物，并在换药治疗前后测量CSF-食欲素水平。
在25例PD患者中，包括4例有SA的患者，CSF-食欲素水平较低与病程较长相关，而病程较长与SA的发生率较高有关。将治疗换为培高利特可显著提高CSF-食欲素水平，并使4例PD患者的SA完全缓解。
尽管研究的患者数量较少，但我们的结果表明，食欲素传递很可能参与了PD中的SA，并且取消D3受体刺激可能会增加食欲素，从而抑制SA。
