Ohno Koyo, Saito Yoshiaki, Ueda Riyo, Togawa Masami, Ohmae Takanori, Matsuda Eriko, Fujiyama Misato, Maegaki Yoshihiro
Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Pediatr Neurol. 2016 Jul;60:54-59.e1. doi: 10.1016/j.pediatrneurol.2016.03.016. Epub 2016 Apr 1.
Rett syndrome is characterized by psychomotor regression during early childhood, autistic-like behaviors, and aberrant breathing patterns. Dysfunction of the serotonergic system has been postulated to play a role in the pathophysiology of these symptoms.
We present an 11-year-old girl with Rett syndrome who exhibited marked respiratory symptoms, including frequent apneic events during sleep. She had been treated for these respiratory symptoms using noninvasive positive pressure ventilation since age six years. Treatment with serotonin 1A receptor agonist was initiated at age eight years, whereas treatment using a selective serotonin reuptake inhibitor began at age nine years. Noninvasive positive pressure ventilation therapy was effective in reducing symptoms of sleep apnea, and administration of serotonergic agents resulted in amelioration of sleep apneic events even in the absence of noninvasive positive pressure ventilation. In addition, improvements in hand stereotypy and social skills were observed after initiation of serotonin-based therapy.
The respiratory difficulties our patient experienced during non-rapid eye movement (REM) sleep are characteristic of post-sigh central apnea. Exaggerated activity of expiratory neurons during such apneic events has been observed in mouse models of Rett syndrome. We suggest that prescribed serotonergic agents might serve to inhibit such activity, attenuating the imbalance between inspiratory and expiratory neurons. These agents might also be useful in the treatment of autistic-like behaviors caused by impaired serotonergic transmission in the brain.
雷特综合征的特征是在幼儿期出现精神运动发育倒退、自闭症样行为和异常呼吸模式。血清素能系统功能障碍被认为在这些症状的病理生理学中起作用。
我们报告一名11岁的雷特综合征女孩，她表现出明显的呼吸症状，包括睡眠期间频繁的呼吸暂停事件。自6岁起，她就使用无创正压通气治疗这些呼吸症状。8岁开始使用5-羟色胺1A受体激动剂治疗，9岁开始使用选择性5-羟色胺再摄取抑制剂治疗。无创正压通气治疗有效减轻了睡眠呼吸暂停症状，即使在没有无创正压通气的情况下，给予血清素能药物也能改善睡眠呼吸暂停事件。此外，在开始基于血清素的治疗后，观察到手部刻板动作和社交技能有所改善。
我们的患者在非快速眼动（REM）睡眠期间经历的呼吸困难是叹息后中枢性呼吸暂停的特征。在雷特综合征的小鼠模型中，已观察到在这种呼吸暂停事件期间呼气神经元的活动增强。我们认为，处方的血清素能药物可能有助于抑制这种活动，减轻吸气和呼气神经元之间的失衡。这些药物也可能有助于治疗因大脑中血清素能传递受损引起的自闭症样行为。
