Macey Paul M, Macey Katherine E, Woo Mary A, Keens Thomas G, Harper Ronald M
Department of Neurobiology, University of California at Los Angeles, Los Angeles, California 90095, and Childrens Hospital, Los Angeles, California 90027, USA.
Pediatr Res. 2005 Apr;57(4):500-9. doi: 10.1203/01.PDR.0000155757.98389.53. Epub 2005 Feb 17.
Patients with congenital central hypoventilation syndrome (CCHS), a condition characterized by impaired ventilatory responses to chemoreceptor stimulation, do not show the normal increase in respiratory rate and respiratory-related heart rate variation to cold forehead stimulation, a challenge that bypasses central chemoreceptors. We hypothesized that a forehead cold pressor challenge would reveal abnormal neural response patterns, as assessed by functional magnetic resonance imaging, in brain regions that are responsible for the integration of cold afferent stimulation with respiratory and cardiovascular output in patients with CCHS. Primary sensory thalamic and cortical areas for the forehead showed diminished responses in 13 patients with CCHS (ventilator dependent during sleep but not waking, no Hirschsprung's disease) compared with 14 control subjects, despite initial signal changes in the cortex being similar in both groups. Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior cingulate, insular, frontal, and temporal cortices showed reduced signal rises in patients with CCHS. Areas within the frontal and anterior cingulate cortices exhibited marked signal declines in control subjects but little change in patients with CCHS. No response occurred in either group in the dorsal medulla, but medial and ventral medullary areas showed enhanced signals in patients with CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that would be affected by PHOX2B (a mutation of which is associated with the syndrome) expression in either group but demonstrated deficient cerebellar and medial medullary influences that, by action on rostral sites, may underlie the loss of respiratory responses.
先天性中枢性低通气综合征（CCHS）患者的通气反应对化学感受器刺激受损，对冷额头刺激（一种绕过中枢化学感受器的刺激）不会出现正常的呼吸频率增加和呼吸相关心率变化。我们假设，前额冷加压刺激会揭示CCHS患者大脑区域的异常神经反应模式，这通过功能磁共振成像评估，这些区域负责将冷传入刺激与呼吸和心血管输出进行整合。与14名对照受试者相比，13名CCHS患者（睡眠时依赖呼吸机但清醒时不依赖，无先天性巨结肠病）前额的初级感觉丘脑和皮质区域反应减弱，尽管两组皮质的初始信号变化相似。CCHS患者的小脑皮质和深部核团、基底神经节以及中扣带回、岛叶、额叶和颞叶皮质的信号上升减少。额叶和前扣带回皮质内的区域在对照受试者中显示出明显的信号下降，但在CCHS患者中变化很小。两组的延髓背侧均无反应，但CCHS患者的延髓内侧和腹侧区域信号增强。冷加压刺激在两组中均未激活受PHOX2B（其突变与该综合征相关）表达影响的延髓背侧部位，但显示出小脑和延髓内侧影响不足，通过对延髓上部部位的作用，可能是呼吸反应丧失的基础。
