Department of Pediatrics, New York Medical College, Valhalla, New York, United States.
Department of Physiology, New York Medical College, Valhalla, New York, United States.
Am J Physiol Regul Integr Comp Physiol. 2024 Jun 1;326(6):R599-R608. doi: 10.1152/ajpregu.00071.2024. Epub 2024 Apr 29.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CB) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, < 0.05) and decreased end-tidal CO (ETCO; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CB compared with control (-22.5% vs. -8.7%, < 0.005). To mitigate the orthostatic CB reduction, we administered supplemental CO, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CB. We evaluated cognitive function before and after CO, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.
慢性疲劳综合征/肌痛性脑脊髓炎（ME/CFS）伴直立不耐受（OI）的特征是神经认知功能障碍，可能与直立性低碳酸血症和大脑自动调节丧失有关。我们对 11 名对照（平均年龄 24.1 岁）和 15 名 ME/CFS 患者（平均年龄 21.8 岁）进行了 N-回神经认知测试，并计算了动脉压（AP）和脑血流速度（CB）之间的相位同步指数（PhSI），作为大脑自动调节的时间依赖性测量。所有 ME/CFS 患者均有体位性心动过速综合征（POTS）。10 分钟 60°头高位倾斜（HUT）显著增加心率（109.4±3.9 次/分比 77.2±1.6 次/分， ＜0.05）和呼吸频率（20.9±1.7 次/分比 14.2±1.2 次/分， ＜0.05），并降低终末二氧化碳分压（ETCO；33.9±1.1 比 42.8±1.2 托， ＜0.05）在 ME/CFS 与对照相比。在 ME/CFS 中，与对照相比，HUT 显著降低了 CB（-22.5%比-8.7%， ＜0.005）。为了减轻直立性 CB 下降，我们给予了补充 CO、苯肾上腺素和乙酰唑胺，并在仰卧位和 HUT 期间进行了 N-回测试。只有苯肾上腺素通过在 HUT 期间恢复 ME/CFS 中的 4 N-回来纠正神经认知的直立性下降，使其与对照相似（ME/CFS=38.5±5.5 比 ME/CFS+PE=65.6±5.7 比对照 56.9±7.5）。ME/CFS 中的 HUT 导致 PhSI 值增加，表明大脑自动调节降低。尽管 CO 和乙酰唑胺对 ME/CFS 中的 PhSI 没有影响，但苯肾上腺素导致 PhSI 显著降低（ME/CFS=0.80±0.03 比 ME/CFS+PE=0.69±0.04， ＜0.05），改善了大脑自动调节。因此，PE 改善了 ME/CFS 患者的神经认知功能，这可能与改善神经血管耦合、大脑自动调节和 CB 维持有关。我们评估了 CO、乙酰唑胺和苯肾上腺素减轻脑血流速度直立性下降前后的认知功能。CO 和乙酰唑胺在直立性挑战期间均不影响 N-回测试（正确答案百分比）。只有苯肾上腺素改善了 ME/CFS 的直立 N-回表现，因为它既阻止了过度通气，又显著增加了 CO，与未治疗的患者相比。只有苯肾上腺素在 ME/CFS 和对照直立时都导致 PSI 值的改善，表明大脑自动调节的改善。
