van Campen C Linda M C, Rowe Peter C, Visser Frans C
Stichting CardioZorg, Planetenweg 5, 2132 HN Hoofddorp, The Netherlands.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Clin Neurophysiol Pract. 2021 Sep 23;6:245-255. doi: 10.1016/j.cnp.2021.09.001. eCollection 2021.
Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.
60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound).
End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients.
During tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients.
The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.
肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)中的直立性症状可能由脑血流量异常减少引起。先前的研究显示脑血流量有异常减少,但未提供脑血流量恢复速度的相关信息。本研究调查了ME/CFS患者脑血流量延迟恢复的患病率及危险因素。
对60名成年ME/CFS患者进行研究:30名患者在倾斜试验期间心率和血压反应正常,4名出现延迟性直立性低血压,26名在倾斜试验期间出现姿势性直立性心动过速综合征(POTS)。在倾斜前仰卧位、倾斜结束时以及倾斜后5分钟仰卧位使用颅外多普勒进行脑血流量测量。此外,使用胸骨上多普勒成像进行心脏指数测量,并进行呼气末PCO₂测量。从仰卧位到倾斜结束时脑血流量的变化以平均减少百分比及标准差表示。疾病严重程度分为轻度(活动减少约50%)、中度(大多居家)或重度(大多卧床)。
倾斜结束时脑血流量减少-29(6)%,倾斜后改善至-16(7)%。将心率和血压正常的患者与患有POTS的患者进行比较,或者在倾斜结束时将血碳酸正常(呼气末PCO₂≥30 mmHg)与低碳酸血症(呼气末PCO₂<30 mmHg)的患者进行比较,在倾斜结束时或倾斜后的测量中均未发现差异。在轻度、中度和重度ME/CFS患者倾斜后仰卧位时,脑血流量异常减少程度存在显著差异:轻度:脑血流量:-7(2)%,中度:-16(3)%,重度:-25(4)%(p均<0.0001)。在所有3个严重程度组中,倾斜试验期间心脏指数均显著下降,组间无显著差异。在倾斜后仰卧位测试中,所有患者的心脏指数均恢复正常。
在倾斜试验期间,颅外多普勒测量显示ME/CFS患者脑血流量减少,尽管心脏指数恢复到倾斜前值,但恢复到正常仰卧位值并不完全。脑血流量的延迟恢复与倾斜试验的血流动力学结果(正常心率和血压反应、POTS或延迟性直立性低血压)无关,也与是否存在低碳酸血症无关,仅与临床ME/CFS严重程度分级有关。我们观察到最严重的ME/CFS患者脑血流量恢复明显较慢。
直立性应激引发应激后脑血流量减少以及疾病严重程度对脑血流量减少有很大影响这一发现,可能对这些ME/CFS患者应激源后的能量管理建议以及应激源后躺下的建议有影响。