Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients

C Linda M C van Campen, Peter C Rowe, Frans C Visser, C Linda M C van Campen, Peter C Rowe, Frans C Visser

Abstract

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Significance: 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.

Keywords: BMI, Body Mass Index; BSA, Body Surface Area; CBF, Cerebral blood flow; CI, Cardiac Index; Cardiac Index; Cerebral blood flow; DBP, Diastolic Blood pressure; Extracranial Doppler echography; HR, Heart rate; ICC, International Consensus Criteria; ME/CFS; ME/CFS, Myalgic encephalomyelitis/chronic fatigue syndrome; NormHRBP, normal heart rate and blood pressure response; Normal heart rate and blood pressure response; Orthostatic intolerance; PET, end-tidal pressure; POTS, Postural orthostatic tachycardia syndrome; Post exertional malaise; Postural Orthostatic Tachycardia Syndrome; Recovery; SBP, Systolic Blood pressure; Tilt table testing; VTI, Time velocity integral; dOH, delayed orthostatic hypotension.

© 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Cerebral blood flow, cardiac index, and end-tidal PCO2 results for all patients, as measured in the supine position pre-tilt, at the end of tilt phase, and post-tilt recovery phase. Cerebral blood flow, cardiac index, and end-tidal PCO2 results for all patients, as measured in the supine position pre-tilt, at the end of tilt phase, and post-tilt recovery phase. PETCO2: end-tidal PCO2; blue points and lines: cerebral blood flow data; red points and lines: cardiac index data; green points and lines: end-tidal PCO2 data. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the supine pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a normal HR and BP response and in patients with POTS. Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the supine pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a normal heart rate and blood pressure response and in patients with POTS. CBF: cerebral blood flow; normHRBP: normal heart rate and blood pressure response; CI: cardiac index; POTS: postural orthostatic tachycardia syndrome; *: columns significantly different from zero (P 

Fig. 3

Percent cerebral blood flow reduction…

Fig. 3

Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the…

Fig. 3
Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a reduced PETCO2 (<30 mmHg) vs patients with a normal PETCO2 (≥30 mmHg) at the end of the tilt phase. Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a reduced end-tidal PCO2 (<30 mmHg) vs patients with a normal end-tidal PCO2 (≥30 mmHg) at the end of the tilt phase. CBF: cerebral blood flow; CI: cardiac index; CO2: P end-tidal CO2; *: columns significantly different from zero (p < 0.0001); #: columns not significantly different from zero.

Fig. 4

Percent cerebral blood flow reduction…

Fig. 4

Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the…

Fig. 4
Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a mild, moderate and severe disease according to the ICC criteria (Carruthers et al., 2011). Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a mild, moderate and severe disease according to the ICC criteria (Carruthers et al., 2011). CBF: cerebral blood flow; CI: cardiac index; *: columns significantly different from zero (p 
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Fig. 3
Fig. 3
Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a reduced PETCO2 (<30 mmHg) vs patients with a normal PETCO2 (≥30 mmHg) at the end of the tilt phase. Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a reduced end-tidal PCO2 (<30 mmHg) vs patients with a normal end-tidal PCO2 (≥30 mmHg) at the end of the tilt phase. CBF: cerebral blood flow; CI: cardiac index; CO2: P end-tidal CO2; *: columns significantly different from zero (p < 0.0001); #: columns not significantly different from zero.
Fig. 4
Fig. 4
Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a mild, moderate and severe disease according to the ICC criteria (Carruthers et al., 2011). Percent cerebral blood flow reduction and percent cardiac index reduction, relative to the pre-tilt values, at end-tilt, and in the supine recovery phase post-tilt, in patients with a mild, moderate and severe disease according to the ICC criteria (Carruthers et al., 2011). CBF: cerebral blood flow; CI: cardiac index; *: columns significantly different from zero (p 

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