Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography - PubMed (original) (raw)

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography

C Linda M C van Campen et al. Clin Neurophysiol Pract. 2020.

Abstract

Objective: The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.

Methods: 429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we administered a verbal questionnaire to ascertain for 15 OI symptoms.

Results: End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P < .0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI symptoms with the degree of CBF reduction at mid-tilt (P < .0005).

Conclusions: During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.

Significance: This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.

Keywords: Cerebral blood flow; ME/CFS; Orthostatic hypotension; Orthostatic intolerance; Postural orthostatic tachycardia syndrome; Tilt table testing.

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Figures

Fig. 1

This shows the flow of recruitment and patient flow explaining reasons for exclusion and number of patients analyzed. ME/CFS: myalgic encephalomyelitis/chronic fatigue syndrome; cOH: classic orthostatic hypotension; dOH: delayed orthostatic hypotension; HUT: head-up tilt test; OI: orthostatic intolerance.

Fig. 2

(A) CBF in ml/min of healthy controls and the 3 patient groups during head-up tilt. The left colored column is supine, the dotted column is mid-tilt, and the hatched column is end-tilt. (B) This shows the % decrease from supine for mid and end tilt data in patients and controls. CBF: cerebral blood flow; HC: healthy controls; ME/CFS dOH: ME/CFS patients with delayed orthostatic hypotension; ME/CFS NormHR/BP: ME/CFS patients with a normal heart rate and blood pressure response; ME/CFS POTS: ME/CFS patients with postural orthostatic tachycardia syndrome. Comparison between mid and end tilt data: *=P < .005; **=P < .0005.

Fig. 3

95% confidence intervals of the %decrease in cerebral blood flow of healthy controls and different ME/CFS patient groups at end tilt. The %decrease of all ME/CFS patient groups and subgroups was significantly larger than that of healthy controls. Abbreviations: Atyp: atypical; CBF: cerebral blood flow; CI: confidence interval; Daily life OI: clinician estimate of orthostatic intolerance symptoms; DisDur: disease duration; dOH: delayed orthostatic hypotension; HC: healthy controls; NormHR/BP: patients with a normal heart rate and blood pressure response; Pat: patients; PetCO2: end-tidal CO2 pressure; POTS: postural orthostatic tachycardia syndrome; yrs: years. **: P < .0005; *: P < .01 between groups.

Fig. 4

Linear regression analysis of the sum of positively answered OI questions per patient and the % CBF reduction at mid-tilt. The linear regression shows that a higher % CBF decrease during HUT was associated with a larger number of symptoms: P < .0005.

Fig. 5

OI symptoms in ME/CFS patients at the first minute and at the 10th minute (A) of tilt, and healthy controls at the first minute and at the 10th minute of tilt (B). MusclWeakn: leg muscle weakness; TinglingRgtHand: tingling feeling of the right hand. The percentage of positively answered symptom questions of patients were all significantly higher than of HC, both at the 1st and the 10th minute of tilt. Comparison between the 1st minute and 10th minute of tilt: **:P < .0005, *:P < .005.

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Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography - PubMed (original) (raw)