Cerebral Blood Flow is reduced in Severe Myalgic EncephalomyelitisChronic Fatigue Syndrome Patients during Mild Orthostatic Stress Testing An Exploratory Study at 20 Degrees of Head-Up Tilt Testing

Aims: An abnormal reduction in cerebral blood flow (CBF) during orthostatic stress is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition with more prevalent joint hypermobility than in the healthy population. As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility. Methods: In this case-control study, 100 female ME/CFS cases with joint hypermobility, who had undergone tilt-testing with CBF measurements, were compared to 100 female ME/CFS patients without joint hypermobility, matched by age and disease duration. Results: No differences in baseline characteristics were found between groups. The hypermobile patients had significantly more postural orthostatic tachycardia syndrome (POTS) during tilt testing than the non-hypermobile ones. Compared to supine CBF, the degree of CBF reduction during the tilt was significantly larger in hypermobile cases than in the non-hypermobile controls: -32 (6)% vs -23 (7)% (p<0.0001) The larger CBF reduction in hypermobile patients was not only present in POTS patients: -33 (6)% vs -24 (4)%, but also in patients with a normal heart rate and blood pressure response to tilt testing: -31 (6)% vs -22 (9)%: (both p<0.0001). Conclusions: ME/CFS patients with joint hypermobility syndromes have larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test.

Download Full-text

Cerebral blood flow during orthostasis: role of arterial CO2

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00446.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. R1087-R1093 ◽

Cited By ~ 46

Author(s):

J. M. Serrador ◽

R. L. Hughson ◽

J. M. Kowalchuk ◽

R. L. Bondar ◽

A. W. Gelb

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Healthy Subjects ◽

Cerebral Arteries ◽

Alveolar Ventilation ◽

Orthostatic Stress ◽

Upright Posture ◽

Head Up Tilt ◽

End Tidal

Reductions in end-tidal Pco2 (PetCO2) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in PetCO2 reflected decreases in arterial Pco2 (PaCO2) and their relation to increases in alveolar ventilation (V̇a) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. PaCO2, V̇a, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in PetCO2 and PaCO2 (−1.7 ± 0.5 and −1.1 ± 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in V̇a (+0.7 ± 0.3 l/min, P < 0.05). However, further decreases in PaCO2 (−0.5 ± 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though V̇a did not change significantly (−0.2 ± 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (−7 ± 2 and −8 ± 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in PaCO2. These data suggest that decreases in PetCO2 and PaCO2 during upright posture are not solely due to increased V̇a but could be due to ventilation-perfusion mismatch or a redistribution of CO2 stores. Furthermore, the reduction in PaCO2 did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in PaCO2 play a role in the CBF response to orthostatic stress.

Download Full-text

The cerebrovascular response to lower-body negative pressure vs. head-up tilt

Journal of Applied Physiology ◽

10.1152/japplphysiol.00797.2016 ◽

2017 ◽

Vol 122 (4) ◽

pp. 877-883 ◽

Cited By ~ 10

Author(s):

Anne-Sophie G. T. Bronzwaer ◽

Jasper Verbree ◽

Wim J. Stok ◽

Mat J. A. P. Daemen ◽

Mark A. van Buchem ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Negative Pressure ◽

Cerebral Blood Flow Velocity ◽

Lower Body Negative Pressure ◽

Orthostatic Stress ◽

Lower Body ◽

Head Up Tilt ◽

End Tidal ◽

Pronounced Reduction

Lower-body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (−50 mmHg) vs. head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler-determined cerebral blood flow velocity (CBF v) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT, leading to an ~15% difference in CPP between LBNP and HUT ( P ≤ 0.020). Mean CBF v initially decreased similarly in response to LBNP and for HUT, but, from minute 3 on, the decline became ~50% smaller ( P ≤ 0.029) during LBNP. The reduction in end-tidal Pco2 partial pressure (PetCO2) was comparable but with an earlier return toward baseline values in response to LBNP but not during HUT ( P = 0.008). We consider the larger decrease in CBF v during HUT vs. LBNP attributable to the pronounced reduction in PetCO2 and to gravitational influences on CPP, and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality. NEW & NOTEWORTHY Lower-body negative pressure (LBNP) has the potential to serve as a MRI-compatible surrogate of orthostatic stress but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco2 together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as MRI-compatible alternative to orthostatic stress.

Download Full-text

Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing

Healthcare ◽

10.3390/healthcare8020169 ◽

2020 ◽

Vol 8 (2) ◽

pp. 169 ◽

Cited By ~ 1

Author(s):

C (Linda) M.C. van Campen ◽

Peter C. Rowe ◽

Frans C. Visser

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Chronic Fatigue Syndrome ◽

Orthostatic Intolerance ◽

Daily Life ◽

Chronic Fatigue ◽

Tilt Test ◽

Fatigue Syndrome ◽

Head Up Tilt ◽

The Mean

Introduction: In a study of 429 adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we demonstrated that 86% had symptoms of orthostatic intolerance in daily life. Using extracranial Doppler measurements of the internal carotid and vertebral arteries during a 30-min head-up tilt to 70 degrees, 90% had an abnormal reduction in cerebral blood flow (CBF). A standard head-up tilt test of this duration might not be tolerated by the most severely affected bed-ridden ME/CFS patients. This study examined whether a shorter 15-min test at a lower 20 degree tilt angle would be sufficient to provoke reductions in cerebral blood flow in severe ME/CFS patients. Methods and results: Nineteen severe ME/CFS patients with orthostatic intolerance complaints in daily life were studied: 18 females. The mean (SD) age was 35(14) years, body surface area (BSA) was 1.8(0.2) m2 and BMI was 24.0(5.4) kg/m2. The median disease duration was 14 (IQR 5–18) years. Heart rate increased, and stroke volume index and end-tidal CO2 decreased significantly during the test (p ranging from <0.001 to <0.0001). The cardiac index decreased by 26(7)%: p < 0.0001. CBF decreased from 617(72) to 452(63) mL/min, a 27(5)% decline. All 19 severely affected ME/CFS patients met the criteria for an abnormal CBF reduction. Conclusions: Using a less demanding 20 degree tilt test for 15 min in severe ME/CFS patients resulted in a mean CBF decline of 27%. This is comparable to the mean 26% decline previously noted in less severely affected patients studied during a 30-min 70 degree head-up tilt. These observations have implications for the evaluation and treatment of severely affected individuals with ME/CFS.

Download Full-text

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

Clinical Neurophysiology Practice ◽

10.1016/j.cnp.2020.01.003 ◽

2020 ◽

Vol 5 ◽

pp. 50-58 ◽

Cited By ~ 6

Author(s):

C. (Linda) M.C. van Campen ◽

Freek W.A. Verheugt ◽

Peter C. Rowe ◽

Frans C. Visser

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Controlled Study ◽

Tilt Testing ◽

Head Up Tilt ◽

Doppler Echography

Download Full-text

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Healthcare ◽

10.3390/healthcare8040394 ◽

2020 ◽

Vol 8 (4) ◽

pp. 394

Author(s):

C (Linda) MC van Campen ◽

Peter C. Rowe ◽

Frans C Visser

Keyword(s):

Heart Rate ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Orthostatic Intolerance ◽

Daily Life ◽

Chronic Fatigue ◽

Tilt Test ◽

Fatigue Syndrome ◽

Previous Diagnosis ◽

Head Up Tilt

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients. Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008). Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Download Full-text

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Medicina ◽

10.3390/medicina58010028 ◽

2021 ◽

Vol 58 (1) ◽

pp. 28

Author(s):

C. (Linda) M. C. van Campen ◽

Peter C. Rowe ◽

Frans C. Visser

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cardiac Index ◽

Orthostatic Stress ◽

Healthy Controls ◽

Age And Gender ◽

Head Up Tilt ◽

And Gender

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

Download Full-text