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

Campen, C. M. C. van; Rowe, Peter C.; Visser, Frans C.

doi:10.3390/healthcare8020169

Cited by 33 publications

(35 citation statements)

References 46 publications

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“…In contrast, in patients with orthostatic intolerance complaints in daily life, sitting resulted in a 26.9% reduction in cerebral blood flow. This is similar to the 27% reduction in cerebral blood flow in an exploratory study with 20 degrees tilting during 15 min in severe ME/CFS patients [ 7 ]. It also is comparable to the 26% reduction observed after 30 min of 70 degree head-up tilt in a less severely affected population of ME/CFS patients [ 2 ].…”

Section: Discussionsupporting

confidence: 84%

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

2020

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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.

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Section: Discussionsupporting

confidence: 84%

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

2020

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“…4 )? Orthostatic stress seems to be more important than assumed so far and manifests as a decrease in cerebral blood flow not only when standing up but in severe cases already in a sitting position [ 8 , 9 ] so that it seems to be a basic stressor to which in real life all other forms of stress are additive. Is the combination of stress of any cause together with stimulation of skeletal muscle thermogenesis causing energy consumption a pathophysiological equivalent in skeletal muscle to low or moderate levels of physical exercise that can induce PEM via the mechanisms described in this paper?…”

Section: Disturbances Of Ions In Skeletal Muscles In Me/cfs As the Mamentioning

confidence: 99%

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Wirth¹,

Scheibenbogen

2021

J Transl Med

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Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.

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“…While the pathophysiology of ME/CFS is not yet fully elucidated [ 12 , 13 ], autonomic nervous system dysregulation, immunological disturbance, viral infections, and metabolic changes were proposed as underlying mechanisms of this malady [ 14 , 15 , 16 , 17 ]. Indeed, previous studies cited all mechanisms as being responsible for endothelial dysfunction [ 18 , 19 , 20 , 21 ]. On the other hand, endothelial damage is also correlated with vasospastic or microvascular angina.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, in the present case, an ECG change attributed to angina was recorded in concurrence with the recurrence of ME/CFS (which had a 3-year history) and deterioration of PS. Endothelial dysfunction was reported to reduce cerebral blood flow, which is correlated with disease severity [ 20 , 21 ], and results in further fatigue [ 22 ]. Therefore, endothelial function might be potentially used to assist the diagnosis of ME/CFS, and serve as an indicator of its severity and the risk of complications [ 7 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Angina Simultaneously Diagnosed with the Recurrence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Otsuka

Nakano

et al. 2021

Diagnostics

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) mainly affects young adults and can have a potential impact on social functioning. As this syndrome is associated with endothelial dysfunction, the heart can be damaged via ischemia due to endothelial damage. This might potentially lead to heart failure, which accounts for approximately 20% of deaths among patients with ME/CFS. While cardiac ischemia is thought be a pathophysiologically important manifestation of this syndrome, this is not yet reported. Herein, we present a case of a young female with newly diagnosed vasospastic or microvascular angina and concurrent exacerbation of ME/CFS severity. Her anginal symptoms, including exertional chest pain and transient chest discomfort, mimicked those of ME/CFS but were relieved after the administration of a calcium channel blocker. We emphasize the possibility of concurrent angina and exacerbation of ME/CFS and the importance of detecting cardiac ischemia to avoid unfavorable outcomes.

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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

Cited by 33 publications

References 46 publications

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

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

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Angina Simultaneously Diagnosed with the Recurrence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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