Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning

Nijs, Jo; Ickmans, Kelly

doi:10.1111/joim.12034

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…Evidence of altered autonomic nervous system (ANS) regulation of cardiovascular function has been observed in patients with ME/CFS. [8,9] Patients commonly present with concurrent cardiovascular conditions such as postural orthostatic tachycardia syndrome (POTS), [10] and disturbances in additional markers of ANS function including blood pressure variability, and altered responses to head-up tilt testing (HUTT). [11–13] However, these studies have used inconsistent methodologies and provided variable results, making it difficult to conclusively establish the nature and extent of any derangement of cardiovascular autonomic regulation.…”

Section: Introductionmentioning

confidence: 99%

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2019

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Background:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition with no reliable diagnostic biomarkers. Studies have shown evidence of autonomic dysfunction in patients with ME/CFS, but results have been equivocal. Heart rate (HR) parameters can reflect changes in autonomic function in healthy individuals; however, this has not been thoroughly evaluated in ME/CFS.Methods:A systematic database search for case-control literature was performed. Meta-analysis was performed to determine differences in HR parameters between ME/CFS patients and controls.Results:Sixty-four articles were included in the systematic review. HR parameters assessed in ME/CFS patients and controls were grouped into ten categories: resting HR (RHR), maximal HR (HRmax), HR during submaximal exercise, HR response to head-up tilt testing (HRtilt), resting HR variability (HRVrest), HR variability during head-up tilt testing (HRVtilt), orthostatic HR response (HROR), HR during mental task(s) (HRmentaltask), daily average HR (HRdailyaverage), and HR recovery (HRR) Meta-analysis revealed RHR (MD ± 95% CI = 4.14 ± 1.38, P < .001), HRtilt (SMD ± 95% CI = 0.92 ± 0.24, P < .001), HROR (0.50 ± 0.27, P < .001), and the ratio of low frequency power to high frequency power of HRVrest (0.39 ± 0.22, P < .001) were higher in ME/CFS patients compared to controls, while HRmax (MD ± 95% CI = –13.81 ± 4.15, P < .001), HR at anaerobic threshold (SMD ± 95% CI = –0.44 ± 0.30, P = 0.005) and the high frequency portion of HRVrest (–0.34 ± 0.22, P = .002) were lower in ME/CFS patients.Conclusions:The differences in HR parameters identified by the meta-analysis indicate that ME/CFS patients have altered autonomic cardiac regulation when compared to healthy controls. These alterations in HR parameters may be symptomatic of the condition.

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Section: Introductionmentioning

confidence: 99%

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2019

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“…Importantly though, steady state muscle sympathetic nerve activity, a direct measure of the vasoconstrictor drive which mediates blood pressure, was found to correlate with fMRI BOLD signal in the medulla, hypothalamus and limbic nuclei ( James et al, 2013 , Macefield and Henderson, 2010 ). Despite autonomic dysfunction being accepted as evidence that CFS is a disorder of the central nervous system ( Nijs and Ickmans, 2013 ), imaging studies of the neural correlates of autonomic function in CFS are also lacking.…”

Section: Introductionmentioning

confidence: 99%

Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome

Barnden

Kwiatek

Crouch

et al. 2016

NeuroImage: Clinical

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Autonomic changes are often associated with the chronic fatigue syndrome (CFS), but their pathogenetic role is unclear and brain imaging investigations are lacking. The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP) and heart rate (HR). In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w) brain MRI in 25 CFS subjects and 25 normal controls (NC). Steady state BP (systolic, diastolic and pulse pressure) and HR in two postures were extracted from 24 h blood pressure monitoring. We performed (1) MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS), and (2) MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS. Significant CFS regressions were repeated controlling for anxiety and depression (A&D). Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter. Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions.

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“…In contrast to physiological 'tiredness', rest and sleep are not physically or mentally rejuvenating in fatigue. As noted in Table 1 [31][32][33][34][35][36][37], fatigue is a common accompaniment of POTS and-as we shall argue-likely has a main common cause.…”

Section: Fatigue and Potsmentioning

confidence: 71%

“…Although well known in other contexts for at least three decades [6,7] (see Table 1), with at least 500,000 cases in the USA alone [8][9][10], mostly in women (5:1) [5,9,[11][12][13][14], POTS has emerged as a frequent symptom of both acute [15] and long COVID (e.g., [16][17][18][19][20][21] as part of the wider cardiovascular dysautonomia spectrum; see Table 1). Autoimmune disorders and Autoimmunity Some strong associations [16,[22][23][24][25][26] Cognitive function Large amount of literature; improved by plasma exchange [27] [27-30] Fatigue [31][32][33][34][35][36][37][38] HPV or other antiviral vaccination An example of induction by a viral protein [39][40][41][42][43][44][45] but cf. [46] Inflammation [47] Irritable bowel disease [48] Long COVID A very common occurrence and a focus of our interest…”

Section: Introduction Orthostasis Orthostatic Intolerance and Potsmentioning

confidence: 99%

Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID

Kell,

Khan,

Kane

et al. 2024

JPM

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Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of a variety of chronic, inflammatory diseases, including long COVID, as are small, insoluble, ‘fibrinaloid’ microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block the flow of blood through microcapillaries and thus cause tissue hypoxia, are not simply correlated with but in fact, by preceding it, may be a chief intermediary cause of POTS, in which tachycardia is simply the body’s exaggerated ‘physiological’ response to hypoxia. Similar reasoning accounts for the symptoms bundled under the term ‘fatigue’. Amyloids are known to be membrane disruptors, and when their targets are nerve membranes, this can explain neurotoxicity and hence the autonomic nervous system dysfunction that contributes to POTS. Taken together as a system view, we indicate that fibrinaloid microclots can serve to link POTS and fatigue in long COVID in a manner that is at once both mechanistic and explanatory. This has clear implications for the treatment of such diseases.

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Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning

Cited by 6 publications

References 28 publications

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome

Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome

Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID

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