Research: Compression stockings improve cardiac output & cerebral blood flow during tilt testing in ME/CFS patients

Posted on 01/05/2022 by wames

Compression stockings improve cardiac output and cerebral blood flow during tilt testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients: a randomized crossover trial by  C. (Linda) M C van Campen, Peter C Rowe and Frans C Visser in Medicina 2022 58:1 [10.3390/medicina58010051] (This article belongs to the Special Issue Chronic Fatigue Syndrome: From Clinical Observations to Unifying Hypotheses of Disease Mechanisms)

 

Research abstract

Background and Objectives:

Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements.

Materials and Methods:

We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries.

Results:

There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001).

Conclusion:

In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.

Comment from full paper:

…using a questionnaire in our previous study on compression stockings, the positive and negative responses of wearing compression stockings to a variety of physical activities was variable and dependent on the degree of physical activity in question. In contrast, in the present study we found a uniform hemodynamic improvement when patients wore the stockings. Future work will be able to address whether specific symptoms such as exercise intolerance, pain, cognitive symptoms, lightheadedness or co-morbid disease will be more likely to improve with compression stockings.

This new finding supports the use of the compression stockings in these patients. Compression stockings may also be beneficial in non-ME/CFS populations with orthostatic intolerance.

See also:

Compression Garment Reduces Orthostatic Tachycardia and Symptoms in Patients With Postural Orthostatic Tachycardia Syndrome by Kate Bourne et al

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Research: Cerebral blood flow in long-haul COVID-19 patients: similarities with ME/CFS

Posted on 01/03/2022 by wames

Orthostatic symptoms and cerebral blood flow in long-haul COVID-19 patients: similarities with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by C (Linda) MC van Campen, Peter C Rowe and Frans C Visser in Medicina 2022, 58(1), 28, 24 Dec 2021 [doi.org/10.3390/medicina58010028] (This article belongs to the Special Issue Chronic Fatigue Syndrome: From Clinical Observations to Unifying Hypotheses of Disease Mechanisms)

 

Research abstract:

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

Comments:

Health rising: The Reduced Brain Blood Flow Diseases? Long COVID, ME/CFS and POTS

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Research: CFS & FM sometimes mistakenly attributed to Lyme Disease (US)

Posted on 12/22/2021 by wames

Mistaken identity: many diagnoses are frequently misattributed to Lyme Disease, by Takaaki Kobayashi, Yvonne Higgins, Michael T Melia, Paul G Auwaerter in The American Journal of Medicine Nov 2021 [doi.org/10.1016/j.amjmed.2021.10.040]

 

Highlights

  • The majority of patients with long-term symptoms referred for evaluation of Lyme disease had alternative diagnoses to explain their symptoms.
  • Among 1061 patients, the 139 diagnoses described suggest that Lyme disease may be a frequent inappropriate diagnosis in this population.
  • Both new and pre-existing conditions should be considered in the differential diagnosis.
  • Patients referred for Lyme disease, especially with chronic symptoms, deserve careful assessment for diagnoses other than Lyme disease.

Research abstract:

Background:

Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

Methods: 

This retrospective observational cohort study evaluated patients referred for Lyme disease to a Mid-Atlantic academic center between 2000-2013 who lacked evidence for Borrelia burgdorferi infection. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Results: 

Of 1261 referred patients, 1061 (84%) had no findings of active Lyme disease, with 690 (65%) receiving other diagnoses resulting in 405 (59%) having newly diagnosed medical conditions, 134 (19%) attributed to pre-existing medical issues, and 151 (22%) had both new and pre-existing conditions. Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%.

Leading diagnoses were anxiety/depression 222 (21%), fibromyalgia 120 (11%), chronic fatigue syndrome 77 (7%), migraine disorder 74 (7%), osteoarthritis 62 (6%) and sleep disorder/apnea 48 (5%). Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis (11), malignancy (8), Parkinson’s disease (8), sarcoidosis (4) or amyotrophic lateral sclerosis (4).

Categories of diagnoses in patients without Lyme disease (% of n = 690*) *Individual patients can have more than one diagnosis.

Conclusions:

Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

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Hypothesis: Lessons from heat stroke for understanding ME/CFS

Posted on 12/21/2021 by wames

Lessons from heat stroke for understanding Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, by Dominic Stanculescu,  Nuno Sepúlveda,  Chin Leong Lim and  Jonas Bergquist in Frontiers in Neurology (2021). [doi: 10.3389/fneur.2021.789784]

 

Abstract:

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS.

Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS.

Notwithstanding important differences – and despite heat stroke being an acute condition – the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS.

Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

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Research review: COVID-19 & CFS: an endocrine perspective

Posted on 12/20/2021 by wames

COVID-19 and Chronic Fatigue Syndrome: An endocrine perspective, by Rashika Bansal, Sriram Gubbi, Christian A Koch in Journal of Clinical & Translational Endocrinology 3 Dec 2021 [doi.org/10.1016/j.jcte.2021.100284]

 

Research abstract:

Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs. Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help.

Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenals, and thyroid.

An uncanny resemblance has been observed between the long-COVID syndrome and clinical features of CFS, though this is not an unfamiliar concept.

The endocrine connection to Long-COVID syndrome:

ACE2 receptors, the route of entry of the SARS-CoV-2 virus into the human body, are expressed (https://www.proteinatlas.org/ENSG00000130234-ACE2/tissue) in the hypothalamus, pituitary, adrenal gland, thyroid, testes, and pancreatic islets leading to the involvement of the endocrine system during and after the recovery of the disease.

Longitudinal and postmortem studies conducted on SARS-CoV patients provide some guidance on the extent of endocrine gland involvement. On postmortem examination, SARS-CoV RNA was found in the pituitary gland, parathyroid, pancreas and adrenal gland (39).

In another study, both parafollicular and follicular cells were found to be apoptotic explaining the low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients of SARS-CoV (40).

Evidence of hypocortisolism was found in 39% of sixty-one survivors of SARS prospectively recruited for hormonal derangements 3 months after recovery (41).

Nonetheless, information about the adverse effects on endocrine function by the SARS-CoV-2 virus remain limited [42], [43].

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Boosting health recovery by food supplements: the case of ME/CFS v Post-Covid-19 syndrome 

Posted on 12/16/2021 by wames

Boosting health recovery by food supplements: the case of ME/CFS versus Post-Covid-19 Syndrome, by Frank Comhaire and Jan Pen in J Clin Pharmacol Ther. 2021;2(3):JCPT-02-1022

 

Research abstract:  

Background and objectives:

Other than the direct impact of cardiopulmonary sequelae, COVID-19 disease may cause persistent signs and symptoms describes as post-COVID syndrome or long COVID. The clinical presentation and neuroimaging aspects of patients suffering from this condition are remarkably similar to those seen in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Inflammation, immune disorder and oxidative damage have been documented to cause metabolic deregulation with decreased glycolysis and impaired mitochondrial function.

Purpose of the study:

It is suggested that these alterations may be improved by the oral administration of a nutraceutical, Meldonium and sodium dichloroacetate (group designated as “oral treatment”; n=79) or intermittent intravenous infusions of magnesium sulphate together with multivitamins and essential amino acids (group designated as “infusion treatment”, n=18).

Materials and methods: 

97 patients suffering from ME/CFS (n=79) or post-COVID syndrome (n=9) were included in a pragmatic prospective open-label trial using either oral or infusion therapy for 1 month, and the effect of treatment was assessed by the Fatigue Severity Scale (FSS).

Results:

Upon interim analysis of 97 cases of ME/CFS and/or Post-COVID-19 syndrome therapeutic approach by either the oral or the infusion therapy was found to result in a reduction of the Fatigue Severity Scale (FSS) in two thirds of patients. The quotient of FSS after treatment divided by the FSS before treatment decreased by an average for all 97 cases by 14% within one month, with no difference between oral and infusion therapy (P=0.70), nor between the ME/CFS patient (mean quotient: 0.85, SD: 0.16) and the post-COVID cases (quotient: 0.87, SD: 0.16). Among the successful cases the FSS decreased by an average of 31%.

Conclusion: 

Preliminary results of the oral and the infusion therapy suggest a similar beneficial effect on fatigue in a substantial proportion of patients suffering from ME/CFS or Post-COVID syndrome. The result should be confirmed in a controlled trial, while the long-term efficacy is presently being investigated in a larger group of patients.

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Biomarker research: The maintained attention assessment in patients affected by ME/CFS

Posted on 12/09/2021 by wames

The maintained attention assessment in patients affected by Myalgic encephalomyelitis/ chronic fatigue syndrome: A reliable biomarker?, by Inigo Murga, Larraitz Aranburu, Pascual A Gargiulo, Juan-Carlos Gomez-Esteban, Jose-Vicente Lafuente in Journal of Translational Medicine Vol 19, #1, p 494, December 4, 2021

 

Research abstract

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Pieron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale.

The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p<0.05).

There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Conclusion

General cognition remains preserved in most patients, only a small group of them shows a significant mild cognitive impairment. Maintained attention is clearly deficient, showing a marked fatigability after the Toulouse-Piéron test. The effort was perceived as very hard by both gender, but higher by women.

This study proposes a simple clinical way to assess maintained attention. Present results support the reliability of maintained attention as biomarker of CFS/ME. Attention deficit is a significant disability in patients affected of central fatigue.

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Hidden from sight: why the complexity of ME/CFS needs to be recognised by policy makers

Posted on 12/09/2021 by wames

Hidden from Sight: Why the complexity of ME/CFS needs to be recognised by policy makers, by Tomruk Ustunkaya and Richard Machin, by People, Place and Policy Vol 15, #2, pp. 91-99, November 2021

 

Background:

An estimated 260,000 people in the UK are living with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS); this neurological condition has been described as

‘a serious, chronic, complex, and multisystem disease that frequently and dramatically limits the activities of affected patients’ (Institute of Medicine, 2015).

Despite this, there remains a lack of clarity about the diagnosis and treatment of ME/CFS. The authors of this paper refer to ME/CFS but recognise that other terms (for example systemic exertion intolerance disease, chronic fatigue immunity deficiency syndrome, and post-viral fatigue syndrome) are used to describe this neurological condition, and for some people these are preferred names. This paper adopts the definition of ME/CFS as a neurological condition of unknown origin as defined by the World Health Organisation and accepted by the UK Department of Health (WHO, n.d.).

The House of Commons debate which took place on 21 June 2018 will be taken as a significant starting point for the discussion on ME treatment and research; this is regarded as a key moment in the public debate and recognition of the condition stating that ME is ‘a hidden illness’ (Hansard HC Deb., 21 June 2018d).

Historically, there has been an emphasis on ME/CFS as being psychological in nature and this continues to exert a damaging influence on key areas of public policy. This paper considers the hidden nature of ME/CFS in relation to two particular issues: funding for research and social security policy.

  1. It is argued that medical research into the condition is impeded by a lack of adequate government funding. This is identified as critical in achieving a comprehensive health regime for sufferers.
  2. Social security is an important area of concern for ME/CFS suffers and a key policy area; correct entitlement to social security benefits is crucial for people with disabilities but appropriate access to welfare benefits is often obstructed by misunderstanding of the condition.

It is argued that in both of these areas, a greater understanding of the impact of ME/CFS is required to allow policy makers and practitioners to more appropriately meet the needs of people living with the condition.

Conclusion

Clarity is paramount to bring ME/CFS out from the ‘invisible’ sphere in terms of both the treatment and definitions of the illness, and the ways in which the condition is
understood by government departments, institutions, and society. This clarity will be
difficult to attain without adequate funding for research into the illness and may explain the ongoing preference for psychological treatments.

The emergence of post-COVID syndrome (long-COVID) has emphasised how important it is to appropriately fund research into long-term and debilitating conditions. Interestingly, the Department for Work and Pensions have issued new guidance stating that children suffering with post-COVID syndrome can be awarded disability benefit for a period of 12 months (DWP, 2021); this has provided the type of clarity that is lacking for ME/CFS patients. The authors of this paper recognise the challenges that a lack of funding presents for the treatment of the condition and are supportive of the medical profession and the on-going medical support provided to ME/CFS patients.

For those members of society with greatly reduced quality of lives due to the
challenges presented by ME/CFS, it is clear that public policy and bureaucratic decision-making processes must respond more appropriately to their needs. Positive government intervention is necessary to end the uncertainty for ME/CFS patients. The human cost of policy failure for people with ME/CFS is paramount; however, the financial costs are also significant. A study estimated that the total cost of ME/CFS to the UK economy is £3.3 billion per year, or only £16,966 per person living with the condition (Hunter et al., 2017).

These figures underscore the importance of providing adequate funding for treatment
and a functioning social security safety net. Until the WHO classification of ME/CFS as a neurological condition is fully recognised by policy makers, we will continue to see challenges for patients, not only in terms of funding for treatment and social security which have been examined in this paper, but across the full spectrum of public policy. ME/CFS patients experience ‘multiple pathophysiological changes that affect multiple systems’ (Centers for Disease Control, 2018). Policy makers must recognise the severity of the condition to make appropriate responses to it.

The hidden nature of this condition can be linked to an absence of a biomarker and
because uncertainty surrounds it medically and in society. However, this should not
mean that the needs of ME/CFS patients are overlooked or marginalised; the challenges presented by the condition are a reality for patients and their families. Patients are entitled to expect appropriate support from the Department of Health, Department for Work and Pensions, employers, and educational establishments.

The words of Alex Chalk, MP, (Hansard HC Deb., 21 June 2018c) offer hope for a future characterised by a determined, active effort to help

“I conclude by paying tribute to the silent sufferers of this cruel disease in our country. Let the word go out from the House of Commons: they shall be silent no longer”.

Read the full paper

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Subgroup research: Tryptophan metabolites, cytokines & FAPB-2 in ME/CFS

Posted on 12/08/2021 by wames

Tryptophan metabolites, cytokines, and fatty acid binding protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Manuela Simonato, Stefano Dall’Acqua, Caterina Zilli, Stefania Sut, Romano Tenconi, Nicoletta Gallo, Paolo Sfriso, Leonardo Sartori, Francesco Cavallin, Ugo Fiocco, Paola Cogo, Paolo Agostinis, Anna Aldovini, Daniela Bruttomesso, Renzo Marcolongo, Stefano Comai and Aldo Baritussio in Biomedicines 2021, 9(11), 1724 [doi.org/10.3390/biomedicines9111724]

 

Research abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease.

Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine.

ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively.

No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease.

Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism.

Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS.

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Raise funds for WAMES by shopping with an Amazon smile!

Posted on 12/01/2021 by wames

You shop. Amazon gives, with a smile.  Choose WAMES!

 

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