Tag: IACFS/ME 2016 conference

A panel of biomarkers accurately identifies CFS/ME patients and contributes to the understanding of the pathophysiology of the disorder

Abstract: 

Background: CFS/ME is a debilitating illness for which no specific biomarkers have been identified, although several immune abnormalities including neuroinflammation have been described. The goal of this study was to assemble a panel of immune and inflammatory markers, with the ability to accurately identify CFS/ME cases.

Objectives: From observations made in clinical practice, four markers were selected (immune and inflammatory). These markers were initially investigated to establish differences between CFS/ME cases and controls. We then evaluated their potential usefulness as a diagnostic biomarker by establishing their specificity and sensitivity.

Methods: Venous blood was collected from 70 male and 70 female CFS/ME patients (mean age 43 and 44 years, respectively – Fukuda case definition was used) as well as 70 male and 70 female healthy controls (mean age 43.5 and 44.5 years, respectively).

Serum Interleukin 8 (IL-8), soluble CD14 (sCD14, a surrogate marker for bacterial LPS), and prostaglandin E2 (PGE2) were measured for all subjects as were absolute CD3- / CD57+ lymphocytes counts (CD57+ lymph), according to accepted clinical laboratory techniques.

We then established median values for all analysed parameters; independent sample t-test, Mann-Whitney test and ROC curve analysis were used to investigate difference linked to gender and age.

Results: ROC Statistics (area under the ROC curve) revealed a significant difference between CFS/ME cases and controls (p <0.001) for the four parameters separately, both in the male and female cohorts. Sensitivity was 74.3 – 80 % (females) and 52.1 – 85.9 % (males). Specificity was 57.1 – 98.1 (females) and 65.7 – 88.6 (males).

Logistic regression analysis for the combination of parameters in our panel (IL-8, sCD14, PGE2 and CD57+ lymph) correctly predicted in 89.36 % of male CFS/ME cases and in 97.14 % of female CFS/ME cases.

Conclusions: This panel differentiates CFS/ME cases from controls with high sensitivity and specificity and therefore represents a potential tool in selecting CFS/ME subjects for clinical studies. Each of these four biological markers relate strongly to the disorder.

PGE2 activates dendritic cells and suppresses their ability to attract T cells. It also suppresses the function of macrophages and neutrophils as well as Th1, CTL-, NK-cell mediated type 1 immunity (e.g. CD3- / CD57+ lymphocytes). PGE2 additionally promotes Th2, Th17 and Tregs and also modulates chemokine production (e.g. IL-8).

When taken together, these data suggest that lipopolysaccharide (LPS), likely from gut bacteria, plays an important role in the pathophysiology of CFS/ME.

This screening panel represents an initial step toward identifying biomarkers to broadly diagnose subjects with CFS/ME.

Subsequent markers will be required to subcategorize CFS/ME subjects in order to tailor therapeutic solutions.

 

Source: Kenny L. De Meirleir1,2, Tatjana Mijatovic3, Eugene Bosmans3, Nossa Van den Vonder2, Vincent Lombardi1. A panel of biomarkers accurately identifies CFS/ME patients and contributes to the understanding of the pathophysiology of the disorder. Abstract from IACFS/ME Conference 2016 Program.

1. Nevada Center for Biomedical Research at University
of Nevada, Reno, USA
2. Himmunitas vzw, Brussels, Belgium
3. RED Laboratories NV, Zellik, Belgium

 

ME/CFS: Discrimination Within Social Institutions

Abstract:

OBJECTIVES: To examine the nature and impact of discrimination experienced by persons with ME/CFS when engaged in interactions with social institutions.

METHOD: The initial phase of the research involved a thorough review of the available literature to establish the interaction of those with ME/CFS with social institutions. Social institutions are the complex social forms that are found within governments, family, universities, hospitals, incorporated entities, legal systems and other social structures and organisations. This paper focuses on the incidence, nature and effect of discriminatory behaviour that participants experience during interactions with social institutions..

In the data collection phase, a pilot study involving an investigation of the Australian perspective of the experience of ME/CFS was obtained. This was expanded in the main study and participants were provided the opportunity to reveal their stories. Participants were required to have a diagnosis of CFS, ME or ME/CFS from a medical practitioner and self-select themselves as compliant to the Fukuda CFS Criteria, Canadian ME/CFS Criteria and Ramsay ME Criteria.

A background questionnaire was provided to give an insight into the history of the participant, particularly interactions with social institutions and pathways to diagnosis. The interview drew upon the questionnaire for guidance, with the primary questions derived from information gained from the literature review. The interviews were transcribed, coded and the relationships and issues identified in order to guide the second phase of the research which was conducted further into the study.

The pilot study involved 3 participants, followed by a second, more comprehensive phase comprising 16 participants. Stories emerged from within those interviews with respect to interactions with society and these were broken down to reveal particular themes relevant to those experiences.

RESULTS: A total of 19 interviews were conducted. The average age of participants was 41.95 with all 14 females and 5 male participants. The mean duration of the condition was 17.66 years, with 8.35 years from onset until diagnosis. A number of issues arose, revealing an insight into the nature of the relationships that exist between persons with ME/CFS and various social institutions. Participants reported interactions that were both positive and negative. Such interactions were directly impacted by the diagnosis of ME/CFS. All participants had experienced some form of discrimination, with the majority being negative discrimination. Within these experiences, issues such as knowledge and understanding of the condition played a significant role in the discriminatory interaction. Misconceptions about the condition played a primary role. Abuse (verbal, physical and mental), withholding or withdrawal of goods and services, individual avoidance, social isolation, adverse employment decision, prescription of no or inappropriate treatment and the like were levelled against participants throughout their and/or a lack of knowledge or desire to go about it.

CONCLUSION: Participants with ME/CFS who engaged with social institutions were subject to various factors (such as abuse, attitudes, behaviours, comments, misinformation, misunderstandings, beliefs and policies) that directly or indirectly arise because of their diagnosis and the contested nature of the condition.

These factors play an important role in the form of discrimination that participants experienced across all social institutions. Positive discrimination was provided in the form of assistance, management, attitudes, comments and accommodations. Participants revealed circumstances in which discrimination was negative, including the refusal of assistance or accommodation, derogatory comments, malicious treatment and behaviours, inappropriate physical environments (due to noise, smells, access, furniture, line ups, public transport, etc.), inappropriate policies or procedures (eg onerous requirements, poor time frames, inability to be accessed remotely) or misinformed statements, treatment that was adverse (ie insufficient, inappropriate, adverse, deficient or damaging, and resulted consequences that were harmful to the physical, emotional or other interests of the participant). Of significance was the incidence of bullying behaviour that was associated with discrimination.

Those with more visible symptoms and presentation of ME/CFS (ie wheelchair and bed bound) received greater assistance at times, while those with more invisible symptoms and presentation found access to assistance a more difficult and at times impossible task.

Negative experiences had an adverse impact upon the person’s condition as well as their emotional wellbeing On occasions the impact and effect was sufficient to constitute trauma. The ability to respond to discriminatory practices was limited by knowledge of process and procedure, the health constrictions that impact the ability to take action, the availability of advocates to assist in such action, and the knowledge of the condition of those taking the action or making decisions. On no occasion was a participant able to follow through on a formal anti-discrimination complaint.

 

Source: Geoffrey Hallmann, Dr Rosanne Coutts, Dr Yvonne Hartmann Southern Cross University. ME/CFS: Discrimination Within Social Institutions. [Abstract from the IACFS/ME 2016 Conference]

 

Are symptoms of ‘hypoglycemia’ in Chronic Fatigue Syndrome (CFS) associated with hypoglycemia or orthostatic intolerance in young people?

Background: Symptoms of nausea, feeling faint, malaise and mild anxiety are common in young people with CFS and popularly attributed to ‘hypoglycemia’ resulting in various dietary interventions with little reported improvement.

Objectives: To determine whether the symptoms are associated with measured hypoglycaemia using continuous tissue glucose monitoring or whether these symptoms are associated with documented orthostatic intolerance.

Methods: Nine young people with CFS (mean age 20 years) and mean duration of 4.5 years with persistently troublesome symptoms were compared with 10 healthy adult controls without diabetes. Each subject agreed to 3 days Continuous Glucose Monitoring System (Medtronic CGMS). This is routinely used in adolescent diabetics to document food intake, tissue glucose levels and activity levels to monitor control.

Subsequently 8 of these had formal cardiac tilt table testing where heart rate and blood pressure are measured supine and during 70 degree head-up tilt for up to 10 minutes to assess the presence orthostatic intolerance (either postural orthostatic tachycardia (POTS) or neurocardiogenic hypotensive syndrome). If positive, appropriate medical management of increasing salt and fluids, gentle improvement of muscle tone and blood pressure support medications, was implemented.

Results: The tissue glucose was calibrated with the blood glucose and all fell within acceptable normal range. There was statistical (but not clinical) significance in average tissue glucose in CFS subjects. 6% of time in controls and 16.8% in CFS was spent in the range <4mmol/L glucose (95% CI -23% to +2%, p=0.1) suggesting weak evidence for a difference given the variability and small sample size. The reported presence of symptoms throughout the day was not associated with significant reduction in tissue glucose levels.

Six had confirmed evidence for POTS, one for neurocardiogenic syndrome and one for a combination of both. All 8 reported improvement in all symptoms especially nausea, dizziness and malaise with active treatment of their orthostatic intolerance.

Conclusion: This study could not confirm a link between putative symptoms of ‘hypoglycemia’ and documented hypoglycemia. This suggests that symptoms frequently attributed to ‘hypoglycemia’ may be due to orthostatic intolerance and further investigation and management of this condition provides more reported relief for these troublesome symptoms.

Dr Kathy Rowe, Senior Consultant Paediatrician, Department of General Medicine, Royal Children’s Hospital, Melbourne, Victoria, Australia 3052
kathy.rowe@rch.org.au  No conflicts of interest to declare. RCH internally funded.

 

Source: Katherine Rowe, Rebecca Gebert, Susan Donath, Angas Hamer & Fergus Cameron. Are symptoms of ‘hypoglycemia’ in Chronic Fatigue Syndrome (CFS) associated with hypoglycemia or orthostatic intolerance in young people? From: The IACFS/ME 2016 Conference Syllabus.

 

Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms

Background: Comparatively little has been published on the clinical features and management of severe forms of ME/CFS.

Objectives: To describe the presenting symptoms and neurological examination findings in three young adult women whose disabling ME/CFS symptoms and orthostatic intolerance improved after the recognition and surgical management of cervical spine stenosis (CSS).

Methods: This retrospective case series includes three consecutive individuals who (1) met the Fukuda and criteria for CFS, (2) had evidence of refractory orthostatic intolerance, (3) were unable to work or attend school, and (4) were minimally responsive to medical and psychiatric management. To investigate pathological reflex findings, all underwent MRI evaluations. CSS was considered present if the AP cervical spinal canal diameter (SCD) was less than 10 mm at any level. Overall function was assessed before and after cervical disc replacement surgery using (1) a clinician-assigned Karnofsky score (range 0 to 100) and (2) the SF-36 physical function (PF) subscale score (range 10-30). Higher scores indicate better function on both measures.

Results: Age at onset of symptoms was 12, 29, and 29 years. The onset of ME/CFS was acute in all three. Neurological exam findings included > 3+ (brisk) deep tendon reflexes (DTR) in 2/3, positive Hoffman sign in 2/3, tremor in 2/3, and absent gag reflex in 1/3. Diagnosis was delayed for 6-9 years after the onset of symptoms. Brain MRIs were normal. The youngest patient had congenital CSS with a single level disc protrusion at C5-6 that caused further ventral cord compression and a SCD of 7 mm. Her mother also has cervical stenosis. A second
patient had two disc protrusions at C5-6 and C6-7 with SCD of 7 and 9 mm, and myelomalacia (this patient has a sibling with Chiari I malformation). The third had acquired CSS due to a single level disc bulge at C5-6 (SCD = 8.5 mm).

Improvements were evident within 2 months of single-level cervical disc replacement surgery (one patient also had fusion at an adjacent level). After 16-40 months of follow-up, all reported improved fatigue, cognitive dysfunction, PEM, lightheadedness, and anxiety. The pre- to post-op SF-36 PF scores improved from 13 to 30, 18 to 30, and 16 to 26, respectively, and the Karnofsky scores improved from 40 to 90, 40 to 90, and 50 to 100, respectively. Standing tests conducted at variable intervals from pre- to post-op showed a reduction in the maximal heart rate (HR) change during 5 minutes of standing from 64 to 22 bpm, 42 to 29 bpm, and 34 to 27 bpm, respectively.

Conclusion: This case series draws attention to the potential for CSS to contribute to ME/CFS and orthostatic symptoms, extending work by Heffez in fibromyalgia (Eur Spine J 2004;13:516). Further work is needed to define indications for surgery. However, the improvements in HR and function following surgery emphasize the importance of detecting and treating CSS, especially in the subset of those with ME/CFS whose severe symptoms are refractory to other interventions.

Peter C. Rowe, M.D.
Professor of Pediatrics
Johns Hopkins University School of Medicine/200 N. Wolfe Street/Room 2077
Baltimore, MD 21287
prowe@jhmi.edu

Dr. Rowe is supported by the Sunshine Natural Wellbeing Foundation Professorship in Chronic Fatigue and Related Disorders. No author has a conflict of interest.

 

Source: Peter C. Rowe, M.D*, Colleen L. Marden, Scott Heinlein, PT, Charles Edwards II, M.D. Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms. Poster presentation, IACFS/ME 2016 conference.

 

Assessment of Cellular Bioenergetics in Chronic Fatigue Syndrome

Introduction: Abnormalities in bioenergetic function have been cited as one possible cause for chronic fatigue syndrome (CFS). One hypothesis to explain this suggests that CFS may be caused, at least in part, by an acquired mitochondrial dysfunction.

Extracellular flux analysers make real-time, in vitro assessment of cellular energy pathways possible. Using this technology, mitochondrial function can be measured in a variety of cell types in real-time thus increasing our understanding of the role of metabolism in CFS.

Objectives: This project aims to utilise extracellular flux detection technology in order to investigate the cellular bioenergetics of different cell types obtained from CFS patients and healthy controls.

Methods: Mitochondrial stress tests were conducted using skeletal muscle cells and peripheral blood mononuclear cells (PBMCs) derived from CFS patients and controls. During this test mitochondrial complexes are inhibited in turn to modulate respiration so mitochondrial function can be evaluated. The oxygen consumption rate of cells is measured which allows keys parameters of mitochondrial function to be measured and calculated in a single experiment, providing an overall assessment of mitochondrial function. Parameters measured are: basal respiration, maximal respiration and non-mitochondrial respiration. Proton leak, ATP-production and spare respiratory capacity are subsequently able to be calculated using the three measured parameters. CFS patients whose samples were used in these studies were diagnosed using the Fukuda definition.

Results: Results using skeletal muscle cells obtained from CFS patients (n=3) and controls (n=5), indicate that there is no difference in the energy profiles of the skeletal muscle cells of CFS patients in any of the parameters investigated.

Mitochondrial stress test results using PBMCs show CFS PBMCs (n=7) to be significantly lower than control cells (n=10) in all parameters investigated (p≤0.016). Importantly, these results suggest that CFS PBMCs perform closer to their maximum under normal conditions. This means that when CFS PBMCs come under stress they are less able to increase their respiration rate to compensate for the increase in stress.

Conclusions: These findings provide an interesting starting point for investigations into cellular bioenergetics in CFS.

Cara Jasmine Tomas; First year medical science PhD student; Institute of Cellular Medicine, Level 1, William Leech Building, Medical School, Newcastle University, Newcastle Upon-Tyne, NE2 4HH, England; c.j.tomas@ncl.ac.uk
This work was funded by the Medical Research Council and Newcastle University.

 

Source: Cara Tomas, Julia Newton, Audrey Brown, Gina Rutherford, Philip Manning
Newcastle University, UK. Assessment of Cellular Bioenergetics in Chronic Fatigue Syndrome. Poster presentation, IACFS/ME 2016 conference.