Work rehabilitation & medical retirement for ME/CFS patients

Posted on 09/25/2019 by wames

Work rehabilitation and medical retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. A review and appraisal of diagnostic strategies
by Mark Vink and Friso Vink-Niese in Diagnostics 2019, 9(4), 124;  [https://doi.org/10.3390/diagnostics9040124] Published: 20 September 2019

 

Review abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome leads to severe functional impairment and work disability in a considerable number of patients. The majority of patients who manage to continue or return to work, work part-time instead of full time in a physically less demanding job. The prognosis in terms of returning to work is poor if patients have been on long-term sick leave for more than two to three years. Being older and more ill when falling ill are associated with a worse employment outcome.

Cognitive behavioural therapy and graded exercise therapy do not restore the ability to work. Consequently, many patients will eventually be medically retired depending on the requirements of the retirement policy, the progress that has been made since they have fallen ill in combination with the severity of their impairments compared to the sort of work they do or are offered to do.

However, there is one thing that occupational health physicians and other doctors can do to try and prevent chronic and severe incapacity in the absence of effective treatments. Patients who are given a period of enforced rest from the onset, have the best prognosis. Moreover, those who work or go back to work should not be forced to do more than they can to try and prevent relapses, long-term sick leave and medical retirement.

Posted in News | Tagged , , , | Comments Off on Work rehabilitation & medical retirement for ME/CFS patients

Quantitative electroencephalographic assessment of ME/CFS

Posted on 09/23/2019 by wames

Quantitative Electroencephalographic assessment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: support for a novel diagnostic protocol, by Andrew E Pellegrini. Laurentian University: a thesis submitted in partial fulfillment for the
Honors degree Bachelor of Science 2019

 

Research abstract:

The historical infectious disease Myalgic encephalomyelitis (ME) also erroneously known as chronic fatigue Syndrome (CFS) termed “ME/CFS” represents a complex area of difficulty for the modern medical profession where it is commonly held that no empirical diagnostic tests exist to solve its mystery. Confusion surrounding ME/CFS has frequently led to unfounded psychiatric interpretations and application of associated treatments including graded exercise therapy (GET)which is harmful to patients (Twisk & Maes, 2009).

The Nightingale Research Foundation (NRF) led by Dr. Byron Hyde have developed an empirically testable and non-falsifiable ME/CFS criteria defined by a) SPECT (Single Positron Emission Computed Tomography) demonstrating diffuse vascular hypoperfusion over key areas of cerebral cortex and b) persisting enteroviral presence in the gut measured with immunoperoxidase staining (Hyde, 2017, Chia et al, 2009). NRF’s data strongly support that both poliomyelitis and ME/CFS represent enteroviral central nervous system pathologies secondary to insufficient blood supply caused by vascular cuffing.

The present study was conducted to independently assess NRF SPECT findings using qEEG (Quantitative Electroencephalography) coupled with sLORETA (Standardized Low-Resolution Electromagnetic Tomography) software.

Forty-five adult volunteers (aged 18 or over) with a medical diagnosis of ME/CFS were recruited. An aggregate brain representing 675 minutes of eyes-closed data was assembled from the group and compared to the sLORETA BRL normative database in the frequency range between 1.5-35Hz.

Results show 13 source localizations significant (z= 3.085, p= 0.001) overlap with key NRF SPECT findings. NRF SPECT findings can be independently confirmed with qEEG coupled with sLORETA and neuroanatomically support signs and symptoms of the disease first documented in 1934.

SPECT and qEEG should be immediately taken up by the scientific and medical professions as definitive standards for measuring ME/CFS.

Posted in News | Tagged , , , | Comments Off on Quantitative electroencephalographic assessment of ME/CFS

Towards a biomarker: Rethinking ME/CFS diagnostic reference intervals via machine learning, & the utility of activin B for defining symptom severity

Posted on 09/19/2019 by wames

Rethinking ME/CFS diagnostic reference intervals via machine learning, and the utility of activin B for defining symptom severity, by Brett A. Lidbury, Badia Kita, Alice M Richardson, Donald P Lewis, Edwina Privitera, Susan Hayward, David de Kretser and Mark Hedger in Diagnostics 2019, 9(3), 79; https://doi.org/10.3390/diagnostics9030079

 

Research abstract:

Test tubes in a beaker.

Biomarker discovery applied to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling disease of inconclusive aetiology, has identified several cytokines to potentially fulfil a role as a quantitative blood/serum marker for laboratory diagnosis, with activin B a recent addition.

We explored further the potential of serum activin B as a ME/CFS biomarker, alone and in combination with a range of routine test results obtained from pathology laboratories.

Previous pilot study results showed that activin B was significantly elevated for the ME/CFS participants compared to healthy (control) participants. All the participants were recruited via CFS Discovery and assessed via the Canadian/International Consensus Criteria.

A significant difference for serum activin B was also detected for ME/CFS and control cohorts recruited for this study, but median levels were significantly lower for the ME/CFS cohort. Random Forest (RF) modelling identified five routine pathology blood test markers that collectively predicted ME/CFS at ≥62% when compared via weighted standing time (WST) severity classes.

A closer analysis revealed that the inclusion of activin B to the panel of pathology markers improved the prediction of mild to moderate ME/CFS cases. Applying correct WST class prediction from RFA modelling, new reference intervals were calculated for activin B and associated pathology markers, where 24-h urinary creatinine clearance, serum urea and serum activin B showed the best potential as diagnostic markers.

While the serum activin B results remained statistically significant for the new participant cohorts, activin B was found to also have utility in enhancing the prediction of symptom severity, as represented by WST class.

Australian researchers explored a potentially effective method of identifying ME/CFS by using a combination of cytokines. By grouping activin B with 24-hour urinary creatinine clearance and serum urea together for analysis, the results show good potential for use in diagnosing ME/CFS. Activin B is a complex protein found to have biological effects in numerous bodily functions.

A previous pilot study showed a significant increase of activin B in ME/CFS patients as compared to healthy controls. The researchers found that including activin B in the panel of pathology markers improved prediction rates for mild and moderate cases of ME/CFS. Additionally, activin B was also found to help with the prediction of symptom severity as represented by weighted standing time tests.

**This paper is from the Emerge Australia sponsored issue of Diagnostics

Posted in News | Tagged , , , , , , , , , , , , | Comments Off on Towards a biomarker: Rethinking ME/CFS diagnostic reference intervals via machine learning, & the utility of activin B for defining symptom severity

ME/CFS: From pathophysiological insights to novel therapeutic opportunities

Posted on 09/18/2019 by wames

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: from pathophysiological insights to novel therapeutic opportunities, by Gerwyn Morris, Basant K Puri, Adam J Walker, Michael Maes, Andre F Carvalho, Ken Walder, Catherine Mazza, Michael Berk in Pharmacological Research [Available online 8 September 2019] https://doi.org/10.1016/j.phrs.2019.104450

 

Review abstract:

Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies reflecting a major unmet need.

Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise.

The presence of a multiplicity of pathophysiological abnormalities, in at least the subgroup of people with ME/CFS diagnosed with the current international consensus “Fukuda” criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics.

In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.

Read full paper

Posted in News | Tagged , , , , , , , , , , , , , | Comments Off on ME/CFS: From pathophysiological insights to novel therapeutic opportunities

Unexplained exertional intolerance associated with impaired systemic oxygen extraction

Posted on 09/17/2019 by wames

The researchers reviewed invasive cardiopulmonary test results of 313 patients with unexplained exertional intolerance. The paper focuses mainly on a small subset of patients: “We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve” They indicate that these patients had a diagnosis of ME/CFS.

Unexplained exertional intolerance associated with impaired systemic oxygen extraction by Kathryn H Melamed, Mário Santos, Rudolf K F Oliveira, Mariana Faria Urbina, Donna Felsenstein, Alexander R Opotowsky, Aaron B Waxman, David M Systrom in Eur J Appl Physiol  Sep 6 pp 1-15 (2019)  https://doi.org/10.1007/s00421-019-04222-6 [Epub ahead of print]

 

Review abstract:

PURPOSE: The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).

METHODS: We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO2)/[Hb] ≤ 0.8 and VO2max < 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO2)/[Hb] > 0.8, VO2max ≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO2 < [1.5 × HCO3 + 6].

RESULTS: Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs.

7.38 ± 0.05 vs. 7.32 ± 0.02, p < 0.001), which was explained by relative hypocapnia (PaCO2 = 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4, p < 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO2 nadir (28 ± 2 mmHg vs. 26 ± 4, p = 0.627) but increased SvO2 at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0, p < 0.001).

CONCLUSIONS: We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.

Read full paper 

Funded by Solve ME/CFS Foundation

Posted in News | Tagged , , , , , , , , , , , | Comments Off on Unexplained exertional intolerance associated with impaired systemic oxygen extraction

Faecal Microbiome Transplantation (FMT) a promising treatment for CFS with IBS

Posted on 09/13/2019 by wames

A retrospective outcome study of 42 patients with Chronic Fatigue Syndrome, 30 of whom had Irritable Bowel Syndrome. Half were treated with oral approaches, and half were treated with faecal microbiome transplantation, by JN Kenyon, Shelly Coe, Hooshang Izadi in Human Microbiome Journal vol 13 August 2019 [https://doi.org/10.1016/j.humic.2019.100061]

 

Research abstract:

The gut microbiome comprises the community of microorganisms in the intestinal tract. Research suggests that an altered microbiome may play a role in a wide range of disorders including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods:
42 participants with ME/ CFS with Irritable Bowel Syndrome (IBS) were allocated into one of two groups, 21 were treated with standard oral approaches, which centred around various nutritional remedies, probiotics, prebiotics, dietary advice and lifestyle advice. The second group who had mostly failed using oral approaches, were treated with Faecal Microbiome Transplantation (FMT). Each patient received 10 Implants, each from a different screened donor, and the Implants were processed under anaerobic conditions. The transplant is delivered via a paediatric rectal catheter, which is inserted through the anus to reach the lower part of the sigmoid colon.

The results were assessed on a percentage basis before and after treatment, 0% being no improvement, 100% being maximum improvement. An exact non-parametric Mann-Whitney (one-tailed) test was used to compare medians from those on FMT compared with those receiving oral approaches only. On clinical experience over many years, the only way to judge improvement in Chronic Fatigue Syndrome as there is no test for Chronic Fatigue Syndrome, is my clinical assessment.

Results:
The median for the FMT group was found to be significantly higher compared to the oral treatment group (Mann-Whitney U=111.5, p=.003). Therefore, the FMT group improved to a greater extent (z=-2.761).

Conclusion:
This study shows that FMT is a safe and a promising treatment for CFS associated with IBS. Adequately powered randomised controlled trials should be carried out to assess the effectiveness of FMT in patients with CFS and IBS.

The First ME/CFS Fecal Transplant Study Suggests the Treatment Holds Promise

Posted in News | Tagged , , , , , , , | Comments Off on Faecal Microbiome Transplantation (FMT) a promising treatment for CFS with IBS

Inflammatory proteins are altered in CFS

Posted on 09/11/2019 by wames

Inflammatory proteins are altered in chronic fatigue syndrome – a systematic review and meta-analysis, by Rebecca Strawbridge, Maria-Laura Sartor, Fraser Scott, Anthony J Cleare in Neuroscience & Biobehavioral Reviews, August 26, 2019 [https://doi.org/10.1016/j.neubiorev.2019.08.011]

 

Highlights:

  • 42 studies meta-analysed, testing 20 proteins between patients with CFS and controls
  • Patients had higher levels of 5 cytokines than controls (TNF, IL-2, IL-4, TGFb, CRP)
  • Group differences were not significant for 12 proteins
  • Results are heterogeneous but provide some support for an inflammatory role in CFS

Review abstract:

Immune dysfunction has been posited as a key element in the aetiology of chronic fatigue syndrome (CFS) since the illness was first conceived.  However, systematic reviews have yet to quantitatively synthesise inflammatory biomarkers across the literature.

We undertook a systematic review and meta-analysis to quantify available data on circulating inflammatory proteins, examining studies recruiting patients with a CFS diagnosis and a non-affected control group.

Results were meta-analysed from 42 studies. Patients with CFS had significantly elevated tumour necrosis factor (ES = 0.274, p < 0.001), interleukin-2 (ES = 0.203, p = 0.006), interleukin-4 (ES = 0.373, p = 0.004), transforming growth factor-β (ES = 0.967, p < 0.001) and c-reactive protein (ES = 0.622, p = 0.019). 12 proteins did not differ between groups.

These data provide some support for an inflammatory component in CFS, although inconsistency of results indicates that inflammation is unlikely to be a primary feature in all those suffering from this disorder. It is hoped that further work will elucidate whether there are subgroups of patients with clinically-relevant inflammatory dysfunction, and whether inflammatory cytokines may provide a prognostic biomarker or moderate treatment effects.

Read full paper

Posted in News | Tagged , , , , , , | Comments Off on Inflammatory proteins are altered in CFS

Management of chronic fatigue syndrome/myalgic encephalomyelitis in a pediatric population: A scoping review

Posted on 09/09/2019 by wames

Management of chronic fatigue syndrome/myalgic encephalomyelitis in a pediatric population: a scoping review, by Sarah S Collard, Jane Murphy in Journal of Child Health Care, 4 Aug 2019 [https://doi.org/10.1177/1367493519864747]

Review abstract:

Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) negatively impacts the quality of life for children with the condition. Although up to 2% of children have CFS/ME, the bulk of research investigates adults with CFS/ME. Using the PRISMA extension for a scoping review and the work of Arksey and O’Malley (2005), a scoping review was conducted of all relevant peer-reviewed research investigating nutrition, exercise, and psychosocial factors within a pediatric population diagnosed with CFS/ME.

Key themes found were nutrition and dietary components, exercise therapy, psychosocial factors, and multifaceted treatment. Nutrition was explored on its own as a tool to decrease symptoms; however, there were very few studies found to examine nutritional deficiency or treatment with those under the age of 18.

Graded exercise and resistance training improved fatigue severity and symptoms of depression in adolescents with CFS/ME. Research exploring psychosocial factors of CFS/ME presented attributes that could lead to being diagnosed as well as barriers to treatment. The multifaceted treatment undertaken typically consists of graded activities/exercise, cognitive behavioral therapy, nutritional advice, and family sessions. This has shown to increase school attendance and decrease the severity of the fatigue for adolescents.

Minimal literature exploring CFS/ME within a prepubescent population presents the need for further research.

 

Posted in News | Tagged , , , , , | Comments Off on Management of chronic fatigue syndrome/myalgic encephalomyelitis in a pediatric population: A scoping review

Brain responses in CFS & TMD to autonomic challenges

Posted on 09/06/2019 by wames

Brain responses in CFS and TMD to autonomic challenges: an exploratory fMRI study, by QC Vuong, JR Allison, A Finkelmeyer, J Newton, J Durham in JDR Clinical & Translational Research, August 28, 2019

 

Research abstract:

Introduction:
Dysfunction of the autonomic nervous system (ANS) is seen in chronic fatigue syndrome (CFS) and temporomandibular disorders (TMDs). Both conditions have poorly understood pathophysiology. Several brain structures that play a role in pain and fatigue, such as the insular cortex and basal ganglia, are also implicated in autonomic function.

Objectives:
ANS dysfunction may point to common neurophysiologic mechanisms underlying the predominant symptoms for CFS and TMD. No studies to date have investigated the combination of both conditions. Thus, our aim was to test whether patients with CFS with or without TMD show differences in brain responses to autonomic challenges.

Methods:
In this exploratory functional imaging study, patients with CFS who screened positive for TMD (n = 26), patients who screened negative for TMD (n = 16), and age-matched control participants (n = 10) performed the Valsalva maneuver while in a 3-T magnetic resonance imaging scanner. This maneuver is known to activate the ANS.

Results:
For all 3 groups, whole-brain F test showed increased brain activation during the maneuver in the superior and inferior frontal gyri, the left and right putamen and thalamus, and the insular cortex. Furthermore, group contrasts with small-volume correction showed that patients with CFS who screened positive for TMD showed greater activity in the left insular cortex as compared with patients who screened negative and in the left caudate nucleus as compared with controls.

Conclusion:
Our results suggest that increased activity in the cortical and subcortical regions observed during autonomic challenges may be modulated by fatigue and pain. ANS dysfunction may be a contributing factor to these findings, and further work is required to tease apart the complex relationship among CFS, TMD, and autonomic functions.

Knowledge Transfer Statement:
Brain activity related to activation of the autonomic nervous system in patients with chronic fatigue syndrome who screened positive for painful temporomandibular disorder was greater than in patients who screened negative; activity was seen in brain regions associated with autonomic functions and pain. These findings suggest that autonomic dysfunction may play a role in the pathophysiology of both conditions, explain some of the apparent comorbidity between them, and offer avenues to help with treatment.

Read full paper

Posted in News | Tagged , , , , , , , , , , , | Comments Off on Brain responses in CFS & TMD to autonomic challenges

A systematic review of cytokines in CFS/ME/SEID

Posted on 08/30/2019 by wames

A systematic review of cytokines in chronic fatigue syndrome /myalgic encephalomyelitis/ systemic exertion intolerance disease (CFS/ME/SEID) by Matthew Corbitt, Natalie Eaton-Fitch, Donald Staines, Hélène Cabanas & Sonya Marshall-Gradisnik in BMC Neurology volume 19, Article number: 207 (2019) [Published: 24 August 2019]

 

Research abstract:

Background: Cytokines in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/ Systemic Exertion Intolerance Disease (CFS/ME/SEID) patients compared with healthy controls have been extensively studied. However, the evidence regarding whether a baseline difference between CFS/ME/SEID patients and the normal population remains unclear.

The aim of this study was to conduct a systematic review of the literature regarding cytokines in CFS/ME/SEID and whether there is a significant difference in cytokine levels between this patient group and the normal population.

Methods: Pubmed, Scopus, Medline (EBSCOHost), and EMBASE databases were searched to source relevant studies for CFS/ME/SEID. The review included any studies examining cytokines in CFS/ME/SEID patients compared with healthy controls. Results of the literature search were summarised according to aspects of their study design and outcome measures, namely, cytokines. Quality assessment was also completed to summarise the level of evidence available.

Results: A total of 16,702 publications were returned using our search terms. After screening of papers according to our inclusion and exclusion criteria, 15 studies were included in the review. All the included studies were observational case control studies. Ten of the studies identified measured serum cytokines in CFS/ME/SEID patients, and four measured cytokines in other physiological fluids of CFS/ME/SEID patients. The overall quality assessment revealed most papers included in this systematic review to be consistent.

Conclusions: Despite the availability of moderate quality studies, the findings of this review are inconclusive as to whether cytokines play any definitive role in CFS/ME/SEID, and consequently, they would not serve as reliable biomarkers. Therefore, in light of these results, it is recommended that further efforts toward a diagnostic test and treatment for CFS/ME/SEID continue to be developed in a range of research fields.

Posted in News | Tagged , , , , , | Comments Off on A systematic review of cytokines in CFS/ME/SEID