Differentiating post-polio syndrome from myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Background: Overlapping and concomitant symptoms among similar chronic illnesses have created difficulties for diagnosis and further treatment. Three such chronically fatiguing illnesses, Post-polio syndrome (PPS), Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS) fall under this category.

Purpose: The aim of this study is to examine and distinguish between core symptoms found in these illnesses (i.e. muscle pain/weakness, fatigue or exhaustion, and autonomic symptoms) via three methods of analysis (DePaul Symptom Questionnaire 2 (DSQ-2), Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and machine learning techniques).

Results: Items assessing onset and severity for individuals who reported having PPS were found to have experienced an onset of PPS related symptoms roughly 30 years after the onset of Polio. Items found in the DSQ-2, SF-36 compared all illness groups and found that participants with ME/CFS were more functionally impaired across symptoms than those with PPS. Across all analyses, three domains most commonly differentiated the illnesses (neurocognitive, Post-exertional malaise, and neuroendocrine).

Conclusion: Examining functional impairment amongst chronically fatiguing illnesses using multiple methods of analysis can be an important factor in distinguishing similar illnesses. These findings support further analysis of analogous symptomatology among other chronic illnesses to assist in diagnosis.

Source: Lauren Klebek, Madison Sunnquist & Leonard A. Jason (2019) Differentiating post-polio syndrome from myalgic encephalomyelitis and chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2019.1687117 https://www.tandfonline.com/doi/abs/10.1080/21641846.2019.1687117

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections

Abstract:

Autoimmunity and chronic viral infections are recurrent clinical observations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease with an unknown cause. Given these observations, the regulatory CD4+ T cells (Tregs) show promise to be good candidates for the underlying pathology due to their known capacity to suppress the immune responses not only to body components but also against infections. Here we discussed the overlooked role of these cells in the chronicity of Human Herpes Virus 6 (HHV6), Herpes Simplex 1 (HSV1) and Epstein-Barr virus (EBV), as often reported as triggers of ME/CFS.

Using simulations of the Cross-regulation model for the dynamics of Tregs, we illustrated that mild infections might lead to a chronically activated immune responses under control of Tregs if the responding clone has a high autoimmune potential. Such infections promote persistent inflammation and possibly fatigue. We then hypothesized that ME/CFS is a condition characterized by a predominance of this type of infections under control of Tregs. In contrast, healthy individuals are hypothesized to trigger immune responses of a virus-specific clone with a low autoimmune potential.

According to this hypothesis, simple model simulations of the CD4+ T-cell repertoire could reproduce the increased density and percentages of Tregs observed in patients suffering from the disease when compared to healthy controls. A deeper analysis of Tregs in the pathogenesis of ME/CFS will help to assess the validity of this hypothesis.

Source: Nuno Sepúlveda, Jorge Carneiro, Eliana M. Lacerda and Luis C. Nacul. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections. Front. Immunol. | doi: 10.3389/fimmu.2019.02684. https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract

Why We Care

BREAKING: A generous donor has offered a matching grant of a thousand dollars. In the donor’s words, “I want to convey how our patient community provides family for one another when our families may not be so supportive. A small inheritance means that I can give when my family did not. It transforms some of that loss.”

You can donate HERE.

…………………………

It’s that time of year again. The leaves are falling, and the weather is turning snappy. Soon, families will gather around the table for holiday feasts. We will give thanks that we are together, share the bounty of the harvest, and enjoy the warmth and comfort we feel when those we love surround us.

For people with ME/CFS the holidays present a challenge. Even for those of us who have warm, loving families, it is difficult to rise to the occasion. We are exhausted easily by interactions, no matter how pleasant those may be. We can’t talk with our relatives as much as we would like, sit through long dinners with them, and participate fully in family rituals.

The holidays present even more of a challenge for those who have no family to share the holidays with. This is an especially painful time for people whose families have ostracized them.

Kristy’s Story

“Kristy” is one of the applicants to the AMMES financial crisis fund. She is severely ill, and lives alone. Her father threw her out of the house when she got pregnant and her boyfriend abandoned her. Kristy had the baby, but was too ill to care for it, so she was forced to give up her child for adoption. She keeps trying, unsuccessfully, to make her family understand how sick she is.

“They just don’t believe me,” she told me in a recent conversation. “They say ‘Why don’t you get up and find a job? You’re just lazy.’” Kristy is so weak she can barely brush her hair. It takes her days to recover from going to the corner to buy food. AMMES has sent her money for food, but she has still lost fifteen pounds, and she was thin to begin with.

“I’m scared,” she says. “I don’t think I will survive.”

Abandonment and Rejection

Kristy isn’t the only person who has applied to the AMMES financial crisis fund for help after being abandoned. Another woman, who I will call Laura, was rejected by her family, and worse.

“My brother told me to just kill myself,” she told me. “I really don’t have family that cares or understands or is safe for me to seek help from. I don’t know which is worse anymore, the disease itself and how it hurts me or the hatred and selfish disregard for my life from other people.”

Laura is housebound. She can only leave her home every seven to ten days to shop for food. In between grocery shopping, she rests to recuperate her strength. Life is a continuous battle for Laura.

What we can do

Laura and Kristy are just two of the applicants who have reported ostracism, neglect, abandonment, and outright hostility from family members, partners, and friends. All too often they say that I am the only person they can trust. This is heartbreaking. We all need friends and family members we can trust.

Let’s make the holidays joyous for those in our community who have suffered the sting of rejection. Let’s include them in our celebrations. Let’s give them the gift of caring.

Please donate to the AMMES fall fundraiser. So far, we have given people like Kristy and Laura over $75,000 in direct aid to help them pay their rent, utilities, medical expenses, food, and other basic necessities. Every penny that is donated will be spent to serve this neglected population.

Our Crowdrise Fall Fundraiser is HERE.

Our goal is to raise ten thousand dollars. That will see us through the next three months.

You can donate directly to our financial crisis fund HERE.

AMMES is a 501(c)(3) national nonprofit. Your donations are tax deductible.

Intra brainstem connectivity is impaired in chronic fatigue syndrome

Abstract:

In myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), abnormal MRI correlations with symptom severity and autonomic measures have suggested impaired nerve signal conduction within the brainstem. Here we analyse fMRI correlations to directly test connectivity within and from the brainstem. Resting and task functional MRI (fMRI) were acquired for 45 ME/CFS (Fukuda criteria) and 27 healthy controls (HC).

We selected limited brainstem reticular activation system (RAS) regions-of-interest (ROIs) based on previous structural MRI findings in a different ME/CFS cohort (bilateral rostral medulla and midbrain cuneiform nucleus), the dorsal Raphe nucleus, and two subcortical ROIs (hippocampus subiculum and thalamus intralaminar nucleus) reported to have rich brainstem connections.

When HC and ME/CFS were analysed separately, significant correlations were detected for both groups during both rest and task, with stronger correlations during task than rest. In ME/CFS, connections were absent between medulla and midbrain nuclei, although hippocampal connections with these nuclei were enhanced.

When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task.

In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity. RAS neuron oscillatory signals facilitate coherence in thalamo-cortical oscillations. Brainstem RAS connectivity deficits can explain autonomic changes and diminish cortical oscillatory coherence which can impair attention, memory, cognitive function, sleep quality and muscle tone, all symptoms of ME/CFS.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Source: Barnden LR, Shan ZY, Staines DR, Marshall-Gradisnik S, Finegan K, Ireland T, Bhuta S. Intra brainstem connectivity is impaired in chronic fatigue syndrome. Neuroimage Clin. 2019 Oct 19;24:102045. doi: 10.1016/j.nicl.2019.102045. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31671321

Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue

Abstract:

The linkage between oxidative stress and idiopathic chronic fatigue (ICF) has not been explored in detail. This study thoroughly compared the serum levels of biomarkers for oxidative stress and antioxidants from 103 subjects with ICF (20 men and 83 women) to those of 82 healthy volunteers (27 men and 55 women).

Oxidative parameters, which included reactive oxygen species (ROS), malondialdehyde (MDA) and F2-isoprotan, and tumor necrosis factor-alpha (TNF-α) were significantly elevated, while antioxidant parameters, which included total antioxidant activity (TAC), catalase, superoxide dismutase, SOD and GSH activity, were decreased compared to those of healthy subjects (by approximately 1.2- to 2.3-fold, p < 0.05 or 0.01).

Our results confirmed that oxidative stress is a key contributor in the pathophysiology of ICF, and firstly explored the features of oxidative stress parameters in ICF subjects compared to a healthy population.

Source: Lee JS, Kim HG, Lee DS, Son CG. Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue. Sci Rep. 2018;8(1):12890. Published 2018 Aug 27. doi:10.1038/s41598-018-31270-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110864/ (Full article)

News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments

Abstract:

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy.

Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Source: Comhaire F, Deslypere JP. News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments. Med Hypotheses. 2019 Oct 22;134:109444. doi: 10.1016/j.mehy.2019.109444. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31669858

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

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.

Source: Nelson MJ, Bahl JS, Buckley JD, Thomson RL, Davison K. Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Oct;98(43):e17600. doi: 10.1097/MD.0000000000017600. https://www.ncbi.nlm.nih.gov/pubmed/31651868 (Full article)

The Effect of Comorbid Medical and Psychiatric Diagnoses on Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To determine if presence of co-existing medically unexplained syndromes or psychiatric diagnoses affect symptom frequency, severity or activity impairment in Chronic Fatigue Syndrome.

PATIENTS: Sequential Chronic Fatigue Syndrome patients presenting in one clinical practice.

DESIGN: Participants underwent a psychiatric diagnostic interview and were evaluated for fibromyalgia, irritable bowel syndrome and/or multiple chemical sensitivity.

RESULTS: Current and lifetime psychiatric diagnosis was common (68%) increasing mental fatigue/health but not other illness variables and not with diagnosis of other medically unexplained syndromes. 81% of patients had at least one of these conditions with about a third having all three co-existing syndromes. Psychiatric diagnosis was not associated with their diagnosis. Increasing the number of these unexplained conditions was associated with increasing impairment in physical function, pain and rates of being unable to work.

CONCLUSIONS: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms.

Key Messages: When physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiatric problem. This paper shows that the presence of co-existing psychiatric diagnoses does not impact on any aspect of the phenomenology of medically unexplained fatigue also known as chronic fatigue syndrome. Therefore, psychiatric status is not an important causal contributor to CFS. In contrast, the presence of other medically unexplained syndromes [irritable bowel syndrome; fibromyalgia and/or multiple chemical sensitivity] do impact on the illness such that the more of these that co-exist the more health-related burdens the patient has.

Source: Natelson BH, Lin JS, Lange G, Khan S, Stegner A, Unger ER. The Effect of Comorbid Medical and Psychiatric Diagnoses on Chronic Fatigue Syndrome. Ann Med. 2019 Oct 23:1-18. doi: 10.1080/07853890.2019.1683601. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31642345

Retinal nerve fiber layer thinning in chronic fatigue syndrome as a possible ocular biomarker of underlying glymphatic system dysfunction

In a recent article published in Medical Hypotheses, my colleague and I speculated that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome (CFS) [1]. We further postulated that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain. In this context, it would be helpful to have a predictive biomarker that can identify CFS patients who are good candidates for this specific treatment. For reasons discussed below, I believe that retinal nerve fiber layer (RNFL) thinning may be a sign of underlying glymphatic system dysfunction in neurodegenerative diseases that result from protein toxicity.

Read the rest of this article here.

Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

For over two decades, the standard of care for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been cognitive behavior therapy (CBT) and graded exercise therapy (GET). Both interventions had been recommended by the US Centers for Disease Control and the UK NICE guidelines. Behavioral intervention as the clinical standard was given a considerable boost by the 5 million–pound PACE trial, a large multi-arm randomized trial of CBT and GET launched in 2007. This British government–funded trial was intended to definitively answer whether such interventions were beneficial in ME/CFS. In their 2011 and 2013 publications, the PACE trial authors announced with widespread publicity that 22% of their patients had “recovered” and 59–61% had clinically improved across the CBT and GET interventions., 

Read the rest of this article here.

Source: Friedberg, F., Sunnquist, M. & Nacul, L. J GEN INTERN MED (2019). https://doi.org/10.1007/s11606-019-05375-y https://link.springer.com/article/10.1007%2Fs11606-019-05375-y