Symptoms – Page 12 – American ME and CFS Society

Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases

Abstract:

Post-exertional malaise (PEM) is a cardinal predictive symptom in the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). If the cases overexert themselves they have what is termed “payback” resulting in a worsening of symptoms or relapse which can last for days, weeks or even months. The aim was to assess the changes in biochemistry associated with the cases self-reported PEM scores over a 7-day period and the frequency of reporting over a 12-month period.

Forty-seven ME/CFS cases and age/sex-matched controls had a clinical examination, completed questionnaires; were subjected to standard serum biochemistry; had their serum and urine metabolomes analyzed in an observational study. Thirty-five of the 46 ME/CFS cases reported PEM in the last 7-days and these were allocated to the PEM group.

The principal biochemical change related to the 7-day severity of PEM was the fall in the purine metabolite, hypoxanthine. This decrease correlated with alterations in the glucose:lactate ratio highly suggestive of a glycolytic anomaly. Increased excretion of urine metabolites within the 7-day response period indicated a hypermetabolic event was occurring. Increases in urine excretion of methylhistidine (muscle protein degradation), mannitol (intestinal barrier deregulation) and acetate were noted with the hypermetabolic event.

These data indicate hypoacetylation was occurring, which may also be related to deregulation of multiple cytoplasmic enzymes and DNA histone regulation. These findings suggest the primary events associated with PEM were due to hypoacetylation and metabolite loss during the acute PEM response.

Source: Neil R. McGregor, Christopher W. Armstrong , Donald P. Lewis and Paul R. Gooley. Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases. Diagnostics 2019, 9(3), 70; https://doi.org/10.3390/diagnostics9030070 https://www.mdpi.com/2075-4418/9/3/70/htm (Full article)

Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong

Abstract:

Chronic Fatigue Syndrome (CFS) and chronic pain syndromes represent major health problems in society. These conditions are disabling and strongly associated with low quality of life. Even though CFS and chronic pain are separate conditions, they have strikingly much in common. Both pain and fatigue are important sensations with protective value in an acute situation. It can be life-threatening not to be aware of them.

However, as these symptoms become chronic, their protective roles decrease and instead they become health problems. Our understanding of the perception of pain and fatigue has shifted through the years, from a dualistic biomedical point of view to a holistic biopsychosocial understanding. This combined with the increasing evidence of how our brain works in a predictive/anticipatory manner, gives a deeper understanding of why treatments like cognitive behavior therapies and stress relief therapies can help these patients recover to better health.

Source: Pedersen M. Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong. Scand J Pain. 2019 Jun 29. pii: /j/sjpain.ahead-of-print/sjpain-2019-0072/sjpain-2019-0072.xml. doi: 10.1515/sjpain-2019-0072. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31256069

Orthostatic intolerance in chronic fatigue syndrome

Abstract:

BACKGROUND: Orthostatic intolerance (OI) is a significant problem for those with chronic fatigue syndrome (CFS). We aimed to characterize orthostatic intolerance in CFS and to study the effects of exercise on OI.

METHODS: CFS (n = 39) and control (n = 25) subjects had recumbent and standing symptoms assessed using the 20-point, anchored, ordinal Gracely Box Scale before and after submaximal exercise. The change in heart rate (ΔHR ≥ 30 bpm) identified Postural Orthostatic Tachycardia Syndrome (POTS) before and after exercise, and the transient, exercise-induced postural tachycardia Stress Test Activated Reversible Tachycardia (START) phenotype only after exercise.

RESULTS: Dizziness and lightheadedness were found in 41% of recumbent CFS subjects and in 72% of standing CFS subjects. Orthostatic tachycardia did not account for OI symptoms in CFS. ROC analysis with a threshold ≥ 2/20 on the Gracely Box Scale stratified CFS subjects into three groups: No OI (symptoms < 2), Postural OI (only standing symptoms ≥ 2), and Persistent OI (recumbent and standing symptoms ≥ 2).

CONCLUSIONS: Dizziness and Lightheadedness symptoms while recumbent are an underreported finding in CFS and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance. POTS was found in 6 and START was found in 10 CFS subjects. Persistent OI had symptoms while recumbent and standing, highest symptom severity, and lability in symptoms after exercise.

Trial registration: The trial was registered at the following: https://clinicaltrials.gov/ct2/show/NCT03567811.

Source: Garner R, Baraniuk JN. Orthostatic intolerance in chronic fatigue syndrome. J Transl Med. 2019 Jun 3;17(1):185. doi: 10.1186/s12967-019-1935-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547462/ (Full article)

Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome

Abstract:

BACKGROUND: Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underlying the association between pain and chronic stress using this rat model.

METHODS: Chronic or continuous stress-loading (CS) model rats, housed in a cage with a thin level of water (1.5 cm in depth), were used. The von Frey test and pressure pain test were employed to measure pain behavior. The neuronal and microglial activations were immunohistochemically demonstrated with antibodies against ATF3 and Iba1. Electromyography was used to evaluate muscle activity.

RESULTS: The expression of ATF3, a marker of neuronal hyperactivity or injury, was first observed in the lumbar dorsal root ganglion (DRG) neurons 2 days after CS initiation. More than 50% of ATF3-positive neurons simultaneously expressed the proprioceptor markers TrkC or VGluT1, whereas the co-expression rates for TrkA, TrkB, IB4, and CGRP were lower than 20%. Retrograde labeling using fluorogold showed that ATF3-positive proprioceptive DRG neurons mainly projected to the soleus. Substantial microglial accumulation was observed in the medial part of the dorsal horn on the fifth CS day. Microglial accumulation was observed around a subset of motor neurons in the dorsal part of the ventral horn on the sixth CS day. The motor neurons surrounded by microglia were ATF3-positive and mainly projected to the soleus. Electromyographic activity in the soleus was two to three times higher in the CS group than in the control group. These results suggest that chronic proprioceptor activation induces the sequential activation of neurons along the spinal reflex arc, and the neuronal activation further activates microglia along the arc. Proprioceptor suppression by ankle joint immobilization significantly suppressed the accumulation of microglia in the spinal cord, as well as the pain behavior.

CONCLUSION: Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS.

Source: Yasui M, Menjyo Y, Tokizane K, Shiozawa A, Tsuda M, Inoue K, Kiyama H. Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome. J Neuroinflammation. 2019 Mar 30;16(1):67. doi: 10.1186/s12974-019-1456-x. https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1456-x (Full article)

Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey

Abstract:

Considerable controversy has existed with efforts to assess post-exertional malaise (PEM), which is one of the defining features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). While a number of self-report questionnaires have been developed to assess this symptom, none have been comprehensive, and a recent federal government report has recommended the development of a new PEM measure.

The current study involved a community-based participatory research process in an effort to develop a comprehensive PEM instrument, with critical patient input shaping the item selection and overall design of the tool. A survey was ultimately developed and was subsequently completed by 1534 members of the patient community.

The findings of this survey suggest that there are key domains of this symptom, including triggers, symptom onset, and duration, which have often not been comprehensively assessed in a previous PEM instrument. This study indicates that there are unique benefits that can be derived from patients collaborating with researchers in the measurement of key symptoms defining ME and CFS.

Source: Carly S. Holtzman, Shaun Bhatia, Joseph Cotler and Leonard A. Jason. Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey. Diagnostics 2019, 9(1), 26; doi:10.3390/diagnostics9010026 https://www.mdpi.com/2075-4418/9/1/26/htm (Full article)

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population

Abstract:

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population.

METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender.

RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12).

CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Source: Khoo T, Proudman S, Limaye V. Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population. Clin Rheumatol. 2019 Jan 31. doi: 10.1007/s10067-019-04447-y. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30706290

Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results

Abstract:

Introduction: Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of orthostatic symptoms.

Methods and results: Twenty consecutive adults with ME/CFS participated in the study. All underwent dual isotope blood volume measurement and were evaluated for a clinical suspicion of orthostatic intolerance (OI). The mean age was 34 (10) years, and median duration of disease was 7.5 (6-10) years. The mean (SD) absolute blood volume was 59 (8) ml/kg, a value -11 (7) ml/kg below the reference blood volume. Of the 12 patients, 4 had no OI and 8 had a clinical suspicion of OI. In 8 patients with OI, absolute blood volumes were significantly lower than for the 4 without OI (56 [2] vs. 66 [5]; p < 0.05) as were the differences between the measured and the reference blood volume (-14 [2]; vs. -4 [3]; p < 0.02).

Conclusions: Adults with ME/CFS had a significantly lower blood volume if they had a clinical suspicion of OI compared to those without a clinical suspicion of OI, as well as a significantly lower blood volume compared to the expected value. The data suggest that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume.

Source: van Campen CLMC1, Rowe PC2, Visser FC1. Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results. Front Pediatr. 2018 Nov 15;6:352. doi: 10.3389/fped.2018.00352. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262290/ (Full article)

Visual aspects of reading performance in myalgic encephalomyelitis (ME)

Reprinted with the kind permission of ME Research UK.

Abstract:

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) report vision-related reading difficulty, although this has not been demonstrated objectively. Accordingly, we assessed reading speed and acuity, including crowded acuity and acuity for isolated words using standardized tests of reading and vision, in 27 ME/CFS patients and matched controls. We found that the ME/CFS group exhibited slower maximum reading speed, and had poorer crowded acuity than controls. Moreover, crowded acuity was significantly associated with maximum reading speed, indicating that patients who were more susceptible to visual crowding read more slowly. These findings suggest vision-related reading difficulty belongs to a class of measureable symptoms for ME/CFS patients.

Publication

Wilson et al, Frontiers in Psychology, 2018 August 17; 9:1468

Authors

Rachel L. Wilson, Kevin B. Paterson, Victoria McGowan and Claire V. Hutchinson

Institution

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, UK

Funding

This work was funded by an ME Research UK (Grant No. SC036942) to CH and KP. VM was supported by an Economic and Social Research Council (Grant No. ES/L010836/1).

Comment by ME Research UK

Many people with ME/CFS suffer from problems with their eyes and vision, such as oversensitivity to light, troubles with focusing, and dry eyes. Reading can therefore be challenging, particularly for long periods, and pattern glare, headaches and difficulty tracking lines of text are commonly reported. However, before now, the reading performance of ME/CFS patients had not been assessed objectively.

Over the last few years, Dr Claire Hutchinson and her colleagues at the University of Leicester have been looking in depth at some of the vision-related problems associated with ME/CFS, supported in part by grants from ME Research UK.

The group has found that most ME/CFS patients experience a degree of eye pain and sensitivity to bright lights. Using sophisticated eye-tracking techniques, they have also shown that patients struggle to focus on one object and ignore irrelevant information, are slow in shifting attention between objects, are slower than normal and less accurate in their eye movements, and are vulnerable to pattern-related visual stress.

In their latest ME Research UK-funded study, published in the journal Frontiers in Psychology, the Leicester team set out to evaluate what impact ME/CFS has on reading performance. A total of 27 ME/CFS patients and 27 healthy control subjects took part in the research; all had normal vision or corrected-to-normal vision (i.e. they wore spectacles or contact lenses) and none had any history of eye disease.

Reading performance was assessed using two standardised tests, the Minnesota Reading Acuity Chart and the Radner Rate of Reading Chart, which between them produced the following measures:

Reading acuity (the smallest print size that can be read without significant mistakes),
Maximum reading speed (not limited by print size),
Average reading speed, and
Critical print size (the smallest print size that can be read at maximum speed).

As expected, the maximum reading speed was significantly slower in ME/CFS patients than in control subjects, and patients also tended to have a slower average reading speed. However, reading acuity and critical print size were not different between the two groups, indicating that the reading difficulties were not due to an inability to make out smaller print.

Furthermore, ME/CFS patients and control subjects performed similarly on a vocabulary test, showing that the differences in reading performance between the two groups were unlikely to be due to cognitive problems.

The researchers also looked at uncrowded visual acuity for individual words and letters (identifying a word or letter on its own) and crowded visual acuity (identifying a target letter surrounded by other letters), using the logMar Crowded Test.

While uncrowded visual acuity appeared to be similar in patients and controls, ME/CFS patients did have greater problems with visual crowding and performed less well on that test. Furthermore, those individuals who were more susceptible to visual crowding were also shown to read more slowly.

These findings build on a considerable body of work from Dr Hutchinson and her team in which they have detailed and explored the vision-related symptoms associated with ME/CFS. While many people with he illness know full well how difficult it can be to read comfortably, particularly for long periods, this is the first time these problems have been assessed objectively in a laboratory setting.

As the researchers conclude, ‘identifying and treating vision-related symptoms of ME/CFS could provide a means of improving the everyday lives of patients’.

________________

ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS.

A Brief Questionnaire to Assess Post-Exertional Malaise

Abstract:

Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) were recommended as a first step in measuring this symptom for patients with ME and CFS by the National Institutes of Health/Centers for Disease Control and Prevention (NIH/CDC) Common Data Elements’ (CDE) working group.

The second step in this process, as recommended by the NIH/CDC CDE working group, involves assembling information from various sources to confirm the presence of PEM. There have not been any efforts, to date, to standardize this second-step process in the assessment of PEM.

The current study examined whether five supplementary items on the DSQ could be used to operationalize the second step of the recommendations made by the NIH/CDC CDE working group. The five supplementary DSQ PEM duration items correctly categorized patients with ME or CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and post-polio syndrome (PPS) as ME or CFS only 16.6% of the time. The findings suggested that a PEM second-step process could be operationalized using supplementary DSQ items.

Source: Cotler J, Holtzman C, Dudun C, Jason LA. A Brief Questionnaire to Assess Post-Exertional Malaise. Diagnostics (Basel). 2018 Sep 11;8(3). pii: E66. doi: 10.3390/diagnostics8030066.

Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME)

Source: Rachel L. Wilson, Kevin B. Paterson, Victoria McGowan and Claire V. Hutchinson. Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME). Front. Psychol., 17 August 2018 https://doi.org/10.3389/fpsyg.2018.01468 (Full article)