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Research Digest 28/07/22

Welcome to the 86th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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Predictors for Developing Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome following Infectious Mononucleosis

Authors: Jason LA, Cotler J, Islam MF, Furst J, Katz BZ (Northwestern University, USA)
Publication: Journal of Rehabilitation Therapy
Link: http://www.rehabiljournal.com/articles/predictors-for-developing-severe-myalgic-encephalomyelitischronic-fatigue-syndrome-following-infectious-mononucleosis.html
 
Many patients report developing ME/CFS following an infection. In the case of infection with infectious mononucleosis (IM), approximately 9-12% of patients are diagnosed with ME/CFS six months post-infection. This study aimed to identify whether it was possible to predict which patients would go on to develop ME/CFS after contracting IM.
Participants were drawn from a previous study of 4501 college students at Northwestern University. Of these students, 238 developed IM, and at a six-month follow-up, 48 students fulfilled the criteria for ME/CFS. Of these 48, 30 met the Fukuda criteria (and were defined as having ME/CFS), and 18 met the Fukuda criteria as well as either the Canadian and/or Institute of Medicine Criteria (and were defined as severe ME/CFS). Participants who met more than one set of diagnostic criteria had worse symptom scores than those who only met the Fukuda criteria. The 48 ME/CFS participants were matched with a control group of 58 participants who had no further symptoms following their IM infection. Participants completed 7 questionnaires, including the severity of mononucleosis scale, and cytokines were analysed at baseline (at least 6 weeks prior to developing IM) and at the time of infection.
The authors found that students who experienced IM symptoms including severe gastrointestinal (GI) symptoms of stomach pain, bloating and irritable bowel pre-illness/at baseline, as well as abnormally low levels of immune markers IL-13 and/or IL-5 at baseline, as well as severe GI symptoms during IM infection, had a nearly 80% chance of having severe ME/CFS post-IM-infection.
The authors conclude that these results highlight the possibility of using pre-illness and illness variables to predict the occurrence of severe ME/CFS following IM. The authors propose that their findings suggest that GI and autonomic symptoms should be considered important symptom categories for ME/CFS and note that the Fukuda criteria do not require these symptoms for diagnosis. Finally, the authors recommend similar studies be undertaken with COVID-19 patients to determine if these same predictors could identify people who are at greater risk of later developing Long COVID.


Impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life of people with ME/CFS and their partners and family members: an online cross-sectional survey

Authors: Vyas J, Muirhead N, Singh R, Ephgrave R, & Finlay AY (Cardiff University, UK)
Publication: British Medical Journal
Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062824/

Existing literature has explored the negative impact of ME/CFS on the health-related quality of life (QoL) of patients, showing a greater impact than for many other diseases. To date, there has been little research completed on the impact of ME/CFS on caregivers. This study aimed to assess the impact of ME/CFS on the QoL of patients, and their relatives or partner and was co-designed by patients and clinical researchers.
Participants were self-selected for this study from 30 countries in response to recruitment via social media. Participants were aged 18 years or over and required a diagnosis of ME/CFS by a health professional. 1418 people with ME/CFS and 1418 family members were included in the study. Participants completed online questionnaires assessing health status and QoL.
The authors found that many ME/CFS participants reported problems performing their usual activities (98.5%), pain (93.9%), and affected mobility (88.6% – either problems walking or being confined to bed). Self-care (washing or dressing) was reported to be affected by 67.3% of respondents. Anxiety and depression were the least affected domains (40.6%). Three participants reported no problem in any domain. ME/CFS participants rated their overall health from 0 (worst imaginable) to 100 (best imaginable health) with an average rating of 33.7.
The authors also found that ME/CFS had a profound impact on family members, almost all of whom were worried (96.1%), frustrated or sad (93%), and many of whom felt angered by their family members ME/CFS (70%). In addition, the majority of respondents found caring difficult (84.7%) and found it difficult to talk to others about their thoughts (73.4%). Family members reported that their loved one’s ME/CFS impacted family activities (91.8%), holidays (85.3%), finances (77.3%) and their sex lives (72.9%). Respondents also reported difficulty finding time for themselves, and that sleep, work, study, or family relationships were affected. Everyday travel and eating habits were the least impacted areas.
The authors conclude these findings demonstrate a significant correlation between the impact of QoL on patients with ME/CFS and their family members. They propose this study highlights the seriousness of ME/CFS and the worldwide impact this disease has on QoL, not just on patients but on family members as well. The authors recommend that education for healthcare professionals be updated to reflect this impact. 

Figure 1. ME/CFS participant results, with activity domains (A), and overall health rating (B).                                   


Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine

Authors: Joseph P, Pari R, Miller S, Warren A, Stovall MC, Squires J, …  Systrom DM (Harvard Medical School, USA)
Publication: Chest Journal
Link: http://journal.chestnet.org/article/S0012-3692(22)00890-X/pdf

The overlap in ME/CFS, postural orthostatic tachycardia syndrome (POTS) and fibromyalgia has led to the study of small fibre neuropathy (SFN) as a possible cause of these conditions. Acetylcholine is a key neurotransmitter in the autonomic nervous system and is thought to be involved in SFN. Pyridostigmine is an acetylcholinesterase inhibitor, preventing the breakdown of acetylcholine), and has been shown to improve symptoms in patients with POTS. The objective of this study was to investigate whether the application of pyridostigmine post-exercise could determine if neurovascular dysregulation has a causal relationship with post-exercise malaise in ME/CFS.
 
The study included 45 participants with ME/CFS (National Academy of Medicine criteria). Participants received either a 60 mg dose of oral pyridostigmine or a placebo drug following an invasive cardiopulmonary exercise test (iCPET). In preparation for the iCPET, participants’ pulmonary and radial arteries were catheterised. Participants then performed incremental, upright exercise on a cycle ergometer as ventilation and pulmonary gas exchange were continuously measured until the predicted peak heart rate was reached. A second iCPET was performed 50 minutes after participants received either the pyridostigmine or placebo drug.
 
Participants who received pyridostigmine showed improved aerobic capacity compared with those administered the placebo who showed decreased oxygen uptake, cardiac output, and right atrial pressure at the peak of exercise, suggesting a physiological mechanism underlying post-exertional malaise. Furthermore, oxygen uptake and cardiac output levels were elevated prior to the second iCPET in the placebo group. Such occurrences are indicative of immune-inflammatory and sympathetic responses, which have been associated with ME/CFS. The authors suggest that these results signify that neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.
 
The authors noted that whilst results were statistically significant, the physiological changes were small and not clinically relevant. The authors suggest that future studies should assess the longer-term effects of pyridostigmine in individuals with ME/CFS.


Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome

Authors: Thapaliya K, Staines D, Marshall-Gradisnik S, Su J, and Barnden L (Griffith University, Australia) 
Publication: Journal of Neuroscience Research
Link: http://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25048
 
The hippocampus is a brain structure involved in cognitive processes such as learning, processing complex information, consolidation of memory, planning, multitasking, and goal-directed behaviour. Studies have shown variations in hippocampal subfield volume to be evident in neurodegenerative diseases and in diseases exhibiting cognitive dysfunction. Approximately 89% of ME/CFS patients demonstrate some degree of difficulty with cognitive functions. This is the first study of hippocampal subfield volume in ME/CFS patients. This study not only aimed to discover the variance of hippocampal subfield volume in ME/CFS patients compared to healthy controls whilst relating these to clinical symptoms, but it also sought to compare ME/CFS diagnostic criteria in order to demonstrate which criteria can more accurately and effectively diagnose patients, and thus to also demonstrate hippocampal volumetric differences as a diagnostic biomarker.  
The study included 25 ME/CFS patients who met only the Fukuda Criteria, 18 ME/CFS patients who met the International Consensus Criteria and 25 age-matched healthy controls. MRI scans were used to determine total hippocampal volume and subfield volume. Subfield volumes were then correlated with clinical measures of fatigue, pain, physical levels, information processing ability, and sleep disturbance.
The authors found significant volumetric differences in hippocampal subfields between ME/CFS patients and healthy controls. Hippocampal subfield volumes also correlated with some clinical measures of ME/CFS. These differences were more apparent in patients who met the ICC compared with those who only met the Fukuda criteria, with all clinical criteria meeting with volumetric alterations.
The authors conclude that hippocampal volume has potential as an imaging diagnostic biomarker, but that their results emphasise the importance of using strict diagnostic criteria with ME/CFS.


Telehealth cuts to hit most vulnerable

Author: Grant L
Publication: 2GB
Link: http://www.2gb.com/podcast/telehealth-cuts-to-hit-most-vulnerable/
 
Emerge Australia’s CEO, Anne Wilson, was recently interviewed by 2GB radio host Luke Grant about the impact of changes to telehealth rebates on people with chronic illnesses like ME/CFS and Long COVID.
“Since the announcement of the plan, the organisation has had many distressed calls, especially from pensioners, who were worried about not being able to pay extra fees for longer telehealth consultations as they battled with their illness”, she said.
The interview runs for 11 mins.

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