Welcome to the 75th 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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Orthostatic stress testing in myalgic encephalomyelitis/chronic fatigue syndrome patients with or without concomitant fibromyalgia: effects on pressure pain thresholds and temporal summation

Authors: van Campen CLMC, Rowe PC, Verheugt FWA, Visser FC (Stichting CardioZorg, Netherlands) 
Publication: Clinical and Experimental Rheumatology 
Link: https://www.clinexprheumatol.org/article.asp?a=15665  

These authors argue that central sensitisation (including sensory processing and pain inhibitory mechanisms) is the mechanism which causes chronic pain in both ME/CFS and fibromyalgia (FM). Pain pressure thresholds (PPT) reflect the intensity of mechanical stimuli required to cause a painful skin sensation, with lower thresholds indicating less pressure required to cause pain. Temporal summation (windup) is the increase in pain perception following repetitive painful stimuli. This study tested the hypothesis that orthostatic stress testing in those with ME/CFS would reduce PPT and increase windup, and that co-morbid FM would worsen both measures. 

Data from 248 females with ME/CFS (diagnosed according to both the Fukuda and International Consensus criteria) and 22 healthy controls (HC) who had undergone a head-up tilt table test (HUT) for orthostatic intolerance were included in the study. 164 (66%) of the ME/CFS group either had a diagnosis of FM or met the criteria of the American College of Rheumatology FM questionnaire.  

Prior to the HUT, the PPT (when measured in the shoulder) was significantly lower in the ME/CFS group compared to HC. When PPT was measured in the finger, there was no difference between non-FM ME/CFS and HC, but in those with FM and ME/CFS results were lower compared to HC. Following HUT, PPT declined significantly across the ME/CFS group while there was no change in HC. Windup was higher in ME/CFS compared to HC.   

This study was the first to demonstrate that orthostatic stress decreased PPT and increased windup in those with ME/CFS, and that the presence of FM in ME/CFS negatively influenced pain perception. Further studies are required to replicate the results, determine the effect in males with ME/CFS, and account for potential confounding factors. 


Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome

Authors: De Bellis A, Bellastella G, Pernice V, Cirillo P, Longo M, Maio A, … Montoya JG (Stanford University School of Medicine, USA) 
Publication: The Journal of Clinical Endocrinology and Metabolism 
Link: https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab429/6319899 


The potential role of neuroendocrine autoimmune dysfunction has previously been proposed as a hypothesis for the pathogenesis of ME/CFS. This study aimed to explore the occurrence of anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunction in ME/CFS patients.  

This study included 30 female participants (Fukuda, International Consensus, and IOM criteria) and 25 healthy female age-matched controls. Participants were aged from 21-44 years (child-bearing age), with a regular menstrual cycle, and had experienced fatigue for at least 3 years. Immunofluorescence scans were used to detect APA and AHA. Hormonal secretions of anterior pituitary and respective target glands, and plasma and urine osmolarity analysis were also performed.  

The authors found that there was a higher prevalence of AHA and APA, as well as lower levels of cortisol and growth hormone (GH) peak, in the ME/CFS group compared to the control group. AHA were detected in 33% and APA detected in 56% of the ME/CFS group, and neither were detected in any of the healthy controls. Further analysis found that ME/CFS participants with a high AHA and/or APA titre had adrenocorticotropic hormone (ACTH)/cortisol and GH peak/insulin-like growth factor 1 levels significantly lower than ME/CFS participants with middle/low or no titre. The group with high titres was also more severely unwell than the ME/CFS patients with low/middle or no titres.  

The authors acknowledged that the small sample size and retrospective nature of the study limit the cause and effect inferences that are able to be drawn from the results.   

The authors conclude that AHA and APA high titres found in some ME/CFS patients suggest that hypothalamic/pituitary autoimmunity may play a role in the manifestation of ME/CFS, especially in more severe ME/CFS. They recommend longitudinal studies to fully test their hypothesis.  


The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

Authors: O'Neal AJ, Hanson MR (Cornell University, USA) 
Publication: Frontiers in Medicine 
Link: https://www.frontiersin.org/articles/10.3389/fmed.2021.688486/full


Research into the role of enteroviruses (EVs) in ME/CFS has decreased in the last 20 years due to difficulties in detecting EVs after the acute infection, the frequency of enteroviral infections in the community, and that many different types of insults can lead to ME/CFS. This paper provides an evaluation of the current research on the involvement of EVs in ME/CFS. 

Different EV serotypes infect different types of cells in the body, with some neurotropic and others myotropic. Many of the autonomic nervous system dysfunctions observed in ME/CFS, particularly altered brain characteristics, are also reported in those with neurotropic enteroviruses. Additionally, literature suggests that the mitochondrial dysfunction seen in ME/CFS may be a result of cellular outcomes of persistent viral infections. The authors note that, while the evidence suggests that at least some ME/CFS patients may have chronic EV infection, confirmation of EV involvement is hampered by limitations in EV detection.  

The authors suggest that future research of EV in ME/CFS must consider the quality and types of samples used, with ongoing investigation into the use of brain tissue, cerebrospinal fluid and muscle biopsy samples. EV detection methodology should be through RT-PCR with optimal primer sets and/or RNAseq with target capture enrichment, with the later allowing for the identification of novel EV serotypes and complete genomic sampling.


‘Wise to be thinking now': Calls for Australia to consider the burden of long COVID

Authors: Brancatisano E 
Publication: SBS 
Link: https://www.sbs.com.au/news/wise-to-be-thinking-now-calls-for-australia-to-consider-the-burden-of-long-covid 


With outbreaks of COVID-19 occurring more frequently around the country, experts are warning of the risk of long-COVID in those who survive the infection. While estimates of the number of people who will go on to develop long-COVID varies, if even a small percentage do, this means many Australians will be left with persistent symptoms.  

Researchers and patients have noted the similarities between long-COVID and ME/CFS, both in symptoms and in many health professionals not taking the condition seriously. Now is the time to start thinking about the long-term effects of COVID-19, and learn from the experiences of the ME/CFS community.