Research Digest 28/04/22

Welcome to the 83rd 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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Physiological assessment of orthostatic intolerance in chronic fatigue syndrome

Authors: Natelson BH, Lin JMS, Blate M, Khan S, Chen Y, and Unger ER (Centers for Disease Control and Prevention, USA)
Publication: Journal of Translational Medicine
Link: https://translational-medicine.biomedcentral.com/track/pdf/10.1186/s12967-022-03289-8.pdf

Orthostatic intolerance (OI) is symptom exacerbation while in an upright position and is common in ME/CFS. The two most well-known forms of OI are postural orthostatic tachycardia syndrome (POTS), and orthostatic hypotension. However, these authors argue that postural orthostatic syndrome of hypocapnia (POSH), which is reduced carbon dioxide in the blood upon being upright, is more common in ME/CFS than other forms of OI, though it is less well-studied. The aim of this study was to determine the physiologic response of those with ME/CFS to an orthostatic challenge (OC) over time.
Sixty-three patients with ME/CFS (Fukuda criteria) who had at least 4 substantial ME/CFS symptoms, but did not have a range of other medical conditions, underwent an OC. The OC involved a 10-minute wall lean test that was conducted after at least 10 minutes of lying supine. Physiological measurements were taken while lying and during the lean test. The OC was repeated on up to 3 occasions at 8–15-month intervals.
Sixty percent of participants had an abnormality during a lean test at any time point, with those who had a sudden onset of ME/CFS more likely to have an abnormal result. Nearly a quarter of participants had more than 1 abnormality. Over 80% of those with an abnormal test demonstrated hypocapnia (either following the OC or supine), compared to POTS being present in 25% of participants. The high rates of hypocapnia were not associated with tachypnea, which was only present in one patient. Hypocapnia was also not associated with anxiety, which did not differ between those with or without POSH.
The authors encourage monitoring of breathing rates and end-tidal CO₂ in practice with associated therapy to improve hypocapnia in ME/CFS. The aetiology of hypocapnia in ME/CFS is unknown but the authors suggest it may be associated with hypovolemia, gravitational stress, or anxiety, though this study found no association between hypocapnia and anxiety scores.

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Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients

Authors: Eaton-Finch N, Du Preez S, Cabanas H, Muraki K, Staines D, and Marshall-Gradisnik S (Griffith University, Australia)
Publication: Journal of Translational Medicine
Link: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03297-8

The pathomechanism of ME/CFS remains poorly understood. However, in recent years studies have consistently found the presence of reduced natural killer (NK) cell cytotoxicity. The function of NK cells is dependent on long-term sustained calcium influx. Recent research by these authors has found impaired transient receptor potential melastatin 3 (TRPM3) function in NK cells of ME/CFS patients, and that mu (µ)-opioid receptor (µOR) agonists (opioids) inhibit TRPM3. This study aimed to determine if naltrexone hydrochloride (NTX), a µOR antagonist, could negate the inhibitory action of µOR on TRPM3 function and restore impaired TRPM3 function in NK cells of ME/CFS patients.
10 ME/CFS patients (Canadian Consensus Criteria or International Consensus Criteria) and 10 age and sex matched healthy controls were recruited from the National Centre for Neuroimmunology and Emerging Diseases’ database. Live cell immunofluorescent imaging was used to measure TRPM3-dependent calcium influx in NK cells that were isolated from participants following modulation with TRPM3-agonist, pregnenolone sulfate (PregS) and TRPM3-antagonist, ononetin. The effect of overnight NTX treatment on TRPM3-dependent calcium influx was examined.
The authors found the baseline amplitude and half-time calcium response was significantly reduced in NK cells of ME/CFS patients compared to healthy controls. It was found that NK cells that were treated overnight with NTX significantly improved the TRPM3-dependent calcium influx in ME/CFS patients. Following treatment, no significant difference between healthy controls and ME/CFS patients was found for half-time response, and the amplitude of calcium influx was significantly increased in ME/CFS patients.
The authors conclude that TRPM3-dependent calcium influx was restored in ME/CFS patients following overnight treatment of isolated NK cells with NTX in vitro, and that NTX may provide a potential therapeutic intervention for ME/CFS.

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Eye movements may be key to chronic fatigue syndrome diagnosis

Authors: Monash University (Australia)
Publication: Monash Australia
Link: https://www.monash.edu/medicine/news/latest/2022-articles/eye-movements-may-be-key-to-chronic-fatigue-syndrome-diagnosis

Associate Professor Joanne Fielding, from the Monash Central Clinical School Department of Neuroscience, received $180,000 funding grant over three years from the Judith Jane Mason & Harold Stannet Williams Memorial Foundation to conduct a project aimed at identifying an objective behavioural marker to assist in the diagnosis of ME/CFS. With no reliable way to diagnose or objectively monitor ME/CFS, clinicians currently rely on the exclusion of other causes for the constellation of symptoms that ME/CFS causes.
Associate Professor Fielding reported, “What we’re trying to do is generate a unique ME/CFS signature based on characteristic changes to eye movements, a behavioural [sic] signature that is specific to the disorder that can be used to help diagnose it and monitor the effects of any treatments.” Associate Professor Fielding and her team intend to use ocular-motor, machine learning and neuroimaging techniques to develop a fast-acting portable eye tracker (utilising video-oculography) that patients can use in the lab or in their own homes, due to the extreme fatigue patients can experience.

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Rise of long COVID highlights the need for support for people with chronic fatigue syndrome

Authors: Scott S, and Thorne L
Publication: ABC News
Link: https://www.abc.net.au/news/2022-04-22/long-covid-chronic-fatigue-syndrome-cfs-need-more-research/101002056

With more money being allocated to research and clinics for long COVID, new insights into post-viral syndromes are emerging. ME/CFS patients should not be left behind. Emerge Australia calls for updated clinical guidelines for ME/CFS, and more funding for research and patient support.

Emerge Australia CEO, Anne Wilson said, “ME/CFS has been called, by people who have got it severely, like a living death. At the severe end, with a post-viral illness like ME/CFS, you can't get out of bed. There's grief and loss for the life you had, let alone navigating how to access supports like the NDIS. The voices of the 250,000 people with this illness need to be heard.”

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Do we take chronic fatigue seriously?

Authors: Hunt R
Publication: ABC Radio Melbourne
Link: https://www.abc.net.au/radio/melbourne/programs/theconversationhour/the-conversation-hour/13848466

The Conversation Hour with Richelle Hunt focussed on what people with Long COVID can learn from people who have been living with ME/CFS. Richelle spoke with Emerge Australia CEO, Anne Wilson, and Emerge Australia’s Medical Director, Dr Richard Schloeffel, as well as patients who live with ME/CFS.

“There’s a true pathology going on here. It’s not an imagined disorder, it’s not a choice disorder. It’s not psychosomatic or psychiatric. It’s a biological, pathological cellular disorder, of cellular fatigue leading to all these disrupted organs and tissues with a multitude of symptoms”, said Richard Schloeffel, calling it “Medical Abuse Syndrome” when doctors ignore ME/CFS or don’t believe patients living with the condition.

The program lasts for about an hour.

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