News Research Digest Research Digest 15/11/19 Rethinking the standard of care for myalgic encephalomyelitis/chronic fatigue syndrome Authors: Friedberg F, Sunnquist M, Nacul L.Link: https://link.springer.com/article/10.1007%2Fs11606-019-05375-y This paper critically examines the results of the controversial PACE trial and offers an alternative clinical approach for practitioners working with patients with ME/CFS. The paper notes that the PACE trial results were falsely inflated, due to the particular definition of ‘recovery’ the researchers used, and the loosening of the outcome criteria that took place during the trial. However, when the data were reanalysed using the trial’s original protocol, with more stringent definitions of improvement and recovery, improvement rates dropped from 59-61% to 20-21%, and recovery levels dropped from 22% down to 4-7%. The paper also notes that the PACE trial found no improvements on objective measures (such as fitness step test) following graded exercise therapy (GET) or cognitive behaviour therapy (CBT). The paper suggests that improvement on subjective measures (self-rating scales) may reflect improvements in participants’ coping or stress levels, rather than actual gains in physical and role functioning. Use of the Oxford criteria is identified as particularly problematic because the criteria are too broad, and only require ‘chronic fatigue’, rather than the hallmark presentations of post-exertional malaise, non-restorative sleep, cognitive difficulties, etc. This paper goes on to suggest a number of practical suggestions for clinicians working with people with ME/CFS including: Acknowledge the biomedical reality of the illness and believe how ill the patient is. Help patients minimise debilitating post-exertional malaise by learning to stay within their energy envelope. Encourage pacing strategies by dividing symptom-producing activities into smaller parts with interspersed rests. Recognise that it is only when pacing is being used effectively that some patients may find they are able to incorporate exercise into their illness management, though this needs to be carefully considered to minimise post-exertional malaise. Use appropriate pharmacological treatments when indicated, starting at low doses due to the likelihood of sensitivities. Refer patients for psychological support to improve coping with the severe impacts of ME/CFS on quality of life, as needed. Work within a multidisciplinary team with educated and experienced professionals. Become familiar with relevant, high-quality research into the condition. Naltrexone restores impaired transient receptor potential melastatin 3 ion channel function in natural killer cells from myalgic encephalomyelitis/chronic fatigue syndrome patients Authors: Cabanas H, Muraki K, Staines D, Marshall-Gradisnik S.Link: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02545/abstract This recent paper from NCNED (National Centre for Neuroimmunology and Emerging Diseases) suggests a potential pharmaco-therapeutic intervention for ME/CFS. This study is based on previous research by the same team, which found an association between ME/CFS and impaired TRPM3 ion channel function. In their previous research, they noted that opioids may indirectly inhibit TRPM3 function, and that the pharmaceutical drug, naltrexone, blocks opioids. In this study, the team explore whether naltrexone can restore TRPM3 function in people with ME/CFS. The research used eight ME/CFS patients and eight healthy controls. Using an electrophysiology technique (patch clamping), they first confirmed impaired TRPM3 activity in the eight ME/CFS patients, and then measured TRP receptor function in immune cells following administration of naltrexone. The authors reported that TRPM3 activity in the immune cells from ME/CFS patients was restored, suggesting that naltrexone may have potential in the treatment for ME/CFS. Intra brainstem connectivity is impaired in chronic fatigue syndrome Authors: Barnden LR, Shan ZY, Staines DR, Marshall-Gradisnik S, Finegan K, Ireland I, Bhutac S.Link: https://www.sciencedirect.com/science/article/pii/S2213158219303924 This study examines the connections and neural signal strength between the brain stem and specific regions of the brain, and finds that ME/CFS patients have impaired connections compared to healthy controls. Functional magnetic resonance imaging (fMRI) was used to study the brain, and compared 45 ME/CFS patients to 27 healthy controls. In ME/CFS patients, 'connectivity is impaired within the brainstem reticular activating system (RAS) and from the brainstem to key subcortical structures. This may explain many of the symptoms of ME/CFS.' The brainstem RAS is a network of neurons that has connections to numerous areas of the brain and governs the different states of human function, namely, waking, sleeping, and sleep-dreaming. A strong correlation was found between brainstem connectivity and ME/CFS severity, especially during tasks, and no correlation was found during rest states. Additionally, in ME/CFS patients, impairments in connectivity were associated with connectivity enhancements between some areas of the brain (though these enhancements were not significant), suggesting a possible compensatory mechanism. This study illustrates impaired brain function within ME/CFS patients, which could directly explain numerous symptoms and suggests opportunities for further examination. Grant call open for research on chronic fatigue syndrome Link: https://www.health.gov.au/ministers/the-hon-greg-hunt-mp/media/grant-call-open-for-research-on-chronic-fatigue-syndrome In March 2019, the federal Health Minister, Greg Hunt, announced that the Morrison government would be investing $3 million in biomedical research into ME/CFS. On 27 October 2019, the National Health and Medical Research Council (NHMRC) called for ME/CFS applications from Australian researchers for this grant. The initiative is designed to attract high-quality collaborative research, and acknowledges that ME/CFS is a complex condition that leaves sufferers with persistent disabling fatigue, particularly after activity. This opportunity should enable Australian researchers to identify: approaches that could help patients be accurately diagnosed and treated the pathophysiology and causes of ME/CFS the impact of the condition. The announcement notes that there 'is a lot more to be done to help Australians living with ME/CFS'.