What’s New in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome Research for 2021?

From the IACFS/ME Virtual Conference 2021

Attending the IACFS/ME Second Virtual Scientific Conference, I was left with hope for the future. The number of serious biomedical researchers in the field is steadily increasing and their findings are providing ever more detail about the core immune, metabolic, cardiovascular and inflammatory abnormalities in ME/CFS. 

Sadly no new treatments for ME/CFS are ready for clinical use. The only treatment information shared at the conference were case studies by experienced clinicians.

• Dr. Hector Bonilla from Stanford University shared encouraging results on the use of the antipsychotic drug aripiprazole in ME/CFS. These results have been recently published and are available online. So far, I have had one patient try aripiprazole with good success (considerable increase energy and ability to engage in daily activities) and another patient with no change. If you have tried aripiprazole (Abilify®) let me know so I can expand my knowledge.

• Dr. Tanya Dempsey shared her approach to treating Mast Cell Activation Syndrome (MCAS), a condition that is increasingly recognized as a possible cause of Multiple Chemical Sensitivity and is often present in patients with ME/CFS. Dr. Dempsey runs a private practice in NY State and is a co-author of an influential consensus paper on how to diagnose MCAS. I share in Pathway 7 of my online course Pathways to Improvement that the MCAS hypothesis seems a good fit for many patients with environmental sensitivities. Once I started diagnosing and treating MCAS, it made a huge difference for people who were reacting to everything and hadn’t responded to previous approaches.
  

• Dr. Peter Rowe from John’s Hopkins Medical School presented a case of Cranio-Cervical Instability (CCI) causing the classical symptoms of ME/CFS – which improved significantly after surgery to stabilize the cervical spine. Dr. Rowe published 3 case studies of CCI in 2018 and this paper summarizes the clinical signs suggestive of CCI. Diagnosing CCI is very challenging in Canada due to the lack of facilities able or willing to provide dynamic CT scan and standing MRI. Advocacy will be needed to ensure the appropriate testing is available for all Canadians.

• Dr. David Kaufman formerly of the Center for Complex Diseases in Mountainview California and now working at the Center for Healing Neurology in Seattle Washington presented an open trial of the energy metabolite oxaloacetate and reported it resulted in increased energy without any significant side effects. He is now gathering funding for a blinded study to validate his clinical findings. 

What Causes Long COVID?

Dr. Avindra Nath, head of the National Institute of Neurological Disorders and Stroke at the NIH presented information on long COVID. Between 10 – 30% of people who contract COVID infection still have symptoms 6 months later. Many of these people have evidence of decreased brain blood flow on PET scans. The symptoms of long COVID are very similar to those of ME/CFS: fatigue, exercise intolerance, brain fog autonomic symptoms, temperature dysregulation and aches and pains. 

Are the Long-lasting Symptoms in ME/CFS and Long COVID due to Persistent Infection or Persistent Immune Activation?

Long COVID researchers are now asking the same questions ME/CFS researchers have been asking for decades “are the long-lasting symptoms in ME/CFS and Long COVID due to persistent infection or persistent immune activation”? In Dr. Nath’s opinion, there is evidence for both possibilities.

Autopsies of brains in people who died of COVID show brain inflammation, immune activation around the small blood vessel in the brain and a disrupted blood-brain barrier. The brain stem is most involved. Although the SARS 2 COVID virus is not being found in the brains of affected individuals, it has been found in the gastrointestinal tract.

Dr. Nath reported on a few patients with long COVID who responded to plasma exchange – a treatment that filters antibodies out of the blood. Plasma exchange is used in autoimmune conditions to lower the load of the autoantibodies causing tissue damage. This suggests there may be an autoimmune aspect to long COVID.

Dr. Nath concludes that long COVID has similar immune findings as ME/CFS: a hyperactive innate immune system, T cell exhaustion (apparently this is suggestive of an active infection or ongoing presence of viral proteins) and some autoimmune features.

Is There a Test to Differentiate ME/CFS From FM?

A study with significant, near-term potential for patients was presented by Evguenia Nepotchatykh, a PhD student in Dr. Alain Moreau’s lab in Montreal Canada. The group reported in November 2020 on a profile of microRNA molecules that were related to post-exertional malaise and which correlated with symptom severity. Since then, the group has investigated some of the identified molecules further. Ms. Nepotchatykh reported that one of these molecules, miRNA 374b-5p, differentiated patients with ME/CFS from those with Fibromyalgia 100% of the time. This miRNA targets a gene called PHB2. This gene expression is also significantly different between the ME/CFS and FM group. The gene and others targeted by the miRNA 374b-5p are involved with mitochondrial function and cell cycle regulation. This finding is very important. We are in desperate need of a biomarker to distinguish ME/CFS from FM both for research and clinical purposes. 

How Does Exercise Affect Brain Function in ME/CFS?

Dr. James Baraniuk is an established researcher in the field of Gulf War Illness and ME/CFS. He has published many important papers showing that the brains of people with ME/CFS respond differently to exercise than those of people with GWI or healthy controls. His new work examines the default mode network (DMN) and the midbrain. The DMN is the part of the brain that is active when we are not thinking of anything when we are daydreaming. The midbrain is part of the arousal fight/flight network.

Baraniuk compared the activity of the DMN and the midbrain both in the resting state (pre-exercise) and after exercise in groups with GWI, ME/CFS and healthy controls. Before exercise, the DMN is less active in the ME/CFS group than healthy controls and less connected with other brain areas. The DMN activity increases with activity in the ME/CFS group but decreases in the healthy controls. If the DMN is active, it is harder to engage in focused thought so this activation after exercise may be related to the brain fog associated with PEM.

Before exercise, the midbrain activity of the ME/CFS group is decreased compared with the GWI and healthy control groups. This may be connected with decrease brain blood flow to the midbrain in ME/CFS. After exercise, the midbrain activity in ME/CFS group increases and is equal to the healthy controls. This increase could be associated with the lasting increased adrenaline (wired by tired) that people with ME/CFS experience after exercise. 

Dr. Gudrun Lange is a neuropsychologist and researcher who works with Dr. Benjamin Natelson at the Pain & Fatigue Study Center in New York. She has published many important studies on cognitive function in ME/CFS. She presented data from the Multi-site Clinical Assessment of ME/CFS study funded by the Centers for Disease Control in the United States. The data from objective measures of cognitive function in the Multi-site study replicates previous research showing patients with ME/CFS have slower cognitive processing and processing speed worsens further after exercise. Dr. Lange's research adds to the evidence that exercise is bad for ME/CFS. It worsens symptoms including cognitive function. Working memory is impaired, more so when the patients are under a time pressure. This is what we find in our ETeam cognitive screening assessments using the CNS Vital Signs online battery. The test runs at a pace that is too fast for most people with ME/CFS. They start making errors of omission because they can’t make decisions fast enough. On occasion, we have asked patients to repeat the cognitive battery before and after chemical exposure and have been able to document changes.

Author: Eleanor (Ellie) Stein MD FRCP(C)

I am a psychiatrist with a small private practice in Calgary and am an assistant clinical professor in the faculty of medicine at the University of Calgary. Since 2000, I have worked with over 1000 patients, all with ME/CFS, FM and ES. My passion for this field comes from my own struggle with these diseases, my desire to improve my health and then pass on what I learn. My goal is for every patient in Canada to have access to respectful, effective health care within the publicly funded system.

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