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[CFS-L] Will there ever be a test for CFS ?

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Dr. Marc-Alexander Fluks

Sep 2, 2021, 3:46:09 AM9/2/21
Source: Medical Device Network
Date: September 1, 2021
Author: Chloe Kent

Will there ever be a test for chronic fatigue syndrome?

Chronic fatigue syndrome is diagnosed not through a blood test or scans,
but by ruling out other conditions with similar symptoms.

Treating chronic fatigue syndrome, also known as myalgic
encephalomyelitis (CFS/ME), starts with getting the right diagnosis -
something that, for many patients, can prove elusive. Characterised by
debilitating tiredness, the condition is notoriously difficult to pin
down and even more challenging to treat. CFS/ME expands far beyond
exhaustion alone, with patients often also enduring flulike symptoms,
musculoskeletal pain and brain fog. Around one in four people with
CFS/ME are so severely unwell they are housebound.

The difficulties in obtaining a diagnosis are numerous. Patients
typically undergo extensive tests for their various physical symptoms
before landing on a diagnosis of CFS/ME when no other condition can be
found to fit. Symptoms can be nebulous and vary over time, leading to
uncertainty about the underlying problem for both the patient and
clinician and many people with CFS/ME also report being repeatedly
disbelieved by doctors. The emergence of long Covid - which some
clinicians believe could be CFS/ME presenting at a large scale from one
single, identifiable cause - has reopened the discussion around ME

Research carried out at Imperial College London recently suggested that
long Covid could be diagnosed through a simple blood test. Researchers
have been able to find specific autoantibodies in the blood of long
Covid patients that were not found in the blood of people who recovered
quickly from Covid-19 or never tested positive for the disease.

Where regular antibodies work to fight off infections, autoantibodies
mistakenly target and react with a person's own tissue and organs,
rather than invading pathogens. But while long Covid may well be a
subsection of CFS/ME, the condition at large is likely to be a
multisystem, multifactorial disease - not every case will have been
triggered by one specific viral infection. This means that any objective
diagnostic test for CFS/ME will need to be far more complex than a
standalone blood test.

'ME as a condition doesn't appear to have a single, unifying trigger,'
says University of Exeter Medical School senior clinical lecturer and
Action for ME medical advisor Dr David Strain. 'We know that long Covid,
for example, has been caused by this particular coronavirus, but there
are many different viruses that can trigger the post-viral syndrome that
we believe is the underlying cause of ME.'

Chronic fatigue syndrome: what are the causes?

The root causes of the disease remain unclear, although several theories
exist. People with the condition often find it initially manifests as a
run-of-the-mill flulike illness, leading many researchers to suspect
that CFS/ME may be triggered by infectious disease. Long Covid could
fall into this category. Others believe that the condition could be
caused by a change in the person's immune system and how it reacts to
infection or stress, through chronic production of cytokines, low
functioning natural killer (NK) cells or differences in markers of
T-cell activation.

CFS/ME may also arise from a faulty hypothalamic-pituitary-adrenal axis
(HPA axis), a network that controls the body's reaction to stress and
regulates processes related to immune response, digestion, energy usage
and mood. People with CFS/ME may also have differences in the way the
cells in their bodies get energy, while studies done in twins and
families suggest that genes and environment might have a role to play

Post-exertional malaise and microRNA

There is no objective test for CFS/ME yet, but there have been steps in
the right direction. A key marker of CFS/ME is post-exertional malaise
(PEM), the worsening of symptoms within 12 to 48 hours of even minor
physical or mental exertion, that can then last for days or weeks. This
symptom was utilised by researchers attempting to develop a molecular
test for the disease in a November 2020 study published in Scientific

The researchers sought to find microRNAs tied to this symptom to try and
pinpoint a specific CFS/ME biomarker. To spare patients a full bout of
PEM, the research team used a therapeutic massager - an inflatable arm
cuff that exerts gentle compressions - to induce a milder form. The 11
housebound CFS/ME patients involved in the initial study all reported
headaches, muscle pain and fatigue following use of the massager.

The researchers drew plasma samples from the participants before and 90
minutes after this activity. The samples were then screened for
differences in levels of microRNAs. The team was able to find 17
microRNAs for which the levels had shifted significantly following the
test. A control group of eight age and sex-matched healthy individuals,
who underwent the same activity but did not report any PEM symptoms, did
not show the same changes.

This experiment was then repeated in a larger cohort of 32 CFS/ME
patients and 17 matched controls. This time, the same response was found
for 11 microRNAs. Seven of these 11 microRNAs were associated with
regulating immune functions, These findings will require validation in
larger cohorts, to see if the test can diagnose patients at different
stages and severities of ME/CFS.

Objectivity in CFS/ME

A key issue that arises during discussions of an objective test for ME
is how useful the tool may be in practice. Since there appear to be
multiple contributing factors that cause the condition, a test that can
only pinpoint one or two may cause problems of its own. 'One of the
problems that we have with doing these tests is that many CFS/ME
patients have spent decades being told there's nothing wrong with them
and have had a series of normal test results,' says Strain. 'This makes
getting cohorts together so that we can start looking for other
underlying cases difficult, with this theory in the background that if
this test is negative too it's just another excuse for a doctor to tell
them there's nothing wrong.'

A test for the condition coming back negative because it assesses a
contributing factor which only some patients experience could be
devastating for those who receive get another negative result.

ME Association honorary medical advisor Dr Charles Shepherd says:
'You've got to end up with a test which is robust and consistent before
you introduce it as a gold-standard diagnostic test. If you've got a
test which is fairly accurate but not totally accurate you could end up
having people who have a firm blood test diagnosis of CFS/ME and then
another group who probably have the condition but don't have that
gold-standard diagnosis.'

However, Strain says that the mere existence of a CFS/ME test could also
be incredibly validating. Even if it worked for only a subsection of
patients, it would prove that the medical system is beginning to take
them seriously. Strain says: 'Even if we develop a test that works for
only 20% of patients, the other 80% suddenly get hope that even if there
isn't a diagnostic test that fits them yet, the fact that this one has
been found means that at least there is recognition in the medical
profession that there is something wrong.'

(c) 2021 Verdict Media Limited
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