Saturday, December 8, 2018

Cardiac abnormalities in ME/CFS not due to deconditioning

MEA Summary Review: Cardiac abnormalities in ME/CFS not due to deconditioning


MEA Summary Review: Cardiac abnormalities in ME/CFS not due to
deconditioning | 26 November 2018

Charlotte Stephens, Research Correspondent, ME Association.


Click to download our 7-page summary review.

Linda van Campen and Frans Visser from the Netherlands have just
published a study
that examined stroke volume and cardiac output in ME/CFS. It confirmed
earlier findings from a smaller study that changes occurred in these
two key cardiac measures despite normal tilt-table results (Timmers et
al., 2002).

Both studies found reduced cardiac output and stroke volumes during a
tilt table test in ME/CFS patients compared to healthy controls.
However, these patients had normal tilt table results, meaning their
heart rate and blood pressure did not change significantly enough to
be diagnosed with orthostatic intolerance.

The authors of the earlier study suggested that these findings were
due to deconditioning, but in this new, larger study, Van Campen and
Visser showed they were not as they found no difference in results
between different disease severities.

If it were a case of deconditioning, the cardiac measurements would be
worse in the more severely affected compared to the mild, as they have
poorer physical functioning.

What made this study better than the previous one?

Much larger patient cohort. The previous study tested 26 ME/CFS
patients, whereas this current study involved 150 ME/CFS patients.
Improved method of measuring cardiac parameters. The reliability of
the previous study's method (pulse contour analysis) is questionable,
whereas the current study used a validated technique (suprasternal
aortic Doppler echography) (van Geldorp et al., 2011).
The latest study compared results across illness severities. This
revealed that the cardiac abnormalities could not be due to

What were the two key measures found to be different?

Cardiac output = The volume of blood pumped by the heart per minute.

Stroke Volume = The volume of blood pumped by the left ventricle of
the heart per heartbeat.

Both of these measures usually decrease upon standing. However, they
were found to decrease more in the patients with ME/CFS, compared to
the healthy controls.



This research review is available for free.


Click to read online or to download.


The MEA Ramsay Research Fund Christmas Appeal

We want to invest in more research in 2019 and we need you help to do it.

If you would like to support our Christmas Appeal, then please:

Donate online via our JustGiving page
Donate by card over the phone to head office (01280 818964).
Donate by cheque payable to The ME Association (with a note saying
that it is for the Christmas Appeal) to ME Association, 7 Apollo
Office Court, Radclive Road, Gawcott, Buckinghamshire, MK18 4DF.

For more information please visit our Christmas Appeal webpage
<> . And if you have any
questions get in touch with Helen Hyland or Head Office. Thank you.

* * *

I once led a doctor by the hand through no, you would not become that deconditioned that quickly; it would take months to become so deconditioned that you can't walk two blocks.  

And half a minute later, he was back to insisting that I was "just deconditioned" and needed to exercise my way back to health.

So I walked him through it again, that in a matter of days I went from being able to walk 5 miles a day to barely making it from the bus stop to my desk, and then having to rest for an hour before I could do any work.  Again, he agreed that it would take months to get that out of shape, and again he promptly reverted to telling me that there was nothing physically wrong other than I'd let myself become deconditioned and would be back to normal in a jiffy if I just pushed myself to exercise a little more each day.

Another Warrior Gone

In Memoriam Jan van Roijen 
June 11, 1937 - December 5, 2018

Today the utterly sad news of the death of Dutch ME-patient Jan van Roijen reached us. He died Wednesday night in a nursing home where he spent the last few months of his life of 81 years.

Jan was known throughout the ME-world for his detailed knowledge of ME in all its aspects, which he shared with the global community through his bulletin Help ME Circle, for his generosity and kindness and for his humour, even in spite of his being so severely ill. Until very short before his death he lived in his apartment at the second storey of a monumental building in the very centre of Amsterdam.

Jan was a top-actor who performed with wellknown actors like Willeke van Ammelroy and other famous Dutch actors on stage when he fell seriously ill. One by one he lost all his friends and was visited by only a handful of friends during the last years of his life.

Rest in peace, dear friend…

Sunday, November 18, 2018

Wednesday, October 24, 2018

Symposium on the Molecular Basis of ME/CFS

At the three-day Working Group Meeting and Community Symposium on the
Molecular Basis of ME/CFS at Stanford University, sponsored by OMF, so
much scientific progress was evident. We are clearly progressing from
just data gathering to formulating new hypotheses as to the causes of
symptoms and even a possible cause of the disease. The buzz of hope
was palpable!

The Working Group Meeting brought together over 50 researchers from
around the world. Ronald W. Davis, PhD, OMF Scientific Advisory Board
Director, invited world-renowned researchers who were open to
collaboration and sharing unpublished data. As Dr. Davis said, "I
invited brilliant people with a high intellect to arrogance ratio who
are working on ME/CFS at the molecular level. The knowledge shared
this year was considerably greater than last year. The excitement to
begin new collaborations was intense. They were so engaged in planning
out their new collaborations that it was difficult to start the next
session. It felt like an explosion of ideas."

The Community Symposium gathered together patients, caregivers,
clinicians, and researchers. We welcomed nearly 300 participants at
Stanford and over 4,800 Livestream participants. The day was filled
with excellent research reports, the warm embrace of community, and
shared tremendous hope.

I want to thank the researchers for their dedication and hard work,
and everyone involved in this great event who made it such a success.
Thank you also to all the donors who made this important work
possible. Without you this progress couldn't have happened.

Below is a summary of the Community Symposium prepared by Christopher
Armstrong, PhD.

With hope for all,

Linda Tannenbaum
Founder & CEO/President


Second Annual Community Symposium on the Molecular Basis of ME/CFS Summary
By Christopher Armstrong, PhD

During the last week of September, a 3-day Working Group Meeting on
the Molecular Basis of ME/CFS was capped off by a Community Symposium
at Stanford University. It was the second annual meeting of its kind
built upon the success of the year before with the working group
meeting stretching out an extra day beyond its predecessor. The
quantity of contributing researchers was impressive, but the quality
of the research was particularly inspiring.

The message of the year before was about trying to accumulate as much
information as possible, to gather the puzzle pieces. This year the
puzzle pieces have begun to be resolved with the next challenge to
determine how they fit together.

The Community symposium began with a welcome from Linda Tannenbaum,
OMF Founder and CEO/President, greetings from Janet Dafoe, patient
liaison, and opening remarks by Ron Davis, symposium chair.

The talks began with Dr. Raeka Aiyar, the Symposium moderator, who now
works for the New York Stem Cell Foundation (NYSCF). Stem cell
applications for research is an area that Dr. Aiyar believes has the
potential for helping understand ME/CFS and to find treatments.

Dr. Oystein Fluge gave the Keynote Address. Unable to provide specific
details about the recent Rituximab trial, Dr. Fluge went on to
elaborate on previous studies of metabolism on ME/CFS patients and
other prospective clinical trials that are underway. Their lab is
uniquely set up to allow interaction between clinical trials and
observational research with both areas concurrently informing the

The current clinical trial Dr. Fluge is working on is CycloMe, an
open-label phase 2 trial looking at the effect of cyclophosphamide on
ME/CFS patients. "The results are interesting!" However, more details
are not able to be shared until publication.

The central point of their metabolism studies is that it is consistent
with several other publications from other researchers. The additional
information they provide is an inhibited pyruvate dehydrogenase
complex (PDH), an enzyme that enables the entry of sugar breakdown
products to enter the mitochondria (the powerhouse of the cell).
Interestingly, this enzyme is a central energy metabolism control
point that can determine if sugar is largely used for energy
production or if amino acids and fatty acids are being utilised
instead. The latter seems to be the consensus findings across research

Dr. Wenzhong Xiao unloads a wealth of findings from the Severely Ill
Patient Study (SIPS) he heads up at Stanford. Sleep monitoring
determined several alterations compared to healthy controls, while
morning cortisol levels were also attenuated. Together this indicates
a significant impact to the sleep/wake cycle of people with ME/CFS.
Viral pathogens have long been tied to ME/CFS with no consistent
findings. Dr. Xiao described an extensive virus search that found no
significant difference in viral pathogens between patients and
controls. The study of the microbiome revealed variations in the
bacteria of the gut, and interestingly, a neuroprotective metabolite
(3-Indolepropionate) produced by gut bacteria appears to be
significantly reduced in ME/CFS patients.

Dr. Xiao caps off his findings by displaying an integrative web of all
associated data points from the SIPS study connected to the central
diagnosis of ME/CFS. The hope is to add the data from other studies to
discover if the connected associations continue to hold.

Next up is Dr. Jonas Bergquist discussing his new study looking at
peptides and protein markers in the cerebrospinal fluid (CSF) from
ME/CFS patients, Multiple Sclerosis (MS) patients and healthy
controls. He reveals preliminary data from the study that show
elevations of protein markers indicative of neuroinflammation, cell
damage and repair in ME/CFS, and significant differences are observed
between MS and ME/CFS patients.

Secondly, Dr. Berquist screens for steroid levels and has found a
decrease of pregnenolone with non-significant downregulation of most
other steroids. Pregnenolone is a neurosteroid produced in the

Thirdly, Adrenergic and Muscarinic receptor autoantibodies were
significantly elevated in plasma from ME/CFS, and this has now been
observed in two separate studies. Importantly, no such autoantibody
changes were found in the CSF.

Dr. Alain Moreau is looking into the role of circulating microRNA in
ME/CFS. MicroRNA are small molecules that circulate throughout the
body and can regulate the production of proteins and enzymes from
genes. He hypothesizes that "ME/CFS is caused by a disturbance in the
expression of microRNAs, which modulate immune functions, energy
metabolism and physiological stress response". Dr. Moreau uses a
massager arm cuff to stimulate a reaction in ME/CFS patients, a simile
to post-exertional malaise. He measures the microRNA before and after
this stimulation and measures the alteration that occurs in ME/CFS as
compared to controls. Significant variations occur between ME/CFS and
controls. Furthermore, the data is able to be split into 4 subtypes
based on the microRNA, which relates to variations in symptom

Dr. Maureen Hanson follows in a similar vein to Dr. Moreau by looking
at studying ME/CFS patients before and after an exercise challenge to
compare the dynamic response of ME/CFS patients as compared to healthy
controls. This study will focus on metabolite, gene expression and
cytokines. Similarly, a second study looking at ME/CFS patients on
Ampligen will look at symptom changes over time in conjunction with
changes in metabolites, gene expression and cytokines.

Dr. Hanson also reports on a new metabolomics study looking at ME/CFS
compared to controls. The findings align nicely with previous studies,
and upon analyzing data across other studies in the field, there were
no separate sub-groups identifiable based on the metabolites.

Dr. Ron Tompkins begins by talking about the initiation of the ME/CFS
Collaborative Research Center at Harvard (which Dr. Davis 
affectionately calls the "Stanford of the East")
. Dr. Tompkins professes his embarrassment as a Doctor by the way his community
generally responds to a disease they don't understand. Dr. Tompkins
has spent a lot of time researching the impact of significant trauma
on the body that was significant enough to kill you (a 20% mortality
rate). Through these studies he has a strong working knowledge on the
interplay of inflammation, immunity and metabolism.

The initial research they aim to begin is a thorough understanding of
muscle recovery with a multi-omic exploration of muscle biopsies from
ME/CFS patients, the first study of its kind. They also wish to begin
functional neuroimaging studies. The focus seems to be on
understanding the differences in tissues of the body as distinct from
blood plasma and immune cells.

With enhanced funding, the Research Center at Harvard would be ideal
for a setup of clinical trials to fast-track promising and potential
treatments for ME/CFS.

Michael Sikora is a graduate student under Lars Steinmetz, professor
of genetics and member of the Stanford Genome Technology Center who
are collaborating with Mark Davis. He has been working to establish
the role of T cells and the immune system in ME/CFS. They have found
the significant increase in T cells in ME/CFS patient compared to
controls indicating an activated immune response. Furthermore, the T
cell expansion signature appears distinct in ME/CFS from other
diseases like Multiple Sclerosis and Lyme disease where immune
activation is also present. Currently, they are focusing on the cause
for the immune activation, whether it's in response to an infection or
in response to self (autoimmunity).

Dr. Jarred Younger discusses his recent research on neuroinflammation.
Using a similar technique to an MRI, Dr. Younger can evaluate the
levels of metabolites in sections of the brain. Lactate is a
metabolite found as the product of sugar breakdown for energy
production (known as the process of glycolysis). Lactate was found to
be elevated in areas of the brain that are responsible for the
sickness response. "This is exactly what would happen if ME/CFS was a neuroinflammatory disorder", Dr. Younger explained. The method used
also enables the prediction of temperature in the brain, and
temperature increase is apparent in the brain of ME/CFS patients.

The same regions of the brain in which Dr. Younger had found
elevations in lactate and temperature indicative of neuroinflammation
were also previously observed to have activated microglia, which are
consistent with neuroinflammation.

Dr. Ron Davis discusses the search for biomarkers with a particular
focus on three new technologies being developed to find differences
between ME/CFS and healthy controls. First, he reintroduces the
impedance test as a marker for ME/CFS. The addition of salt to ME/CFS
and control plasma was enough to produce a significant alteration in
the ME/CFS impedance signal as opposed to the control signal. Second,
new technology produced in conjunction with San Jose State University
looks to assess red blood cell deformability in ME/CFS patients by
evaluating the speed of transit through a tiny capillary. They have
found that ME/CFS cells are significantly less deformable than healthy
cells. Finally, magnetic levitation of cells shows that ME/CFS white
blood cells are lighter than those of healthy controls. All these
instruments effectively separate ME/CFS and control plasma, red blood
cells or white cells, and each is fabricated for a very low cost. It's
possible to create a device that combines these methods of detection
to enhance specificity. All these instruments in conjunction with
metabolite tests from Dr. Robert Naviaux and Dr. Robert Phair will be
compared in a "bake-off" to determine the most effective diagnostic
for ME/CFS. The key for a successful diagnostic is that it accurately
identifies illness (low false positives and false negatives, is easy
to produce and simple enough to perform that it may be usable

Dr. Robert Phair is now known as the "metabolic trap guy". He comes
from a background of engineering and physiology and hopes to apply
systems engineering to human physiology. His focus is on modeling of
complex metabolic systems, with a corrent focus on substrate
inhibiting enzymes.

He emphasizes that the outbreaks of ME/CFS were a particularly
important clue to him that suggested that any genetic component
related to the illness would likely be common.

He discusses non-linear system theory as important for biology but
especially important in explaining some of the confounding elements of
ME/CFS. His hypothesis began with identifying areas of metabolism that
could form bi-stability, two steady states that can be entered into
that are functionally distinct from each other, one healthy and one

First he found mutations in a gene called IDO2. IDO2 is an enzyme that
converts tryptophan (an essential amino acid) to kynurinine.
Tryptophan is also processed to seratonin. IDO2 is one of two enzymes
that process tryptophan, the other being IDO1. These two enzymes seem
to do identical things, but it's actually more complicated. At lower
levels of tryptophan, IDO1 converts tryptophan to kynurenine, but IDO2
is inactive. But IDO1 is a substrate-inhibited enzyme whereby too much
tryptophan in a cell stops its function, causing tryptophan to no
longer be processed and build up its levels in the cell. At these high
levels of tryptophan, IDO2 takes over the processing of tryptophan.
However, all the ME/CFS patients in the SIPS cohort had mutations in
IDO2 making it non-functional. Without IDO2 there is essentially a
block created that stops tryptophan converting to kynurenine and could
force it through to serotonin.

Flux experiments were initiated to measure the levels of tryptophan
and kynurenine in ME/CFS white blood cells; these showed that
tryptophan is higher and kynurenine is lower than in healthy controls,
consistent with the existence of a metabolic trap in the patients
tested. These experiments have only been conducted on 6 ME/CFS
patients and 6 healthy controls so far, and more patients will be
tested as fast as possible.

Dr. Ron Davis closes the symposium by explaining the importance of Dr.
Phair's findings but also warns about cherry-picking of data to
support a hypothesis. Good science is accomplished by forming a
testable hypothesis that makes specific predictions and doing
experiments to see if those predictions obtain. This work is still at
the beginning and will require much more exploration to determine
whether it is definitive of ME/CFS. Dr. Davis also emphasizes the need for funding at the present time. To any big donors out there, he urged, "This is the time to donate, as we may be on the precipice of a crucial finding for the illness." Dr. Davis then explained how
fundamental these pathways are to the control of a person's
biochemistry, and that It's exceptionally dangerous to begin
experimenting on one's self without more information.
Self-experimentation could have dire consequences. Dr. Davis implores
the patients to be patient.

In summary, Dr. Davis states: "A lot of progress has been made in the
last year. There is a lot more data and it is now generating testable
hypotheses. More exciting collaborations are being established.
Excellent new people are entering the field. The future is looking
even more hopeful. Our partnership with OMF has been instrumental for
this progress and for the support of this symposium. We are now on the
brink of even more exciting progress, but as always, funding is the
rate-limiting step. Now is a crucial time to donate to accelerate the

Tuesday, October 23, 2018

NIH Funding Down for 2018

NIH Funding for ME Goes Down in 2018

Posted on October 21, 2018 by Jennie Spotila


Fiscal year 2018 is over, so now we can answer the question of whether
ME research funding at NIH would go up or down. As I predicted back in
July, the answer is down.

Here's the TL;DR version:

- NIH funding for ME research decreased 17% in 2018.
- Funding for non-Center grants will decrease an additional 30% in
2019 unless NIH funds enough new grants to replace the expired ones.
- NIH's funding is now heavily concentrated at a small number of institutions.
- NIH's ancillary activities are not sufficient to overcome the funding problem.
- Some of the most important contributors are missing in action.
NIH must stop blaming people with ME for the low number of research
- Given that NIH funding has decreased, how should we respond?

Friday, October 19, 2018

Medical Providers can Watch UNREST for Credit


October 17, 2018
By #MEAction

Categories: Actions, Featured actions, Uncategorized, United States

We are so thrilled to announce that US healthcare providers –
including doctors, nurses, pharmacists, therapists and social workers
– can now watch Unrest and receive continuing education credits
through the American Medical Women's Association and Indiana
University School of Medicine, in partnership with #MEAction.

Healthcare providers can attend a live, continuing education event
screening of Unrest – at a theater, hospital, university, clinic or
community center – or register to watch Unrest online; watch a
10-minute video on the diagnosis & management of ME by Dr. David
Kaufman; take a short test; and receive 2.0 American Medical
Association PRA Category 1 Credits™.

We are so excited for the new way to use Unrest as a tool to educate
even more doctors and healthcare providers, and continue to raise
awareness about the realities of ME. Read on about our plans to
disseminate this new educational module and learn about how you can
help us get the word out!

The Unrest CE program is currently only available to medical providers
in the U.S. However, we would love to launch similar programs in other
countries around the world, and are currently working on accrediting
Unrest for CE in the UK and Australia. If you are interested in
learning how you can support these efforts, please email

1. Support #MEAction's 10-City medical education tour

The Time for Unrest campaign kicked off this tour with a packed
screening at Harvard Medical School in February. In March, we
transitioned the film campaign to #MEAction. Leveraging our staff and
network of volunteers, we want to bring the live event to ten more,
major medical schools, nursing schools, hospitals, and other leading
health institutions around the country in the next year, starting with
our screening at Stanford Medical School on November 15th. You can
support those efforts by making a donation to fund outreach and

Students, faculty, residents, and physicians gather for a Q&A after a
screening of Unrest at Harvard Medical School.


2. Host a medical education screening in your city

Bringing together medical providers for an in-person event is a
powerful way to educate them about ME. When you sign up to host a
medical education screening via #MEAction, you'll receive a fee waiver
code to publicly screen Unrest for free and a toolkit with soup to
nuts advice on outreach to your local medical community, sample
posters and graphics to promote your event, inclusion of your
screening on the Unrest website, and sharing of your event on Unrest
and #MEAction social media channels.

Host a CE Screening of Unrest

3. Ask your doctor to complete the course online

If you are unable to host a community screening, we encourage you to
reach out to your doctor or medical provider via email or in-person
(at your next appointment!), and ask them to complete the Unrest CE
course online.

Print out or email this flyer to let your doctor or medical provider
know about the Unrest CE program.

Share our one-pager on the diagnosis & management of ME
Is your doctor a science geek? You can also share this #MEAction's
summary of recent ME/CFS research

4. Join the organizing call

We will be hosting a call next Thursday, October 25th to talk about
the Unrest CE program, answer any questions about how to host a CE
Unrest screening, and discuss how to reach out to your medical
provider about completing the course online. Learn from experienced
screening organizers and brainstorm even more ways to get the word out
to the medical community!

Join the Call

One of the biggest challenges we face as a community is that so many
clinicians don't have the information they need to diagnose and treat
people with ME. Medical practitioners are required to complete CEs in
order to maintain their licenses. Continuing medical education is a
necessity for them and presents an opportunity for us. We're going to
work hard with our partner organization, the American Medical Women's
Association, to get the word out about this CE opportunity to national
and state medical associations across the country, and are so excited
about our ten city tour. But reaching medical providers in your local
community begins with you.

You have the power to change what clinicians will tell their patients
and colleagues, what they will teach in their classrooms, what they
will talk about around their dinner tables — to transform care. Now is
the time to educate our doctors and medical providers about ME.

* Feature photo by Cynthia Abatt. | Photo caption: Moderator Deborah
Becker, panelists Michael Van Elzakker, Mary Dimmock, Kiki Zeldes and
Lisa Hall, RN at a screening of Unrest in Arlington, MA, organized by
the Massachusetts ME/CFS & FM Association.


Categories: Actions, Featured actions, Uncategorized, United States

Support our work!

Did you find this content useful?

Help us keep going and keep growing. Make a recurring donation today.

Most people don't take the time to donate but if every visitor pledged
just $1 per month on a recurring basis, we could fully fund #MEAction.
Tags: CE credit, CME, Unrest

Thursday, September 27, 2018

When Medical Symptoms are Dismissed as "All In Your Head"

Expert Q&A

When Medical Symptoms Are Dismissed as 'All in Your Head'
by David Tuller, DrPH

Journalist Maya Dusenbery's new book—Doing Harm: The Truth About How
Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and
Sick—is an in-depth examination of how gender bias in medicine has
negatively impacted women's health for generations. In a starred
review, Publishers Weekly noted that Doing Harm "skillfully
interweaves history, medical studies, current literature, and hard
data to produce damning evidence that women wait longer for diagnoses, receive inadequate pain management, and are often told they are imagining symptoms that are taken seriously in men."

Dusenbery, a Minnesota native, has written about women's and
reproductive health issues for a wide variety of media outlets,
including Slate,, HuffPost,, and Teen
Vogue. She is the editorial director of the feminist site, and she has previously been a fellow at Mother Jones
magazine and a columnist at Pacific Standard. Before becoming a
full-time journalist, she worked at the National Institute for
Reproductive Health. Doing Harm, which was published by HarperOne, is
her first book.

We recently talked with Dusenbery about her book and her other work.

What started you on this book project?

About five years ago I was diagnosed with rheumatoid arthritis, and
that got me started down this path. I had a pretty easy time getting
diagnosed and always felt my concerns were taken seriously. Once I was
diagnosed, I got interested in learning more about autoimmune
diseases. I learned that many autoimmune patients—most of whom are
women—aren't as lucky as me. According to one recent survey, the
average autoimmune patient sees four doctors over four year before
being properly diagnosed, and about half report being dismissed as
"chronic complainers" during that time. And as I started to tune into
it, I started hearing lots of stories from female friends and peers
who'd struggled to get diagnosed with other health problems and felt
like their symptoms weren't being taken seriously, or that they were
being treated as if the symptoms were "all in their head." And as a
feminist I wanted to understand what those experiences were rooted in.

The book reviews how ME/CFS (myalgic encephalopathy/chronic fatigue
syndrome), fibromyalgia, many autoimmune diseases like multiple
sclerosis, and other chronic illnesses are all part of the group you
refer to as "the disorders formerly known as hysteria." Can you

There are a lot of diseases we recognize today that have been carved
out of a wastebasket diagnostic category of illness that in past
centuries was called hysteria and since then has gotten different
euphemisms, like psychogenic, psychosomatic, or somatization
disorders. ME/CFS is one of them—I think that is a pretty dark example
of a condition that disproportionally affects women and is very much
stereotyped as a women's disease. That is in large part why, I would
argue, it is understudied and belittled. Skeptics of the illness have
often pointed to the fact that it mostly impacts women as a reason to
believe that it's psychosomatic.

That's a common pattern. Conditions like interstitial cystitis,
fibromyalgia, endometriosis, and vulvodynia also have a very similar
history: You find descriptions in the past medical literature that
match them, but for decades beginning in the early 20th century, when
hysteria came to be seen as a psychological problem post-Freud, they
were just assumed to be psychosomatic. It wasn't until the eighties
and nineties that some of these conditions were even named and
defined, let alone studied. And for all of them, it's been very
difficult to get research funding because they were assumed to be
psychosomatic. But that's the catch-22: You can't prove they're not
psychosomatic unless you do the research. And again, I think a major
reason that medicine has been so content to believe these conditions
are psychosomatic is that they disproportionately impact women, and
there's this long tradition of viewing women as especially prone to
"hysterical" symptoms.

What were your main findings about why we're in the situation we're in?

The book lays out two problems that I see in the system—what I refer
to as the knowledge gap and the trust gap. The knowledge gap refers to
the deficit of knowledge we have had about women's bodies and about
conditions that disproportionately affect women. That's a legacy of
the many decades during which women were excluded from clinical
research and their concerns were a low priority on research agendas.
And the trust gap has been the tendency on the part of health care
providers to not trust women's self-reports of what they're
experiencing in their bodies—to minimize, normalize, or psychologize
their symptoms. And that, in turn, has led to a lack of trust in the
medical system on the part of women who have experienced this

For me, the most striking thing that I discovered in the research was
how those two problems seem to be so mutually reinforcing. The less
knowledge we have about women's health, the more women find their
symptoms are "medically unexplained," and then the symptoms often get
dismissed as psychological. So the knowledge gap sort of creates this
presumption that women's symptoms are often psychosomatic. On the flip
side, the tendency to assume that women's unexplained symptoms must be
psychosomatic has perpetuated these knowledge gaps, since it leads to
a lack of research—and even a lack of awareness of the need for

I think this is very much a problem that's rooted in systemic and
unconscious gender bias. I certainly don't think in most cases it's
based in any sort of consciously held prejudice—it's about these
implicit assumptions that we all have, male or female, in the medical
profession or not. And it's also in large part about how medical
knowledge itself has been impacted and skewed by gender bias over the
centuries. I'm hopeful we can turn this around, because there does
seem to be somewhat more openness within the medical profession today
to thinking about these implicit biases and acknowledging that there
are some gaps in medical knowledge.

Can you elaborate on the concept of medically unexplained symptoms?

Medically unexplained symptoms, or MUS, is a phrase that applies to
individual symptoms that patients present to a doctor that the doctor
doesn't think are attributable to a physical cause. The term is also
used to refer to a range of illnesses, like fibromyalgia, ME/CFS,
irritable bowel syndrome, and others without identified causes. Most
patients with MUS—about 70 percent, according to the medical
literature—are women. In the literature, MUS is often used
synonymously with terms that imply a psychogenic cause, like
somatization disorder. That reflects a deeply ingrained tendency in
medicine to assume that anything that is "medically unexplained" must,
by default, have a psychological explanation instead.

So the problem is that medicine tends to see medically unexplained
symptoms not just as medically unexplained but medically
unexplainable. And the term is also used as if it is a disease
category in and of itself. That is, MUS is talked about as if it's a
'thing,' even though it covers everything from idiopathic low back
pain to unexplained seizures or other symptoms that are only united by
the fact that they're not fully explained by medical science. These
symptoms go into that diagnostic wastebasket, which is where
everything we can't explain goes until we can explain it. Over the
decades, many conditions have been removed from the wastebasket and
accepted as legitimate diseases as we have come to better understood
their underlying mechanisms. But, as we've seen with ME/CFS and other
"disorders formerly known as hysteria," that evolution can take a long
time because they're less likely to be researched if they're in the

Another big problem with how the concept of medically unexplained
symptoms is used is that it tends to obscure the reality of diagnostic
errors. In the medical literature, it's reported that a high
percentage—from one-third to two-thirds—of patients seen in both
primary and secondary care have MUS. But there is not much
acknowledgment that at least some of these cases are patients with a
perfectly diagnosable disease who just haven't gotten that diagnosis
yet. There are very few follow-up studies to show how many patients
with alleged MUS actually get diagnosed down the line. Often it's not
even acknowledged that you need that follow-up study—that saying X
percent of symptoms are medically unexplained without knowing what
happened afterwards isn't very meaningful data.

What are the implications for patients if something is treated like MUS?

Symptoms that are lumped into this category are thought to be already
explained by psychiatric problems, so patients are inappropriately
treated with psychotropic drugs or referred for psychotherapy. And, of
course, they're also not getting the treatment they do need. If
patients are labeled with MUS when they actually have a
yet-to-be-diagnosed disease—like an autoimmune disease—that can mean
lasting disability or death.

There is also a lot of circular reasoning when it comes to deciding
that a patient is experiencing MUS. Doctors are told that patients
with MUS tend to insist that their disease is physical, resist
psychiatric treatment, and see many health care providers—or "doctor
shop." But, of course, all of those things are exactly what a patient
with an undiagnosed medical condition would be doing. These are
perfectly rational behaviors and yet they're somehow taken as hallmark
signs that these patients don't have a physical disease. This creates
a very dangerous dynamic where once a patient has been labeled as
having MUS, it becomes extremely difficult to convince doctors
otherwise—everything you might do will just seem to confirm it.

Isn't this situation frustrating for doctors as well as patients?

Very much so! And I'm certainly sympathetic to individual doctors—I
can see how it would be very easy to be frustrated with patients
experiencing an illness you can't explain, and then project some of
that frustration onto the patients. But it's important for doctors to
recognize that a patient who is reporting symptoms that they don't
have any explanation for might have her symptoms explained down the
line by another doctor. And what I learned from experts in diagnostic
error is that there is overconfidence among doctors about their
diagnostic skills—they recognize that diagnostic errors happen but
think that they personally don't make them very often.

And that's not even their fault. The problem is we don't have feedback
systems in place that will actually let doctors know they made an
error. So they assume they've gotten the diagnosis right unless they
hear otherwise—and they usually don't unless the patient themselves
comes back to tell them they were wrong. In other words, they
overestimate their batting average, and they also continue to hold the
same stereotypes they had about her: that she was yet another woman
complaining of "medically unexplained symptoms." And that affects how
they perceive the next woman who comes to them reporting similar

Frankly, doctors should be on the front lines calling for an
investment in scientific research to explain these poorly understood
conditions so that they are no longer in the position they're
currently in: unequipped to offer a large percentage of their patients
an explanation and effective therapies for their illnesses. This
status quo is bad for everyone, doctors and patients, and severely
erodes the doctor-patient relationship. But doctors are in a better
position to bring about the change that's needed to close these
knowledge gaps.

Published September 27, 2018