Saturday, December 26, 2015

Ian Lipkin: Three to Five Years* to Solve Chronic Fatigue Syndrome

In a talk covering his virus hunting career, the threat of pathogens to humanity, and his work with chronic fatigue syndrome (ME/CFS), he dropped a bombshell: he stated that he believes it's possible to solve ME/CFS in three to five years. 
Called the top virus hunter in the world, Ian Lipkin runs the Center for Infection and Immunity at Columbia, and is the director of the Center for Research in Diagnostics and Discovery (CRDD) at the NIH. He also worked closely with Steven Soderbergh on his film Contagion.

Likpin cited the findings of their work to date.

  • The suspected pathogens don't appear to be the problem (the CII is reportedly looking further at herpesviruses.)
  • Evidence suggests altered microbiomes (gut flora) are present
  • Striking differences in immune expression between shorter and longer duration patients appear to be present
  • Preliminary evidence suggests that levels "X" and "Y" metabolites and, at least, one immune protein are significantly altered in ME/CFS. (Lipkin embargoed this information pending publication of the paper. One of them is highly unusual.)

Lipkin emphasized, though, that ME/CFS is not a one-size fits all disease. For instance, it's possible that fungi may be a problem for some patients. That's an intriguing idea given the recent fungi funding in Alzheimer's disease published in Nature.

Then Lipkin made his bold declaration "We're going to solve this in three to five years", with a big proviso. Provided the resources are made available, he believes science can crack ME/CFS fairly quickly.


Lipkin was at the event to support the Simmaron Research Institute's next spinal fluid study. The results of the first one – the most extensive spinal fluid study ever done in ME/CFS – were eye-opening. A comparison to multiple sclerosis (MS) found evidence of immune dysregulation almost equal to that found in MS. The difference was that instead of being raised, the cytokine levels were reduced in ME/CFS.

That finding surely left a big smile on Lipkin's and Hornig's faces.  Earlier they had found evidence of a profound reduction in immune functioning in the blood of later-duration ME/CFS patients. Now a similar reduction was found in their spinal fluid. Having findings in two different systems match has rarely happened in ME/CFS. That suggested they were uncovering system-wide problems.

No wonder Lipkin was eager to begin a new and larger spinal fluid study. It's part of achieving his bucket list.



- See more at:

Sunday, December 13, 2015

“Vexatious”: King’s College London dismisses James Coyne’s request


neuroscientist Professor Chris Chambers of Cardiff University, who tweeted, "If @KingsCollegeLon is seeking to do itself 'reputational damage', hiding trial data shd do the job", and leading University of Virginia research psychologist Brian Nosek, whotweeted, "King's College data sharing refusal and rationale are antithetical to science". Dr Nosek is the Executive Director of the Center for Open Science.

It is possible to leave comments on the PLOS ONE site in relation to the PACE paper. Professor Coyne has posted a comment about the study authors' refusal to share their data and in response, one patient wrote, "Patients are relying on PLOS One to be the first scientific institution to stand up for good scientific practice in the context of the PACE trial… Patients don't risk their health in clinical trials so that study authors can misrepresent the results and prevent independent researchers from investigating them."

Tuesday, December 8, 2015

10th Invest in ME International ME Conference Report

Invest in ME
PO Box 561, Eastleigh SO5O OGQ, Hampshire, UK
Telephone: 02380 251719 – 07759 349743

10th Invest in ME International ME Conference

INVEST IN ME – 10th International Conference
29th May 2015, London

Rosamund Vallings MB BS

I was privileged to attend the 10th Invest in ME conference in London
on 29th May 2015 following on from the 2-day colloquium attended by 60
invited delegates from around the world.

Participants from 17 countries were welcomed to the conference opening
by Invest in ME and the chair was then taken by Dr Ian Gibson.

The keynote speech was given by Professor Ian Charles (Norwich, UK).
He has recently been appointed by the Institute of Food Research to
lead the programme to develop the UK's new centre for Food and Health
based at Norwich Research Park. This is a large complex incorporating:
The Institute of Food Research, The University of East Anglia, the
Norfolk and Norwich University Hospital and the Genome Analysis
Centre. There will be interdisciplinary approaches to address many
complex problems.

He discussed the gut microbiome, explaining that we have ten times
more bacteria than cells. He asked the questions: "Do alterations in
intestinal barrier integrity and microbiota exist in ME?" and "Is
there evidence of immune exposure and reactivity to commensal microbes
in ME patients?" He will be working within an interdisciplinary model,
which will become an international hub for food and health research,
with top class scientists appointed. Many departments will be working

This new approach will be holistic, systematic and integrated to
deliver faster innovation. It will be a site of excellence and will
liaise with government. The aim is to lead to personalized nutrition
to benefit the individual microbiome.

The first presentation was given by Mady Hornig (Columbia, USA). She
discussed markers of immunity and metabolism in ME. She described a
3-strikes hypothesis regarding development of the illness, involving
genes, environment and timing. These affect brain outcomes, and she
discussed the effects of the mother's own immune system on the
developing foetal brain. Her cytokine profile could be implicated in
the risks of the infant developing nervous system disorders, even
years later. The microbiome of the mother also influences the
offspring's immune system with potential risks. Many disorders of the
nervous system may stem from immune-mediated pathogenesis.

She then described how there is an increase in plasma levels of
pro-inflammatory cytokines associated with recent illness in ME, and
as the illness progresses, these levels fall. A striking finding is
the very high level of IFN-gamma in short duration illness. It is
possible that different cytokine profiles may affect the potential
benefit of different types of therapies. Therapies may need to be
different at different stages of the illness.

Looking at the cerebrospinal fluid (CSF) comparing ME, MS and
controls, there were some similarities between ME and MS but the
controls had very different immune signatures.
The patterns of immune
molecules in the CSF of ME subjects, who largely had been ill for many
years, were similar to those Invest in ME

Page 2 of 8

observed in Hornig et al.'s immune profiling studies using blood from
ME subjects of long-standing duration.

Discussing metabolomics, she then described 7 classes of 180
metabolites. Alterations were found in a wide range of metabolites in
ME, including ADMA, which is associated with nitrosative stress, and
in tryptophan and serotonin. These metabolomic changes were found to
be correlated with changes in cytokines.

In the gut, there may be imbalances due to foods leading to bacterial
fermentation. Probiotics and faecal transfers do have potential, as
have been found to prevent encephalopathy in cirrhosis of the liver.

A question was asked as to whether the effects of SSRIs may be
affected by the serotonin levels and whether the duration of the
illness could be implicated here. It may be that patients will need to
be categorized according to illness duration, and there may be a
subgroup who will respond. But serotonin levels are not the only
mechanism. It is likely to be more complex than that.

Jonas Berquist (Uppsala, Sweden) describing himself as an analytical
chemist, discussed the Proteomics in ME/CFS. The first ever analytical
chemist was Tobern Olaf Bergman from Sweden. So there is a strong
Swedish tradition in this field. Berquist's lab does general research
and uses mass spectrometry looking at endogenous analytes. He
described proteomics as life's molecular machines – i.e. proteins
which carry out all functions of the body.

He looked at when, where, how proteins are expressed.
Post-translational modifications (PTMs) occur. This can be measured
using 3D gel electrophoresis, but nowadays "shotgun" proteomics is
used to separate them out. Many instruments are used and some of them
are very big machines, using high resolution mass spectrometry. It is
important to use the correct samples from serum and tissues. The tests
are extremely sensitive. He compared the small concentrations
measurable with these techniques as the amount found if a cup of
coffee is poured into a swimming pool.

When looking at the CSF, the total volume is about 150ml and 5-600ml
daily is produced. Sample handling needs to be extremely careful. His
labs have produced a 776 page list of the peptides in the CSF. There
are different ranges with overlaps in different conditions. The study
gives meaningful insights into the biological processes in ME/CFS.
There are significantly changed proteins involved in neurologic,
metabolic and immune diseases. He has looked at upstream and
downstream analysis.

The conclusion is that this work could lead to biomarkers, which maybe
diagnostic, prognostic and therapeutic.

Luis Nacul (London, UK) reviewed the epidemiological evidence on
ME/CFS looking at the current status and implications for research and
service delivery. He described it as a jigsaw coming together. He felt
that the symptoms of encephalitis were very similar to the symptoms of
ME, which MAY therefore BE indicative of neuro-inflammation. He said
that the diagnosis of ME SHOULD BE DISTINGUISHED FROM THAT OF Chronic
Fatigue Syndrome, AS usually the term ME was indicative of more
symptoms. He mentioned a variance in prevalence rates, with females
more commonly affected than males. Overall population estimates are
between 0.1% and 0.7%. Young adulthood is the commonest age of
incidence. In patients with ME/CFS, activity is significantly
diminished. He stressed that we need to look at specificity and
sensitivity, and risk ratio and risk difference. Specificity should
take precedence over sensitivity for validity.

The NICE guidelines ON MANAGEMENT were mentioned. There are LIMITED
effects shown in the clinical response to CBT. But the results may not
A LARGE PROPORTION patients DID not complete a trial, and therefore
results may not be valid. It could be described as an additional

Page 3 of 8

We need to concentrate on biomarkers for the future, with case
stratification and intervention strategies. The current UK biobank has
500 participants, with 17,000 aliquots stored as of March 2015.

Amolak Bansal (Surrey, UK) gave an overview of the diagnosis and
differential diagnosis on ME. He explained how fatigue occurs in many
illnesses, but is the cardinal feature of ME/CFS. He said the
post-exertional malaise is hard to explain. He then went through the
various criteria being used to diagnose the illness. He discussed the
differences between the criteria (CDC, ICC etc.). He thinks that the
term SEID may be too simple. He talked of exclusion criteria,
including temporary exclusion criteria, such as hypothyroidism and
morbid obesity leading to sleep apnoea; and psychiatric exclusion
criteria. He mentioned comparisons which are made between the terms
CFS and ME.

He then went through the Sutton scoring system developed at his
clinic. The main symptoms have a "loaded" score: e.g. PEM scores 3
points, sleep problems 2 and all other symptoms 1 point. 8 or more
points out of 13 points is needed for a diagnosis. All patients must
have post exertional malaise. For subjects involved in research he
uses a score of 10+ from 13 to ensure a critically well-defined
population. Subjects with a significant depression or anxiety are
excluded from research but can still be diagnosed with ME/CFS for
management purposes if they have sufficient points and the depression
and anxiety is secondary to the ME/CFS. Treating the depression,
anxiety and ME/CFS are all critical to improvement in these people. It
is important to note that sensitivity to medication, and alcohol
intolerance are very common in ME/CFS. Fewer than 10% patients can
tolerate alcohol. Another unusual sign in 60 % patients is altered
pupillary reflexes (alternating dilatation and contraction while a
light is shined) and sighing respirations. Other physical signs
include: joint hypermobility (20%), increased respiratory rate (80%),
coldness of peripheries (70%). Conditions that can cause symptoms
similar to ME/CFS include: hypothyroidism, Addison's disease,
pituitary dysfunction, Sjogren's syndrome, gluten sensitivity,
persistent anxiety, primary sleep disorder, Ehlers Danlos Syndrome
joint/hypermobility type, cardiac dysfunction, Parkinson's disease and
temporo-mandibular joint disorder.

He then compared ME/CFS with depression and anxiety. The sleep
disturbance in ME/CFS is different to that in depression and the
former are also markedly hypersensitive to psychoactive medications.
Functionally those with ME/CFS can start a task, but then trend
downwards while those with depression cannot start a task as they have
reduced motivation, but once started they can often manage to complete
it. Those with ME/CFS rarely resort to alcohol, while those with
depression do frequently.
However chronic anxiety associated with
ME/CFS will deplete energy further, contribute to faintness, cognitive
difficulties and increased respiration.

He then talked about appropriate investigations. The basic blood
workup should be done as for all fatiguing illnesses and these are
sufficient to exclude other causes for chronic fatigue in the majority
of patients. Things to add in depending on history and symptoms may
be: ANA, CK, calcium, magnesium, tests for Addisons and on rare
occasions infection serology (Lyme, viral) and neurological
abnormalities (MRI, fMRI, PET scans). Other tests that are
occasionally considered include tilt table, ECG monitoring and
neuropsychological tests. Unfortunately in the UK searching for
triggering infections, such as viral, bacterial (incl spirochaetes),
protozoa and fungi (no evidence for involvement of candida) is rarely
rewarding in terms of offering specific therapeutic options. History
of immunisations on rare occasions may suggest a possible trigger and
there is recent controversy about the HPV vaccine.

Quite often it is a difficult question of how far to delve into issues
such as life events, stress, physical injuries, environmental toxins
and childhood trauma as there is at least some evidence that they may
all play a cofactor role in precipitating ME/CFS. He then discussed
the importance of the control population in ongoing ME/CFS Invest in

Page 4 of 8

research. Although the ideal control group would be family members
this is often difficult and perhaps monitoring people with ME/CFS
through several periods of relapse and remission would be best way

Sonya Marshall-Gradisnik and Don Staines (Griffith University, Gold
Coast, Australia) presented their work on biomarkers in ME/CFS. They
had had two recent papers published –


The two researchers highlighted these papers are from a series of
papers that will be released in the coming months.

These two papers discussed this important work on single nucleotide
polymorphisms (SNPs) in both transient receptor potential (TRP) ion
channel genes and acetylcholine (AChR) receptor genes. TRP and AChR
are part of the ancient or innate immune system. The TRP ion channels
respond to environmental threats, temperature, chemicals etc. They are
distributed throughout virtually all cells of the body. The range of
threats may lead to widespread symptoms. Imposed physical activity is
the wrong thing to be doing as it will likely exacerbate adverse
signaling in patients expressing these SNPs.

Acetyl choline is a major neurotransmitter seen throughout the entire
peripheral, autonomic and central nervous systems and is also part of
the non-neuronal signaling mechanisms of the ancient immune system.

SNPs may cause change in protein structure of translated protein and
therefore possibly change in function of these ion channels or

280 people were recruited and screened using the CDC criteria and
exclusion criteria. 115 had ME/CFS, 90 were non-fatigued and 75 were
excluded. Those included were given questionnaires (SF36, FSS, KPS),
and included housebound patients. Bloods were taken for testing.

13 SNPs were associated with ME/CFS compared to controls (9 – TRPM3, 2
– TRPA1, 2 – TRPC4). TRPA1 is activated by exogenous and endogenous
inflammatory agents, leading to pain and inflammation.

It regulates neuropeptides and is a multiple chemical receptor. It is
associated with changes in neuropeptide receptors and inflammatory
cytokine profiles. TRPM3 is located on the pancreaticβ cells and in
the CNS. It is associated with pain. TRPC4 is associated with
vasomotor function and smooth muscle function.

17 SNPs were associated significantly with AChRs in ME/CFS patients (9
– mAChM3, 5 - nACh alpha 10, 1 -AChR alpha 5 and 1 - nAChR alpha 2

Collectively, AChR and TRP SNPs likely influence the gastrointestinal
tract involving insulin and glycogen secretion, B and T lymphocyte
development and proliferation, and neurological systems associated
with sleep, pain and arousal.

This research highlighted the possible role of TRP ion channels and
AChRs in the onset of ME/CFS.

Next Generation: A panel discussion then ensued involving 4 new
student researchers, and it was good to hear their involvement, which
bodes well for the future. The students were - Invest in ME

Page 5 of 8

- Bharat Harbham (UEA/IFR
- Fane Mensah (UCL
- Navena Navaneetharaja (UEA/IFR
- Daniel Vipond (IFR)

Jo Cambridge (London, UK) then talked about B cell biology and ME/CFS.
She gave some background history explaining that Rituximab had been
used in 1998 to treat Rheumatoid Arthritis and SLE. The work of Mella
and Fluge then further drove the hypothesis that B cell depletion
could be implicated in ME/CFS. Her group looked at B Cell biology,
biomarkers for response and relapse and other B cell directed
therapies. The B cell has a large number of markers. Markers tell the
age of the cell and other expressions. Every new B cell has a
different receptor. Adherence is involved. B cells move through plasma
cells to make antibodies. Antibodies are a form of B cell receptor,
and are released onto surfaces, and bind to help clear macrophages
from the body. They are made in the bone marrow and circulate to
lymphoid organs. Antibodies recognize the different stages on the
target bug. (e.g. antigen). IgM, IgA, IgG are all a different shape,
all recognize the same antigen, but bind to cells in different ways.
In a normal immune response, IgM is apparent in the first 7-10 days,
then IgG. Memory B cells also form to attack recurrent bugs. There is
interaction with T cells causing cytokines to help B cells make the

Cytokines interleukin8 and interleukin5 are elevated in ME/CFS and
interleukin23 is down. There are also early and late effects in this
illness leading to different cytokine levels. Antibodies in disease
can form to "self" giving rise to immune complexes lodging in tissues
leading to inflammation (e.g. lupus, rheumatoid arthritis). The
antibodies bind and damage or change cell function. They can interfere
with communication between cells.

Rituximab works in diseases where there are antibodies, leading to B
cell depletion by recognising CD20 on the B cell. This in turn leads
to B cell destruction in the circulation. B cells can regenerate.
Changes occur in levels of Anti CCP after a single rituximab course.
It is very complicated.

In ME/CFS there were positive results from use of rituximab in Norway.
Patients do differ and there is no clear picture of the B cells. The B
cell phenotype can be compared to the ME/CFS demographics using flow
cytometry. One can look at complex things such as maturation, plasma
cells, percentage of B cells in the blood, associated demographics,
percentages of memory and naïve B cells etc.

CD24 is present on B cells associated with maturation (mainly on young
cells). CD38-CD21 – memory B cell subsets – high expression in
controls, less so in ME/CFS. Duration of illness gives different
levels, with B cells normalizing over time. There are no differences
in classical B cells.

Immune brain communication and relationship to inflammation induced
fatigue were discussed by Neil Harrison (Sussex, UK). He outlined the
symptoms associated with sickness behavior and listed the behavioural
changes that occur to protect the body. He explained how cytokines
injected into rodents led to symptoms of sickness behavior. Humans
given high doses of interferon-αto treat Hepatitis C also develop
sickness behavior and often experience severe fatigue. There is
immune-brain communication via a number of pathways, and in particular
via the vagus nerve. The microglia are also activated leading to brain

Typhoid vaccine was used as a bacterial mimic. The fMRI showed
activity++, and PET showed increased metabolism particularly within
immune-brain communication pathways. Inflammation induced insular
activity, which predicts fatigue. Interferon mediated fatigue is a
side effect of interferon-αtherapy (a viral mimic). MRI scans were
done before, and shortly after beginning Interferon-alpha therapy then
patients followed up for their 6-month duration of treatment. A
challenge with IFN lead to the onset of fatigue and Invest in ME

Page 6 of 8

MRI changes within 3 hours. One could also use changes observed on MRI
to predict which patients would subsequently develop the worst fatigue
during their 24 weeks of treatment. There are implications for
post-IFN fatigue and post viral fatigue. He asked the question "Do
structural brain abnormalities persist post-inflammatory challenge?".

John Chia (California, USA) updated us on his work with enteroviruses.
He explained that there are many illnesses associated with
enteroviruses. Most doctors are not trained to diagnose enterovirus
infection. They are difficult to recognize. In 1995 41% CFS patients
had positive serum enterovirus. He presented his research up to the
present. He worked initially with blood samples, but moved onto tissue
samples. In patients with persistent gastrointestinal symptoms, there
was no evidence of H Pylori. But there were positive abdominal tender
points, and focal gastritis on endoscopy (often mild).135 out of 165
patients were positive for VPI within the parietal cells, compared to
7 out of 34 controls. He tried to culture the viruses, but none
survived. In 2008, viruses were found in biopsies (Enterovirus capsid
protein) 81% showed VPI and 91% dRNA. Work with SCID mice showed
effects of enterovirus infection after injection. (66% positive
compared to 10% controls). He says that initial infection in the
stomach is not controlled by the immune response. Enteroviruses travel
via the vagus to the brainstem.

Claire Hutchinson (Leicester, UK) had looked at visual processing in
ME. She talked about how visual symptoms were commonly reported in the
63 patients studied, using questionnaires and free report of symptoms.
She wanted to map anomalous visual behavior onto the visual pathway,
and to provide evidence to support symptom reports. There was
experimental for the existence of visual stress/pattern glare in 20
patients compared to controls, which may reflect cortical
hyperexcitability. In a study looking at visual attention and the
ability to ignore background information (29 patients, 29 controls),
found basic visual processing speed was normal, but both divided
attention and selective attention were slow. She also presented data
showing that, under some conditions, eye movements are less accurate
in people with ME.

Betsy Keller (Ithaca,USA) went through activity guidelines to avoid
symptom flares. This was an active talk incorporating audience
participation. She talked about energy currency and post-exertional
malaise (PEM), describing short term anaerobic, long term anaerobic
and aerobic stages (>2 minutes) - the latter not being suitable for a
person with ME/CFS because this energy system fails to recover
normally. She described the abnormal recovery response, with ME/CFS
patients taking 3 days or longer to recover from 5-10 minutes on a
treadmill. PEM is the defining quality of this illness. It is easier
to avoid it than to recover from it. Her advice is to pre-empt PEM
with scheduled rest periods, do not wait for a crash, pace carefully,
know your triggers and avoid or minimize them. Exercise should be
redefined with focus on quality of life and use of the short-term
energy systems that do work. Yoga and Tai Chi are suitable forms of
exercise. The strategy for physical activity should use functional
movement that is restorative, with a goal to improve. Aim should be to
use the anaerobic energy systems with a work/rest ratio of 1:3, 1:4 or
more if needed. That is, 'work' for 30 seconds, recover for 90 seconds

She went on to explain the importance of core stability to conserve
energy. The core includes muscles, bones, connective tissue of the
trunk from the neck to hips- it connects the extremities. She
explained the weight of the head and how it increases if one slouches
(using extra energy unnecessarily). Warm up should begin with focused,
square or nose-breathing (4 sec inhale, 6-8 exhale). This will often
help symptoms too by better oxygenating the tissues.

5 steps to align core: 1) Contract pelvic floor (contract muscles that
stop flow of urine or Kegel), 2) draw in umbilicus (draw belly button
toward spine), 3) raise ribcage (rib cage points up toward ceiling or
umbrella diaphragm). 4) Lift shoulders up to ears then back and let
drop down, 5) retract chin. (Some of these exercises can be done lying
down). Back extension is important (lying on floor on belly). She then
ran through some exercises on the floor or Swiss ball straightening
arms and legs - alternate and opposite sides. These exercises
strengthen the core. It is important to assess how one feels the next
day to determine if the work/rest ratio is sufficient. If structured
activity works, core stability improves, movement Invest in ME

Page 7 of 8

becomes more efficient and less energy draining. Activities need to be
monitored and modified. The exercises should be very brief e.g. 30
seconds of activity, 90 seconds of rest, 3 times. The heart rate (HR)
can be monitored and should not exceed the anaerobic threshold, and
watch to see which exercises work at what HR. There is a perceived
exertion scale and the aim should be to stay at the bottom level.

She described structured activity as empowering, improving quality of
life, giving a sense of control and being off the rollercoaster.
Energy conservation involves pacing, body position, joint protection
and activity planning. There is need to think circularly not linearly
(use a work/rest ratio all day), acknowledge limitations, aim for core
stability and structure physical activity. She then outlined 10 simple
energy-saving tips shared with her by Staci Stevens of the Workwell

Make bed while you are in it or not at all
Take things around the house in a back pack.
Shower sitting down
Simplify clothes and hair
Use an answering machine
Pack groceries smartly ready for unpacking
Cook ahead
Get disabled car park
Prioritize chores
Learn to say No and Yes

Olav Mella (Bergen, Norway) brought us up to date discussing the Phase
2 and 3 studies of the rituximab trial. The Phase 2 study will be
published shortly. 20% patients had a transient worsening of symptoms.
There was marked improvement of physical function in 6 of 9 previous
placebo patients. Half of the original responders were still
responding at the end of follow up (36 months). The quality of life of
the responders was very good. Only 5 patients were as low as 30%.
During the trial levels of function were tested using a bicycle on a
ramp. Experience with measuring endothelial dysfunction was gained.
Maintenance therapy may sustain response

A new study is now underway. Patients recruited have been ill for 2-15
years. The Canadian criteria were used for diagnosis. 4 university
hospitals and a community hospital were involved. Patients were given
information and filled in the De Paul questionnaire. Biobank material
was withdrawn and frozen. Patients undergoing the ramp test may need
to wait 3 months before start of treatment to get back to their normal
level. The study is randomized, double blinded, placebo-controlled.
Study period will be 24 months, so results will be available in summer
2017, unless there are serious side effects. There will be no access
to randomisation. All monitoring will be external. The physicians
concerned will not see the patients. Rituximab 500mg/m2 will be given
on days 0 and 15, and then 500mg at 3, 6, 9 and 12 months. Patients
will monitor themselves. SF36 will be used every 3 months and FSS at
zero, 6, 12, 18 and 24 months. Electronic activity will be assessed at
zero and 18 months, using a wrist band. Blood samples will be drawn
regularly for biobank freezing.

The primary endpoint will be the level of fatigue over 24 months. The
secondary endpoint will be changes in QOL, and any effects of

Sub-studies will include endothelial dysfunction (large vessels -
ultrasound and microvessels - PORH analysis) – Is there correlation
between endothelial dysfunction and ME and improvement parallel to
endothelial dysfunction? Ergo spirometry can be used, if patient is
able, to see if there are changes in the anaerobic threshold.

Another sub-study will look at gastro-intestinal function. Invest in ME

Page 8 of 8

These are high quality studies hoping for good clinical response. One
must expect up to 20% placebo response, and hope for a 50% rituximab
response. One needs to look at clinical characteristics of the
responders. There may be a 4-5 month delayed response. The biobank
will be useful. There may be political impact. Another multicenter
trial elsewhere is needed. Toxicity also needs to be considered. Some
patients cannot tolerate the treatment.

A further new study using cyclophosphamide started in March 2015. This
is a cheaper immune-modulating drug. It shows major improvement in
treatment for breast cancer. 40 ME patients have been recruited with 6
infusions to be given every 4 weeks. There are 3 groups of patients:
those not treated with rituximab, previous non-responders to rituximab
and those who have recurred after rituximab. Patients with mild to
moderate illness are recruited and the trial will last 2 years. It
does not include young patients or those at risk of pregnancy. It will
be tried later on for 20 more severe patients.

The conference concluded with thanks to all speakers and closing
remarks from Dr Ian Gibson and Invest in ME, and all agreed it had
been the very best yet.

I would like to thank Invest in ME and ANZMES for making it possible
for me to attend this excellent event.

Rosamund Vallings MNZM, MBBS

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We're Making Progress

June 15, 2015

News About Chronic Fatigue Syndrome: We're Making Progress
Diane E. Judge, APN/CNP

Dispelling the myth that CFS is "all in your head"

Chronic fatigue syndrome (CFS) is a devastating illness that can
interfere with all facets of life. It's not clear how many people
suffer from CFS, but a recent estimate suggests the number is between
836,000 and 2.5 million in the U.S. According to the Centers for
Disease Control and Prevention (CDC), women are two to four times as
likely as men to get a diagnosis of this condition. You might also see
CFS called by an older name, myalgic encephalomyelitis (ME), or a
combination of the two names (ME/CFS).

Yes, It's "Real"

When we first began hearing about CFS decades ago, many clinicians
(doctors, nurse practitioners, physician assistants), and even friends
and relatives of people with CFS questioned whether it was a "real
disease" or "just a mental health condition" or a "figment of the
imagination." They had a hard time believing that a condition that
couldn't be diagnosed with a blood test, x-ray, or physical
examination could be real. Diagnosis depended (and still depends)
solely on what the patient reports.

Recently the Institute of Medicine (IOM) and the National Institutes
of Health took a strong stand on CFS. Based on more than 9000 research studies, these organizations concluded that CFS has a biological basis (occurs because of one or more body malfunctions), declaring it "a serious, chronic, complex systemic disease that can profoundly affect the lives of patients." They also stated that CFS is not "a psychological problem."

The studies identified many differences between people with CFS and
healthy people or those with other conditions that cause severe
fatigue (such as depression or multiple sclerosis). Differences were
identified in the brain and nervous system, the immune system (which
defends the body against infection), and the endocrine system (which
regulates body function through glands and hormones). The IOM also
noted that CFS sometimes occurs following infection with the
Epstein-Barr virus and possibly infections with other viruses,
bacteria, and protozoa. Learning more about these factors may help
researcher develop tests for diagnosing CFS, as well as medications
and other approaches for treating it.

Diagnosing CFS

A diagnosis of CFS still relies on the patient's description of
symptoms. CFS is identified when what you are experiencing matches
guidelines developed in 1994. According to those guidelines, you have
CFS if, for 6 months, you have had severe, constant, unexplained
fatigue that interferes significantly with daily activities and work,
and four or more additional symptoms from a list of eight that
includes unrefreshing sleep (awakening as tired as you were when you
went to bed) and fatigue made worse by exertion.

The IOM proposed a simpler definition for identifying people with CFS,
which may become the new standard. If you fit the criteria listed
below, if no other cause can be found, and if the problems are
moderate, substantial, or severe and happen frequently (at least half
the time), the likely diagnosis is CFS:

- A substantial loss of ability to engage in preillness levels of
work-related, educational, social, or personal activities that
persists for more than 6 months and is accompanied by fatigue, which
is often profound, is of new or definite onset (not lifelong), is not
the result of ongoing excessive exertion, and is not substantially
relieved by rest
- Postexertional malaise (worsening of symptoms after physical,
cognitive, or emotional activity)
- Unrefreshing sleep, PLUS one or both of the following:
   - Cognitive impairment (trouble remembering, learning new things,
concentrating, or making decisions)
   - Orthostatic intolerance (changes in heart rate and blood
pressure, often resulting in feeling dizzy or lightheaded when
standing; improving when lying down)

Treating CFS

No specific medication or other treatment can reliably relieve or cure CFS — but since CFS affects lives to such an extent, doing nothing is not acceptable. Treatment is aimed at easing at least some of the
symptoms. For instance, a very low dose of a medication called a
"tricyclic" may allow you to get more hours of deep, restorative sleep
at night, resulting in more energy the following day.
Graded exercise
therapy (supervised physical activity starting at a low level and
increasing gradually) may improve fatigue and function, although it
doesn't help everyone and sometimes causes problems. Counseling,
including cognitive behavioral therapy (CBT), may also help. CBT is a
therapist-guided method of changing your thinking and fears about your
health situation, which may make CFS easier to live with.

The lack of treatment options may make complementary and alternative
treatments, such as acupuncture, massage, and herbal and botanical
products, seem attractive. There is little research proving that these
approaches are safe and helpful, but some women report relief with
them. If you choose to try these options, find out about any possible
negative effects. Advertising might claim that herbal and botanical
remedies will help you, but the quality, safety, and content of these
products is not regulated by the U.S. Food and Drug Administration. If
you are considering such a product, check it out at National Center
for Complementary and Integrative Health (see Resources below). And be
sure to let your clinician know.

You may also want to consider participating in a research program
investigating possible treatments for CFS. Places to look for such
programs include hospitals associated with universities, or the CDC
and support groups such as Solve ME/CFS Initiative (see Resources

Coming Soon: A New Name for CFS?

Some experts believe that the term "chronic fatigue syndrome" makes
light of an illness that so profoundly interferes with peoples' lives.
Because CFS is a systemic (affecting the whole body) illness marked by
exertional intolerance, the IOM proposed a new name that acknowledges
the true problem: "systemic exertional intolerance disease." That name
has not yet been formally adopted, but you may see it used in the

In Conclusion

There is still no cure, or even any reliably effective treatment, for
CFS. But the IOM report should dispel the myth that CFS is "all in
your head." With more research, more clinician education, and more
support for those who have CFS, this illness should receive the
validation and attention it deserves.


Solve ME/CFS Initiative

Centers for Disease Control and Prevention

National Center for Complementary and Integrative Health

Institute of Medicine, Beyond Myalgic Encephalomyelitis/Chronic
Fatigue Syndrome: Redefining an Illness

Monday, December 7, 2015

It’s time for doctors to apologise to their ME patients

It's time for doctors to apologise to their ME patients

For too long the medical community has dismissed 'Chronic Fatigue
Syndrome' as a mental illness which can be cured with therapy and

By Dr Charles Shepherd
9:35AM GMT 07 Dec 2015

Back in 1955, a mysterious polio-like illness affected 262 doctors and
nurses at London's Royal Free Hospital. The hospital had to close for
just over three months.

The outbreak was written up in The Lancet and a new neurological
disease entered medical language: myalgic encephalomyelitis, or ME, as
it still remains in the WHO Classification of Diseases. "Myalgic"
referred to the muscle symptoms; "encephalomyelitis" referred to the
various neurological symptoms.

Others were not convinced that ME was a neurological disease, and two
decades later two psychiatrists, without interviewing any of the
patients, wrote a paper for the British Medical Journal where they
concluded that the Royal Free outbreak was due to mass hysteria.

The mud from the BMJ stuck. Like most doctors at the time, I left
medical school believing that ME was not a real disease and I would
probably never see a case. I was wrong.

Ignored or dismissed by doctors, people with ME went undiagnosed or
misdiagnosed for long periods of time, often combined with harmful
management advice – as is still the case. I can confirm this after
developing classic ME following chickenpox, caught from one of my
hospital patients. Some developed severe ME, becoming housebound or
bed-bound with no medical help. Some never recovered.

During the 1980s, ME was redefined and given a dreadful new name:
chronic fatigue syndrome (CFS). The term CFS trivialised a serious
medical condition – the equivalent of trivialising dementia by calling
it a chronic forgetfulness syndrome – and shifted the focus from a
"disease" to a single symptom, "chronic fatigue".

CFS also brought in a much wider group of people suffering from
chronic undiagnosed fatigue. A powerful body of psychiatric opinion
convinced the medical profession that CFS was basically a mental
health problem whereby people became trapped in a vicious circle of
abnormal illness beliefs and behaviours, inactivity and
deconditioning. In other words, there was no "disease" present.

The CFS model of causation resulted in two controversial forms of
behavioural management – cognitive behaviour therapy (CBT) and graded
exercise therapy (GET) – being recommended by NICE as the main form of

Now we have the PACE trial – the largest and most recent assessment of
CBT and GET, which has cost the taxpayer almost £5 million. At long
term follow-up, and contrary to what was reported in the press, the
PACE trial found no significant difference between CBT, GET, adaptive
pacing and specialised medical care.

Public reaction to the spin that has been put on the PACE trial
results for CBT and GET has resulted in over 10,000 people signing a
petition calling for claims relating to so-called recovery to be
retracted and six academic researchers calling for an independent
review of the study.

By contrast, in evidence collected from 1,428 people with ME by the ME
Association, for which I am medical adviser, 73 per cent reported that
CBT had no effect on symptoms while 74 per cent said reported that GET
had made their condition worse. The MEA has therefore recommended that
NICE withdraws their advice relating to GET.

On the progressive side of this medical divide are physicians and
researchers who, like the patient community, believe that ME is a
serious multi-system disease, often triggered by infection, but
maintained by abnormalities involving, neurology, muscle, and the
immune system.

In the UK, a research collaborative with a strong emphasis on the
biomedical research has been established. And a major report from the
prestigious US Institute of Medicine has recently concluded that ME is
a "serious, chronic, complex, systemic disease that can profoundly
affect the lives of patients". ME is not a psychological problem.

Biomedical research into ME is revealing abnormalities in the way that
muscle creates energy, along with evidence of an ongoing overactive
immune system response. New types of brain imaging are demonstrating
low-level inflammation in several specific parts of the brain.

At the same time, a large multi-centre clinical trial is taking place
to assess the use of Rituximab – a drug that depletes immune system B
cells and which is normally used to treat a form of cancer called

The argument here is not with mental illness, which is just as real
and horrible as physical illness. As with any long-term illness, some
people will develop mental health problems where talking therapies can
clearly be of help.

The argument is with a simplistic and seriously flawed model of
causation that patients know is wrong and which has seriously delayed
progress in understanding the underlying cause of ME and developing
effective forms of treatment.

Opening the 2015 research collaborative section of neuropathology,
Jose Montoya, professor of medicine at the University of Stanford,
said: "I have a wish and a dream that medical and scientific societies
will apologise to their ME patients."

I agree – the time has come for doctors and scientists to apologise
for the very neglectful way in which ME has been researched and
treated over the past 60 years. Doctors need to start listening to
their patients and there must now be increased investment in
biomedical research to gain a better understanding of the disease
process and to develop treatments that these patients desperately

Dr Charles Shepherd is medical adviser to the ME Association


Fact box

Symptoms of Chronic Fatigue Syndrome

The main symptom of CFS is persistent physical and mental fatigue
(exhaustion). This does not go away with sleep or rest and limits your
usual activities.

Most people with CFS describe this fatigue as overwhelming, and a
different type of tiredness from what they have experienced before.

Other symptoms include:

- Muscular pain, joint pain and severe headaches
- Poor short-term memory and concentration, and difficulty organising
thoughts and finding the right words ('brain fog')
- Painful lymph nodes (small glands of the immune system)
- Stomach pain and other problems similar to irritable bowel
syndrome, such as bloating, constipation, diarrhoea and nausea
- Sore throat
- Sleeping problems, such as insomnia and feeling that sleep is not refreshing
  -Sensitivity or intolerance to light, loud noise, alcohol and certain foods

Thursday, November 19, 2015

Journalist David Tuller writes about how he became interested in CFS

Journalist David Tuller writes about how he became interested in Chronic Fatigue Syndrome and what brought him to write so much about the PACE Trial (the largest CFS trial ever)

Read David's informative articles on the PACE Trial here:

Monday, November 16, 2015

Chronic Fatigue Syndrome in Oprah magazine

"After a battery of diagnostic tests for viruses and bacteria, [Montoya] continued Cavanagh Kramer on one of the antivirals she'd been prescribed, but made a few important changes: He added anti-inflammatory and immune-modulating drugs, as well as an antibiotic for the bacteria he found in her blood. ... Historically, many doctors considered CFS a psychosomatic disorder that required psychological—not medical—intervention. But recent research by Montoya and others has compelled the medical community to take the condition much more seriously. ... Montoya and his colleagues, however, were able to pinpoint immune abnormalities in the blood of CFS patients who had recently become ill, suggesting possible biomarkers for the disease. ... A picture of patients with highly inflamed bodies emerged before our eyes and validated what they've been telling us for decades."

Thursday, November 12, 2015

Right to Try: How Govt Prevents Americans from Getting Lifesaving Treatments

Darcy Olsen is President of the Goldwater Institute, a research and legal center, which is currently behind the Right to Try initiative, to give terminally-ill patients access to medications before the FDA approves them.
I saw her on TV this morning.  She asked pointedly why drugs which are available in Europe are not FDA-approved for use in the US.  Apparently Right to Try would allow Americans to use anything that's approved elsewhere.
Ampligen has been used in both Belgium and Canada, but in the US, FDA just keeps asking for more testing.
Could that possibly be because Dr. Reeves and Dr. Straus so vehemently insisted that CFS is all in our heads, and it wouldn't be politic for FDA to approve an anti-viral drug for something CDC says is purely psychiatric?
Unfortunately, the magic words in the proposed legislation are "terminally ill" and I don't think anyone classifies ME/CFS as "terminally ill".

Wednesday, November 11, 2015

Anosognosia - Neurological Inability to Recognize Illness

"anosognosia is the lack of awareness of the deficits, signs and symptoms of an illness. It is not merely a denial; it is an actual neurological deficit"
"anosognosia is one of the more troubling symptoms of severe mental illness as it prevents a person from getting the help they need. The "easy" way to handle this is to rely on a "doctor knows best" approach and simply medicate without consent."
"you can't talk someone out of a delusion. That's the definition of delusion. It is a belief in the face of contrary evidence."
* * *
A lot of people (doctors and psychobabblers included) think this is our problem -- that we don't want to admit that we have a mental illness and are clinging to the delusion that we are physically ill, and therefore need to be medicated without consent for whatever erroneous amateur psych diagnosis that particular doctor likes best (I've been tagged with anxiety and depression, while psych experts have never found signs of either).  Doctors dismissed those psych reports and wanted me to go see another shrink, one who might agree with them.
But the reality is, it's those psychobabblers who have the problem.  "You can't talk someone out of a delusion. That's the definition of delusion. It is a belief in the face of contrary evidence."  Shown evidence of physical illness (abnormal temperature, swollen glands, abnormal test results), they will continue to insist that there is nothing physically wrong with you.  At one appointment, my temperature was 95 -- hypothermia -- which did not disturb the doctor as much as it should have, because he refused to accept any contrary evidence.  When confronted, he shrugged, "you were outside".  Yes, I was outside for a few minutes in the sun on a 60-degree day, but that wouldn't push my temperature down to 95.  He wanted to see a depressed divorcee too lazy to work, and was willing to dismiss any symptoms or evidence that there was more to it than that.  He was delusional, and in order to continue his delusion, he had to convince me that I was delusional in thinking that I was physically ill.   He couldn't do any tests that might prove I was right and he was wrong, so he simply refused to order those tests.

Tuesday, November 10, 2015

A New Type of Treatment for Chronic Fatigue Patients - Autonomic Specialists

"TVAM is a treatment involving the endovenous stimulation of autonomic nerve fibers via a minimally invasive procedure. The process of manual stimulation of these nerve fibers appears to have a modulatory effect on the autonomic nervous system."

Tools for Critical Thinking in Biology - Stephen H. Jenkins

Dr. Marc-Alexander Fluks reports "Student textbook has section about XMRV-fraud and CFS"
Title: Tools for Critical Thinking in Biology
Author: Stephen H. Jenkins
Publisher: Oxford University Press
ISBN: 978-0-19-998104-5
Date: April 28, 2015
Price: US$ 49.95

The full text about the XMRV-fraud and CFS is available online,
Chapter: Science as as Social Process
Section: Correction of Faulty Results after Publication
Pages: 219-226
"Extreme cases of CFS are similar to end-stage AIDS."
"Until recently, the Centers for Disease Control and Prevention has emphasized the psychosomatic hypothesis in their research on CFS, although several scientists have looked for associations between CFS and infection with various viruses."
Then there's a description of the XMRV fiasco.  "This outcome doesn't mean absolute refutation of the hypothesis that CFS is caused by an infectious agent -- another virus or even another type of infectious agent could be responsible for the disease. ... the research that followed Mikovits's study and culminated in Lipkin's project has spurred greater scientific attention to CFS and may stimulate more research on various hypotheses about causes of the disease."
* * *
The good news is that students are now being taught the possibility that CFS is not just all in our heads, but caused by a virus.
Unfortunately, the whole XMRV mess is exposed to a wider audience in a way that could scare students off getting involved in controversial research like CFS.  Since this is a book about "critical thinking", it was a good description of something that was disproved by critical thinking (trying to replicate research and not just accepting it as true based on one study), so there is some benefit to it if you turn it on its head, the studies claiming IAIYH also cannot be replicated when using real CFS patients rather than "tired all the time" depressives.

Saturday, November 7, 2015

Polio: Global vaccine campaign may eradicate the virus by 2018.

If they can do it for poliomyelitis, why not for myalgic encephalomyelitis?  The ability is there, just the specific research is missing.
In polio epidemics, they found that those who had ME/CFS were immune to polio, therefore, they have to be related viruses.  Dr. Bruno tells me the polio vaccine prevents the three worst forms of the virus, leaving lesser mutations unguarded against.  Including the relative that causes ME/CFS.

Because of the aggressive campaign, it's expected that the last cases of polio seen in the wild will happen sometime in the next two to three years. The World Health Organization is so confident about this that it actually has what's called the Polio Eradication and Endgame Strategic Plan, a strategy on how to make the world polio-free by 2018.

That's extraordinary. This has only happened once before in history, when smallpox was eliminated in 1977. Smallpox killed hundreds of millions of people, and now it's gone, wiped clean off the face of the planet.

Why? Again: vaccines.

This is why I consider vaccines to be one of the very best medical health innovations in human history, if not the best.

Wednesday, November 4, 2015

Why the Disabled Don't Vote, and what we can do about it

Over the past year, I've been invited to a few sessions about the problem that the disabled don't vote.  The able-bodied people in government can't figure out the problem themselves.
If we don't vote, that means we're not voting out politicians who want to cut Disability checks and services to the disabled.  Yes, thousands of us show up on the front lawn of the State Capitol every year for Disability Capitol Action Day, to prove to the legislators (who are used to seeing us in onesie-twosies representing individual diseases) that the disabled as a whole are a large voting bloc.  But are we really?  How much of a voice do we have if many of us don't actually vote?
One of the issues brought up repeatedly was inability to get to the polls.  We don't drive or we can't afford a car.  My local polling place was moved from across the street to a building several blocks away where I would actually have to walk further to take the bus than I would to walk there directly.  Out in rural areas, it's even worse -- no buses at all.
Yes, you can vote by mail (and for the homebound, that's the only option).  But charities and clubs could provide free rides to the polls if they realized there's a need.  Call some in your local area and suggest it.
Check with your local voter registration office whether you can register as a Permanent Absentee Voter, so you will always get your ballot by mail, or whether your local law requires you to request an absentee ballot each time.  Then once you have the ballot, make sure you mail it back in plenty of time to be counted.  Sign the back of the envelope to prove you're you.  Put enough stamps on it.  If you can't get out to put it in the corner mailbox, hand it to the mail carrier and ask him to take it to the post office for you.
In my state, a few weeks before an election, we're sent a booklet with the full text of all the propositions, brief candidate statements, and a sample ballot.  You can take your time going through it, use a highlighter to mark up the sample ballot, and then when you have your real ballot (whether vote by mail or at the polls), it's a simple matter to just transfer your choices from the sample ballot to the actual ballot.  You don't have to strain to read the fine print while you're at the polls.  This information is often available online, for those who use a screenreader or need to increase the size of the print.
Did you know that there are now computerized voting machines for the disabled?  Bring your own headphones, and your own puff straw if you're paralyzed, and cast your secret ballot.  But you may need to know that it's there, because the pollworkers may not know they have such a machine tucked off in the back corner, and you may need to know how to use it, because the pollworkers may not know enough to teach you.  At the Secretary of State's workshop, we were each given a one-on-one demo specific to our own disability, but they wouldn't let us bring one home so we could teach others, so all I can teach you is to ask if there's a machine available.  Again, you'll have to call your own state's Secretary of State or county Registrar of Voters to find out if these are available and if they can show you how to use it.  Maybe they'll bring one to your next support group meeting.  Don't wait till just before the election when they're busy with preparations -- invite them for a few months before when they have time.
If the pollworkers are helpful, send an e-mail to the Registrar of Voters to thank them.  If the pollworkers are rude because of your disability, send an e-mail to the Registrar of Voters explaining the problem and requesting sensitivity training.
Don't think that politics is boring -- politics is what decides whether we get a cost of living increase (which we won't for 2016) or a 20% benefits cut (which was threatened) combined with a huge increase in Medicare premiums (they were threatening to increase it 50% while simultaneously reducing benefits by 1/5).  Politics determines everything about how the disabled are treated. 
You don't need a lot of money to have an impact on politics -- it costs nothing to go to a campaign office to volunteer your time (and you'll often get fed while you're there), and almost nothing to get a campaign button/bumper sticker (sometimes free, sometimes a dollar or two), T-shirt (a few dollars), or lawn sign (I paid $10 for the last one, and they installed it for me).
You can call their offices for free.  You can e-mail their offices for free.  We may not have a lot of money, but we do have time.
And you can vote out the people who threaten to reduce our benefits and services, refuse to enact expanded Medicaid for the working poor (which is a lot of the disabled), or any of the other things that politicians like to do in hopes the disabled will just go away.