The Symposium on Viruses in Chronic Fatigue Syndrome (ME/CFS) (June
2008): Part II by Cort Johnson
A Neuro-Immune Fatigue Subset?
D. Peterson. Antiviral treatment of patients with HHV-6, EBV and enterovirus:
case reports
There’s this 15-30% percent number floating around ME/CFS. Several doctors
have spoken of the 20% of patients who seem immune to their approach. There’s
about 20-25% dropout rate in behavioral studies. There’s the 25% ME group of
really disabled patients.
Then there’s Dr. Peterson 15-20% group. This is a group for whom the standard
toolbox doesn’t fit; they don’t respond to supplements or the commonly used
drugs and behavioral modification has no effect. Dr. Peterson thinks they have a
different kind of disease altogether. He calls them the neuro-immune fatigue
group.
These patients generally have headaches, cognitive problems, paresthesias
(pins and needles feelings), autonomic dysfunction (presumably increased heart
rate, trouble standing, etc.), abnormal MRI reading and SPECT scans. Cerebral
spinal fluid (CSF) studies indicate increased total protein, myelin basic
protein, lactic acid, lymphocytes and opening pressure.
They have active viral infections usually with cytomegaloviruses, HHV-6,
Epstein-Barr virus (EBV), a gamma herpes virus and enteroviruses. Their gene
expression, cytokine and protein expression results suggest their immune systems
are chronically activated – as one would expect.
The antiviral drugs Dr. Peterson uses to treat these patients include
Foscavir, Valcyte, Cytovene, Zovirax, Valtrex, Vistide and Ampligen (approved
for use in Canada).
A Cancer Subset? Dr. Peterson reported that a subset of his patients with
chronic HHV-6 infection exhibit a kind of process – called T-cell receptor gene
re-arrangement – that’s usually found only in lymphoma patients. This process
apparently increases the risk of T-cell becoming cancerous. The Whittemore-Peterson
Institute is reportedly focusing on this subset of patients.
Dr. Peterson’s work, if substantiated, underscores how important subsets may
be in this disease and how incredibly damaging researchers inability to ferret
them out has been. A twenty percent subset in a disease will do two things; it
will make it difficult to find consistent findings for the other 80% of the
patients and make it almost impossible to detect the subset itself If Dr.
Peterson’s subset is a truly different kind of patient the 20% subset represents
an ongoing tragedy. (One study of the longterm effects of ME/CFS did not find
increased mortality in the disease).
Dr. Peterson’s work, too – despite his years of experience - must be also
regarded as ‘preliminary’ as is any unpublished work. In order to truly impact
the course of ME/CFS research must be published and replicated – hopefully by
different researchers. The word is, though, that Dr. Peterson, a busy
physician will, with the help of Judy Mikovitz, the new Director of Research at
the Whittemore-Peterson Institute (WPI) will be publishing shortly.
Dig Deeper: the
Whittemore Peterson Institute Comes Out of the Closet /
The Whittemore-Peterson Institute
Antiviral Drugs – Hope on the Horizon?
Prichard, New Developments in therapies for HHV-6 Infection
‘Precious few molecules with good activity against HHV-6 have been identified
and none have been approved.” M. Prichard
Dr. Prichard noted we have a long way to find a really good drug against
HHV-6. One problem with the current batch is dose-related toxicity. At high
enough doses they can indeed kill the bugs but at the risk of injuring or
killing the patient. Dr. Prichards presentation suggested that the next round of
antiviral drugs will be more effective and less toxic.
In Development
Artesunate - Artesunate is a well tolerated drug approved for malaria (in
Europe) that possess antiviral activity as well. In vitro (lab) studies found it
was highly effective against one of HHV-6’s cousins; the cytomegalovirus.
An HHV-6 Foundation funded study indicates artesunate also effectively inhibits
HHV-6A in the lab. This drug is particularly promising because, in contrast to
ganciclovir and foscarnet, it hits HHV-6 early in its life cycle. If HHV-6
produces a kind of smoldering infection that alters cell functioning in ME/CFS
and other diseases then hitting it early will be critical. What a boost it would
be to find an already approved drug that was effective against HHV-6.
Cycloprovir – analogue of ganciclovir but potentially much more effective
against HHV-6. (Valcyte converts to ganciclovir in the body. Ganciclovir
interferes with viral replication.
CMX001 – a variant of Cidofovir – is highly effective again many DNA viruses
and is 3x’s better than Cidofovir against all herpes viruses in the lab. Its
antiviral activity in animal models is very good as well. In the first clinical
study it was well tolerated.
CMV423 – a new compound very effective against HHV-6 and cytomegalovirus
HPMP-5-azal – Six times more effective against HHV-6 than Cidofocir. Much
more efficient and much less of the drug is needed. This is important because
toxicity is a big problem with cfidovir. Possibly a big hit.
Marabavir (MBV) – inhibits cytomegalovirus replication. Currently in Phase
III trials. Good against EBV. Contrary to previous reports, possibly good
against HHV-6. About 50-100 times more efficient than cidofovir in some tests.
Arysulfone derivatives – good antiviral activity, among most potent of
anti-virals.
Valomaciclovir and foscarnet-AZT and HHV-6. K. Yao.
Laboratory studies suggest that using Valomaciclovir and foscarnet-ZT in
combination resulted in greater than 90% suppression of HHV-6 after three days.
This drug is also being tested in a clinical trial at the University of
Minneappolis to treat EBV mononucleosis.
Report From the Bench: An ME/CFS Physician on
Antiviral Treatments in Chronic Fatigue Syndrome (ME/CFS)
K. De Meirleir Antiviral Treatment
Strategies in Chronic Fatigue Syndrome
"Today using combinations of immunomodulators, antivirals, nutriceuticals and
antibiotics we are able to obtain an acceptable clinical results in 70% of CFS
patients.”
Dr. De Meirleir has treated 1000’s of ME/CFS patents. He pointed out how
little hard data there was on the efficacy of anti-viral treatments in the
disease.
Antiviral Treatments
Immunoglobulins – could benefit ME/CFS patients by neutralizing viral
antigens and by rebalancing the immune system. They’ve had mixed results in
placebo-controlled studies. One study on adolescents suggested they can be very
effective. He used low doses of IgG1 or IgG3.
Dig Deeper! IVIG in chronic
fatigue syndrome (ME/CFS)
Antivirals – Again we hear the big problem with using antivirals
is diagnosis. Physicians need solid and reliable viral markers to determine
which patients antivirals will be effective with. Until they can get them they’ll continue to
use broad spectrum antivirals and immuno-modulators that may or may not be
effective against a particular pathogen.
Dig Deeper!
The Antivirals in Chronic Fatigue
Syndrome (ME/CFS)
Ampligen – physicians using the drug now have 20 years of experience with it.
He noted that two double-blinded, placebo-controlled and two open label studies
have found increased cognitive functioning and exercise capacity. Ampligen may
be particularly effective in post-EBV cases of ME/CFS.
Kutapressin (Nexavir) – in test tubes Kutapressin (now called Nexavir) inhibits EBV
replication and blocks EBV from infecting macrophages. Anecdotal activity
suggests that Kutapressin works. Dr. Enlander has unpublished data indicating
that 63% of ME/CFS patients ‘respond’ to a brand of Kutapressin he uses called
Hepapressin + B-12. Dr. De Meirleir found that 70% of his patients responded
quite well to Nexavir (20+ increase in Karnofsky scale in 6 months. This is
about double the increase Dr. Cheney’s patients showed on porcine cell factors).
Dig Deeper!
Nexavir (Kutapressin in Chronic Fatigue Syndrome (ME/CFS)
Aciclovir – no beneficial effects found over placebo. No positive
immunological effects.
Amantadine – inhibits viral infection of the cell and increases dopaminergic
activity in the brain. Amantadine has been used to relieve fatigue in MS
patients for years. Dr. De Meirleir said it does relieve fatigue in CFS patients
as well but a cross-over study found no significant benefit and increased
numbers of side effects.
Dig Deeper! Amantadine
in chronic fatigue syndrome (ME/CFS)
Thymalfasin (Zadaxin) – new drug used in Italy and Asia to fight chronic
hepatitis C. Excellent results reported in off-label uses on chronic fatigue
syndrome (ME/CFS) patients in Europe. A placebo-controlled trial is planned.
Azithromycin – an antibiotic that appears to have antiviral properties and is
able to penetrate the blood-brain barrier, an important consideration with
central nervous system infections. One study reported 50% response rate in
ME/CFS. His and Dr. Nicholson’s findings in the US are similar.
Dig Deeper!
Azithromycin in chronic fatigue syndrome (ME/CFS)
The Future - is about using new tools such as gene and protein expression and
better viral diagnosis protocols to put ME/CFS patients in the correct subset
and then targeting the right (new) antivirals and other therapies at them.
(This might not be as difficult as it sounds. If gene and protein expression
technologies can just find these subsets then the rest, at least so far as I
understand, might be fairly cheap and easy. From what I’ve heard it’s not
expensive or particularly difficult to test for a single or couple of
upregulated genes – the key is finding them. )
(The gene expression news right now is ‘pretty good’. Dr. Kerr was able to
replicate his former results – a big step forward – and it seems like almost
every major group - from the CDC to the Whittemore-Peterson Institute to the
Montoya studies to the NIH
– is taking a hard look at them. Dr. Kerr believes he has found some
subsets but it’s not clear yet how ‘tight’ they are.
(Gene expression studies are not at the point, though, where they can
identify, say, a central nervous system HHV-6 subset. Dr. Kerr’s repeated
identification of high levels of activity in a gene known to be upregulated
during Epstein-Barr Virus infection suggests he could be beginning to open up a
viral reactivation subset. The Dubbo gene expression studies, on the other hand,
found few meaningful correlations in their gene expression studies of their acute
onset post- infectious chronic fatigue syndrome (ME/CFS) and Dr. Lloyd does not
believe they will play a major role.)
(One key to improving gene expression’s efficacy may be doing complex analyses that
combine clinical, laboratory and gene expression data together to ferret out
specific sets of patients. This was tried in 2006 in the Pharmocogenomics
projects to quite mixed results. The winner of the CAMDA competition that used the
same dataset did, however, use complex multidimensional analyses to pick out a
gene (FORKHEAD BOX gene) that was associated with immune depletion. Perhaps in
the absence of reliable pathogen data these complex multi-variate analyses will
eventually be able to
pick out pathogen (and other) subsets.
(The FORKHEAD BOX study was one of the most tantalizing studies to come out of
the Pharmocogenomic’s study effort. One wonders if, with the financial hit the
CDC’s CFS research program has taken funding wise, if it was just left on the
shelf.)
(If researchers can find key indicators across a variety of tests they should be able to
formulate an algorhythm that could be cheaply tested for. Such an algorhythm
could be something like ‘Subset A” = low cortisol plus X, Y, Z upregulated genes
plus D and C parameters. These studies are expensive and will require a boost in
federal funding for them to come to fruition. )
Dubbo: Not Dead At All
Andrew Lloyd. Investigation of the pathogenesis of post-infective fatigue in
the Dubbo infection outcomes study (DIOS)
Dubbo (pronounced ‘duh-bow’ not ‘dew-bow’) has had its troubles lately. When
funding for the CDC’s CFS research team tanked they were cast adrift. Attempts
to get several NIH Neuroimmune CFS Grants inexplicably failed leaving them in
even deeper waters. One wondered if the Dubbo’s projects time – once one of the
shining lights of ME/CFS research – was over. Somehow, though, they’ve managed
to keep going.
The Dubbo study’s finding haven’t exactly lit the ME/CFS world on
fire either. Dr Lloyd’s rather categorical announcement that neither
infectious activity nor immune over activation was driving this illness
didn’t endear him to a good number of researchers. It didn’t help that
the Dubbo studies have found more about what chronic fatigue syndrome is
not than what is; thus far their results have suggested ME/CFS is not
due to an inability to fight off the infection or an over-active or
under-active immune response.
Dr. Lloyd’s recent statement that based on his findings he believes
the jury is still out as to whether gene expression will tell us
anything about this disease was probably not eagerly greeted in many
quarters. One began to wonder if the Dubbo study was ever going to
announce anything positive at all about this disease.
Dig Deeper: the Dubbo studies
in review
A Remarkable Unanimity. But the Dubbo studies
are back and in a big way. The data from all the pathogen cohorts (EBV,
Ross-River and Q-fever) have now been analyzed and they all show a
remarkable unanimity. In each of the cohorts the acute symptoms (fever,
sore throat, etc.) fade leaving behind a fatigue, muscle and joint pains
and, in some, mood disorders.
The rate of post-infectious fatigue or ME/CFS is almost identical at
12 months (6%) and 24 months (3%) among the three cohorts. The key
findings of the early studies were repeated in each of the other
pathogen cohorts. It turned out the prior findings weren’t a case of
concentrating on the wrong pathogen (EBV) as some have suggested; these
appear to be standard outcomes for acute onset ME/CFS patients.
Different Pathogens / Different Patients = Same
Disease: Consider how different these pathogens are to get a
sense of how remarkable these findings are; the Epstein-Barr Virus
strikes younger people, the Ross River Virus hits middle-aged people and
Coxiella burnetii stricks only middle-aged males in the farm community.
Two are viruses and one is a bacteria and they all produce different
symptoms in the beginning but all produce not only the same kind of
ME/CFS but they produce the same rates of ME/CFS a remarkable finding!
Until the latest study (see below) the only abnormality the Dubbo
groups been able to distinguish was that the patients who stayed ill got
whacked hard early in their illness. Dr. Vollmer-Conna explained that
the initial illness severity was not a trivial factor; it was in fact a
surprisingly strong indicator of who was going to stay ill. It also
appeared to predict duration as well; the people who got really sick
early on generally stayed sicker longer.
Still this wasn’t much – it was after all just a self-reported
symptom – not exactly the kind of fact that could turn the scientific
world on its head. It did suggest, though, that the problem in chronic
fatigue syndrome (ME/CFS)
occurred very early - during that period when the patients had little
idea they were fighting off anything more than another cold and
certainly long before they could begin to guess their lives were being
perhaps irrevocably altered. The next phase of Dubbo studies may have
uncovered a piece of what happened.
Breakthrough in Dubbo?
Uté Vollmer-Conna. Cytokines in post-infective fatigue.
Dr. Vollmer-Conna started off her talk by noting how disappointing
the cytokine findings thus far had been. Cytokines – immune agents that
travel through the blood turning on immune cells when the body is
fighting off infection – produce the ‘sickness response’ that makes us
so miserable when we are ill. The infectious onset and similar symptoms
seen in ME/CFS seemed to make cytokines the perfect fit for this disease
but thus far the Dubbo studies had found no evidence that cytokine
levels were increased as the disease progressed.
Armed with evidence suggesting the early stages of the disease were
the most important they took a close look at the early cytokine data.
They found that the people with the severest symptoms (i.e. the soon to
be ME/CFS patients) had the highest levels of cytokines, but
perplexingly this was only true in the acute illness and not later in
the ME/CFS phase.
An Illness Begins Unraveling? This suggested that
the chronic fatigue syndrome (ME/CFS) patients had a tendency to pump out more
cytokines than normal early in an infection. Next they asked
why. They found the ME/CFS patients had very significantly increased
risks of carrying two variants of genes that could increase their
symptoms during illness. (Different types of a single gene (a
polymorphism) are common in population. Typically these variants tend to
code for stronger or weaker gene activity).
One of these gene variants coded for increased pro-inflammatory
cytokine activity; the other for decreased anti-inflammatory activity.
Having either by itself significantly increased the risk of illness but
the risks were increased considerably more in people who carried both of
them – these were pretty strong indicators.
Their findings suggested that people who carried these gene versions
strongly tended to (a) get sicker early in the infection, (b) produce
more cytokines early in the infection and (c) come down with ME/CFS. In
short the genetic predisposition of these patients seemed to set them up
for a particularly strong pro-inflammatory immune response early in an
infection.
The Next Step. But then what? What might high
cytokine levels do? I asked Dr. Lloyd, Dr. Vollmer-Conna and Dr. White
about this. The Dubbo’s team current theory is that high cytokine levels
early in the infection alters patterns of brain functioning.
Specifically they believe they thrust the brain into a state of
hyper-vigilance in which it over-reacts to signals coming from the body.
They suggested ME/CFS was a kind of post-traumatic stress disorder with
the proviso that the brain was overreacting to internal, physiological
signals (as opposed to cues in the outside environment.)
This theory, which is close to the interoceptive theory, suggests
that the state of illness disappeared from the body but not from the
brain. The brain - believing the body is still sick – continues to
produce sickness signals; it is these unrelenting signals that damage
the HPA axis, immune system, and the other systems involved in chronic
fatigue syndrome (ME/CFS)
etc. over time.
Dr. White noted that these signals all occur under the level of
consciousness – in the subconciousness. Given the benefits I’ve accrued
from the Gupta Amygdala Retraining program which attempts to combat
negative subconscious activities I asked them what they thought about
it. I noted that meditation and other techniques (which the Gupta
program among others employs) have been shown to reset autonomic nervous
system functioning (i.e. retrain the brain). Dr. White felt that the
program was good but that the problem may not specifically originate in
the amygdala.
Dig Deeper: The Amygdala Retraining Program -
A blog plus patient reports
The location of this central nervous system deficit is a matter of
dispute. Ashok Gupta believes it originates in the amygdala, Dr.
White in the anterior insular, Dr. Baraniuk in the Papez Circuit, Dr.
Lloyd in another region, Dr. Chaudhuri and apparently Dr.
Reeves in the basal ganglia. Most of these are in similar parts of the
brain that effect cognition, emotions and autonomic nervous system
functioning. A good deal of brain imaging research is going on right now
and we should know fairly soon if these researchers are on the right
trail
Questions/Questions – Given the Dubbo studies
inability to find overt immune dysfunction/pathogen activity in a
post-infectious set of ME/CFS patients does this mean that the
immune/infection question has been answered? Apparently not to
everyone’s satisfaction.
The CDC is taking another look at the Dubbo team’s long term cytokine
data and the HHV-6 Foundation questions whether the right cytokines were
measured. The Foundation believes it’s possible that original infections
reactivated a central nervous system pathogen (HHV-6, enterovirus,
endogenous retrovirus). They also question
whether they were cleared out. Specifically they question whether the
tests used to assess EBV activity would adequate to detect an active
infection. They suggest that EBV EA antibody tests should have been
used.
(The pathogen diagnosis questions really bedevil this field. During the lunches
several researchers noted now difficult it was to find evidence of X
pathogen in blood even when biopsies (or autopsies) revealed it was readily present in an organ. Throw in the possibility of a central nervous system infection and
at least some researchers raise
serious questions arise about the efficacy of blood-based tests. A recent study showed that HHV-6 can persist in the spinal fluid
long after it’s disappeared from the blood. Another study found no
evidence of HHV-6 infection in the spinal fluid even though later autopsies suggested it had been active in the brain
)
(Dr. Klimas asked if the team had looked to see if virus’s such as
HHV-6 had reactivated as the patients got ill. Could the initial
pathogen have cleared out a space for another virus to pop up? Dr. Lloyd
didn’t know and felt the jury was still out on that question. )
Biomarker (!)(?)
Nancy Klimas, Immune Markers in Viral Reactivation
Dr. Klimas looks at ME/CFS from the eyes of an immunologist and what she sees
is an immune system that’s been revved up too long and has begun to bug out.
Simply put ME/CFS patients immune systems are like auto’s with 250,000 miles on
them and are fraying at the seams.
What in the body is putting chronic fatigue syndrome (ME/CFS) patient’s
immune systems through their paces? Dr. Klimas believes a chronic viral
infection is the culprit but in something of a departure from others believes it
is found not in just 15-20% of patients but in a ‘large subgroup’ of them.
The evidence for immune activation is long and includes increased levels of
cell suicide, poor NK and T-cell functioning, increased pro-inflammatory
cytokine production and macrophage abnormalities.
NK cell dysfunction is a key immune problem in ME/CFS but it has a catch – a
big catch – it’s expensive to test for. This has lead Dr. Fletcher and Dr.
Klimas to look for a cheaper test that reflected poor NK cell functioning and
they think they’ve found one – neuropeptide Y. In doing so they got an added
bonus: the cheaper test may provide a clue to what’s causing the problem.
“A Very Good Biomarker for ME/CFS”
We regularly hear that this or that might be a biomarker for ME/CFS but as the
years drag on there’s still no biomarker. Now Dr. Klimas says CD26 - a receptor
found on immune cells and in soluble form in the blood – is ‘a very good
biomarker for this disease’. This receptor apparently reflects immune depletion
and is significantly, very significantly decreased (p<.0001) in ME/CFS patients.
Establishing A Neuro-immune Connection – Neuropeptide Y - The biomarker is big but there was also big news regarding a substance called
Neuropeptide Y (NPY). We hear a lot about a neuro-immune connection in ME/CFS
but little direct evidence of it. Neuropeptide Y may provide the bridge between
the two that researchers are looking for.
NPY is stored in the nerve terminals of the sympathetic nervous system (SNS)
and is released in conjunction with SNS nerve agents called catecholamines
(norepinephrine, epinephrine). Recent evidence suggests that the activity of the
SNS – which is part of the stress response - is increased in ME/CFS. Given that
it stands to reason that NPY levels would be increased in ME/CFS as well - and
they are – quite significantly so (p<.001). Intriguingly given the stress
connection NPY levels are associated with an increased stress index and, given
that, not surprisingly with increased anger, confusion, frustration, etc.
Dig Deeper: Nancy Klimas on
immune dysfunction and the future in chronic fatigue syndrome (ME/CFS)
The Fletcher/Klimas team is one of the few that’s been able to crack the NIH.
They’ve been getting NIH grants to study ME/CFS patients for over 15 years now.
I asked Dr Fletcher if getting a grant was any easier now. She looked at me and
laughed and said ‘Are you kidding?’. Their latest grant – which examines immune
measures when ME/CFS patients are experiencing ‘good days’ and ‘bad days’ - took
three rounds to get approved. She said it was roundly rejected until it was
finally approved and that the makeup of the committee was key.(Advocates have saying
this for years. Not only is it rare for panelists that sit on the Chronic fatigue syndrome Special Emphasis
Panel to have expertise in ME/CFS its equally rare for them to know anything about the
immune system. (Thats right - few panelists that sit on the CFS review committee
typically
know anything about CFS))
Dirt in the Gears
Suzanne Vernon - Genetic variation and altered immune activity in Chronic
Fatigue Syndrome
Dr. Vernon’s talk really got some people buzzing. She’s been searching for
patterns in large, complex data sets that contain gene expression, gene
polymorphism and laboratory data. This is the kind of unique cutting edge stuff
that exemplified the Pharmacogenomics efforts. This is not cutting edge ME/CFS
stuff its cutting edge period. It’s a new way of looking at complex
multi-systemic diseases.
Her evidence suggests ME/CFS really is a multi-systemic disease but on a
scale that hasn’t been comtemplated before. We’re going to wait for the papers
publication- hopefully in a few weeks – but suffice it to say that her recent
evidence suggests that entire systems – not just x or y types of cells – but
entire systems are operating abnormally in ME/CFS. It’s a fascinating thesis.
The HPA axis – a important part of stress response system - appears to be
ground zero in this scenario of systemic derangement. Dr. Vernon was the leader
the CDC’s Pharmacogenomic’s projects which ended up again and again pointing at
the HPA axis, in particular, at the adrenal stress hormone cortisol. Since then
the CDC has run off a nice string of ‘successful’ papers on the subject. In the
abstract for her talk Dr. Vernon put the HPA axis front and center stating that
“hypoactivity (reduced activity) of the HPA axis leads to neuroendocrine and
immune alterations”.
What’s the evidence for that? And what kinds of alterations is she talking
about? We’ll have to wait for the paper.
Dig Deeper: the
Pharmacogenomics Papers - the Overviews
The Fatigue Syndromes
An Overview of Post-Viral Fatigue: CFS or What? By Peter White
As time goes on researchers are trying to dig deeper and deeper into the
‘fatigue syndromes’. Dr. White a well known UK psychiatrist asked whether the
post-viral fatigue commonly after infectious mononucleosis (glandular fever) is
different from chronic fatigue syndrome (ME/CFS).
The fatigue after infectious mononucleosis is not trivial; studies show that
about 40% of IM patients will complain of fatigue six months after the onset and
that 12% will go so far as to see the doctor for it within a year. Most do
appear to recover over time.
Mood disorder, PVFS and ME/CFS - Most people who get post infectious fatigue
syndrome (PIFS) do not come down with CFS. They often suffer from depression
early on but it disappears quickly. Interestingly Dr. White stated the
depression process found in ME/CFS is kind of unique; they could find all sorts
of factors that could predict who will get depressed in PIFS but they couldn’t
find them in ME/CFS. Indeed Dr. White was clear that ME/CFS is not – as was
proposed for years – a kind of atypical depression.
Dr. Enlander asked about the relationship between mood disorder and ME/CFS.
Dr. White felt it was quite complicated. Depression is a risk factor for chronic
fatigue syndrome but it is not a ‘big driver’ for it; i.e. other still
unelucidated factors than depression are much more important in producing the
disease. He noted that many ME/CFS patients are not depressed.
PVFS and ME/CFS: similar but different - That both PVFS and ME/CFS patients
were more likely to have seen their doctor for fatigue before they became ill
suggested that some processes that later became amplified were already present.
A finding that PVFS patients tended to experience more infections than normal
before they come down with PVFS suggested they may have had immune problems
beforehand. (Dr. Chia will report he sees the same process). CFS patients, on
the other hand, tended to have more mood disorders than PVFS patients or healthy
controls before they became ill. PIFS patients also tended to suffer from
insomnia while CFS patients tend to experience hypersomnia (increased sleep).
Interestingly data is emerging to suggest that not all infections trigger
chronic fatigue syndrome. Flu pathogens, for instance, do not appear to. ‘Just
for fun’ Dr. White guessed that about 20,000 people in the US come down with
chronic fatigue syndrome (ME/CFS) after having infectious mononucleosis every
year (60/day).
Activity and ME/CFS - Dr. Bell asked what role activity level prior to
getting sick played in the disease. Dr. White replied that evidence is emerging
that both decreased and increased activity levels put one at increased risk of
ME/CFS. He noted that people who experienced fatigue and kept exercising had an
increased risk of coming down with ME/CFS.
Dr. Lloyd noted that behavioral therapies were very helpful early in the
illness. This was an interesting statement given evidence that people who try to
bull their way through it (or exercise) place themselves at increased risk.
Apparently the behavioral paradigm for ME/CFS no longer includes ignoring or
denying the manifestations of the illness (???).
One wonders if these behavioral therapies are actually reducing activity levels?
Or if their new focus on ensuring one gets enough sleep, for instance, is
particularly early in the disease? In an upcoming interview Dr. Friedman
will point out that most ME/CFS patients are too active for their own
good.
Thanks to the HHV-6 Foundation and PANDORA for their assistance in
attending the Baltimore Conference, thanks to Tom Hennessey for getting me back and
forth several times from DC and thanks to my brother for his
twisted but still much appreciated hospitality. Thanks to the HHV-6
Foundation for their comments on this paper.
To The Symposium on Viruses
in Chronic Fatigue Syndrome (ME/CFS): Part I