Thursday, April 2, 2009

Reno Wrap-Up

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Reno Wrap-Up: A Report
on the 2009 IACFS/ME

By Kim McCleary and Suzanne Vernon, PhD

The CFIDS Association of America

In mid-March, researchers, clinicians, patients,
caregivers and advocates from around the world
gathered in Reno, Nevada, to share information,
critique the latest research and network in the
hallways and over meals. The 9th research and
clinical conference sponsored by the International
Association for CFS/ME (IACFS/ME) drew about 220
participants for the four-day event held at the
Peppermill Resort & Casino.

Marking the 25th year since CFS was first brought to
national attention, pioneering clinician and
researcher Dr. Daniel Peterson had the honor to be
the local host as well as to open and close the
conference sessions. Dr. Peterson is well-known for
having been among the first, with his then-partner
Dr. Paul Cheney, to recognize CFS among a cluster
of ill patients in his internal medicine practice in
Incline Village, Nevada, just over Mount Rose from
Reno. Dr. Peterson has stuck with CFS and by his
patients with CFS, so it seemed a fitting tribute to
hold the meeting in his backyard. Philanthropists
Annette and Harvey Whittemore, whose adult
daughter Andrea has CFS, have founded a center for
research and clinical care, the Whittemore Peterson
Institute, that will open mid-2010 on the campus of
University of Nevada Reno. Several conference
attendees drove past the construction site at
McCarran & Virginia streets while they were in Reno.

Patient Conference

IACFS/ME conference organizers established the first
day as a patient-oriented conference designed to
provide an overview of current research and
management, with longer presentations delivered by
current and past members of the IACFS/ME Board of
Directors. Dr. Peterson delivered the opening talk,
followed by Dr. Anthony Komaroff of Harvard
Medical School. Both gave summaries of some of the
most promising and durable research findings about
abnormalities in many body systems of CFS patients.
Two presentations on coping were then given by Dr.
Fred Friedberg of Stony Brook University and Dr.
Leonard Jason of DePaul University. Both spoke to
the need for pacing and energy management to avoid
the "push-crash" cycle of overactivity followed by a
relapse that can be so destructive over time.

Dr. Hirohiko Kuratsune of Osaka City University in
reviewed his group's experience with research
and treatment over the past 19 years since he saw
his first CFS patient in 1990. The Japanese group has
taken a holistic approach to therapy, incorporating
everything from medications to anti-fatigue foods to
laughter to healthy housing. Dr. Ken Friedman of
University of Medicine and Dentistry of New Jersey
(UMDNJ) highlighted central nervous system
abnormalities and problems with the body's
energy-producing cells in CFS. Dr. Gudrun Lange,
also of UMDNJ, gave a detailed tour of brain anatomy
and function and then provided several coping tips to
compensate for the attention and processing deficits
that can be so problematic for CFS patients.

Dr. Nancy Klimas, concluding a four-year term as
president of the IACFS/ME, provided an overview of
pharmacologic therapy for CFS, emphasizing that
people with CFS often cannot tolerate the usual
doses of medications used to treat sleep, pain and
depression, and that starting low and very gradually
increasing dose can be the key to deriving a benefit
from a particular drug. She also talked about the
importance of gentle exercise, made easier by doing
things like swimming, recumbent biking and pilates
in a horizontal position to get around the orthostatic
problems with upright posture that many patients
A panel of all the day's speakers
concluded the formal program; they took questions
that people in the audience submitted on written

During the day, researchers and clinicians had the
opportunity to attend four three-hour workshops, two
of which were offered concurrently in the morning
followed by two other sessions in the afternoon.
CFIDS Association scientific director Suzanne
Vernon, PhD, led one of the workshops. Dr. Vernon's
session attracted approximately 40 people who spent
the afternoon in dialogue about research design and
how genomics can inform clinical practice of CFS.

That evening, an unreleased documentary,
"Invisible," produced by Rik Carlson and Michael
Thurston, was shown. Although it focuses on CFS
patients living in Vermont, its themes were
recognized by all present. A patient reception
sponsored by Sierra Internal Medicine enabled
participants to socialize and network. Annette
Whittemore recognized the local volunteers who
helped make the meeting a success.

Research and Clinical Conference
The sessions on Friday, Saturday and Sunday were
dedicated to short (11-minute) data presentations by
researchers on specific study results that bridged
somewhat overlapping topics of treatment,
epidemiology, immunology, assessment, pediatric
CFS, genomics, genetics, brain functioning and the
integrative approach being utilized by the Japanese
to study CFS. Dr. Komaroff closed Sunday's session
with a brilliant overview of the 115 presentations
delivered from the podium and via two poster
sessions displayed in the exhibit hall.

Taking a step back from the order of the
presentations, several themes emerge, although
there is overlap among them, too. We've organized
our summary this way to draw attention to some of
the most interesting studies reported at the
conference. You can also read the daily updates: .aspposted
from the conference for more information.

The brain: Two studies used different techniques
to document brain abnormalities in CFS patients. Dr.
Frank Duffy, a Harvard neurologist, studied a large
group of patients using spectral coherence EEG and
was able to discriminate, with nearly 90% accuracy,
patients with rigorously defined CFS from healthy
control subjects and from subjects with major
depression. He stopped short of calling this pattern
diagnostic, but stated that it did define CFS as an
organic brain-based condition
. The study was large,
with a total of 632 subjects; however, the CFS
patients referred by community-based physicians did
not demonstrate the same frequency of EEG
patterns, suggesting that the label of CFS may be
misapplied in some settings
. Leighton Barnden,
PhD, of the University of Adelaide in Australia,
analyzed brain magnetic resonance (MR) images from
25 CFS patients and 25 healthy control subjects.
Comparing volume differences in specific areas of the
brain, Dr. Barden reported that changes in CFS
subjects were consistent with the symptoms and
symptom severity they reported. For example,
changes in the medulla and insula are consistent
with the autonomic dysfunction reported in CFS.
was unable to determine based on this study alone
whether the changes represent the cause of the
symptoms or the effect of CFS.

Triggering agents/factors for CFS: While early
studies of CFS sought to identify a single agent that
caused the illness, most researchers now appear to
agree that CFS can be "triggered" by a number of
different insults including microorganisms (bacteria,
viruses, etc.), environmental exposures and severe
injuries (such as closed head trauma).
At this
conference, researchers reported data on a number of
agents that set off a CFS-like illness. Here is a list of
the agents explored by researchers who gave

     * Giardia lambia (Eva Stormorken, RN,
        University of Oslo, Norway)
     * Coxiella burnetii (Andrew Lloyd, MD, University
        of New South Wales, Australia)
     * Parvovirus B19 (Jonathan Kerr, MD, PhD, St.
        George's University of London, England)
     * Parvovirus B19 and herpesviruses (Kenny
         DeMeirleir, MD, PhD, University of Brussels,
     * Mammalian viruses (Judy Mikovits, PhD,
        Whittemore Peterson Institute, USA)
     * HHV-6 and -7 (Modra Murovska, MD, PHD,
        Riga Stradins University, Latvia)
     * Epstein-Barr virus (EBV), CMV and HHV-6
        (Barbara Cameron, PhD, University of New
        South Wales, Australia)
     * Enteroviruses, EBV, Chlamydia pneumoniae,
        coxiella burnetii and parvovirus B19 (Lihan
         Zhang, St. George's University of London,

The main debate about these various triggers
seemed to be whether different subgroups of illness
were defined by the specific trigger (B19 vs. EBV), or
whether the resulting illness was the same
regardless of the triggering event/agent. More
research will be required to sort this out. It is worth
noting that none of the agents studied were found in
all the CFS patients studied and that none of the
researchers suggested that the agent alone caused
the CFS.

Other triggers explored were repetitive strain injury
(Eliana Lacerda, MD, PhD, London School of
Hygiene and Tropical Medicine) and disruption of
normal diurnal rhythms in children (Teruhisa Miike,
MD, Kobe, Japan).

Subgrouping by biologic abnormalities:
Another sign of the maturing of the CFS research
field is the broad agreement that the definition for
CFS results in a rather heterogeneous patient group
and that studies should seek to define subgroups of
patients using one or more biologic measures.
Several research groups reported evidence of immune
system and neuroendocrine abnormalities
, building
on some of the earliest CFS reports in the biomedical
literature. One of the most impressive presentations
was delivered by Alan Light, PhD of University of
Utah. His group reported differences between CFS
patients, healthy controls and a smaller group of MS
patients on adrenergic and sensory receptor
peripheral blood cell gene expression after a modest
exercise challenge
. The CFIDS Association of America
is providing support to expand the study that was
begun with a grant from the National Institutes of

The CFS group at the University of Miami (UM) and
collaborators presented several immune system
abnormalities in Gulf War Illness/CFS patients
following a graded exercise test, including elevated
levels of neuropeptide Y (NPY) (Mary Ann Fletcher,
PhD, UM) and a plasma cytokine shift from Th1
(antiviral defense) to Th2-type (proinflammatory
activation) immune response (Nancy Klimas, MD,
UM). These observations were confirmed by Gordon
Broderick, PhD, at University of Alberta who found
distinct patterns of coordinated change in NPY,
cytokine and cortisol concentrations at rest and
under challenge using data collected from the UM

Researchers working with the Whittemore Peterson
Institute studied a group of CFS patients who were
found to have clonal T-cell rearrangements,
predictive of non-Hodgkin's lymphoma.
patients demonstrated chronic inflammatory
stimulation and differential expression of human
endogenous retroviruses (Judy Mikovits, PhD).
Vincent Lombardi, PhD, showed that a distinctive
pattern of serum cytokines and chemokines could
distinguish between CFS patients who did and did
not have the clonal t-cell receptor gene

Andrea Suarez Segade, MD of the University of
Barcelona, reported that there were significant
differences in the values of growth hormone,
prolactin and cortisol in women with CFS compared to
healthy women after an exercise challenge
. A small
study at Bond University in Australia reported by
Ekua Brenu, HBSc, found that CFS patients
demonstrated significant decreases in respiratory
burst, while the number of T cells, monocytes and B
cells were comparable to healthy controls.

Most of these investigators expressed hope that
these findings, perhaps combined with other
measures of symptom expression or severity or other
biological measures, would yield characteristic
"fingerprints" for subtypes of CFS that would aid in
diagnosis and therapy.

Several of these studies (Light, University of Miami,
Segade) have used exercise challenge to identify
biologic differences that seem to be subtle at rest,
but are more pronounced after exertion
. One
important study that found no meaningful difference
between CFS cases and controls, was presented by
Christopher Snell, PhD, of University of Pacific. His
group tested for a low-molecular weight RNaseL (37
kDa) and elastase activity as biomarkers for CFS, as
had been reported previously by other groups to be
abnormal in CFS. 22 CFS patients and 21 matched
controls underwent serial exercise tests and samples
were taken at various time points and then
processed by a commercial lab. Results were variable
and did not correlate with symptoms, illness status
or pre- and post-exercise. Dr. Snell concluded that
neither "RNase L ratio nor elastase levels have any
efficacy as biomarkers for CFS."

Metabolic/mitochondrial dysfunction: Three
researchers suggested that CFS stems from a
problem producing energy at the cellular level in the
mitochondria. Dr. Norman Booth of University of
Oxford presented results obtained from 71 CFS
patients using an ATP profile test combined with the
Bell Ability Scale as a measure of functional capacity.
The two collaborating physicians found a correlation
between the degree of mitochondrial dysfunction and
the severity of illness, suggesting that the fatigue in
CFS is due to cellular respiration dysfunction
. Mark
Van Ness, PhD, of the University of Pacific reported
that half of the women with CFS displayed metabolic
dysfunction as assessed through a test-retest graded
exercise protocol; 56% of a group of patients with
high EBV/HHV-6 viral levels also showed quantifiable
metabolic dysfunction. Finally, Alan Light's data
(described above) indicate a problem in metabolism
that prolongs the sensation of muscle fatigue and
pain after exercise, even when the muscles are not

Therapy/treatment: Although two sessions were
dedicated to pharmacologic and non-pharmacologic
treatment advances, unfortunately there was little
new presented. Cognitive behavioral therapy (CBT)
was addressed by two speakers, Greeta Moorkens,
MD, PhD, of Antwerp University Hospital, and Elke
van Hoof, PhD, of Vrije Universiteit Brussel. Dr.
Moorkens reported that the majority of 180 patients
treated with 10 sessions of CBT over six months
reported some improvement but did not show
statistically significant improvement on fatigue or
physical functioning scores. Dr. van Hoof confirmed
earlier studies that show a high percentage (30%) of
drop-outs due to deterioration during CBT trials.
indicated that differing expectations between the
provider and the patient for treatment can affect
satisfaction and that communication is essential; yet
her studies do not support large scale application of
CBT. Michael Antoni, PhD, of University of Miami,
discussed a telephone-based program of Cognitive
Behavioral Stress Management that allowed patients
to receive information, relaxation training and
support without leaving home. Preliminary data
suggests that the program was well-accepted and
that patients showed improved quality of life and
some reduction in symptoms. Dr. van Hoof also
presented a study on Eye Movement Desensitization
and Reprocessing (EMDR) to decrease hypervigilance
seen among CFS patients. Preliminary data analysis
was also showing some benefits with physical
functioning. Patricia Fennell, MSW, identified
several types of trauma induced by CFS and other
chronic conditions.

Nicole Porter, PhD, of DePaul University presented
a review of trials of alternative therapies and
concluded that several have some potential for
future clinical research, but that no firm conclusions
can be drawn because of the limited number of
subjects and somewhat suspect methods used.
Among those with the most promise are acupuncture,
meditative practice and magnesium, L-carnitine and
S-adenoslymethionine (SAMe) supplements
. Hirohiko
Kuratsune, MD, of Osaka City University reported
that supplementing the diet with essential fatty
acids (EFAs), zinc, copper, manganese and vitamins
B6 and B12 had demonstrated some effectiveness in
his patients. Dr. Yasuyoshi Watanabe, proposed
using functional foods, coenzyme Q10, applephenon,
imidazole dipeptide and crocetin to combat fatigue
based on his studies at Osaka City University and
RIKEN (of Japan).

The studies of three pharmacological treatments
were presented: Ampligen, isopinosine and sodium
oxybate. David Strayer, MD, of manufacturer
Hemispherx, reported that Ampligen improved the
physical function of CFS patients as measured by
exercise treatment duration
. He indicated that the
drug, now under review by the Food and Drug
Administration (FDA) for marketing approval, was
well-tolerated and that its use allowed patients to
reduce their dependence on other drugs. A decision
is expected from FDA in May 2009. Isoprinosine is
sold in Ireland and Costa Rica under the trade name
Maria Araceli Vera, MD, of University of
Miami, presented a chart review of 61 patients who
took isoprinosine for six months. Using data from
their charts to assess both clinical status and
immune status, Dr. Vera concluded that there was
highly significant improvement in both clinical and
immunological status, stating that a large,
randomized clinical trial would be appropriate based
on this review. Natalie Hone, MD, of University of
Miami, also presented results of a chart review of 27
CFS patients with documented alpha-wave intrusion
in slow-wave sleep who had taken sodium oxybate
(Xyrem) to treat this condition
. 20 of these patients
reported improvement in their sleep after treatment.
Like her colleague, Dr. Hone concluded that further
studies are indicated.

Pediatric/childhood CFS: Several presentations
throughout the conference focused attention on kids
who get CFS. Leonard Jason, PhD, of DePaul
University reported that the pediatric ME/CFS criteria
published in 2006 were more effective than the 1994
Fukuda (adult) criteria as a diagnostic tool for
children and adolescents. Ritchie Shoemaker, MD,
of the Center for Biotoxin Associated Illnesses,
conducted a retrospective chart review of 163
patients ages 10-17 years to identify biomarkers that
would separate cases of CFS from non-cases. He
found an association of increased autoimmune
abnormalities and elevated levels of a regulatory
cytokine, TGF beta-1, that merit additional
evaluation. Greta Moorkens, MD, PhD, reviewed the
clinical charts of 81 patients ages 14-21 years who
were referred to a hospital clinic. Headache, muscle
ache, concentration or memory disorder and joint
pain were the symptoms most often reported. She
reported that vitamin D deficiency was common,
especially among the housebound patients,
and that
there were three suicide attempts among the patient
group. 13 of 22 patients tested for sleep problems
were found to have them and 11 of 19 patients
referred to a psychiatrist were found to have a
depressive disorder as well. She underscored the
importance of thorough sleep and psychiatric
evaluations in this population.

Dr. Esther Crawley of University of Bristol (United
Kingdom) presented two studies of children with CFS.
First, she followed 46 children with CFS who were
housebound for one year at three different
assessment points. She compared them with children
with CFS who were able to attend clinic. The
housebound patients had higher scores on the
symptom inventories and had more co-morbid
conditions. 30% of the more severely ill patients
either recovered completely or had improved
sufficiently to attend some school by the time of
follow-up. Dr. Crawley's second study focused on
grouping 333 children with CFS/ME by symptom
assessment to determine if clusters would emerge
that might represent different underlying disease
processes. Factor analysis suggested three groups of
patients, while cluster analysis produced five

Laura Younis of Deakin University in Victoria,
Australia, studied cognitive function in a group of 27
adolescents and young adults with CFS and 27
healthy matched controls. She found that the CFS
patients missed 8.28 days of school per month,
compared to the 1 day per month for the healthy
students. While the CFS patients were unwell and
reported high levels of distress and disability, their
objective performance on the cognitive tests
performed in a laboratory setting was comparable to
that of their healthy peers. Dr. Younis suggested this
reflected the motivation of the CFS patients to do
well in the study and that it may not be indicative of
performance in classroom or home settings where
there are other influences and distractions.

The final group of childhood CFS (CCFS) studies came
from the group in Japan. Sanae Fukuda, PhD,
attempted to identify common characteristics of
children with CFS as risk factors for developing the
illness. She found that school problems were a better
predictor for boys who went on to develop CFS, while
family problems were more common among the girls.
They found that the "sleep score" was a predictor for
both groups. Kei Mizuno, PhD, found that selective
and divided attention processing was impaired in the
414 children with CFS studied, compared to 190
healthy children tested. He indicated that they are
now using functional MRI testing to clarify the neural
substrates associated with different subtypes of
attention processing deficits. Teruhisa Miike, MD,
PhD, showed that over 20 years during which CCFS
has been studied in Japan, they have linked it to
disruptions in the normal biological clock that is
evident in contemporary Japanese culture. Long-term
sleep deprivation, coupled with excessive bright light
exposure during nighttime hours (from TV, video
games, cell phones, etc.) upset the normal diurnal
rhythms and developed into CFS. He also noted that
30% of the CCFS cases have tested positive for
HHV-6A. He urged the importance of preventing CCFS
by maintaining normal activity and sleep schedules.

Genetics and genomics studies: There were several
presentations describing genetic contributions to
CFS. Marc Fremont, PhD, of Protea Biopharma
(Belgium), reported on differences in toll-like
receptor genes that are important for modulating
bacteria-induced immune activation that were more
frequent in CFS. Also, these investigators found
genetic differences in genes important in TH17
protein function. TH17 cells fight off bacterial
infections and abnormal function has been implicated
in intestinal diseases of autoimmunity. Mangalathu
Rajeevan, PhD, of the U.S. Centers for Disease
Control and Prevention, presented results from the
first CFS genome-wide association study. He
reported that variants in GRIK2, a gene involved in
glutamate transmission, and NPAS2, a gene
important in brain function, were associated with
CFS.  Further, CFS subjects with these gene
differences also showed correlation with gene
expression providing further evidence of
neuroendocrine and immune dysfunction in CFS. In a
targeted genetic analysis, Judy Mikovits, PhD of the
Whittemore Peterson Institute, found that variations
in HLA and KIR genes – genes important in a proper
immune response – might increase the risk for CFS.
Andrew Lloyd, MD, PhD, of the University of New
South Wales presented exciting findings on changes
in the functional polymorphisms for two cytokines in
particular, IL-10 and interferon-gamma. Subjects
with a "low-risk" combination of sequences were ill
for an average of 34 days, whereas those with the
"high-risk" combination remained unwell for 80 days
on average. Therefore, he posited, the intensity of
the inflammatory response may determines the
severity of the acute infection and duration of the
illness that follows.

Other Events

On Thursday evening, to welcome colleagues from
Japan and return the hospitality extended to us last
year when we visited Osaka City and Kobe, we
hosted a small dinner for Dr. Watanabe's team and
three of our funded investigators, Dr. Dikoma
Shungu and Drs. Kathy and Alan Light. While this
took us away from the patient reception at the hotel
that evening, it was a good opportunity to catch up
on the recent approaches being taken and advances
being made on both sides of the Pacific.

The Keynote Address was delivered on Friday, March
13, by the Honorable John Kitzhaber, former
governor of the state of Oregon. Dr. Kitzhaber spoke
about the need for sweeping health care reform. As
founder of the Archimedes Movement, he is
challenging the federal government to replace the
current outdated framework with a totally new
approach to providing health care services and
covering costs.
His talk was not specific to CFS, but
was informative to providers and patients alike.

On Friday evening, about 75 people gathered at the
Nevada Museum of Art for a reception in support of
the IACFS/ME sponsored by Annette and Harvey
Whittemore of the Whittemore Peterson Institute.
There was no formal program, but Annette welcomed
the Honorable John Kitzhaber and several guests
representing the Nevada state legislature and
University of Nevada Reno who were pivotal in
helping establish the Whittemore Peterson Institute.
The museum's exhibits were open to attendees and
the event offered an opportunity for informal
socializing and networking.

On Saturday afternoon, the IACFS/ME held its
biennial business meeting for members and others to
hear organizational plans and to vote on nominees
to the Board of Directors. Installed as president was
Fred Friedberg, PhD and four newly elected
directors joined five others continuing for another
term on the Board. Suzanne Vernon, the CFIDS
Association's scientific director, is one of the four
individuals who joined the IACFS/ME Board.

It has become a tradition at these conferences to
hold an awards banquet on the night of the last full
day of the schedule. On Saturday, March 14, the
awards ceremony followed a large buffet dinner,
emceed by new IACFS/ME president Fred Friedberg.
The following individuals were honored:

     Benjamin Natelson, MD
     Governor Rudy Perpich Memorial Award

     Charles Lapp, MD
     Nelson Gantz Clinican Award

     Nicole Porter, PhD
     Junior Investigator Award

     Annette Whittemore
     Special Service Award

     Michael Antoni, PhD
     Nancy Klimas Research Excellence Award

     John Chia, MD
     Nancy Klimas Research Excellence Award

     Suzanne D. Vernon, PhD
     OFFER Research Excellence Award

     Molly Brown, MA
     OFFER Research Excellence Award

In summary, at this truly international meeting,
represented by 17 countries where CFS is being
studied, there was much enthusiasm for the varied
approaches being taken and the new technologies
being employed to investigate CFS. There was some
disappointment with the small and preliminary
nature of many of the studies, but this was largely
seen as a function of the meager funding streams
available in the U.S. and most other countries.
Hopefully when IACFS/ME convenes its next
conference in two years, some of these
investigations will have matured and there will be
more standardization of studies through enhanced
communication, established networks (like the one
being formed by the CFIDS Association's funded
investigators) and expanded funding opportunities.

for links to daily conference reports posted by the
Association to its Facebook page and links to other
organizations and conference resources.
( ~jan van roijen: see following bulletins of *Help ME
Circle* )

Keep the CFIDS Association of America on the
leading edge. If accelerating the pace of CFS
research matters to you, donate now:

© 2008 The CFIDS Association of America, inc

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