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THE INTERNATIONAL
CONFERENCE ON FATIGUE SCIENCE
February 9-11, 2005,
Karuizawa, Japan
From Co-cure
Dan Peterson, MD (Sierra Internal Medicine,
Incline Village, Nevada, 775-832-0989, ext 201)
Dr. Peterson found HHV-6A in 29%
of the serum and in 20% of the spinal fluid of his
patients with prominent CNS symptoms: neurocognitive
problems, headaches, paresthesias or autonomic
dysfunction. Of those with virus in the spinal fluid,
the blood tests were negative 40% of the time. This
means many physicians get false negative results when
they test for HHV-6 in the serum.
Peterson tested 430 patients by PCR or rapid culture,
and found 126 were positive at least once. He performed
145 spinal taps on patients with an abnormal MRI or
severe problems with cognitive functioning. Peterson
found one case each of EBV and CMV and 27 cases of
HHV-6, all variant A. He has been treating them with
intravenous antiviral therapy and the majority have
responded. Peterson has had success using Ampligen, an
antiviral that is currently in clinical trials, and
cidofovir, an antiviral approved for CMV retinitis.
Dharam Ablashi, MD (Scientific Director, HHV-6
Foundation - 302-947-9634)
Dr. Ablashi reported that when studies used the correct
testing method, over 80% of the studies showed a strong
association between HHV-6 and CFS.
When you look only at the studies that tested for active
(vs. latent) virus in CFS patients, then 10 out of 12
showed a strong positive association between HHV-6A
infection and CFS", he said. Ablashi found the same to
be true in the studies on MS patients: 29 out of the 37
studies on MS and HHV-6 showed a positive association.
Many of the early studies were done on whole blood, a
technique that picks up latent virus, leaving the
results muddled. The best tests are those that only pick
up active virus - tests done on plasma, serum or spinal
fluid with no cells. The problem is that although these
are the only tests that can indicate active infection,
they aren't very sensitive.
"There is a good reason why it has taken a long time to
build a case for this virus playing a role in chronic
fatigue - this is a very difficult virus to find," said Ablashi. "The virus is 'neurotropic meaning it prefers
to live in the brain tissue. "It is quite frequent that
a patient might have a significant infection in the
brain tissue, but no virus evident in the serum by PCR."
Takeshi Sairenji, MD Department of Biomedical
Sciences, Tottori University, Tottori, Japan - sairen@grape.med.tottori-u.ac.jp
Dr. Sairenji showed evidence that 60% of CFS patients
vs. 11% of controls had evidence of chronic activated
antiviral pathways. He suggested that chronic
fatigue might be caused by interferon from viral
infections such as HHV-6, Epstein Barr Virus and Borna
virus. Sairenji's study supports the previous work of
Dr. Kenneth De Meirleir of Brussels and the scientists
associated with RED Laboratories who have found similar
distinct physical
abnormalities among CFS patients. The chronic
activated antiviral pathways apparently include RNase L.
Kenneth De Meirleir (Department of Human
Physiology, Vrije Universiteit Brussel, Brussels,
Belgium - de.meirleir@pandora.be)
Dr. Kenneth DeMeirleir, who has published similar
findings on elevated antiviral pathways, said that these
abnormalities result in the inactivation of the thyroid
receptors - so that CFS patients are functionally
hypothyroid even though their lab results may appear
normal. He reported that these abnormalities also cause
an increased sensitivity to heavy metals such as nickel
and mercury, as well as a sluggish cortisol response.
Kazuyoshi Ikuta, MD Research Institute for
Microbial Diseases, Department of Virology, Osaka
University, Osaka, Japan - ikuta@biken.osaka-u.ac.jp
Dr. Ikuta reported his group found a higher prevalence
of Borna virus antibodies in both psychiatric and
CFS patients compared to controls. He demonstrated that
mice injected with Borna virus developed low-grade Borna
viral infections in the glial cells of the brain. This
low grade infection disrupted neuronal function causing
the mice to behave abnormally.
Abbijit Chaudhuri, MD (Division of Clinical
Neurosciences and Molecular Pathology, University of
Glasgow, Scotland, UK - Ac54@udcf.gla.ac.uk)
Dr. Chaudhuri, a neurologist from Glasgow, explained
that one way that poorly performing glial cells cause
fatigue is by altering ion channels and creating a 'channelopathy.'
He believes that there are many triggers for CFS, but
they ultimately all end up with a common pathway in
creating fatigue: a disruption of the ion channels.
Chaudhuri used as an example, chronic fatigue caused by
ciguatera fish poisoning. The ciguatera toxins
block the sodium ion channels, which result in too much
extra-cellular potassium, which in turn creates fatigue.
Glial cells, which are supposed to buffer the amount of
potassium released from the neurons, do not function
well when they are infected with virus. HHV-6A virus
actively reproduces inside the brain's glial cells,
while the B variant simply smolders - but both strains
induce inflammatory cytokines.
Kazuhiro Kondo, MD (Chairman of the Department of
Microbiology, Jikei University School of Medicine,
Tokyo, Japan kkondo@jikei.ac.jp)
Dr. Kondo found that 88% of Japanese workers expressed
HHV-6 B virus in their saliva when they were
stressed just before the holidays, but found it in only
24% after the holidays when the same workers were
refreshed. There is almost no variant HHV-6 A in Japan
so his studies were
based on the B variant, which according to Dr. Kondo is
far less pathogenic than the A variant but much quicker
to activate.
Norihiro Sadato, MD (Osaka University School of
Medicine, Osaka, Japan sadato@nips.ac.jp)
Dr. Sadato used advanced, quantitative MRI techniques to
examine 16 CFS patients and 49 controls and found marked
differences. CFS patients had reduced gray-matter volume
in the prefrontal cortex and the severity of the
atrophy related to the severity of fatigue in the
patients. Furthermore, when the dysfunctional areas of
the brain were pinpointed, they turned out to be the
centers of the brain that control emotion, executive
functioning and motivation. Sadato noted that these
results were consistent with previous reports of
abnormal acetyl-L-carnitine uptake in the pre-frontal
cortex in CFS patients. These abnormalities are similar
to those reported in MS patients.
Benjamin Natelson, MD (Department of
Neurosciences, UMDNJ-New Jersey Medical School, Newark,
NJ 973-972-2550)
Dr. Natelson, a neurologist who runs a large CFS clinic
in New Jersey, was among the speakers presenting
evidence of brain inflammation due to
encephalopathy. Natelson found evidence of inflammation
in the spinal fluid in 30% of his CFS patients. Natelson
concluded that this study supports the hypothesis that
some CFS patients have a brain disease.
Gundrun Lange, MD (Department of Radiology, UMDNJ-New
Jersey Medical School, Newark, NJ - 973-97-6273)
Dr. Lange declared chronic fatigue to be a 'brain
disease'. Lange used functional neuroimaging to
examine verbal working memory in CFS patients and found
dramatic differences in performance that could not be
explained by mood or anxiety. The neural networks in CFS
patients, as measured by blood oxygen signals, worked
much harder than non-CFS patients when given the same
task to complete. Lange said this would explain the
subjective reports of neuorocognitive difficulties in
information processing that are a common complaint among
CFS patients.
Nancy Pederson, MD (Department of Medical
Epidemiology and Biostatistics Karolinska Institute,
Stockholm, Sweden )
Dr. Pederson reviewed telephone interview data from
12,407 sets of twins enrolled in the Swedish Twin
Registry and found that genetic factors in CFS
were "modest", explaining only about 35% of the disease.
This suggests to Pederson that environmental triggers,
such as toxins, stress and viruses, are important to the
pathogenesis of CFS.
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