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Report from the 9th International IACFS/ME Research and Clinical Conference Reno, USA, 12-15 March 2009 By Dr Ros Vallings MNZM, MB BS
I was privileged to attend the IACFS/ME 9th
International Research and Clinical conference from 12-15th March, 2009 in
Reno, Nevada. Attendees from all around the globe were present and much
lively discussion ensued following the papers presenting the latest
cutting-edge research.
Fatigue Science for
Human Health. The main conference opened with an invited lecture from Yasuyoshi Watanabe (Osaka, Japan). He spoke on the importance of Fatigue Science for Human Health. He told us that fatigue is an important bio-alarm, without which we might lapse into unrecoverable exhaustion, or even die. Fatigue is strongly correlated with motivation, and decreases efficiency, and scientists are extensively analysing the causes of fatigue, looking at therapy to aid recovery and preventative strategies.
Of fatigue related illness, 30% suffer from
Chronic Fatigue Syndrome in Japan, of which 1.3% are children. Other main
causes of fatigue are other organic illnesses (28%), mental illness (30%),
drug side effects and the effects of surgery. The Japanese have developed
a new questionnaire and a fatigue scale. Much research is occurring in
Japan with the development of large new centres. Dr Watanabe then focused on CFS, discussing potential immune, biochemical and endocrine biomarkers. Plethysmography, visible and near infra-red markers for analysis of serum samples, gene expression and APISST (which relates to cytokine signals) are all being researched. HHV6 has been found to be physiologically increased in saliva after hard work, with levels improving after holidays.
There are increases in HHV7 also after hard work
and slightly less so in CFS. HHV6 is directly shed into the saliva, while
HHV7 is amplified in the peripheral T cells. Brain function is studied
using PET, functional MRI and MEG. Areas of the brain associated with
fatigue, pain and attention have been demonstrated. Other CNS
abnormalities include: abnormal acetylcarnitine levels in PET scans,
reduced binding potential of 5HTT, mood changes shown to relate to the
dopamine system, visual task activity lower in CFS on fMRI, and on MRI
morphometry, there was volume reduction in the prefrontal cortices. This
latter finding may relate to cortical plasticity, as it improves with CBT.
Pharmacologic and Non-pharmacologic Treatment Advances
The first paper was presented by Greta Moorkens
(Antwerp,Belgium) and was focused on their studies using combined CBT and
Graded Exercise. 180 CFS patients were studied and a number of onset
triggers were identified, together with co-morbidity factors such as
depression, busy lifestyle and violence.
Patients and staff reported some personal benefits, but statistical
analysis did not show any significant improvement with combined CBT and
graded exercise, and this negative outline warrants further research.
Recommendations were that GPs needed help with suitable interventions via
specialist expert advice.
Elke van Hoof (Brussels, Belgium) had looked at
the influence of EMDR (eye movement desensitization and processing) and
biofeedback on the hypervigilance in CFS. EMDR reduces amygdala
reactivation.
Patients were given 4 sessions of EMDR and followed up 4 weeks later.
There were no significant differences in heart rate variability, but a
positive trend was evident.
All patients however improved in physical functioning significantly in
areas of vitality, fatigue and concentration. They reported feeling more
insight, more control and were enthusiastic about this approach., but
there is need to look at the protocol further and also deal thoroughly
with other life stresses to get the maximum benefit.
Nicole Porter (Chicago, USA) reviewed some
alternative medical interventions in the management of ME/CFS and
fibromyalgia. She found that several modalities have potential for future
clinical research.
A limited number of studies have been done with often suspect
methodological quality. Few studies have been done looking at laboratory
outcomes of immune function, and there have been inconsistencies of
assessment instruments. There is a lack of randomized trials and a lack of
reporting of negative results.
The strongest evidence for treatments of useful value were in the cases of
acupuncture and meditation, but There is great research potential for
looking at supplements such as carnitine, magnesium and
S-adenosylmethionine. Qigong may also be helpful, but studies have lacked
controls. Interferon and cytokine levels
in the phase III trial of Ampligen Interferon and cytokine levels in the phase III trial of Poly I: Poly C12U (Ampligen) was presented by David Strayer (Philadelphia, USA). Pre-treatment and intra-patient changes from baseline were compared to see if the treatment had a significant effect on serum levels. Patients had improved significantly in treadmill tests and decreased use of other medications with this treatment, but there was no significant modulation of interferons or cytokines. No safety concerns were raised and the treatment was well tolerated. The decrease in use of concomitant medications was an important point, as several of the medications used regularly in CFS do cause prolongation of the QT interval, with possible risk of death. Overall death rates in CFS patients due to heart failure, suicide and cancer were reduced. The patients’ own experience of living with post-infectious fatigue syndrome (PIFS) following an GI infection caused by Giardia lamblia in 2004 – Eva Stormorken – (Vaaler, Norway) – Preliminary findings from a qualitative interview study suggest that all the participants were healthy pre-giardiasis and were either working or studying on a full time basis.
Four years later the mean functional level was
still below 50% compared with pre-illness functional level, and none were
able to either study or work on a full time basis. Findings also suggest
that PIFS affects all aspects of life, including disrupted partnership and
identity, and loss of friends, leisure activities, as well as work or
education. In addition, most of the interviewees reported difficult
encounters with health personnel who lacked. Both physical and cognitive
complaints varied in number and severity.
Cognitive behavioural therapy was looked at from a
patient perspective by Elke van Hoof (Brussels, Belgium). 96% of the 100
patients studied were motivated when starting CBT. 25% were using parallel
medical treatments. Only 2% of those
studied reported total recovery, and 30% mentioned some improvement. 30%
reported no change,38% were worsened and 25% were able to complete the
programme, due to the physical component. Results of this study do not
confirm effectiveness of CBT for ME/CFS, and large scale application is
not supported.
CBT was reframed by Michael Antoni (Miami, USA),
and he hypothesized that chronic stress influencing the HPA axis may
influence the severity of CFS via changes in the pro-inflammatory
cytokines. A cognitive behavioural stress management programme
(CBSM) was devised using a telephonically designed programme (T-CBSM),
after earlier success with group programmes. Participants received
12 weekly sessions via a phone link. Muscle relaxation, imagery, autogenic
training, meditation and breathing exercises were included. Controls
received a series of health education modules also by phone link. Pain,
cognition and sleep symptoms all improved in the T-CBSM group and
reduction in Il-6 equated with symptom reduction. The role
of trauma experiences causing increased stress
Patricia Fennell (Albany,USA) addressed the role
of trauma experiences causing increased stress, which needs to be
considered in chronic health management. Trauma may be disease/syndrome
related, iatrogenic, cultural, vicarious, pre-morbid or co-morbid. Trauma
is not a steady state and effects may wax and wane. In CFS, disability
issues can provide added stress/trauma.
The Fennell Four phase model can be an effective method for assessing and
treating illness-induced trauma.
The clinical
and immuno-modulatory effects of Isoprinosine
The clinical
and immuno-modulatory effects of Isoprinosine were discussed in a paper
presented by Maria Vera, (Miami, USA). 61 patients fulfilled the criteria
for inclusion in this study. Patients were treated with Isoprinosine
500/1000mg (odd/even weeks) 3 times a day from Monday to Friday for 6
months, and Clinical and immunological assessments were made pre-treatment
and post therapy. There was highly significant improvement in the clinical
scores of patients treated with this drug at 6 and 12 month follow up.
CD4+CD38 T cells were normalizing at 6 and 12 months, NK cell activity was
improved and EBV titres had a highly significant decrease after 6 months.
No patients developed gout (a recognized side effect) but 26% did
experience gastro-intestinal symptoms. A larger randomized trial would
seem appropriate, because the downside is that this is a very expensive
drug.
New
Developments in Epidemiology
Causes
of death in patients with CFS compared to deaths in non-CFS patients Causes of death in 36 patients with CFS was compared to deaths in non-CFS patients by Rosamund Vallings, (Manukau, NZ). Causes of death in CFS patients did not differ from non-CFS patients or NZ norms apart from a higher rate of accidental deaths. It is probable that CFS patients can easily tire and overdo physical and mental activities, putting them at greater accident risk. Risks of late diagnosis of cancers were addressed, with a warning to make sure patients do report new symptoms and attend for regular screening.
Revise
exclusion criteria for mental health disorders in order for a diagnosis of
CFS
Tokuzo Matsui
(Osaka, Japan) reported the need to revise the exclusion criteria for
mental health disorders in order for a diagnosis of CFS. The number of CFS
patients diagnosed initially by the 1992 definition increased by 10% when
the Japanese 2007 guidelines were used. Anners Lerdal (Drammen,Norway)
also found that mental stress, such as PTSD symptoms are strongly
associated with fatigue. Using multivariate analyses, demographic
variables, mental stress, somatic conditions and self rated health all
made significant contributions.
Dubbo Infection Outcomes Study
Further work from the Dubbo Infection Outcomes Study was presented by
Andrew Lloyd (Sydney, Australia). Q fever is a zoonotic illness caused by
Coxiella burnetii infection. Some patients suffer long term serious
disability.Prolonged symptoms of post-infective fatigue were associated
with more severe illness, but not with persistence of the genomes of the
infecting organism in peripheral blood cells, alterations in immune
responses or changes in the proportions of immune cell subsets. The
importance of prospective studies was stressed.
Related risk factors for chronic fatigue
Eliana Lacerda (London,UK) had looked at work related risk factors for
chronic fatigue. Bank workers in Brazil were the subjects of this study.
Fatigue and Chronic Fatigue in this group were strongly associated with
RSI. Ergonomic variables were also important determinants of CFS/ME like
syndrome. Looking at preventative measures in the work place seems
essential, and also paying attention to such issues as breathing, posture
and adequate organizational structures. Early menopause, hysterectomy, may be associated with CFS
Roumiana Boneva (Atlanta, USA) found that in a community study, a positive
gynaecological history, such as early menopause, hysterectomy,
oophorectomy etc may be associated with CFS. The patients had more
irregular periods than controls, more births, and pain associated
endometriosis. 53% had had a hysterectomy compared to 40% of controls, 37%
had had a D&C compared to 11% of controls. She recommends a larger study.
Classification of persons with ME/CFS by types of fatigue
Classification of persons with ME/CFS by types of fatigue was a useful
study by Aaron Boulton (Chicago,USA). Important subgroups emerged, and it
is possible that the fatigue patterns in these people may represent
different subtypes. The fatigue patterns are heterogeneous, and future
research needs to focus on this.
Measurement of hormonal values in CFS patients could help with
diagnosis. A.Suárez (Barcelona,Spain) suggested that the measurement of hormonal values in CFS patients could help with diagnosis. There were no significant differences in ACTH parameters, but those with CFS had significant lowering of cortisol levels on the 3 days of exercise challenge testing. The differences in prolactin and growth hormone were not significantly different to controls. Patients with fibromyalgia and/or CFS demonstrate sustained increases in gene expression for metabolite sensing receptors and βadrenergic receptors on leucocytes from 0.5 to 48 hours after exercise. This is the time when pain and fatigue worsen, even when muscles are inactive. This study by Alan Light (Utah, USA) suggests a predisposition for these receptors to increase dramatically after exercise, stress and infection. There is potential for the increases in gene expression to provide biomarkers.
Neuropeptide Y (NPY) correlates with symptom severity in CFS.
Mary Ann Fletcher (Miami, USA) found that Neuropeptide Y (NPY) correlates
with symptom severity in CFS. NPY was elevated in CFS compared to controls
(p=.001) though there was some overlap between controls and CFS. This
could be used as an assay to correlate with severity of illness,
particularly in relation to psychological symptoms. NPY may be a potential
biomarker for CFS and may be an important mediator of the illness itself,
thus it is a target for therapeutic strategies. But for now it needs to be
combined with other potential biomarkers such as gene expression. NPY
needs radio-active assay and cheaper methods need to be developed.
The impact of stress on the likelihood of developing CFS
Jonathan Kerr (London,UK) discussed the impact of stress on the likelihood
of developing CFS following Parvovirus B19 infection using negative life
events, perceived stress and negative affect. 5 of 39 cases developed CFS
and 4 of the 5 were viraemic at follow up. Stress index was significantly
associated with the development of fatigue during the acute phase of
illness, and also with chronic fatigue and arthritis in the 3 years
following the acute B19 infection.
Statistically it was found that a high stress index was the primary
predictor of CFS/ME 1-3 years following the initial infection. Of the 5
cases followed, IV immunoglobulin therapy for B19 gave benefit, with 3
patients recovering completely. 2 withdrew because of headaches.
400mg.kg/day was given IV for 5 days.
The immunomodulatory effects of sodium oxybate
The immunomodulatory effects of sodium oxybate in patients with α-wave
intrusion during deep sleep was studied by Natalie Hone (Miami, USA). The
average dose was 6.1gm daily. The study revealed a high rate of sleep
disorders in CFS patients. α intrusion was the most common disorder, more
so in women than men. 45.9% of patients had sleep apnoea (males more than
females). Sodium oxybate had no significant immunomodulatory effects in
patients with α intrusion, but sleep improved markedly clinically.
Research looking at herpes virus and parvovirus B19 DNA
Kenny de Meirleir (Brussels, Belgium) opened this session with an overview
of his research looking at herpes virus and parvovirus B19 DNA in the
gastric and intestinal mucosa of patients with CFS. HHV7 was frequently
found in both patients and controls. EBV and HHV6 were also detected in
patients and controls, and HHV6 was detected significantly in a small
subset of patients in duodenum and stomach.
However, parvovirus B19-DNA was detected significantly more frequently in
the stomach of patients more frequently than controls, and B19 DNA was
found in the peripheral blood of those biopsy-positive patients. One case
study of a 20 year old female (+ve B19) was treated for 4 months with γ
globulin and there was no residual load of B19.
Viral gene micro-array
Viral gene micro-array was used to detect viral DNA in 40 patients by the
team led by Judy Mikovits (Reno,USA). 1608 viral transcripts, microRNA or
endogenous viral elements were observed in the subgroups of patients and
controls. Adeno- and rhino-viruses were the most commonly detected in the
controls. Herpes viruses (particularly HHV7 and CMV) predominated among
the CFS patients. Human endogenous retroviral elements were also
differentially expressed. This may be significant in CFS as
neuro-degeneration can result. Bombyx mori densovirus was the 5th most
highly expressed virus in CFS patients, and adeno-associated-virus 3,3e,4
and 2 were all in the top 20expressed in patients but not in the controls.
These viruses require helper viruses such as herpes or adenovirus to
replicate. These studies may provide insight into the immuno-pathogenesis
in CFS.
Active infection with HHV6 and HHV7 is more frequent in CFS
patients
Studies by Modra Murovska (Riga,Latvia) concluded that active infection
with HHV6 and HHV7 is more frequent in CFS patients than in healthy blood
donors. B19 DNA was also found in the plasma of patients but not controls.
Reactivation of these viruses may lead to immune dysfunction.
The evolution of CFS following PIFS
Barbara Cameron (Sydney, Australia) presented further work from the Dubbo
Infection Outcomes Study. This study looks at the evolution of CFS
following PIFS prospectively. All 20 of the subjects (10 patients and 10
controls) were sero-positive for HHV6 and 10 were positive for CMV (5
patients and 5 controls) at baseline. Some EBV titres increased over time
in patients and controls. Over time there was no correlation between
symptom scores and antibody titres. The data do not support the hypothesis
of ongoing active EBV,HHV6 or CMV in the pathogenesis of PIFS or CFS. The immunological profile of an Australian CFS female population The
immunological profile of an Australian CFS female population was presented
by Ekua Brenu (Gold Coast,Australia). She noted a 0.2% prevalence of CFS
is Australia, with $A59 million per annum spent in the management of CFS.
Blood samples were taken from 8 CFS patients and 8 controls. Neutrophil
function was studied with respect to respiratory burst and phagocytic
activity. CFS patients demonstrated significant decrease in respiratory
burst, but increased phagocytic activity did not attain significance. T
cells, B cells and monocytes were observed in patients and controls. RNaseL ratio or elastase do not have any efficacy as biomarkers for CFS.
Christopher Snell (Stockton,USA) did not find that either RNaseL ratio or
elastase have any efficacy as biomarkers for CFS. There was high
variability for both measures in CFS and controls, and these levels may be
influenced by factors other than illness. RNaseL activity may not be
unique to CFS. Subjects with Gulf War Illness
Gordon Broderick (Edmonton, Canada) found that subjects with Gulf War
Illness (GWI) can be discriminated by demonstrating significantly
different neuro-endocrine-immune dynamics in response to exercise. Changes
in cytokines, NPY and cortisol are evident both at rest and much more so
under challenge, and could separate subjects completely from the control
group. Sub grouping of CFS patients
Sub grouping of CFS patients was addressed by Vincent Lombardi (Reno,USA)
looking at cytokine and chemokine profiles. He used microarray, a Random
Forest computational programme, to delineate CFS patients from healthy
controls. Each subgroup was found to display a unique cytokine/chemokine
signature. This has potential to subgroup patients using serum biomarkers
in an approach to appropriate treatments. (Anti-inflammatory, antiviral or
antimicrobial). Cytokine abnormalities are common in CFS
Nancy Klimas (Miami,USA) has found that cytokine abnormalities are common
in CFS, with potential as biomarkers or targets for treatment strategies.
Cost effectiveness with newer techniques should make these tests more
readily available to evaluate a large panel of cytokines. The study
presented demonstrated a disorganized pattern of the cytokines regulating
Th1 dependent lymphocyte function, critical to antiviral defence. The data
supports a Th2 shift, proinflammatory cytokine cascade activation and down
regulation of components of cytotoxic cell function. The importance of looking at viral versus non-viral onset in CFS Nicole Porter (Chicago,USA) showed the importance of looking at viral versus non-viral onset in CFS, with differences in cytokine production and expression. In the viral group there was Th1 shift and in the non-viral group a Th2 shift. Viral and bacterial onset patients should be separated in future studies. A pattern of protein production in the non-viral group is likely to be immune cell mediated anti-inflammatory activity with chronic suppression of immune system activation. In the viral group, there is pro-inflammatory activation with persistent hyper-immune response. Assessment
Issues from Biological to Behavioural CFS heterogeneity
Structural Equation Modeling (SEM) is a
data-analytic technique. Brian Gurbaxani (Zurich,Switzerland) has used it
to look at CFS heterogeneity. This is an attempt to integrate the
variables in CFS particularly in relation to HPA and stress related
variables. Brain MRI images
Leighton Barnden (Adelaide, Australia) analyzed
brain MRI images in 25 CFS subjects and 25 matching controls. Voxel based
analysis of the images was used, and a voxel was described as a 3D pixel.
There were changes in the midbrain of patients, which could account for
some of the CFS symptoms, such as changes in the reticular activating
system and the red nucleus. No changes were seen in the amygdala and there
was no significant difference in grey or white matter. Changes in the
medulla and insular were consistent with the autonomic dysfunction seen in
CFS.
A diagnostic test for the identification
of metabolic dysfunction
A diagnostic test for the identification of
metabolic dysfunction was discussed by J.Mark VanNess (Stockton,USA). Two
graded exercise tests with cardio-pulmonary analysis were performed within
24 hours of each other. There was a “fatigue effect” of prior physical
activity not characteristic of other illnesses. There was reduction of
peak oxygen consumption and/or oxygen consumption at anaerobic threshold
in CFS patients and in particular those with a high viral load. This
provides evidence of metabolic dysfunction.
Mitochondrial dysfunction in CFS
Norman Booth (Oxford,UK) described work on
mitochondrial dysfunction in CFS. An “ATP profile test” has been designed
for CFS and other energy depleted conditions. 5 factors were collated and
multiplied together to produce the mitochondrial energy score. CFS affects
every cell in the body and a mitochondrial disorder seems a likely
possibility. This test is able to differentiate patients whose fatigue is
due to psychological factors from those who have insufficient energy due
to cellular respiration dysfunction.
New Developments in Pediatric ME/CFS
Identification of biomarkers for CFS in children (8-17 years old)
Identification of biomarkers for CFS in children (8-17 years old) looking
at specific genetic and innate immune parameters was the object of study
presented by Ritchie Shoemaker (Maryland, USA). He had found an
association of increased auto-immune abnormalities and elevated TGFβ, a
cytokine associated with abnormalities in T regulatory lymphocyte
function. All cases of CFS were clearly identified.
The criteria used to diagnose ME/CFS in pediatric samples
Leonard Jason (Chicago, USA) examined the criteria used to diagnose ME/CFS
in pediatric samples. The 2006 criteria for diagnosing pediatric CFS
evidenced 97% sensitivity and 100% specificity. Findings suggest that the
1994 Fukuda criteria are less effective in making a correct diagnosis,
with only 76% sensitivity.
The clinical characteristics of 81 Belgian adolescents
The clinical characteristics of 81 Belgian adolescents with Chronic
Fatigue were described by Greta Moorkens (Antwerp, Belgium). One in three
complained of headache or muscle ache, one in five complained about
concentration or memory problems. Sleep studies and psychological testing
was only performed in one in four of the group (probably due to parent or
adolescent opposition) but were found to be abnormal in 60% of those
tested.
Children with CFS are prevented from attending school
Up to 68% of children with CFS are prevented from attending school and the
characteristics and recovery of these housebound children was addressed by
Esther Crawley (Bristol, UK). Of 46 children assessed, 13 did not have a
primary diagnosis of CFS, despite having been diagnosed by a pediatrician.
This was a prospective study and at follow up (between 8 and 39 months) 4
had recovered completely and 6 were well enough to attend school. She then
looked at whether patterns of symptoms suggest distinctive subtypes of
pediatric CFS. She concluded that CFS is heterogeneous in children and the
different factors may represent different underlying disease processes.
Age, length of illness, anxiety or depression had no bearing on the 3
different factors identified by factor analysis. Cluster analysis
identified 5 groups of children, which could be discriminated using
regression analysis, which showed significant differences between the
groups in terms of number of symptoms, fatigue and physical functioning. Sleep scores to distinguish between children at risk of developing childhood CFS
Sanae Fukuda (Osaka, Japan) used sleep scores to distinguish between
children at high risk of developing childhood CFS and general healthy
students. The sensitivity of the sleep score was 85 with a specificity of
75.4. Intervention with sleep practices and CBT should be considered for
high risk children. Also from Japan Kei Mizuno (Osaka,Japan) had looked at
selective and divided attention in childhood CFS. Findings suggest that
this maybe impaired. 3 types were identified. Functional MRI will be used
to clarify the neural substrates associated with divided attention.
Research Developments in Genetics
An overview of Genomics
The session opened with an overview of Genomics in CFS by Jonathan Kerr
(London, UK). 88 CFS associated genes have been identified by microarray.
85 are upregulated and 3 downregulated. Several other diseases have also
been looked at. Clustering has identified 7 subtypes in the 55 patients
studied, and 5 genes showed therapeutic potential. There is therapeutic
potential in that 5 of these genes are known to be targeted by
experimental or licensed drugs. These include some of the cancer and
rheumatic drugs.
Microbial infections are associated with CFS, and it is hypothesised that
specific organisms maybe associated with the subgroups. A trial of 62
patients (including 6 with Q fever) was undertaken. There were 14 with
endogenous depression and 29 normal blood donor controls. Differential
expression was seen for all 88 genes in the patient group. Similar genes
were seen in the Q fever-CFS group.
The depressed patients were similar to the normals except for 5
upregulated genes. QPCR data for the 62 new patients were clustered with
the 55 previously tested CFS patients. 8 subtypes were identified. 12 of
the genes are known to be linked with the pathogenesis of EBV infection.
Future work needs to look at larger cohorts, longer term studies and
biological relevance of the subtypes.
Gene polymorphism
Marc Fremont (Brussels,Belgium) reported on gene polymorphism, studies of
which support the implication of intestinal dysfunction and activation of
the Th17 axis in CFS. This opens a new perspective regarding treatment.
The hypothesis that immune activation is mediated by Th17 cells in these
patients is supported. There was a higher frequency of alleles making
these patients more susceptible to gram negative enterobacteria.
Mediators of NK cell function
Toni Whistler (Atlanta,USA) used gene arrays to look at the mediators of
NK cell function. She found that there was decreased functional capacity
of NK cells in Gulf War Illness. There was impaired immune function
involving Th2 and proinflammatory cytokines, cytokines, cytotoxic NK cells
and T cells, and dysregulated mediators of the stress response such as
salivary cortisol. These differences were augmented by exercise challenge.
Laboratory diagnostic tests maybe developed as a result of this research.
MicroRNA patterns in CFS
Further work from St George’s,London was presented by Robert Petty
(London,UK) who had looked at microRNA patterns in CFS. MiRNA expression
was analysed in PBMC samples of 15 patients and 30 normals. Microarray
analysis identified differential expression of 28 miRNA, 5 of which were
confirmed using Taqman QPCR. Using this method, each of the 5 showed
elevated expression in CFS with increases over 1.5 fold compared to
controls. There is potential for this to be used as a biomarker.
Common triggers in CFS
Lihan Zhang (London, UK) discussed their gene database of 117 CFS
patients. The 8 genomic subtypes had distinct differences in SF-36 scores,
clinical phenotypes, severity and geographical distribution. Antibody
testing was done for EBV, enterovirus, Chlamydia pneumoniae, Coxiella
burnetii and parvovirus B19 an revealed subtype-specific relationships for
EBV and enterovirus – both being common triggers in CFS. There is
potential for treatment and further study is warranted.
CFS identified candidate genes
A
genome wide study of CFS identified candidate genes not considered in
previous studies and was discussed by Mangalathu Rajeevan (Atlanta, USA).
Polymorphisms were found to correlate with gene expression and were strong
predictors of disease, and need further investigation.
HLA and KIR variation
Judy Mikovits (Reno, USA) concluded that preliminary data suggests that
HLA and KIR variation might contribute to the risk of CFS. If HLA is not
expressed, NK cells kill the target (viral infected) cells
Cytokine polymorphisms have a synergistic effect on the severity
and duration of acute infective illnesses
Andrew Lloyd (Sydney, Australia) found that cytokine polymorphisms have a
synergistic effect on the severity and duration of acute infective
illnesses and PIFS. Analysis of samples from 300 patients who had had EBV,
Q fever and Ross River Virus (from the Dubbo Infection Outcomes Study)
were analysed.
High producing IFNγ+874 T/A and low producing IL10-592C/A polymorphisms
were both significantly associated with increasing illness severity.
Variations in intensity of the inflammatory response underpin the severity
of acute illness and can predict the duration of PIFS across varied
infections. He stressed the importance of looking at phenotypes
prospectively. The Dubbo study found no evidence of persistent antigen or
chronicity of cytokines.
CFS influences cognitive functioning, attention and memory
.Elke van Hoof (Brussels, Belgium) discussed the issue that CFS influences
cognitive functioning, attention and memory. There seems to be slower
information processing. Her study examined reaction speed in CFS, and
looked at whether this is negatively influenced by external stimuli such
as physical complaints. It was found that CFS patients were more
distracted by their bodily focus, which in turn negatively influenced
cognitive performance. This slow processing speed is partially responsible
for the cognitive malfunction in CFS. Tasks requiring complex processing
are affected.
The diagnostic label of CFS may often be misapplied in community
practices
EEG data can discriminate 905 of CFS patients from healthy controls and
patients with depression according to work by Frank Duffy (Boston, USA).
The diagnostic label of CFS may often be misapplied in community
practices, and this can lead to data discrepancies. This study has shown
that CFS is a condition causing objective and measurable peturbations in
CNS function.
Cognitive function in adolescents and young adults with CFS
Cognitive function in adolescents and young adults with CFS was presented
by Laura Younis (Melbourne,Australia) The CFS patients did perform as well
as controls on educational tests (verbal and mathematical) These findings
were unexpected as the tests were challenging and fatiguing and involved a
large neuropsychological test battery.. These patients had reported more
school absenteeism, depression, sleep disturbance, cognitive dysfunction
and other symptoms than controls. Strong motivation to perform well may
not reflect typical performance of these students if they had been in an
educational setting.
Assessment of amino acid neurotransmitter function
Assessment of amino acid neurotransmitter function was performed in CFS,
major depression and healthy volunteers and was presented by Dikoma Shungu
(New York, USA). There were no significant abnormalities in regional amino
acid neurotransmitter function in CFS. There was confirmation of
reductions in occipital GABA in major depressive disorder.
Japanese development of anti-fatigue food and equipment
Yasuyoshi Watanabe (Osaka, Japan) gave a good overview of the Japanese
development of anti-fatigue food and equipment, and animal and human
studies were covered. They had developed scales for quantification of
fatigue, and then tested a variety of products. Animal models were
initially used to evaluate the effects of supplements, anti-oxidants and
substances for energy and many biological and physical measures were done.
Various products were found to be of use. These included: 1).Applephenon –
a polyphenol extract from unripe apples. 2) Imidazole dipeptide (high in
chicken breast and animal muscle) which has an antioxidant effect and is
produced as a drink. 3) Co-enzyme Q10. 4) Epigallo catechin gallate. 5)
Crocetin (carotinoid dicarboxylic acid) from the crocus flower. Physical
therapies found to be of use included mildstream bathing (a micro-bubble
bath). Animal therapy and music therapy were among other approaches found
to be of use.
The relationship between fatigue and diet
The relationship between fatigue and diet was covered by Hirohiko
Kuratsune (Osaka, Japan). A 20 item questionnaire was administered to 131
female students, and they were then classified according to the fatigue
score. It was found that students frequently missed breakfast/lunch, and
there was low calorie, fat and carbohydrate intake in the most fatigued.
Very significant fatigue correlated with low rice, fish and omega 3
intake. Zinc, copper and magnesium, vitamins B6 and B12 were all low in
the severely fatigued.
Autonomic nervous system activity using HRV analysis was also studied in
fatigued patients and a relative sympathetic nerve dominance was
associated with the fatigue state.
The fatigue state associated with labour
Chaos analysis was used to evaluate the fatigue state associated with
labour, and discussed by Seiki Tajima (Osaka, Japan). Overwork is a big
issue in Japan, and beverage factory workers were assessed using the
Artett C system. Subjects were divided into 3 groups depending on fatigue
level, and autonomic function was assessed. There was no significant
difference in the 3 groups using analysis of maximum lyapunov exponent and
correlation dimension analysis, and between low frequency and high
frequency ratio (spectral analysis). This is the ratio between the
sympathetic/parasympathetic systems. Further studies are needed to reveal
differences from pathological and recoverable fatigue using these methods
Pathophysiology of CFS in childhood in Japan
The pathophysiology of CFS in childhood in Japan was presented by Teruhisa
Miike (Kobe, Japan). Japanese children are found to be often active till
late at night, exposed to a lot of bright lighting and a hard daily
schedule coupled with excessive information from TV, games, cell phones
etc. Despite going to bed very late, children still need to get up early,
and thus become sleep deprived. There is a breakdown in the body clock,
and they can then suddenly develop a hypersomnia type sleep disorder and
childhood CFS.
Long sleep gives no improvement, and many symptoms occur fitting the
criteria for CFS. Activated enzyme depletion leads to mitochondrial
dysfunction. There is decreased cerebral blood flow. There may also be
increased risk of cancer. The aim should be to prevent this set of
circumstances. Workshops and Poster presentations
Before the
formal conference began four Workshops were available and well attended,
also a large number of Posters were presented with a wide range of topics
from around the world.
ROSAMUND VALLINGS, MB BS
With thanks to ANZMES, who have provided funding for me to attend this
conference.
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