Report From the AACFS 7th International Conference
Oct. 8-10th, Madison Wisconsin
by Dr. Rosamund Vallings
A day of research presentations was followed by two clinical days with a patient conference running alongside. I felt privileged to attend the research and clinical segment
RESEARCH CONFERENCE
RESEARCH OVERVIEW, by A.Komaroff (Boston) - In Chronic Fatigue Syndrome, functional status is much reduced in all areas and
$9 billion is lost annually in productivity in the USA. Over time 10% of
sufferers can expect complete remission and 23% will receive an alternative
diagnosis eventually. The illness follows a relapsing and remitting course, and
research has shown abnormalities in many systems:
Brain - Abnormalities seen on MRI and SPECT scans
Cognition - IQ within normal range, but marked difficulties in mental
processing etc.
Sleep - polysomnographic abnormalities, with up to 28% increase in
non-refreshing sleep.
Neuro-endocrine dysfunction
Autonomic dysfunction - basal and postural hypotension, reduced
peak O2 consumption and haemodynamic instability
Immune activation -Activated lymphocytes cross the blood-brain barrier
leading to microglial activation and perivascular activation. These effects
can last decades, and lead to the secretion of pro-inflammatory cytokines and
nitric oxide, with resulting injury to the peripheral nervous system and
chronic low level immune activation in the brain. There is also increased
neutrophil apoptosis.
Microbiological studies: Many different post-viral fatigue states have
been described. Examples include:
Enteroviruses (Coxsackie, polio, echo) abnormal lactate response to
sub-anaerobic exercise demonstrated. Enteroviral RNA in muscle without nP-1
protein suggests defective viral replication. Q Fever (rickettsial) nucleic
acid persists for up to 10 years in circulating mononuclear cells. Parvovirus:
ongoing elevation of IFNn with associated fatigue. Mycoplasma: found in up to
68% of European CFS patients (5.6% in controls)
Energy metabolism: Disturbances seen in urinary metabolites: such as
depletion of amino-hydroxy-N-methyl pyrrolidine, slight elevation of â alanine
and depletion of UM2 (serine).
Gene expression: The genes involved in immune activation and energy
metabolism are turned on more often in CFS.
Vitamin D connection: Low levels lead to musculo-skeletal pain. Patients
who have fibromyalgia tend to have lower plasma levels of Vit D as do
people living in areas with long periods of darkness in the winter, with
resultant tendency to osteoporosis.
Treatment: Placebo controlled trials of treatment with omega-3 fatty
acids have shown benefit in CFS. There is decreased production of inflammatory
mediators and direct antiviral activity. Endogenous levels may be reduced by
chronic viral infection.
````
EPIDEMIOLOGY OVERVIEW, by W C Reeves (Atlanta) -
Fatigue is a very common symptom in medical practice, involved in up to 50%
consultations of which 75% are psychiatric. The prevalence of CFS (existing
cases) in the US is 4 - 75 per 100,000. Onset is usually sudden and average
duration is 5 years (range 2-7 years). In the US it is more common in rural
areas, with a predominance in females and lower socio-economic groups. Minority
races are at greatest risk. Annual loss in productivity in the US is $US9
billion and the average annual loss in family income due to CFS is $20,000. In
the UK, $US4 billion is spent on direct costs such as medication. Patients are
often as severely or more disabled than those with heart failure or COPD.
FIBROMYALGIA OVERVIEW, by D Clauw (Michigan)
There has been a paradigm shift in diagnosis of fibromyalgia (FM) considering
tenderness as part of a continuum rather than relying on definite numbers of
specific tender points. The tenderness is usually diffuse and using tender
points for diagnostic purposes is affected by anxiety, expectation and
distress. Random measures of tenderness are more relevant and accurate.
Causes of FM include a strong genetic tendency, and abnormality in
pain-processing. This correlates with abnormalities in other sensory areas such
as light and sound.
There is generalised hyperalgesia and allodynia. Pain processing is either
psychological (expectancy, hypervigilance) or neurobiological (peripheral or
central). Dimensions of pain may be sensory, cognitive or affective.
Functional MRI (fMRI) shows brain changes correlating with pain experiences and
there is no correlation with depression. Cognitive factors such as
catastrophisizing and loss of locus of control may cause changes in pain
processing and correlatewith poor prognosis. Other regional pain syndromes
show similar changes in fMRI to that seen in FM.
Treatment: SSRIs, tricyclics and norepinephrine reuptake inhibitors all have
some benefits in FM. Amitriptyline and imipramine are more analgesic than
nortriptyline. Milnacipran is a new drug showing promise.
MICROBIOLOGY and IMMUNOLOGY
This part of the conference was introduced by Dharan Abalashi who listed the
many viruses and other microbial agents studied in relation to CFS.
HHV6, enteroviruses, Mycoplasma, Chlamydia and parasitic infections are all
creating interest.
R. Suhadolnik (Philadelphia) discussed the current immunological
situation 20 years after the Lake Tahoe epidemic and reported on a recent
study of 66 CFS patients, 62 controls and 51 depressed patients. CFS patients
showed marked impairment compared to the other 2 groups. The study supports the
cytokine/immune activation model, showing direct correlation between the
abnormalities in the RNase L pathway and NK cell function. The 37/80 kDa ratio
strongly correlated with the
changes seen in CFS and symptom severity. The RNase L activity leads to an ion
channelopathy with patients experiencing many symptoms.
C. Raison (Atlanta GA) had experience with the use of IFN á in the
treatment of Hepatitis C. IFN (interferon) is a cytokine released early in
viral infection and causes a variety of symptoms including fatigue. 109
patients receiving IFNá-26 for treatment of hepatitis C were studied. During
treatment 70% of patients reported marked fatigue and 30% developed symptoms
sufficient to fit the criteria for CFS. (p=.0001) This study supports the role
of antiviral immune response in the pathophysiology of fatiguing illnesses.
J. Jones (Atlanta GA) reviewed the Dubbo Infections Outcome Study on
behalf of Sydney colleagues. Patients who had had infectious mono, Q Fever and
Ross River virus were followed up. He concluded that post-infective fatigue
states (PIFS) following documented infection represent a valid and
informative model for CFS. CFS occurred in 10% after these illnesses. Severity
of the primary illness was the strongest predictor of development of PIFS and
was not associated with premorbid
psychiatric characteristics.
Signal transducers and activators of transcription (STAT) are a family of
proteins playing a central role in the responses of cells to cytokines and were
discussed by K. Knox (Milwaukee WI). She suggested that a study of a sub
group of CFS patients who had an abnormally low STAT1 response to interferons,
may
explain the increased susceptibility to infections sometimes seen in this
illness.
Decreased NK cell cytotoxicity is a frequently reported abnormality in
CFS patients, and K.J. Maher (Miami FL) reported abnormalities in
cytotoxic T cells and NK cells including reduced perforin and reduced
concentrations of Granzyme A and B. These changes may provide biomarkers in the
future.
D. Raciatti (Chieti,Italy) reported on a study of 130 patients looking at
the potential role of STDs in the pathogenesis of rheumatological
syndromes characterised by prolonged fatigue. Significantly high percentages of
infections with Chlamydia, Ureaplasma and Mycoplasma were found serologically
and when treated there was recovery from fatigue and other symptoms.
M. Fremont (Brussels, Belgium) discussed immune dysregulation associated
with interferon á synthesis. He explained how RNase L is cleaved
by apoptotic and
inflammatory proteases, and said that mycoplasma infections are strongly
associated with RNase L cleavage. PKR is also shown to be activated in the PMBCs
of CFS patients, and this can lead to immune dyregulation and induction of iNOS,
with resulting muscle dysfunction and CNS and neuro-endocrine dysfunction such
as hypothyroidism with intense fatigue
EPIDEMIOLOGY
D. Wagner (Atlanta GA) compared 2 scales measuring fatigue and
health; the MFI and the SF36. These 2 scales as anticipated were found to be
negatively correlated i.e higher fatigue associated with lower mental
functioning, and this supports the construct validity of the MFI.
Artificial neural networks are computer generated networks likened to the
human brain and are used for example, to help with decision making. A system
has been devised, and was described by A Morris (Chicago) to help
determine the types ofsymptoms that maybe useful in diagnosing CFS. 2 different
networks were created with 26 relevant questions common to both networks, but
this is early stage work and cannot yet be generalised.
H. Harrison (Phoenix AZ) produced support for the hypothesis that there
are genetic contributions to coagulation protein abnormalities seen in
some CFS/FM patients. Distinguishing these factors may help to guide therapy.
R. Underhill (New Jersey) in a pilot study showed that secondary cases of
CFS occurring in unrelated household members may indicate that a low level
infectious agent causing CFS may persist and be shed into the environment.
Increased prevalence in genetic relatives indicates that genetic factors maybe
involved in a subgroup of CFS patients.
NEUROPHYSIOLOGY
J. Stewart (New York NY) overviewed the varieties of orthostatic
intolerance in CFS. He described 3 types of peripheral blood flow in these
patients: low flow, normal flow and high flow. During orthostasis it was shown
that there is enhanced thoracic hypovolemia related to inadequate cardiac venous
return.
H. Kuratsune (Osaka,Japan) showed results of PET scans showing cerebral
hypoperfusion in CFS suggesting that CNS dysfunction maybe related to the
neuropsychiatric symptoms found in CFS. Density of 5HTT in the anterior
cingulate cortex was significantly reduced in a study of CFS patients and this
was negatively correlated with pain scores. This alteration in seratoninergic
neurons is thought to play a key role in the pathophysiology of CFS. These
results may help explain why SSRIs are sometimes helpful in CFS patients.
Elastase activity in relation to impaired exercise capacity in CFS was
demonstrated in a study presented by J Nijs (Brussels, Belgium). The data
provides evidence for an association between intracellular immune dysregulation
and impairments in cardiorespiratory fitness. Results showed correlation
between increased elastase activity and exercise functionability and maybe
related to impairments of lung diffusion and oxygen delivery to the tissues. NB
Antibiotics decrease elastase activity
in humans.
Reduced cerebral blood flow (CBF) in CFS was further confirmed in a study
presented by K.Yoshiuchi (Newark NJ), who also found that psychiatric
status and severity of illness do not play a role. Xenon CT was used which
provides absolute measures of CBF.
PHYSIOLOGY
S. Levine (Columbia) analysed the metabolic features of CFS using
multislice 1H MRSI. There was elevated lactate production in a
significant number suggesting the possibility of a mitochondrial metabolism
dysfunction. Elevation of thalamic choline was also demonstrated in some
patients, suggesting the presence of neuronal damage.
U. Hannestad (Stockholm, Sweden) showed in a small study that the more
severe the symptoms of CFS the greater the excretion of â-alanine. The
level in one patient was exceedingly high and was associated with severe
symptoms. There are structural similarities between â-alanine and GABA, and high
concentrations in the CNS may account for some of the typical CFS symptoms.
Symptoms similar to CFS are often seen as side effects in those with epilepsy
being treated with drugs which increase GABA.
M. Fremont (Brussels,Belgium) presented a further study showing that cells
expressing ankyrin fragments of RNase L have been demonstrated, and this
can contribute to increased sensitivity of patients to chemicals including heavy
metals. Involvement in the maintenance of Th1/Th2 balance by interaction of the
multidrug-resistance protein (MRP-1) and the ankyrin fragments is also relevant
in CFS.
M. Pall (Washington State) described a number of mechanisms operational in
CFS and related illnesses and produced evidence of increased nitric oxide and
peroxynitirite levels in CFS, which lead to oxidative damage and further
increase in cytokine levels. He described Vitamin B12 as a nitric oxide
scavenger, which may help explain why some people do well on B12 despite having
normal blood levels
CLINICAL CONFERENCE
The day began with an excellent
overview of the previous day's research papers by A Komaroff. Presentation of
clinical papers then followed.
A. Lyden (Michigan MI) presented evidence that 2 disparate sensory
experiences (somatic pain and exertion during exercise) are processed similarly
in patients and controls. There is a left shift in FM patients, who feel more
pain at the same time as feeling more "work".
CFS patients were shown by C. Javierre (Barcelona, Spain).to have
lowered oxygen uptake when exercising. She had compared CFS patients with
sedentary and physically active people using both an exercycle and an arm
ergonometer. Maximum power output was higher for all groups on the cycle as
compared to the arm ergonometer.
J. Alegre (Barcelona,Spain) evaluated 511 outpatients at a fatigue clinic
and found that 350 fulfilled the CDC criteria for CFS. These patients had
substantial reduction in physical and work actiivities. 50% experienced gradual
onset and there was significant elevation of RNase L (ed.- activity?). 10% patients
improved over time and 53% worsened. Only 33% were able to work.
F. Friedberg (Stony Brook) had done a cross sectional study of support
group attendees looking at the benefits and problems encountered. In
general subjects had found the group experiences helpful, but somewhat
surprisingly active support group members reported greater symptom severity and
less illness improvement than inactive members.
Level of occupational disability comparing a maximal exercise stress test
and 2 self report disability measures was presented by J. Nijs (Brussels,
Belgium). The associations were too weak to predict occupational disability, and
more work is required to establish valid methods of assessment.
The Phase III clinical trial of Ampligen v placebo in CFS was discussed
by D. Strayer (Philadelphia PA). The trial involved 234 severely affected
patients. 400mg ampligen or placebo equivalent in saline infusion was given IV
twice weekly for 40 weeks. Exercise treadmill duration was improved two-fold
over placebo. There were no significant differences in laboratory parameters. Ampligen has provided the most promising results compared with other drugs tried
such as galantamine,
antidepressants and corticosteroids.
L. Jason (Chicago) compared and contrasted the various case definitions
for CFS/ME. The London ME criteria select a more symptomatic group of
individuals than the Fukuda criteria. Using the Canadian criteria, there is less
psychological morbidity included and more physical and functional impairment.
There are more symptoms relating to fatigue and weakness coupled with
neuropsychological and neurological symptoms.
Fatigue was defined by J. Jones (CDC, Atlanta) as a regulatory or
protective process in illness a component of illness behaviour. It is
controlled by antagonistic activity of inhibitory/activating systems in the
brainstem. Mediation of immune responses occurs in illness and prolonged
illness maybe due to exuberant or inadequate host responses. Damage is a trigger
for immune response. He described also the effects of unconscious self
regulation which included psychological and philosophical components. Acute
sickness causes a response to primary altered self, and repeated episodes can
lead to conditioning and produce effects such as chronic fatigue. Targetting
the prevention of the circle of CFS seems appropriate for further research and
treatment.
K de Meirleir (Brussels, Belgium) described CFS as an immuno-vigilance
disorder, with host/environmental problems. The initiating factors are
heterogeneous. There is an abnormal level of apoptosis, and the nuclei cannot
ingest all the resulting fragments. RNaseL fragments then accumulate. Some
thyroid suppression may occur without abnormalities in TFTs. PKR activity is
increased along a continuum. A number of patients are IgM positive to
intestinal pathogens, and when treated with
antibiotics (eg ciprofloxacin) these patients show a 74% decrease in elastase
and 58% clinical improvement over 3 months. Therapeutic strategies should
include: restoration of immune competence, elimination of micro-organisms,
restoration of hormones, restoration of normal intestinal flora and decrease of
PKR activity.
The next clinical segment was devoted to issues around autonomic dysfunction.
C. Lapp (Charlotte NC) gave an overview. He described the autonomic
nervous system as controlling all the automatic functions in the body. He gave
background to the original research by P Rowe et al and described the various
types of orthostatic intolerance: Orthostasis, Postural Orthostatic Tachycardia
Syndrome (POTS), Symptomatic Orthostatic Tachycardia (SOTS) and Neurally
Mediated Hypotension (NMH). These conditions can be distinguished using tilt
table testing. Various causes were outlined including: low blood volume, low
total body water, CNS
disorder, venous pooling. Possibilities for managing orthostatic intolerance
include: volume expansion (salt and water), fludrocortisone, midodrine,
beta-blockers, SSRIs,
amphetamines, IV fluids and erythropoietin.
D. Bell (Lyndonville NY) discussed his findings relating to volume
depletion and ADH in CFS. He described how polyuria and thirst maybe early
symptoms in CFS. He reviewed his original study where red blood cell (RBC) mass,
plasma volume and circulating volume were found to be significantly depleted in
CFS patients studied. RBC mass is probably the most important issue. 73% of
patients studied had low RBC mass. If blood volume is low, ADH should rise but
if levels are low there is increased osmability leading to low BP, nausea and
hypoxia. Some patients in the past have responded to various IV infusions (eg
n-globulin, Vit C, antibiotics) and it is probable thatthis has been a "placebo"
type response just due to increasing blood volume. Bell has used daily one
litre IV saline infusions
with some encouraging results in 17 patients. 2 stopped treatment, 5 had slight
improvement and 10 had good to excellent results. However serious risks such as
line infections maybe encountered.
Therapy using erythropoietin was then addressed by B. Hurwitz. He
described patients who suffered from episodic hypotension with a tendency to
syncope when upright. These patients had a lowered cardiac ejection fraction and
decreased cardiac tone. Lowered blood volume was associated with mildly elevated
ESR, suggesting the presence of a heightened inflammatory process. Earlier
studies using volume expansion had produced some good results, but adding
erythropoietin has the potential to improvement in non-responders.
Erythropoetin is produced in the kidneys and stimulates the production of
erythroid cells. A deficiency leads to normocytic anaemia. Production is
modulated by the sympathetic nervous system. His hypothesis focussed on
treating with erythropoietin to improve cardiovascular and autonomic symptoms
and thus improve quality of life. Ongoing research with 94 patients to test
thishypothesis was outlined, and involved 3 subcutaneous injections
weekly. Supplemental iron and salt were included. There is one year left in
this promising study.
Discussion as to whether CFS and chronic Lyme disease are the same was
addressed by S. Schwarz (Tulsa OK) and an excellent overview of the research into
diagnosis and management of Lyme disease was presented. It seems still unclear
as to whether fatigue after Lyme disease is a form of CFS or is due to
unresolved infection with persisting immune dysfunction. Antibiotic treatment
has not conclusively been shown to be effective in randomised trials, but this
maybe due to the choice of antibiotics used. There may also be different
varieties of Lyme in different parts of the world.
N. Klimas (Miami,FL) AND L. Jason (Chicago) discussed the
subgroupings of CFS by various means taking care to avoid the tendency to
generalise. CFS represents a heterogenous syndrome. Subgroups can be based on
biological markers; duration, severity and symptom complex (predominantly
cognitive or associated with pain), and acute versus slow onset. There are a
number of overlapping subpopulations with symptomatology relating to the immune
system, the autonomic system, HPA etc. all within the chronic fatigue complex.
Subgrouping could also been done looking at gene _expression. Finding distinct
sub-populations has clear clinical implications
by defining groups for targeted intervention. Objective measures are needed for
this approach and can include issues such as: neuroendocrine (hypocortisolism),
autonomic (orthostatic intolerance), immune (cytokines, cell function),
cognitive (PASAT), psychological co-morbidity (SCID), Physicalexam findings (+ve
Romberg,hypermobility), documented infection at onset etc. Subgrouping is the
key to understanding how CFS begins, how it is maintained, how medical and
psychological variables influence its course and how it can be prevented,
treated and cured.
A lawyer, T.Bush (Madison WI) provided some good useful advice for
doctors who have to produce reports determining disability impairment.
An objective opinion of the level of function is needed. Patients may be turned
down for disability benefits if there is no medically determinable impairment.
There is considerable difficulty in proving one cannot do a sedentary job.
Doctors must record detail in the medical records such as distance patient can
walk, time able to stand etc. Including lab
results can help in explanation. It is not often possible to perform a work
simulation. If there is past history of annual physical examination, previous
capacity etc this should be included and there needs to be stress on the issue
of "changed health".
A panel discussion/advocacy workshop was led by . Klimas
(Miami FL). Various points were noted. There is risk of defining the
illness behaviourally if research is not supported. Physicians' voices carry
more weight than those of patients. The WHO has reclassified CFS as a
neurological illness rather than psychological. The word "fatigue" however
is still very unpopular and unhelpful and many felt, outdated, but it was
unlikely to bechanged in the immediate future. Continuing action for
recognition and support was strongly supported.
WORKSHOPS
EXERCISE WORKSHOP
Because studies have shown that exercise can be beneficial in CFS a full
session was devoted to an exercise workshop, and the first presentation was by
exercise scientists S. Stevens and C Snell who discussed
strength and conditioning in CFS. Emphasis was on forgetting the "Athlete
Model". Aim should be
to focus on improving quality of life and developing coping tools to manage the
illness and restore function. They described 2types of patients: the roller
coaster and the activity avoider, the latter compounded by the fear factor.
When planning a strategy, questions need to be asked such as issues of post-exertional
malaise (immediate and delayed), recovery responses including length taken to
recover etc. The aim should be to pay back oxygen debt with rest. Fatigue after
exercise is due to oxygen deficiency. A programme of "analeptic exercise"
should be initiated which trains the short term system, restores functional
movement and improves range of motion and strength. Appropriate exercise should
be included in the daily routine and payback involves focussed breathing (3
seconds in/3 seconds out). The programme needs to be justified and the
therapist needs to understand the physical limitations of the illness. The progressions should include:
1) Stretching/strengthening 2) Stretch with resistance training 3) Dose
controlled interval training and 4) Maintenance.
C. Lapp (Charlotte NC) discussed interval exercise in CFS/FM. He
pointed out the fact that even minimal exercise can trigger a flare of symptoms,
while there is a fantasy that exercise is the cure. People often get sick when
the patient aims for the anaerobic threshold (AT). This threshold occurs much
sooner in those with CFS than healthy people. The relationship of energy
expended to impairment is used to measure the impairment, the AT can be worked
out and that should be the maximum time and level that the patient exerts.
Interval exercise can slowly improve fitness. A study example was given showing
how using repeated bursts of 3 minutes of exercise followed by 3 minutes of rest
over one hour led to benefit. These patients were quite severely affected and
none relapsed.
J. Hoffman has developed an exercise and conditioning programme for
those with FM. Aerobic fitness, flexibility and strength are all decreased due
to lack of activity rather than the disease. 4 steps were outlined to improve
muscle fitness: 1) Alignment of body, breathing and relaxation 2) Flexibility by
stretching with rest and relaxation between moves. 3) Resistance training to
build core strength (maximum of twice weekly, and avoidance during relapse) 4)
Endurance training for
20 minutes 2-3 times weekly of low to moderate intensity.
Repetition and holding poses should be avoided. During relapses there should be
emphasis on reducing level of exercise, decreasing endurance, hydrating well and
using
warmth and medication. The patient should be encouraged not to stop
altogether. Patient needs to constantly "hold back" toavoid the roller coaster
crash and burn effect. Exercise needs to be fun with extrinsic rewards and
group adhesion.
COGNITIVE BEHAVIOR THERAPY WORKSHOP
F. Friedberg (Stonybrook) explained the importance of understanding and
utilising CBT in the management of CFS. He gave a detailed overview of
his approach pointing out that many CFS patients often had poor coping styles
leading to greater illness severity. For improvement to occur there needs to be
sustained lifestyle change, with efforts equal to that seen in investments in
alternative treatments. If a full programme is undertaken for 6 months, there
is likely to be at least 20% improvement and 50% is possible. Relaxation,
sleep, anger management, pacing with graded activity, easing into pleasurable
feelings and enlisting support networks are included in Friedberg's protocol.
E.Van Hoof (Brussels, Belgium) continued with this workshop presentation
and stressed that there should be an aim to change cognition and behaviour
to improve quality of life and allow life within the constraints of the
illness. She utilises a phase approach, which includes: explanation and
understanding, illness awareness and shift of locus of control, stabilization
based on behavioural therapy, restructuring and re-integration. Patients often
improve by not focussing on bodily symptoms and
by setting realistic goals.
12 weeks of CBT group therapy is utilised by M.Segota (Miami FL)
taking a stress management and relaxation (SMART) approach aiming to interrupt
the CFS - stress illness continuum. In each 2 hour session, 90 minutes is
spent on CBT and 30 minutes using relaxation and imagery. The primary goal is
to provide cognitive skills, optimize activity, relieve anxiety etc. The
sessions cover stress management, cognitive restructuring, resolving
interpersonal difficulties, self esteem enhancement
and personal fulfilment. Working in groups has been shown to be cost effective.
POSTERS
Over 50 papers were
displayed and while it is not possible to summarise them all in detail,
important points will be covered.
EPIDEMIOLOGY
Subgrouping in CFS was addressed by K. Coradi (Chicago) Those with
no evidence of ongoing infectious or inflammatory processes had the greatest
level of physical disability, while those with evidence of ongoing infection
were at increased risk of psychiatric co-morbidity. Minority groups were more
likely to be in the group suggesting ongoing infection.
In a 9 year follow up of Danish patients presented by M. Anderson
(Copenhagen, Denmark) there was no evident significant overall improvement in 35
adults with CFS. There was evidence of severe disabling illness, not typically
associated with depression or hysteria.
In Norway, a population based registry for patients with ME/PVFS has been
established and reported on by S. Kreyberg (Oslo,Norway), and this is a
useful tool for understanding and intervention, and provides opportunity for
choice and understanding for those with the illness.
A. Morris (Chicago) had used the Geographic Information Systems (GIS) to
allow investigators determine associations between environmental risk factors
and location in CFS. This seems a promising method for these studies.
S. Torres-Harding (Chicago) compared the prevalence of fatigue
among English and Spanish-speaking Latinos, who appear to be 2 distinct
sociodemographic groups. The English speakers were found to have higher levels
of overall fatigue, higher physical fatigue and were more likely to have
chronic fatigue. M. Njoku (Chicago) also found that different coping strategies
were employed by different ethnic groups (African American, Latino and
Caucasian) and are related to disability and fatigue severity. Cultural
practices, resources, life experiences etc may influence the coping strategies.
A study looking at the biopsychosocial model of post infectious fatigue
in adolescents may help to explain the aetiology of this subtype according to
R. Taylor (Chicago).
SPECIALISED CFS CENTRES
5 clinical networking centres for CFS patients were established in
Belgium, and although this has proved to be far from
adequate, G. Moorkens (Antwerp, Belgium) showed the concept is excellent
and future programmes should follow.
E Van Hoof (Brussels,Belgium) discussed the findings regarding patients
attending a tertiary CF clinic. 80% are diagnosed with CFS according to
the CDC criteria. Only 5%of these were not given a diagnosis of CFS.
RNase L
was found to be elevated in 92% of the CFS patients.
PHYSIOLOGY
Autonomic dysfunction is identifiable with the use of a tilt table and
this should be utilised as one of the assessment tools for those with CFS,
according to C Lapp (Charlotte NC). There is a high rate of positivity
in CFS particularly those who have symptoms suggestive of orthostatic
intolerance. He has shown that the symptoms do predict the likely outcome of
tilt table testing.
Coagulopathies in relation to CFS and other chronic illnesses may have a
common aetiology due to immune system activation of coagulation (ISAC). Increased
plasma fibrin (causes?) deposits on capillary walls and also increases plasma
viscosity, decreasing blood flow. Low dose heparin therapy (not warfarin)
decreases thrombin generation leading to an anticoagulant environment in the
capillaries, but specific protocols do need to be developed. H. Harrison
(Phoenix AZ) provided further studies on coagulation issues showing an increased
prevalence of abnormalities in inherited thrombophilic and hypofibrinolytic
proteins in those with CFS and HHV6 infection. Patients may need to be
monitored for overt thrombotic phenomena.
Autonomic function in MCS patients (and CFS?) and controls was compared by analysing
heart rate variability by K. Yoshiuchi and H. Kikuchi (Tokyo,Japan).
Spectral analysis showed consistent differences in autonomic function between
the patients and controls both while awake and asleep. CFS also appears to
influence á-2 heart rate variability before and after exercise, while POTS
appeared to alter it in the opposite direction.
R. Shoemaker (Pocomoke.MD)
outlines a number of immunological and neurochemical pathways involved in
the pathogenesis of CFS and proposes the study of the physiology of biotoxins as
a potential treatment approach.
IMMUNOLOGY and MICROBIOLOGY
G Quintana (Barcelona,Spain) produced results on a series of CFS patients
showing that 93% had a positive RNase L protein which correlated
positively with RNase L activity and monocyte elastase activity. This suggests
that elastase maybe implicated in the development of CFS. New pharmacological
strategies looking at elastase inhibitors may prove worthwhile.
D. Racciatti (Chieti,Italy) confirmed the potential role of immune
activation in precipitating and perpetuating CFS. Further research looking
at specific immunological markers may help identify sub groups of patients, and
this may improve the chances of identifying pathological mechanisms in this
disease.
Guidelines have been produced to define if there is a causal relationship
between development of fatigue states and immunization. K. Kohl
(CDC) presented this work which included recommendations for testing usefulness
and clinical trials.
A. Chester (Washington DC) has found that functional endoscopic sinus
surgery is a successful treatment for CFS associated with rhinosinusitis.
The presence of methylobacteria in the bloodstream as a possible
relationship with CFS needs further addressing according to L Lindner (Bryan,TX).
The importance of these bacteria in health and disease is yet to be determined,
but he raises the possibility of further research.
PHYSICAL ASPECTS including EXERCISE PHYSIOLOGY
Role of Kinesiophobia in CFS disability J. Nijs (Brussels,
Belgium) This is likely to be clinically important as is associated with
limitations and participation in physical activity. This may affect daily
functioning.
Hypermobility J Nijs (Brussels, Belgium) showed that there is a
subgroup of CFS patients with this condition who fulfil the criteria for benign
joint hypermobility syndrome.
B Adams (Fall River NS,Canada) noted that pedometers are an
inexpensive tool for assessing physical ability in CFS and MCS and helped
identify those that would best benefit from physiotherapy.
F. riedberg (Stony Brook) concluded in his study that there is
preliminary evidence for physical activity-related post-exertional symptoms
and negative affect. Measurements were taken over 3 weeks using an actigraph.
J.M. VanNess (Stockton CA) found that 24 hours after initial testing
for aerobic capacity in CFS patients there was significant reduction as a
result of the first challenge. The effort of the first test seemed to act as a
trigger for symptom response unique to CFS.
L. Bateman (Salt Lake City, UT) concluded that active massage therapy
was more successful at reducing the symptoms of FM than passive control
treatment. M.Egger (Utah) had a study suggesting a relationship between FMS and
history of head and neck trauma among patients referred to a CFS clinic.
NEUROPSYCHOLOGY
C. Lapp (Charlotte NC) concluded that testing of CNS vital signs in
patients with CFS in an office setting is simple and correlates with
computerized testing. It is inexpensive, and can provide objective evidence of
neuro-cognitive impairment for disability purposes. Neurocognitive response to
therapy can also be useful.
The CDC Symptom Inventory was shown by D. Wagner (Atlanta GA) to be a
reliable and valid instrument to assess symptoms that accompany CFS.
There is impairment in operative and immediate memory (frontal lobe) and
cognitive function of right hemisphere (vision, attention and concentration)
according to a study on cognitive function in CFS by G. Quintana (Barcelona,Spain)
and the impairment seems related to organic dysfunction rather than age changes.
L Jason (Chicago) presented results indicating that the circadian
rhythm for activity level is blunted. Medical treatment of sleep disorders
in CFS may reduce symptomatology, but does not cure the illness
Alexithymia (a deficit in cognitive processing and regulation of emotion)
was found to be inversely related to physical activity levels in adults with CFS
in a study by F. Friedberg (Stony Brook), but this did not relate to pain,
fatigue or affect.
E Van Hoof (Brussels, Belgium) found that subjectively reported
neurocognitive symptoms disappear as the condition improves. Telling
patients that cognitive difficulties are reversible can keep patients motivated.
B. Hyde (Ottawa,Canada) showed that dedicated brain SPECT scans
taken 6-24 months apart can be utilized to determine the severity and chronicity
of this spectrum of
illnesses.
PSYCHOSEXUAL ISSUES
It is suggested by H. Wynants (Antwerp, Belgium) that decreased libido
in CFS maybe due to the effects of stress. Sexual dysfunction is common in
both sexes in this illness, and possibly medication may compound the problem.
M. Arasanz (Barcelona,Spain) found that 27 females studied with CFS and
compared to controls had experienced exhaustion and negativity in relation to
their sex life, and the level of dissatisfaction correlated with the
Fatigue Impact Scale (FIS).
BIOCHEMISTRY
R. Van Konynenburg finds compelling evidence that glutathione
deficiency in implicated in the pathogenesis of CFS in a number of patients.
Supplementing with glutathione however is only of limited use as many other
factors are involved, so that a multifaceted protocol is necessary, as for
example, plasma cysteine levels, which can be neurotoxic, may rise during
supplementation.
T. Wijlhuizen (Rotterdam, Netherlands) presented a study using high dose
sublingual vitamin B12 in the form of hydroxycobalamin.. A number of
theories as to how B12 maybe helpful were suggested. Patients studied were
suffering from debilitating fatigue due to several diagnoses including those
with CFS. Blood levels were normal to low. Following treatment blood levels
were found to rise 2-3 times in 2 weeks, and remained elevated for several
weeks. Minimal side effects were
seen. Further research needs to be done to investigate the role of B12 in
fatigue, performance and recovery.
PSYCHOLOGY
N. Klimas (Miami FL) provided evidence that a 12 week Cognitive
Behavioral Stress Management Intervention within a supportive group may
improve psychosocial and physical status in those with CFS.
A. Forsberg (Stockholm, Sweden) hypothesised that those with CFS have
experienced more negative life events than controls. They did find that
negative life events influenced the current symptoms in the CFS patients, who
also had less positive life events.
Doctor-patient relationships are seriously undermined if the doctor does not
have the necessary knowledge to diagnose and manage the illness. E. Van Hoof
(Brussels, Belgium) concluded that good prognosis depends on diagnosing and
treating the illness early. CFS patients were also compared to psychiatric
patients in relation to how their primary caregivers/partners handled the
illness and ability to cope. Sufferers with other chronic illnesses seem to go
through similar coping mechanisms, and it seems that social support in CFS is an
important factor providing understanding, acceptance and support. Attitudes
of future physicians towards CFS following an
education programme showed some positive results in a study by T.Lu
(Loyola).
PEDIATRIC ISSUES
A detailed analysis of CFS in children in Japan revealed a high level of
symptom severity and poor school performance ability. T. Joudai (Kumamoto,Japan)
had found a significant correlation between symptom severity and depressive
symptom scores in children
A study looking at the biopsychosocial model of post infectious fatigue
in adolescents may help to explain the aetiology of this subtype according to
R Taylor (Chicago).
The conference closed with a briefing from D. Bell (Lyndonville,NY) on the activities of the Health and Human Sciences Advisory Committee. They have come up with a number of recommendations to integrate clinical evaluation and treatment with basic research. Centres of excellence should be established where the doctor finally has somewhere to send CFS patients and would no longer feel helpless, but would be seen by the patients as being supportive. The criteria for a centre of excellence would include scientific opportunities, an organizational environment and provision of critical research resources. He finished with an very apt quote from Goethe:
"Knowing is not enough, we must apply. Willing is not enough, we must go"
My thanks to ANZMES for enabling me to attend this
conference.