A friend of mine attended last week's Stanford CME Symposium and IACFS/ME Conference, and took detailed notes which are reproduced below with permission. My friend wishes to remain anonymous. If you've been reading Seacher's summaries on Phoenix Rising, or Cort Johnson's summaries on Health Rising, much of this will be review. However, for those that like to really "geek out" on this vital information (myself included), you will find additional details in these notes. Some portions of these notes have also been published on PR forums.
My friend attended the Wednesday Stanford Symposium, the Thursday IACFS patient session, rested Friday, and then attended the professional sessions on both Saturday and Sunday.
My friend attended the Wednesday Stanford Symposium, the Thursday IACFS patient session, rested Friday, and then attended the professional sessions on both Saturday and Sunday.
I want to thank my anonymous friend, plus Searcher and Cort Johnson, for the valuable information they provided us over the last week. In some cases, they sacrificed their health to bring us these summaries.
Warning: This is long - it was 18 pages as a Word document.
4/7/14 Edit: here are the same notes in a Google Doc for better readability
4/7/14 Edit: here are the same notes in a Google Doc for better readability
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MONTOYA MORNING SESSION:
- Case study with the researcher with HHV6:
- There is a clear presence of virus during symptoms
peak, as well as coronal flare and other brain lesions --> improved on
Valcyte; but weren't in the blood after acute period (?)
- anti-inflammatory treatment and anti-virals
reintroduced
- disease course usually fluctuates around a set point
largely variable among patients
- Gastrointestinal, cardiovascular/autonomic,
neurological, intolerance of extremes to temperature
- cardiovascular symptoms include: lightheadedness,
exertional dyspnea, palpitations, POTS (postural orthostatic tachycardia
syndrome)
- Symptoms involving several organs, chronic,
fluctuating, subsets of patients, evolution of disease over time
- Stanford's approach:
- cutting-edge technology: high throughput technology to
study immune system and genes (HIMC, Genetics department), exponentially
increase the amount that we can measure (cytokines)
- neuroradiology, EEG, cardiology, infectious diseases
- thoughtful and compassionate care for CFS patients is
possible
- His heart goes out particularly to patients who are
bedridden, crippled by disease, sensitive to stimuli
- Stanford got involved as a response to the suffering
experienced in solitude by millions of patients who have waited for an
answer form the medical research community
- Stanford’s first patient cohort exhibited a dramatic
response to Valcyte
- Valcyte has a degree of immunomodulatory effect -
monocyte and neutrophil levels changed
- current trial: use of a stimulant Methylphenidate/Ritalin
--> this study needs to be tested at a very high level
- scientific rigor (from Montoya’s mentor Jack
Remington), candid approach, multidisciplinary, clinical and translational
research
- the Wild child French film -- CFS is analogous to the
deaf mute child who no one understands
- Clinic ~ 600 patients, waiting list 300 patients, new
patients currently see his Physician Assistants
- research efforts: multidisciplinary team, weekly
executive and research meetings, recruitment for trials
- external collaborators (Ian Lipkin)
- case control studies: 200 CFS patients v. 400 healthy
controls
- in an attempt
to determine whether circulating cytokines were
associated with severity, a linear regression cytokine by cytokine
analysis and adjusted for matched set
- as disease progresses, progressive worsening
inflammation (circulating cytokine profile)
- IL-17 is a cytokine that has been associated with
autoimmune disease (RA, IBD, psoriasis, experimental allergic
encephalitis in mice and MS in humans)
- in an attempt to determine whether cytokines were
associated, LASSO used. TGF-B (anti-inflammatory cytokine, which inhibits
activation of macrophages) related to duration of illness
- progressive increase of cytokines with disease
severity, and decrease of key anti-inflammatory cytokine
- we believe that the data opens door to the treatment
with anti-inflammatory agent
- Double blind, randomized placebo trials (as well as
interventions like sleep, meditation, anti-inflammatory)
1.
BETH UNGER FROM CDC:
1.
Areas of consensus for
ME/CFS:
1.
Severe fatigue,
unexplained, not relieved by rest, reduces activity
2.
PEM
3.
May be accompanied by
co-morbid conditions such as fibro, IBS, TMJ, interstitial cystitis, migraines
(pain syndrome)
4.
MCS, Lyme, Gulf War
Illness
5.
Sleep, pain, fatigue all
interact
2.
Areas of disagreement
for ME/CFS:
1.
Duration of fatigue (6
months)
2.
Symptoms required
3.
PEM a required symptom
or not
4.
Conditions that exclude
diagnosis (medical/psychiatric conditions)
3.
FUNCTIONAL IMPAIRMENT
COMPARABLE TO CONGESTIVE HEART FAILURE, MULTIPLE SCLEROSIS, CANCER, DIABETES,
AND LUNG DISEASE - CONSISTENT FINDING IN MULTIPLE STUDIES
4.
INABILITY TO ATTEND
SCHOOL (as many of 1% who miss at least one day of school per week) à many of these young
children have ME/CFS
5.
Decreased working memory
and motor speed on neurocognitive tests
Jarred Younger's speech
- ME/CFS study: Fatigue
and Leptin
- Primary hypothesis: leptin is correlated with fatigue
- Some correlated strongly, others did not
- Examine different cytokines --> leptin is the only
one that significantly correlated with fatigue in the group
- Machine learning algorithm used à IL6 and leptin correlated with fatigue --> model
was 78.8% accurate
- Leptin: appetite regulatory hormone, produced by white
fat tissue, increases with obesity and stress-eating, inflammatory
(ability to change immune system drastically)
- Microglia: immune system cells in brain and spinal
cord; serve as the primary defense mechanisms there; interact with
neurons and lower their threshold to fire if something bad is happening;
pushes brain into pro-inflammatory state --> sickness response like
body aches and pain, fatigue, cognitive dysfunction
- Microglia sensitized and becomes "PRIMED" –common
causes including aging, exposure to diesel gas, chronic stress, immune
hit, multiple immune hits à this process is similar to that which occurs in ME
- Leptin serves as a microglia primer (activates at both
a lower threshold AND much more vehemently)
- If introduce leptin to cells,
nothing happens
- BUT in presence of leptin +
hit by trigger, then cells (microglia) react much more forcibly
- Some solutions:
- Leptin-antagonists
(also low glycemic index, behavioral treatment like meditation
- Microglia modulators:
Naltrexone (worked well with fibro)
- Chinese herbs that reduce
leptin: panax ginseng, tumeric, resveratrol, gastodia elàinflexin
(gastrodia elata??)
- Subtyping of patients: most important things with CFS
-- grant with 200 CFS women
- Improving methodology (for example the use of saliva)
Amit Kaushal from Stanford on Genomics and bioinformatics with Ron Davis, Wenzhong Xiao: Analyzing Data at the Genomic Level
- 200 patients meeting 1994 case definition v. 400
controls
- Underlying heterogeneity, can we stratify the
phenotype
- 5 dimensions: general fatigue, physical fatigue, reduced
motivation, reduced activity, mental fatigue
- 20 questions total used in patient populations like
cancer, fatigue
- Correlation between MFI components for CFS subset:
however, different subsets and different manifestations of CFS
- MFI scores result (slides)
- Gene expression: since we're testing 470000 genes, we
can plot all these p values
- Conclusion: large number of genes are different in CFS
v. Healthy controls
- Nextbio Disease Atlas --> the disease with the
highest correlation was Systemic Inflammatory Response Syndrome
- CFS seems to be a pro-inflammatory syndrome given all
the cytokine lab results
- Compared CFS with other datasets with inflammation:
ubiquitin and immunoglobulin heavy chain, protein phosphatase, dynein,
immunoglobulin, La antigen (Sjogren's antigen B)
- Molecular differences between CFS v. Non CFS (Whole
blood MRNA analysis)
- Goal
is to stratify the heterogeneous patient population, correlate with other
CFS datasets (CyTOF and cytokine sets)
Dr. Montoya Talk ABOUT CYTOKINES AND DISEASE
SEVERITY:
- measured 51 cytokines at the same time, 2 serums taken
2/day to control for variations
- 2 sided independent t-test, linear regression, linear
regression, LASSO method
- cytokines are a highly interconnected network, so very
complicated
- Healthy control cases (similar ages, gender
distribution, PEM was present in 96% of patients who met the Fukada
criteria)
- 26 cytokines decreased over time, associated with age
- important because we need to control for age
- cytokine differences between females (Leptin, ENA78,
IL1RA, Resistin are all higher) v. males
- certain cytokines were higher in CFS v. control
(abnormal, pro-inflammatory)
- In an attempt to determine whether there was a
correlation for cytokines with disease severity, the scientists plotted a
LINEAR LINE
- Healthy patients v. Sick: less cytokines
- Montoya also treats toxoplasmosis patients in
infectious diseases clinics
- In toxoplasmosis patients dump cytokines during early
stage of infection (immune system reduce cytokines in peripheral blood) –leading
to a mild shift of cytokines from blood to tissue containing inflammation
- As inflammation progresses in tissues, then cytokines
spill over back to blood (the theory!); other theory: initial
stages – characterized by immune down regulation in the acute phase
- 13 cytokines (these were identified as increasing with
CFS severity) and as related to the following responses: cell trafficking,
cell activation, cell growth and differentiation, cytokine production, Th1
v. Th2 responses
- IL-17 = cytokine associated with autoimmune disease
(RA, IBD, MS); 2 cytokines are also highly associated with females (sex
ratio in ME?)
- TGF-B levels are lower in patients who experience the illness
for longer periods of time (it’s a powerful anti-inflammatory cytokine)
- as disease lasts longer, the immune system loses its
capacity to suppress inflammatory T cell responses
- progressive
increase of cytokines + decrease of anti-inflammatory cytokine with
disease duration à
“a perfect storm”
- PATIENTS’ BODIES INFLAMED, SENSITIVITY TO STIMULI AND PAIN
--> supported by cytokines
- 12 cytokines identified as having a dose response
behavior
- data opens door for treatment with anti-inflammatory
agents (which treat other inflammatory diseases)
- Question and Answer
- Q what is the definition for "untreated" patient
population?
- A: no treatment for a year (no anti-microbials or
antivirals)
- *microglasia sensitivity increases with age
IAN
LIPKIN TALK:
- Columbia’s team includes Dr. Mandy Hornig (director of
the CFS program)
- Koch's hypothesis: microbes are in every pathogen
- Levels of certainty in Pathogen Discovery: If find
evidence of microbe --> probable (causal relationship between exposure
to microbe and disease) à a few more steps to ensure certainty
- Entered the field through the AIDS virus situation;
advocacy of the community changed the situation
- detection of serum antibodies to Borna
disease virus in patients with psychiatric disorders --
took 20 years to demonstrate no evidence for link between infection
and disease
- entry into CFS, since many at the CDC suggested Borna
disease agent responsible for CFS
- Zoonotic Diseases: (PowerPoint contained a map
detailing zoonotic diseases)
- looking at the animal kingdom for agents to cause
human diseases
- most important part of pathogen discovery: clinician
who recognizes disease
- Staged strategy for pathogen discovery:
- analytical stage: look across the tree of life
(bacteria, viruses, fungi)
- evolution of high throughput sequencing (Roche 454,
Illumina, Ion torrent, Illumina Hiseq Xten) --> feasible to look at
the host in the future as technology progresses
- use linguistic/probabilistic approaches (analogous to
the pathogen discovery process)
- consistently look for new infections outside of
humans too (many originate outside)
- high frequency sequencing (next generation sequencing)
- models for bacterium-triggered mental illness (like
schizophrenia example)
- CNS autoantibodies in mice exposed to group A
Streptococci
- took mice prone to autoimmune disease, immune
stimulant injection and streptococci
bacterium implicated, and found that had the same syndrome with
antibody regions in the brain, then pulled proteins from brain,
micro-sequenced them, found the protein and cloned it, then demonstrated
that humans and mice reacted to the same protein
- model: move and integrate animal and human models
- agent could be lurking anywhere, then invoke an immune
response (hence the importance of the examination of antibodies)
- toxins can be important as well, although present as
infectious diseases
- Not all infectious disease consults are for infectious
diseases
- Plant in Minnesota processed pork, and originally
considered it as an infectious disease
- Air hose blowing the myelin out, so workers exposed to
large amounts of CNS tissue and developed antibodies to it-->
exaggerated immune response to these like an allergy response
- it's not actually an infectious disease but immune
response –consider in light of ME/CFS
- technology uses:
- use Peptide microarray to find diseases
- serochip results:
- use human samples exposed to
various viruses (SAR, CORONA)
- effective in finding the
origins of the viruses (MERS-CoV survey of Saudi camels)
- Kawasaki disease:
- Symptoms include inflammation of blood vessels + fever
(kids die if not treated with IVIG or electrophoresis? experience death
by cardiac arrest)
- association of Kawasaki disease with tropospheric wind
patterns (7-20 miles above earth)
- (similar in multiple various agents for CFS)
- During the experiment, things that
seem sterile are NOT: Lipkin had to eliminate contaminants
that confound 16s Analysis (in equipment); treat them by getting rid
of the bacteria (use restriction enzymes)
- look 10-2 days prior to onset of K disease
- airplanes collected filters à scientists conducted viral sequencing of filters’
particles in order to identify major pathogen dominant in these filters
from China before they were dumped in Japan and America
- lots of Candida species (a type of fungi) in the
atmosphere
- Kawaskaki disease resulted as ***an autoimmune
response to environmental trigger!! we need to consider this case
study with regards to CFS**
- Many with CSF have gut disorder –potentially address
symptoms by treating gut
- His theory: ME/CFS is very complex, scientists should
stay open to a wide range of interpretations (but not psychosomatic!)
- Discovery of tick-borne viruses by high throughput
sequencing (maybe not just borrelia but another bacterium)?
- Collected 500 ticks, characterized through high
throughput sequencing and high PCR à wide variety of viruses à whether people with chronic Lyme react to these new
viruses
- When does clinical status changes, when titers for
these agents vary
- initially got into CFS with Dan Peterson in
1980’s
- "absence of evidence of
Borna disease virus infection in Swedish patients with CFS)”
- the patients had immune
activation
- Although there was a false
lead by Judy Mikovits with XMRV à Lipkin gives her credit
because the hypothesis garnered support at the NIH for pathogen search
- Chronic Fatigue Initiative
- Plasma study: Masstag PCR and Consensus PCR screening:
found 2 HHV6 positive, 1 parovirus B19 (control)
- extracted Nucleic acid from 486 plasma samples, found
HHV6 in 6 plasma samples (very small percentages)
- retroviral reads present in 85% of sample pools
(Montoya)
- annelloviruses found in 75% of sample pools --
associated with immune suppression and commonly found in high throughput
sequencing; respond to immune stimulants –but Lipkin doesn’t think
annelloviruses will be helpful
- Each time we don’t find a relationship, IT’S STILL AS
HELPFUL AS A RELATIONSHIP! (rules out external pathogens)
- 211 PBMC samples--13% samples positive for HHV6 but
11% controls positive for HHV6
- Plasma cytokines in long and short duration ME/CFS
(DATA ARE CONVERGING WITH JARRED YOUNGER’S STUDY): elevated levels of IL
17, other inflammatory cytokines
- Spinal fluid showed lower levels of proinflammatory
cytokine (difference in the CNS department v. periphery systems)
- dramatic increases of cytokines in long-term v. short-term
CFS
- caution - modulation of the immune system is very
dangerous
- Batch effect in CFS (RNASeq Project); the way it is set
up changes the dataset
- in science, one has to be able to replicate data
- messed up and had to redo the experiment
- future CFS studies: RNA Seq, CFS gastrointestinal microbiome
(progress), Metabolomics, Proteomics, High-throughput sequencing of PBMC
(but need funding)
- question - why not look at tissues if doctors have
found enteroviruses and endogenous retroviruses elsewhere? they're not
going to be the prime mover but set off an inflammation response
(like schizophrenia, MS)
- the prodrome seems to be an
upper respiratory infection
- originally wanted to do fecal
and PBMC samples
- microbiome that we should
access should be relatively a-traumatic
- Autism risk factors:
- bowel abnormalities in
children with autism as high as 25%
- GI therapeutic strategies -
worth comparing to CFS patients with bowel disorders
- Explains why children have
difficulties processing some environmental toxins (NSAIDS, wine, etc)
- if pregnant woman gets
fever, higher chance the fetus develops autism. (genetic susceptibility
and environmental factors)
- has applied for an NIH grant for ME/CFS
- colon cancer - right side is associated with weird
methylation patterns - model for butyrate defiency in colon cancer; more
fiber the healthier the gut biome (you are what you eat according to
grandmother)
DR.
MONTOYA'S Symposium Conclusion:
1.
super momentum in
determining the pathogenesis of CFS
2.
urgency to CFS NOW and our
attendance is a testament to the urgency
IACFSME SF CONFERENCE 3/19-3/23
1)
Initial
Approach to Management by De Paul’s Charles Lapp, MD
a) Energy
envelope: stay within the boundaries (symptoms worsen if body functions beyond
current capacities, so overtime patient will restore energy, lessen pain and
other symptoms, lessen illness severity)
b) Think
about person with Me/CFS as battery with 20% (envelope theory related to
perceived energy)
c) Buddy
system improved in terms of vitality and energy conservation (vitality v.
baseline/post treatment timeline)
d) Helping
individuals monitor and stay within energy envelope has helped levels of
functioning over time
e) Self
regulate!!!!
2) Charles
Lapp from Charlotte, NC Treatment strategies
a) 4
cardinal symptoms: pain, cognitive difficulties, fatigue, sleep disruption
(non-restorative sleep)
b) Comorbidities:
IB, IBS, migraine, Sicca/Sjorgen’s complex (dry mouth and dry eyes), POTS,
Gluten sensitivity, Prostatosis, chemical sensitivities
c) Standard
addressing of symptoms (sleep, pain, fatigue)
d) Managing
sleep problems: suggested list of pharmacological therapies and non –
pharmacological (rest, cold/heat packs, balneotherapy, massage, PT,
chiropractic, acupuncture, ENS, EMS)
e) Characteristics:
exertional, positional, hypersensitivities, stress intolerance
f) Plan
for days of recuperation after exertion
g) Can
and must be active – objective limits of aerobic interval activity, heart rate
limited, pedometer
h) Therapies:
i) POTS:
water, salt
ii) Modified
Elimination Diet (avoid gluten, dairy, SCANT – sugar, alcohol, nutrasweet,
tobacco)
iii) Viral
or immunological symptoms (Valtrex, inosine, nexavir, valycte)
iv) Human
growth hormone?
v) Ampligen
vi) Rituxan/rituximab;
TNF alpha inhibitors
i) Theoretical
approaches:
i) Coagulation
defects
ii) Marshall
protocol
iii) Nitric
oxide
iv) Glutathione/methylation
deficiency
v) Cardiomyopathy,
vi) Toxic
exposure
vii) Stem
cell therapy
j) Final
reflections:
i) No
known cause or cure
ii) Most
important to stay within limits imposed by intervals, heart rate, steps per day
iii)
Symptomatic therapy focuses on sleep
management and pain control
3) JOSE MONTOYA TALK – ANTIVIRALS!
a) Herpes
viruses are ubiquitous, infect a significant proportion of individuals and
establish life-long latency
i) Example
of HHV6-stricken researcher, detected in blood and spinal fluid during height
of researcher’s symptoms, but not presented in health controls
ii) Herpes
virus is a good candidate for the trigger of the illness
iii) life-long
latency – once infected, difficult to remove them from system
iv) 8
Herpes: HSV 1, 2, VZV (chicken pox), HHV5 (Cytomegalovirus), HHV6 and 7, HHV4 (Epstein
Barr), Kaposi’s sarcoma associated with herpes (8)
(1) When
genital herpes recur, then symptoms flare with the activation
(2) Herpes
viruses have been known to activate even without obvious physical lesions
(3) Disease
model: herpes 2 is reactivated periodically in health individuals, goes into
the spinal fluid, causes meningitis (without individuals being
immunocompromised)
v) Antiviral
approach: Acyclovir, Famciclovir, Valtrex, IV ganciclovr, Valcyte, IV
foscarnet, IV cidofovir, Combination therapy
(1) Leflunomide
(CMV IgG) – immunomodulator used in RA
(2) Infusion
of CMV specific T spells (sepsis patients)
vi) Possible
candidates for Antiviral therapy:
(1) Ascertain
patient has ME/CFS
(2) PCR
positive patients
(3) Oral
Herpes HSV1
(4) Genital
herpes HSV2
(5) Shingles
VZV
(6) High
titers against EBV VCA, EBV EA, HHV6, HSV 1, HSV 2
(7) HHV7,HHV
8 (very rare in America)
(8) When
everything has been tried, go with fluctuating but suggestive symptoms
vii) Dose
of antiviral regimen: give lowest dose then increase as tolerated
(1) Remarkable
worsening in the beginning phase
(2) Is
duration important? Longer valcyte treatment correlated with improved response
(3) Trial
published for 5 months acyclovir not effective
(4) Valcyte
results graph: cognitive function improved significantly; many patients
OVEREXERT AND GET PEM
viii)Antiviral
therapy of 2 patients with chromosomally-integrated HHV6
(1) Improvement
after foscarnet
(2) Indicative
that antivirals work for CFS patients, but difficult to determine WHO needs
antivirals?
4) Nancy Klimas talk on
immunomodulatory medications:
a) Exercise
stress test first, then test for cytokines compared to baseline
i) Dynamic
challenge studies
ii) Genomic
results
iii) RedCAP
platform for assessment
iv) Computational
biology/modeling analysis with data scientists
b) Publications:
homeostatic drive in perpetuation of complex chronic illness – GWI and CFS
i) After
being pushed over, CAN YOUR BODY BE PUSHED BACK INTO BALANCE?
ii) Mining
Drug-action data
(1) Reverse
directory for drugs
(2) for
example, reverse TNF drug, test on animals/humans, potential repurposing of
anti-TNFa Infliximab
iii) 95%
of immune system is in lymph nodes and immune system
c) Overview
of the Immune Response
i) Immune
abnormalities:
(1) Immune
activation: DR, CD 26 expression
ii) Functional
defects (NK cell dysfunction, C8 cells)
d) Immunomodulatory:
i) Ampligen
(both immune modulator and antiviral) but failed to pass FDA
ii) biologic
response modifiers (targeted approaches) – Humera
iii) Rituximab
(phase 2); deplete B cells
iv) Alpha
and gamma interferon (chia talk)
v) Isoprinosine
(Phase 2)
e) Reducing
inflammation:
i) Omega3
quiets TNFa, LDNF reduces neuro-inflammatory pathways
ii) Food
and allergens
f) Antivirals:
help with immune exhaustion
g) Immunovir
(Newport Pharma), Inosine (OTC) à
start LOW LOW LOW dosage and titrate up because people feel ill when clearing
bugs so start with small dose
5) Jarred Younger on Fibromyalgia:
a) Fibro
patients (25% improve over an 11 year period, 39% get worse)
b) The
problem of fibro: so many levels to examine – DNA, RNA, etc; is the problem in
the muscles or the central nervous system?
c) Most
people believe: Fibro is a central sensitivity disorder, despite fact that you
feel it in the body
i) Analogy
of a car alarm – everything including flying bird makes you feel horrible and
sets off the alarm
ii) Pain
= bodily alarm system, most important sense, tells you when you’ve gone too far
(tells you when you shouldn’t be doing this)
iii) FIBRO:
threshold dramatically lowered like getting groceries/gardening , faulty alarm
system
d) New
research
i) The
flu – cytokine induced sickness response (body aches, fatigue, cognitive
dysfunction, sleep disturbances, depressed mood, social isolation,
headache) à
results from the immune system
ii) Microglia
(cell in the brain) – responsible for protecting us from everything
(1) Looking
for cell death, bacteria, viruses
(2) Microglia
activation: When find problem, change shape and pump out chemicals affecting
neurons and changing the way their function (neurons fire and make you feel
“sickness”)
(3) With
Fibro/ME/CFS, the microglia are the worst instead of the best in terms of the
sickness response
(4) Primed
microglia (triggered when exposed to huge immune hit like Lyme, chronic
disease, aging, opiates for long term use, obesity – release of leptin from fat
cells)
(5) Sensitized
microglia: overexpress receptors, keep in active state, least factor will set
them off and feel horrible
(6) Issue:
can’t test theory directly because too invasive.
(a) Doctors
can’t get into the brain for direct testing of hypothesis
(b) ANOTHER
PROBLEM: when diagnosed with fibro, all other tests cease, so fail to do
external tests (small fiber peripheral neuropathy, vitamin D deficiency,
central nervous leak) so it’s important to continue to do tests
(7) Day
to day variability (how to track this?)
(8) Also
tracked leptin – as people’s pain increased, leptin increased
6)
Closing
keynote speaker: The physician – patient relationship in the genomic era by
Abraham Verghese
a) What
ET sees: rounds removed from the living patient, rounds centered around the
iPatient, no need to examine patient, bedside = toxic, point of admission is to
reduce 3d patient to 2d
b) Joseph
Leopold Auenbrugger – “new invention” book was seminal of its time
i) Physician
Jean Corvisart was physician to Napoleon Bonaparte
ii) His
student discovered the stethoscope
iii) Back
then the barber surgeons treated everyone, but the carrying of the stethoscope
signaled to the world the transition from barber surgeon to physician; it was a
moment with tons of discoveries of medical equipment
iv) Luke
Fildes: the doctor = seminal painting (child occupies the center of the
painting, the doctor is in a passive; “I was ill and you cared for me” Matthew
25:30 à calls to the Samaritan functioning of
being a physician)
v) Stanford
Medicine 25 Sessions – bedside manner with real patients (hands-on session)
vi) Relationship
between doctor and patient is a human-human exchange, embody the Samaritan
qualities, human understanding, empathy, human skills
(1) Straying
from this = great disservice
(2) Questions:
(a) The
success of alternative medicine is the abundance of hands-on interaction
(b) How
do you propose to get the computer out of the exam room? It mostly is related
to billing, monopolize the system
(i) Exposing
the ludicrousness of this
(ii) Lost
privileges when didn’t complete the ICD coding training in EPIC (exemplified
how the medical profession is so far removed from the patient experience)
(iii) Health
care in America –ordering tests instead of examining and talking to the patient
(c) Do
patients have a role in treatment guidelines: if we have a doctor physician
test to examine how to examine a patient (ACTUAL TEST V. MULTIPLE CHOICE). Who determines whether the physician is accurate
and detailed during diagnosis of illness – does anyone test Varghese aside from
a MC choice exam?
(i) The
multiple choice test’s easy reproducibility is the main reason for its
implementation NOT its ability to measure the effectiveness of the physician(compared
to the drunk who loses his keys in the dark and looks for it in the light)
(d) HIPPA:
doesn’t see the point of it
(e) Given
the multi year wait list for Montoya, and the apparent urgency of ME/CFS as a
field needing physicians, how do you propose a strategy to train future
Montoya’s:
(f) Answer:
the dearth of physicians is related to reimbursement issues, what is
societally-valued?
(i) CFS
is not a sexy field to enter
(ii)
Long wait list due to how unique his
treatment is
------------------------------------------------------------------------------------------------
Patient
Adaptive Techniques:
Heart
rate monitor
Pacing
Deep
breathing through the stomach, (in through nose, out through mouth), tissue box
on stomach
Fred
Friedberg EDM Fibromyglia study
Day
3 and 4 of IACFSME
1) Prevalence and Health-related
Characteristics of ME and EMS/MCS – results from the Canadian Community Health
Survey
a) Summary:
CFS is chronic and disabling, with little change in symptom severity over time
b) Those
with the most severe initial symptoms seem to have a higher likelihood of
symptom improvement, although improvement does not necessarily mean recovery or
markedly improved functioning
c) Severe
initial post-exertional malaise may be an important marker of functional
outcomes and long term health status
d) Onset
type is not important in the long term course of CFS
e) Episodic
remissions occur in a reasonable proportion of CFS
f) Patients
have number of comorbid, chronic conditions
g) Acknowledgement:
chronic fatigue initiative clinical epidemiology study subjects – Stella Lee,
Komaroff, Bateman
2) Aims:
study prevalence of cancer in patients with CFS
a) Specific
conditions including fibro, sleep apnea, bunch of other comorbidities
b) Chi-square
analysis, principal factor analysis (14 conditions à
4 comorbidity factors)
i) Anxiety,
depression, PTSD
ii) Hypothyroidism,
autoimmune disease
iii) Narcolepsy
iv) Neurological
disease
v) Cancer
c) Correlation
and regression analysis
d) Top
4 conditions: Fibro, depression, anxiety, hypothyroidism
i) Comorbidities
decrease odds of better health over time, and their participation of
extracurricular activities, school, etc
ii) Comorbidities
increase odds of CFS symptoms worsening over time
3)
Lucinda
Bateman: Evidence from a Multi-Site Clinical Epidemiology study
i) Patient-identified
effective treatments
ii) Initial
and current severity of 9 CFS symptoms from Fukada criteria + orthostatic
intolerance
iii) Results:
(1) Self-help
strategies 65% (rest including efforts to improve sleep and pacing, diet,
exercise like strength conditioning)
(2) Traditional
medicine 53% prescription medications and vitamins, OTC medications, herbal
remedies, acupuncture, massage
(3) Dan’s
clinic: traditional medicine listed as the more effective treatment of major
symptomology of illness v. Bateman clinic: empower patients to live with this
illness (self-help strategies, value and manage health over time) à
(a) Variables
that may reflect the clinic differences including patient age, stage of
disease, location?
(b) Autoimmune
diseases (including hypothyroidism) more associated with traditional medicine
(since that seems to help them the best)
(c) Neurological
diseases –> complementary medicine
(4) Summary:
self help and traditional medicine are the most effective treatment types in
CFS patient population but vary in magnitude by site
(a) Treatment
type effectiveness varies by:
(i) Severity
of initial symptoms
(ii) Initial
symptom cluster severity
(iii) Current
health status and functioning
(iv) Remission
(ever)
(v) number
of comorbid conditions
(5) Cancer
diagnoses by system: skin, blood, nervous system, thyroid,
colon/liver/pancreas, kidney/bladder, breast, cervix/uterus/endometrium/ovary,
prostate
(a) Prevalence
of any cancer: 15.5%
(b) Excluding
skin cancer, prevalence of any cancer: 8.1%
(c) Prevalence
of any cancer in US: 4.1%
(6) Question
and Answer session:
(a) Q:
how do comorbid conditions related with CFS compare to the percentages of the
normal healthy population?
(b) A:
great question and study will result soon
(c) Q:
on neurological symptoms:
(d) A:
slides depicted mild improvements across wide range of the symptoms (including
neurological ones); other epidemiology studies with more granular information
about neurological symptoms are taking place beyond CFS community, but they
can’t definitively make any statements about neurological symptoms specifically
(e) Q:
why does it seem that most of the highest improvements corresponds with the
type of clinic (Peterson’s traditional medicine v. Bateman’s lifestyle and
symptom management example)
(f) A: It’s probably just the nature of medicine
and how we treat patients and practice medicine
4)
Superior
Ability of a 2-day CPET Protocol to Detect Functional Impairment in ME/CFS
compared to either a single CPET, submaximal exercise test, or a VO2 prediction
equation
a) CFS
frequently use these types of energy: they require frequent rest breaks
i) Short-term
anaerobic (to get up with fire alarm calls, brief)
ii) Long-term
anaerobic (15-75 sec)
iii) VO2
peak measured directly during CPET is valid, standardized, reliable in health
and diseased patients
(1) Maximal
effort CPEP exacerbates symptoms of PEM so use of submaximal test is of
interest à get the necessary info without max
testing them and crashing them
(2) CPET
1: measures baseline functional capacity Vo2 peak and ventilator (anaerobic
threshold), induces PEM
(3) CPET
2: determine if patient can reproduce CPET 1 results within well-established
normative data variability (not compared to a matched healthy control); very
well established that these are repeatable tests
iv) Accuracy
of predicting Vo2 peak:
(1) Linear
relationship between HR and oxygen consumption (as workload increases, HR
increase, O2 consumption increases in a linear fashion)
(2) Predicted
maximum HR = valid for all subjects (200 – age)
(3) Constant
work economy and mechanical efficiency during exercise
(4) Normal
day to day HR variation exhibited by patients
(5) Prediction
accuracy using submaximal HR has a standard deviation (standard error)
v) The
problem:
(1) Detecting
functional impairment requires accurate measures of functional capacity
(2) Can
functional impairment accurately be detected by Vo2 during 1 and 2 CPET tests?
(3) Summary:
measured vo2 peak using 1 CPET, 2 CPET, predicted Vo2 using validated ACSM
cycle ergometer equation, predicted VO2 from submax HR
vi) Subjects
and Procedures:
(1) Oxygen
consumption (VO2), heart rate (HR), workload (work), respiratory exchange ratio
(RER > 1.1), functional impairment determined
vii) Results:
(1) Predicted VO2 peak was higher than actual VO2
peak for both CPETs
(a) CPET
VO2 actual tests dropped significantly
(2) Predicted
higher than actual VO2 peak for both CPETS
(3) Compared
to health controls, PEM really lowers our ability to reproduce the tests
viii)Summary:
Validated prediction equation consistently over predicts the VO2 max in Me/CFS
patients
(1) Interesting
point: HR at three submax workloads are same for CPETS 1, 2
(2) The
linear relationship between HR, Work, VO2 are not maintained in Me/CFS with PEM
(3) Regression
showed poor ability to predict VO2 peak from any single or combination of
variables
(4) Submax
HR-work relationship during CPET 2 did not reflect the 13% decrease in Vo2 peak
(probably due to PEM)
ix) Cardiac
failure experiment – tried to test severity of impairment
(1) 43
% of sample appeared to have some degree of functional impairment on day 1 of
SPECT, but when they were tested the 2nd day, 67% met functional
impairment criteria
(2) Takeaway:
using only 1 CPET, it failed to detect 15% of those with functional impairments
– then the speaker said 55% (so confusing)
(3) It’s
dangerous to over predict VO2 because patient can overexert, or patient’s exercise
therapy can be overprescribed
x) Conclusion:
(1) 2
CPETS are required to accurately detect functional impairment in ME/CFS
(2) 1
CPET is sufficient to characterize functional capacity of ME/CFS or correlate
functional capacity with other objective measures
(a) However,
assessment based on 1 CPET should acknowledge the inability of 1 CPET to detect
deleterious effects of PEM on functional capacity in ME/CFS
xi) DANGERS
OF PREDICTING VO2 PEAK
(1) It’s
not linear so might over predict VO2 peak from heart rate à
very dangerous for reasons such as the patient over working, the physical
therapist making the patient push beyond limits
5)
Diminished
Pulmonary Ventilation in CFS patients – effects of deconditioning and
post-exertional malaise
a) Definition
of ventilation: when one breathes in O2 and subsequently removes CO2
b) Results
from exercise test day one and retest day two
i) Huge
similar reduction in ventilation at peak exercise and at the anaerobic
threshold
ii) Greater
reduction in ventilation on test 2, especially at the anaerobic threshold à
shows the PEM effect on CFS patient’s ability to exchange air
c) Ventilator
anomalies in CFS – what are they attributed to?
i) Skeletal
muscle fatigue? Oxidative deficiency?
ii) Autonomic
drive? Related to dysautonomia
6)
Introduction:
Potential value of Exercise testing in ME/CFS
a) Identification
of measurable physiological markers to aid or confirm diagnosis or to help
classify disability
i) A
drop in anaerobic threshold on the second day of exercise testing was present
in ME/CFS but not in controls
ii) Goal
is to identify discrete subtypes within ME/CFS
iii) Why
submaximal exercise testing was used: screening for other disorders such as
mitochondrial dysfunction, maximal cardiopulmonary exercise tests, test people
without inducing a flare (CPET consistently causes flare)
b) CONCLUSION:
submaximal exercise testing procedure didn’t clearly distinguish between ME/CFS
cases and healthy controls
i) Subset
of 19% of ME/CFS patients met criteria
ii) Greater
level of self-assessed exertion at lower exercise intensity experienced in
ME/CFS might be explained by central perceptions (neurology component?)
iii) Even
submaximal testing was intolerable for a subset
7)
Examining
Exercise Tolerance in CFS patients
a) Retrospective
study of 6 year exercise testing
i) Cardiac
output was monitored (pulse contour analysis)
ii) Lactate
levels
b) Conclusion:
i) peak
O2 uptake is low in CFS patients
ii) Circulation
is not different
iii) What
explains the low values?
c) What’s
the underlying reason for this??
i) ADP,
Pi, and H+ are recycled in the mitochondria
ii) Perhaps
the cause of PEM is that several complex biological pathways might possibly
go wrong:
(1) down-regulation
of the entire system – lowering of lactate and H+
(2) a
block in the system resulting in lower lactate and higher H+ production
(3) or
something goes wrong in the mitochondria and the system compensates by
overproducing H+ (protons)
iii) low
lactate after exercise in several patients –similar to another doctor’s work
iv) I
think the speaker said….”the problem is the low proton à
low lactate consequently”?
d) Question
and Answer session:
i) Q:
what are your thoughts about a portable CPET machine to observe an individual’s
given HR and VO2 max at any time while traveling, or during the specific moment
of PEM after a particular exertion? A: The researcher owns such machine which
cost $30,000 !!!
ii) Q:
do other patients outside of CFS have PEM?
A: Danish Dr. Vermeulen treated a HIV patient had PEM as well – second
test a lot worse than the first test
iii) Q:
do you see other patients with PEM? A: No, and we have tested many patients
with cardiovascular conditions etc, and they have nothing like CFS patients –
both high and low functioning (yet the closest to the PEM was the HIV patient
from that Dr. Vermeulen)
iv) Q:
What defines the minimal exercise threshold that induces PEM? A: the patient – it has to be a very
individualized approach to physical activity guidelines
v) Q:
there are potent PEM responses to CPET 1 and 2 testing… A: Researchers agreed
that there was a concern
(1) Some
patients relapsed for 1 month
(2) All
docs need to be very cautious about the possibility of PEM
(3) Patients
need to expect a relapse and to be surprised if there is none
vi) Researcher
comments:
(1) Lung-wise
speaking: There was nothing wrong with the pulmonary function BEFORE THE EXERCISE
(2) It’s
the diminished functional capacity of the lungs itself WITH THE PEM AFTER
EXERTION
8) PET
studies with CFS patients: sectors in the anterior cingulate
a) Correlation
between severity of disease and brain anterior cingulate
b) Functional
Somatic syndromes – doctor is investigating a whole constellation of syndromes
c) Positive
correlation between something in the brain + pain
d) C-PK
11195 binds to the translocator protein, the index of activated microglia à
when activated, translocator is upregulated and binding occurs
e) Correlation
between BP and attention impairment, yes there is neuro-inflammation according
to Yamamoto
f) Brain
science of fatigue: PET imaging in the patients with CFS
i) Overdepression
of brain activity in CFS patients (overprotection) – for example, when patient
is stimulated in one region, the auditory region is depressed….
ii) Mirror
system of Fatigue
g) Fatigue
and motivation – they are mirror images of each other (directly proportional)
h) Neural
circuits for fatigue: from acute to chronic phase (in beginning there is
oxidative stress, cytokines, maybe something changes in the brain)
i) Future
studies - start with healthy people,
then go to CFS patients and needs to recruit many people
i) Center
for Health Science Innovation recently opened in summer 2013 – I think the
speaker said 50,000 people recruited
ii) Many
partnerships in Japan (large centers of research)
9)
MARCIE
AND MARK ZINN EEG AND CFS
a) 50
CFS patients, 50 matched controls
b) Measures
included 19 channel EEG, measured fatigue using the Multidimensional fatigue
inventory, fatigue severity scale
c) Examined
Peak Alpha frequency – found that CFS people are lower in PAF (lower energy for
energy and sensory inundation)
i) Reduction
in PAF activation, this widespread and in the absence of known cerebral lesions
or head injury, usually suggests a deregulation of thalamo-cortical circuits
ii) PAR
and effects of fatigue: higher scores on fatigue are associated with lower PAF
scores
iii) Implication
of reduced PAF in bilateral frontal, parietal, and central areas
(1) Associated
with interruptions in goal-directed behavior (coordinate cognitive functions in
formation of coherent behavioral sequences ) – hard to keep it together
(2) Parallels
mental status changes – such as alertness and attention, decision making, etc
iv) Conclusions:
CFS subjects have lower PAF and correlation with fatigue and PAF
(1) EEG
can be used to evaluate the extent and nature of the brain disregulation once a
CFS diagnosis has been established – as well as monitoring disease progression
and treatment response
d) IMPLICATIONS
OF ABNORMAL BETA-2 SOURCES IN CFS: primary motor deficits, reduced
responsiveness, slower motor performances, delayed reaction times, andmuscle
weakness – hallmark features of CFS; sensory ataxia: reduced proprioception
i) Disturbances
in pain sensation, alterations in the process in go sensory stimuli (more
generalized hypersensitivity) – instead of happening at the neocortical level,
it’s like a more crude processing of stimulus
ii) Slides
also discussed reduced motivation -
hypofunctioning Broca’s area consistent with studies showing deficient verbal
working memory and language deficits in CFS
iii) Summary:
global expression of CNS hpoactivation was found in CFS patients
(1) Link
between CFS symptoms and brain regions with quantifiable changes in brain state
and function
(2) These
can be used to evaluate nature and extent of CFS –not a diagnostic but
assessment!
10) Q
and A
a) Some
of the viruses (HHV6 and EBV) have an affinity for the brainstem, so the
researcher is very interested and only recently has the tech enabled us to examine
the brainstem
b) Q:
Are there other diseases with similar cognitive deficiencies in EEG; A: can’t
use EEG purely as a diagnostic – only to confirm the diagnosis within the scope
of other information and symptoms (like epilepsy)
11) New international Primer:
a) Revisions
include the following: handouts for patients, index, sections on prognosis and
mortality, expand section on severely ill patients, Pathophysiology: immune
system changes, updated use of dietary supplements including CoQ10,
acknowledgements, some typos
b) Why
a primer not guidelines?
i) Guidelines
limited to info found in systemic review of literature
ii) Well
received enough to be on the HHS website next to many guidelines
c) All
revisions brought to the entire authoring committee
i) Statements
appearing in the revised primer are conseus statmeents approved by the entire
authoring committee
ii) Committee:
chair = Fred Friedberg, Lucinda Bateman, Lenny Jason, Lapp, Bested, Davenport,
Staci Stevens, Rosalind Underhill, and etc
iii) Arrangements
made to translate the primer into French (the committee will reconvene about
various translations)
iv) Lily
Chu: there is no evidence to say that ME is NOT fatal
(1) There
are no longitudinal studies of ME population to address this question
(2) The
one study cited in primer only had 600 sample size and was not tailored to this
question
(3) Rare
cases where deaths attributed to ME
(a) 2005
Sophie Mirza was the first person in UK to have CFS listed as cause of death on
certificate
(b) Emily
Collinbridge – died of ME at 31 in UK
(c) Casey
Fero – mother has ME, he died in 2003 at age 9 with cardiac arrest
(d) Dr.
Knox found higher risk of non-Hodgkin’s lymphoma in ME/CFS population; Sears
study needs to be replicated
(e) CFI
– 4 fold increase of cancer rates in subjects
(f) Suicides
– should not be rated as second rate deaths, but many with ME who commit
suicide aren’t depressed; but rather driven to suicide due to exhaustion based
on daily struggle to exist
(4) The
“lack of mortality” statement – some providers might conclude that the patients
are exaggerating the severity of the illnesses
(5) IACFSME
is the only international organization dedicated to CFS – everything has to be
evidence-based, qualified statements, should be listed as an underlying not
direct cause of death on death certificates; documenting mortality influences
issues like research and funding; survey of deaths by Leonard Jason à
contact them if interested in participating
(6) Once
information gets out, hard to correct
(7) Question
and Answer
(a) Researcher
found “presence root ganglionitis in patients” – inflammation within ganglion
which sits outside the spinal cord (and is part of the nervous system) shown in
autopsies
(b) Lily’s
experience has experience with filling out death certificates not pathology
(c) Mortality
is on page 26
v) Q:
How can we encourage health care practitioners to read the primer? A: we need to get it out hardcopy so that
physicians have the copy in office
vi) State
medical society – get on their program for annual meetings; get on the workshop
for various practitioners like Physical therapists, General Practitioners,
pediatrician
12) Conclusion by Dr. Anthony Kamaroff
a) Questions
addressed by many of the presentations
i) Is
there evidence of objective underlying biological abnormalities?
ii) Could
these theoretically explain the symptoms and do they correlate with the
symptoms?
b) Huge
New CFS Databases and Biosample Banks
i) Nova
Southeastern University/U. Miami/Miami VA Medical center
ii) Stanford
Medical School
iii) Chronic
Fatigue Initiative (multicenter)
iv) NIH
Multicenter Sutdy: Columbia University (*Hornig and Lipkin)
v) UK
ME/CFS Biobank
c) Immunology
Overview 1
i) Elevated
levels of allergy –associated cytokines and chemokines and other
pro-inflammatory cytokines (*CFI)
ii) Ability
of other cytokines to separate CFS from healthy control (Stanford) – Jarred
Younger findings
iii) Stanford
inflammation studies: levels of 51 inflammation –related molecules – cytokine
family/chemokines/hormones measured
(1) Unparalleled
study even outside of CFS
(2) Correlation
of inflammation related molecule levels with illness severity!!! (as symptoms
progressed in severity, linear correlation with the inflammation molecules)
(3) Jarred
Younger’s cytokine network – primacy of leptin (hormone discovered in 1994 made
by fat cells and diminishes appetite)
(a) Leptin
is closely tied to immune molecule CYTOKINES – correlate with the levels of
fatigue in CFS patients
(4) Elevated
levels of Interleukin -17 – strongly associated with autoimmunity; elevated IL
17 compared with T-regulatory cells makes the risk of an autoimmune diseases
worse, suggests that autoimmunity playing role in CFS
(5) Significant
decrease in mRNA’s would increase PROINFLAMMATORY molecules -- > internal
biological confirmation validating Younger’s findings
(6) Elevated
levels of interferon-gamma
iv) Interferon-gamma
and CFS
(1) Released
by lymphocytes in response to viral and intracellular bacterial infections
(a) CFI
study – a HUGE difference between subsets of patients <3 years and >3
(b) Interferon-gamma
correlated with cognitive impairment (frequently associated by intracellular
bacterial or viral infection – suggests an underlying infectious agent)
v) Telemoeres:
ends of chromosomes, shorter in CFS patients than healthy subjects
(1) Length
= marker for cellular aging, shorter telomeres denotes cells aging more rapidly
– the short cells has divided many times and is older, hence short telomeres =
> increased vulnerability to variety of disease associated with aging like atherosclerosis
(2) Life
stress associated with shorter telomeres (parents carrying for sick children)
(3) Telomeres
are shorter in patients with CFS v. healthy à suggests
underlying biological process that is making us age faster
vi) Virology
and Infectious Agents
(1) CFI
study – reported no microorganisms in serum
(a) Q:
what about circulating white cells, brain, other tissue?
(b) A:
we will be investigating these
(2) Enteroviruses:
Dr. John Chia –antigen and nucleic acid found in biopsies between CFS and
controls
(a) When
you took biopsy specimens with enteroviruses and injected into the mice, you
found enteroviral infection in mice
(b) Indicative
of an infectious agent (since mice were infected)
(c) Impressive
research, yet it is depressing that no one else has used the existing CFS
biopsies to do this on a mass scale. Dr.
Komaroff hopes that it changes in the future
(3) Public
health /epidemiology
(a) Canadian
Community Health Survey estimates that 411,500 of 35 M Canadians (1.1%) have
CFS
(b) Nearly
a third has experienced at least one remission, which had lasted 1 year
(median)
(c) Rest/exercise/diet
are more likely to reduce symptoms than medications or alternative treatments
(d) CFI
study reported that patients more comorbid illnesses than healthy controls
(4) Case
definition
(a) Need
to be precise: the way each component (mild, moderate, severe) need to be
specified
(b) Empirically
derived case definitions are superior to consensus-drive case definitions
(i) Better
at defining subgroups – use statistical subgroup through the big data
(ii) Better
at predicting an endpoint – prognosis, a laboratory finding thought to define
the pathology of the illness
(5) Exercise
provocation studies:
(a) A
stressor that makes a patient feel worse should also bring out the underlying
pathology, and a 2x dose of stressor should bring it out even more
(b) On
a single exercise study CFS patients did not consistently perform below normal,
a second test the next day found abnormal VO2 max in 9% patients – not even
people with heart and lung disease experienced this degradation à
in their experience, exercise physiologists haven’t seen this before,
indicative of the uniqueness of PEM
(c) Low
peak oxygen extraction relative to increase in cardiac output
(6) Pediatric
CFS:
(a) Surprisingly
high prevalence of delayed milk protein sensitivity in kids – changing dietary
patterns might be able to alleviate some of the suffering in kids
(b) Combination
of widely available/inexpensive laboratory tests may predict which people with
mono go on to post-mono CFS
(i) 15
years of research show post-mono CFS
(ii) WHICH
TESTS ARE THESE? Very inexpensive!
(c) Depression
was found only in 25% of pediatric CFS patients – even after onset of illness
(i) Teenagers
– background healthy sample’s prevalence of depression à15%,
so it seems only marginally higher in CFS teens
(7) Neurology:
(a) qEEG
changes in CFS – peak alpha wave frequency significantly reduced over 58% of
cerebral cortex, delta wave frequency increased particularly in frontal and
limbic areas of the brain
(b) Correlated
linearly with the SYMPTOMS (fatigue or pain)!! Validates the symptoms!
(c) Indicating
likely disruptions of information transfer across cortical networks, and
inhibition of ascending arousal systems
(d) Neuro-inflammation
by PET Scan –
(i) iv
injection of compound that binds to a translocator protein in microglial cells
and astrocytes, image uptake by PET scan à show increased
signal in multiple areas of the brain
(ii) Intensity
of the signal correlated with cognitive impairment
(8) Conclusion:
yes, abnormalities in fact do theoretically explain symptoms and DO CORRELATE
with the symptoms
(a) Case
control studies comparing CFS to health and disease-comparison groups
(fatiguing ones) find robust evidence of an underlying biological process
involving brain and autonomic, immune system, energy metabolism, oxidative and
nitrosative stress
(b) Illness
is not simply the expression of somatic symptoms by people with a primary
psychological disorder
(i) It
was fair to ask 30 years ago to ask whether it was psychiatric stress,
amplifying normal body sensations
(ii) But
today, it’s no longer a valid question!
(9) Q
and A
(a) Q:
are we at the point where we can have biomarkers?
(b) A:
EEG might be a biomarker, since it showed near-perfect correlation between CFS
and healthy controls
(c) Q:
What about NK cells and biomarkers?
(d) A:
immune based biomarkers are reasonable places to define subgroups; Dr. Klimas
believes confidently that NK cell function can be used to determine severity
[3/30/14 Update: Since posting this, I've come across some additional summaries of the IACFS proceedings from someone who I consider one of the best ME/CFS bloggers, Christopher Cairns. I was beginning to lament that the notes above don't include much on Dr. Chia's presentations, but Mr. Cairns has taken care of that. His is a more editorialized account of certain lectures, which I find refreshing. For more, please see:
and
[4/3/14 Update: Got 51 minutes to spare? Health Rising posted a video of Dr. Komoroff's closing speech, which is traditionally a summation of all the presentations at the IACFS Conference. http://www.cortjohnson.org/blog/2014/04/02/report-san-francisco-ii-komaroff-summary/]
Fantastic info. Many thanks for sharing this!
ReplyDeleteSeriously interesting stuff!
ReplyDeleteI didn't read all of it - I scanned for the practical things that I can control in my life now. But the exercise measurement stuff was interesting - I've just been to an exercise physiologist who used a few similar techniques to measure my ability. Graded exercise does not work for me, but finding a safe way to measure/quantify ability is really important, especially in the context of studies - measuring ability before/after treatment. This is an exciting time for CFS! Lots of development and new ideas!
Claire (livebedocfs.wordpress.com)
very interesting, thanks very much for posting
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