Thursday, March 27, 2014

Neuroinflammation in CFS

J Nucl Med. 2014 Mar 24. [Epub ahead of print]

Neuroinflammation in Patients with
Chronic Fatigue Syndrome/Myalgic
Encephalomyelitis: An
11C-(R)-PK11195 PET Study.

Nakatomi Y1, Mizuno K, Ishii A, Wada Y,
Tanaka M, Tazawa S, Onoe K, Fukuda S,
Kawabe J, Takahashi K, Kataoka Y,
Shiomi S, Yamaguti K, Inaba M,
Kuratsune H, Watanabe Y.


Chronic fatigue syndrome/myalgic encephalomyelitis
(CFS/ME) is a disease characterized by chronic,
profound, disabling, and unexplained fatigue.

Although it is hypothesized that brain inflammation
is involved in the pathophysiology of CFS/ME, there
is no direct evidence of neuroinflammation in
patients with CFS/ME.

Activation of microglia or astrocytes is related to
(11C-(R)-PK11195) is a ligand of PET for a
translocator protein that is expressed by activated
microglia or astrocytes.

We used 11C-(R)-PK11195 and PET to investigate
the existence of neuroinflammation in CFS/ME


Nine CFS/ME patients and 10 healthy controls
underwent 11C-(R)-PK11195 PET and completed
questionnaires about fatigue, fatigue sensation,
cognitive impairments, pain, and depression.

To measure the density of translocator protein,
nondisplaceable binding potential (BPND) values
were determined using linear graphical analysis with
the cerebellum as a reference region.


The BPND values of 11C-(R)-PK11195 in the
cingulate cortex, hippocampus, amygdala, thalamus,
midbrain, and pons were 45%-199% higher in
CFS/ME patients than in healthy controls.

In CFS/ME patients, the BPND values of
11C-(R)-PK11195 in the amygdala, thalamus, and
midbrain positively correlated with cognitive
impairment score, the BPND values in the cingulate
cortex and thalamus positively correlated with pain
score, and the BPND value in the hippocampus
positively correlated with depression score.


Neuroinflammation is present in widespread brain
areas in CFS/ME patients and was associated with
the severity of neuropsychologic symptoms.

Evaluation of neuroinflammation in CFS/ME patients
may be essential for understanding the core
pathophysiology and for developing objective
diagnostic criteria and effective medical treatments.


11C-(R)-PK11195, chronic fatigue syndrome (CFS),
myalgic encephalomyelitis (ME), neuroinflammation,
positron emission tomography (PET)

PMID: 24665088 [PubMed - as supplied by publisher]

The link to donate to Lipkin's study

The resources are do what the community deserves
Posted 3/17/2014 2:30:42 PM

We are actively seeking funds to support comprehensive studies into
the role of the bacteria, fungi and viruses in CFS. Research into the
human microbiome is an exciting new pathway to advance our
understanding of the role that over a trillion microorganisms in our
body play in health and in the development of disease. An altered
microbiome may cause not only gastrointestinal problems but also
immunological and brain dysfunction. As the world's largest and most
advanced academic center in microbe discovery, identification and
diagnosis, the Center for Infection & Immunity at Columbia University
is optimally positioned to embark upon the challenge to determine how
bacteria, fungi, viruses and toxins (and the immune response to them)
contribute to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME).
Discoveries in these areas may point us toward treatment strategies
that reduce vulnerability through exclusion diets, probiotics or

The goal of this effort is $1.27 million by December 31, 2014.

Click here to donate now-

Donate to Lipkin's Research

The Lipkin Microbiome Crowdfunding Campaign Launches!
March 27, 2014

An ambitious $1.27m international, patient-led fundraising campaign
storms into action. Sasha invites you to join it!

This week sees the launch of a major new crowdfunding campaign: the
Microbe Discovery Project. The campaign aims to raise $1.27 million
(£760,000; €910,000) by 31 December 2014 to fund world-famous
virus-hunter Dr. Ian Lipkin's ground-breaking study of ME/CFS and the
gut microbiome – our intestinal ecosystem of bacteria, viruses and

The study

The study is spectacular, because of the series of crucial, cumulative
steps that it makes to identify what might be driving our immune
problems and hence our symptoms.

The study will take place at Dr. Lipkin's 60-strong Center for
Infection and Immunity at Columbia University in New York, the world's
largest and most advanced academic center in microbe discovery and

First, blood and faecal samples will be taken from 100 patients who
each fulfil both the Fukuda and Canadian Consensus diagnostic
criteria, and from 100 matched controls. Dr. Lipkin's team will
identify the viruses, fungi and bacteria in the guts of the study
subjects using high-throughput DNA sequencing. They will then
determine the amounts of each microbe using highly accurate real-time
PCR assays that are specific to each microbe.

Next, blood levels of cytokines (immune-system messenger molecules)
will be measured to produce an immune profile for each patient.
Biostatisticians will then analyze the cytokine and microbiome
profiles to identify a potential link to ME/CFS and to define the
relationship between immune markers and candidate microbes. In
addition, the team will develop antibody tests for any microbes that
appear to be related to immune dysfunction.

These stages together will make this a definitive study that has the
potential to produce diagnostic tests for key microbes and to lead to
treatments using drugs, probiotics or exclusion diets.

Some of these treatments, such as exclusion diets, have the potential
to be rapidly adopted without having to go through the lengthy process
of clinical trials and approval by the US FDA and other countries'
health institutions. In the absence so far of any FDA-approved drug
treatments for ME/CFS, Dr. Lipkin's study therefore appears immensely

The NIH falls short

Dr. Lipkin and his researchers have already sought funding and have so
far been unable to fully finance the study. The NIH, of course, has always treated ME/CFS research poorly, giving us roughly $5 million a year to MS's $115 million. Dr. Nancy Klimas has reported that in 2014, the NIH will give $3 million to ME/CFS and $18 million to study male-pattern baldness.

So, with funding to do only 10% of the work for the study, Dr. Lipkin
put out a plea for funds during the 10 September 2013 CDC PCOCA
Telephone Broadcast, saying, "[...] it is probably inappropriate for
me to be passing the hat, but that's precisely what I am doing."

Video: Dr W. Ian Lipkin appeals for support for the ME/CFS microbiome study

One patient makes a difference

Vanessa Li, an ME/CFS patient, heard the broadcast and was so
frustrated that such an important and promising project could be lost
that she decided to start a campaign to crowdfund it. She contacted
Dr. Lipkin's office, gained their agreement for a campaign, and
recruited other patient-volunteers to help.

Her timing for such a crowdfunding project is perfect. During the last
year, patients have learned that together they can raise very
substantial sums extremely quickly if they're donating to a specific
project rather than to a charity's bottomless general research fund.

We've seen patients and supporters in Norway – with a population of
only 5 million – raise $430,000 in 90 days for a clinical trial of
Rituximab and, since then, a slew of US-based ME/CFS crowdfunding
campaigns reaching or exceeding their targets at astonishing speeds:
$213,000 in 31 days for the Canary in a Coal Mine documentary film;
$18,000 in 35 days for the documentary The Blue Ribbon; and $150,000
in 75 days for an Open Medicine Foundation study of Vitamin B12.

It's clear that when patients see a project that inspires them and an
organised campaign gets behind it, the donations come storming in. We
also know that when many small donors get the fundraising total to a
certain level, large donors come forward: this is exactly what
happened when a single donor gave $300,000 to Invest in ME's UK
Rituximab trial for ME/CFS after patients had raised $90,000.

The campaign

To get the fundraising drive underway, the campaign team have created
a Facebook page with news and updates and a website designed to funnel
people straight to Columbia's donations page (if you need help, visit
the campaign website's donations page for instructions). The site
includes a video message from Dr. Lipkin, information about the study
and the scientists, the latest news, updates on the total sum raised,
and suggestions for how you can fundraise and help spread the word
about the campaign, including a template letter you can send to your
local newspaper.

The Center for Infection and Immunity themselves are, of course, also
promoting the study to potential donors via their own social media.

The campaign team have contacted leading bloggers to ask for coverage;
this article on Phoenix Rising alone will reach thousands of readers.
To get the message out even further, the fundraising team will conduct
a mass email and Facebook contact campaign to tell individuals and
organisations in our community about the project and to ask them to
spread the message through their own social networks.

The team have plenty of other plans up their sleeves, which you can
find out about on their website and Facebook page as things start

A rising tide

It's hard to overstate Dr. Lipkin's international reputation – he has
just been awarded the highly prestigious Mendel Medal, given to
outstanding contemporary scientists of the calibre of Nobel Laureates
– and it is also hard to exaggerate what his involvement in our
disease could mean for us. A finding from his laboratory would get the
kind of attention from scientists and clinicians that at present we
can only dream of and has the potential to lead rapidly to treatments.

There is already tremendous excitement about the study in the ME/CFS
community and it's building. A crowdfunding campaign for Dr. Lipkin's
project will attract attention from our own community that other
studies would struggle to get and will allow us to reach out beyond we
few thousand who follow blogs and forums and access the wider world of
ME/CFS patients and beyond, just as Maria Gjerpe's MEandYou campaign
raised the profile of the disease across Norway.

Our donation base will permanently grow. Every other study that we
want to crowdfund in future will benefit. A rising tide floats all

So, donate from anywhere in the world, visit the campaign website,
find out how to fundraise and to spread the word, and join with us.

Dr. Lipkin's involvement gives us an unprecedented opportunity to
change the game. Let's take it!


Given the importance of spreading the word about this major appeal,
Phoenix Rising is happy to permit immediate republication of the
entire article. Please accompany with the following accreditation:
'Article by Sasha, first published on Phoenix Rising:′ Thank you.

Wednesday, March 26, 2014

#1 thing to advocate for

The take-home message from the conference was that the #1 recommendation of CFSAC has always been to have Centers of Excellence -- that's the thing to advocate elected officials for

2014 IACFS/ME Conference -- Jarred Younger on fibro

"I believe there is significant overlap between FM and CFS"
future research and treatment
BAD NEWS: 25% improve over time, 39% get worse
GOOD NEWS: increased scientific interest -- there were 600 papers on fibro last year
Central nervous system? or muscles? brain? spinal cord?
Central Sensitivity Syndrome = brain and spinal cord
pain is our alarm system, and fibro is a broken alarm
the flu produces a sickness response -- your immune system does that to you on purpose
microglia protect us from everything -- they change shape, pro-inflammatory chemicals make neurons make you feel bad -- they function to make you rest so your body can divert all resources to fight infections
what if the microglia dysregulate? get stuck "on"
similarity between fibromyalgia and sickness response hints that they're related
primed, hair trigger, easy to activate, reaction to something that's not supposed to
we can't directly test this, can't get into the brain
CSS? undiagnosed other? SFPN? CSF leak? Vitamin D deficiency?
N.B. -- once you get a CFS/fibro diagnosis, all other testing stops
SFPN -- starts more distant from the heart, and treatment differs from fibro
pain worse, leptin rises -- chicken/egg
brain imaging -- some regions of brain are changing -- pain and emotion areas are shrinking -- this may be an adaptation rather than the cause
PET -- tracer is soaked up by activated microglia -- this has been tested in MS
brain temperature
low dose naltrexone -- prevents microglia from reacting as strongly -- 50%+ improve
ibudilast (AV 411)
some herbs suppress microglia, but this has not been tested in fibromyalgia

2014 IACFS/ME Conference -- Bateman on Fibro

fibromyalgia = amplified pain
American College of Rheumatologists 1990 defined it around pain exclusively
the criteria miss 12% of patients, conversely 19% are told they have fibro but are misdiagnosed
we have learned the limitations of the diagnostic criteria, so they must change
other central sensitivity symptoms: migraine, restless leg syndrome, IBS, etc.
women are 11x more likely than men to have fibro
2-3% prevalence
3-5% of women, 1/2 to 1.6% of men
6-10 million Americans
if a fibro patient has to decrease their activity by 50%, it's CFS -- clinicians generally pick one, whichever is their favorite
Bateman diagnoses FM vs. CFS/FM vs. CFS depending on pain level
Neurontin got a $430M fine for marketing it off-label for migraine and chronic pain, but that did lead to the development of fibro specific drugs
address all other medical conditions
address pain, sleep, mental health, fitness/exercise -- pain is affected by the others
history and exam
preventive screening -- exclude other diagnoses
sleep study
non-fibro pain (e.g., arthritis) will respond to different prescriptions than fibro pain
small fiber peripheral neuropathy (SFPN) is a distinct disease
does not show up on neuro exams -- must be biopsied
CLUES: activity tolerance, sleep problems
response to treatment can be an important diagnostic tool
13 of 20 patients benefited from Lyrica in a study by Alan and Kathy Light
gene expression in responders looks like controls
in non-responders it looks less like controls
Needs work: cause and prevention

2014 IACFS/ME conference -- Bruce Campbell on Pacing

"Stress is a big deal -- including the extra stresses that come from having CFS"

2014 IACFS/ME Conference -- Staci Stevens

Effective Management of Activity Intolerance -- used to be Pacific Fatigue Lab -- now in Ripon CA, with an affiliated site in Santa Ana
The Stigma of CFS/ME
great reception from physical therapist community -- they educated PTs to not overdo us
biological basis for activity intolerance
post-exertional malaise -- "this is not a normal response"
at 24 hours, 85% of controls had recovered from the exercise test -- zero of the CFS patients
at 48 hours, 100% of controls had recovered, but only one of the PWCs
EVERY other diagnosis can duplicate the results on Day 2, EXCEPT us
something is wrong with recovery system, metabolic system
objective measures of fatigue:
VT and peak workload and oxygen consumption
PWC cannot reproduce on Day 2, substantially less than Day 1
this may serve as a biomarker
"a broken energy production system"
Aerobic exercise -- CO2 byproduct, oxygen dependent, 30-36 ATP per unit of glucose
Anaerobic -- lactic acid is byproduct, no oxygen needed, 2 ATP per glucose
she worked with a marathon runner who lost half her capacity with CFS, but her heart rate did not do what a deconditioned person would do -- on Day 2, just walking into the office exceeded her threshold
if you can't talk, that's over the threshold for healthies -- CFS always has shortness of breath
she cannot cure, but can improve quality of life
energy conservation therapy is regularly provided for other sources of fatigue (e.g., cancer)
do not know about oxygen delivery, oxygen utliization
"for you guys, sitting up is like running a marathon"

2014 Conference -- ERISA, Disability and Tort

ERISA -- Everything Rotten Imaginable Since Adam
- Federal Court
- no jury
- no experts
- no testimony
- absence of discretion review assumes deference of employer -- he's had judges tell him "I believe this person is disabled but I have to give deference to the employer, so there's nothing I can do."
- no depositions or written discovery
- must exhaust internal remedies first before filing, and the company can start a statute of limitations on you without your knowledge
29 CFR 2560.503-1(G)
You only get one appeal -- don't write that "I appeal" letter until you have a lawyer, because that letter starts the clock
3 best items of evidence for CFS
CPET -- cardiopulmonary exercise test -- Day 2 will be worse than Day 1, which is unique to CFS/fibro
neuropsych testing -- cognitive problems that are not the result of a mental health issue ["Osler's Web" has a good description of the pattern that Sheila Bastien found -- with depression, results would be lower across the board, but with CFS there's a specific pattern, not every score is lower]
tilt table test
doctors do not know what "disabled" means -- bedridden? -- so ask them to say that you cannot work 8 hours a day, 5 days a week, week in/week out, or that you can't be productive at work
genetics + trigger (infection, trauma, emotional distress)
15-20% of whiplash cases result in fibro
Speaker is S. Krafchick, MPH, JD -- he is willing to work on cases in all states
(206) 374-7370           Fax (206) 374-7377
Krafchick Law Firm
100 West Harrison Street, South Tower, Suite 300
Seattle WA 98119
they will try to argue psych exclusion -- you counter that the physical problems disable you regardless of psych problems
If they claim they exclude psych, self-reported conditions, CFS, complain to the Department of Labor and Department of Insurance
does your policy say "total disability"?  Partial disability may have an 80% cut-off  (i.e., won't pay if you can work 32 hours a week, or 4 days a week, but will pay if you can work less than that)

Treatment of severe patients -- Dr. Lapp's lunchtime lecture

In order to fit in everything they wanted to tell us, Dr. Lapp even spoke during the lunch break.  I missed a few minutes at the beginning by going out to get some food.
treat the sleep problem first
tell the patient that the pain cannot be totally relieved
there are only 13 papers on the severely ill
Cardiac Output -- Peckerman AmJMedSci 2003; Hurwitz ClinSci (London) 2009
Should we treat for mild congestive heart failure?
hypovolemia -- rehydrate the blood volume with saline
DON'T ATTRIBUTE ALL SYMPTOMS TO CFS/ME/FM -- You may miss something new
no medication known to help "tired but wired"
He recommends supportive counseling (a "coach"), rarely psychiatry -- help the patient accept and adapt
aromatherapy -- orange for alert, lavender for relaxation
balneotherapy -- mineral bath
prognosis is better for adolescents -- Burgess & Chalder (2011) followed teens, they returned to school full-time (but no gym classes) and gains were maintained at 3 years
Hill/Tiersky/Natelson (1999) -- 23 severe patients, 13 remained severely ill over 4 years

2014 IACFS/ME Conference -- Klimas

she's using immunomodulatory drugs
she's now at an osteopathic medical school, moved from an allopathic medical school -- her treatment is very integrative
look at the genes that are turned on/off in response to exercise
9 million bits of data
computational biologists say that's not much data -- they do modeling analysis
Homeostatic Drive in Perpetuation of Complex Chronic Illness, by Craddock, et al.
3 minutes of exercise, 10 pathways activate -- this is NOT NORMAL
She's mining drug action data -- what drugs do what in other illnesses with similar abnormalities
immune activation and functional defects are dysfunctional
"Rituximab opened the door to autoimmune thinking"
amantidine works on MS fatigue -- low dose naltrexone, too -- CoQ10
Isoprinosone (Immunovir from Newport Pharmacy, Inosine is OTC here) -- available in Canada
Oxidative stress:
alpha lipoic acid
B vitamins
essential fatty acids
there is a close link between the immune system and the autonomic system
In a normal person, exercise brings extra energy to cells, but we turn those pathways OFF
a VO2Max test will tell you your threshold pulse, but then you have to rest all the way back to resting baseline heart rate
"if you can prevent flu, you should" -- if you've been OK with the flu shot in the past, by all means get it

2014 IACFS/ME Conference -- Lapp

"if you try to push, it just makes things worse"
7-9x more likely to have co-morbidities (IBS, migraine, MCS, gluten sensitivity, etc.)
NSRIs, anti-epileptics, each can take pain down 1-2 levels; take them together and you can take it down 4 levels
"there's something magical about lying flat"
dedicated rest period, 10-30 minutes, several times a day
lie down, clear your mind (no lists, no phone, no distractions)
Lapp uses "energy dollars" concept -- you will pay it back the next day, plus a penalty
AVOID sugar, caffeine, alcohol, nutrasweet, and tobacco
DO NOT exceed your anerobic threshold, which is very low in CFS patients.  10-12 minutes is the max you can do.
230 minus your age = the maximum heart rate (e.g., 50 years old, 230-50=180)
anerobic threshold is 0.6x that (180 x .6 = 108)
cut your activity back by 50% if you become symptomatic
multivitamin                        B12
D3                                    magnesium
calcium                            DHEA
Carnitine                            NADH
CoQ10                                Lysine
Ribose                                Methylfolate
Lapp is always taking new patients in Charlotte, but he's not always covered by insurance

2014 IACFS/ME Conference -- Jason

7.4% thought CBT helped, 26% felt worse
GET made more people worse than ANY other treatment
"Staying within the energy envelope" rather than pushing the envelope
symptoms worsen when body and brain are pressured to function beyond their current capability
the battery charges only to 20%, so don't try to function at 100%
benefit from social support and personal assistance -- even just one hour of help per week -- quality of life is improved, symptoms decrease -- this was patient-driven intervention: some needed conversation, some needed shopping/chores -- "This is what patients need/want, why is it not available everywhere?"
changes in physical function with CBT/relaxation/non-pharma intervention were modest -- few experienced remission -- Jason's 2008 study -- lowered T&B cells, increased NK cells -- the most severe did not improve -- the people who were healthiest got improvement
Q&A --
Lyndonville kids who PERCEIVED themselves as "pretty good" were still "incredibly symptomatic" -- compared to as sick as they were, they were better, but not normal

IACFS/ME Conference -- Friedberg on Coping

a BALANCED lifestyle, regardless of severity
- reduce stress
- increase social support and pleasant experiences
- balance activity level
"Rest does not mean doing nothing.  Rest is repair."
if you're not asleep in 20 minutes, get up and do restful activity till you feel sleepy
resolve anger -- minimize your expectations of support [or, as I've often said, "Blessed is she who expects nothing, for she shall not be disappointed."]
However, "I have the right to ask for help and support."  [But, as many people around me fail to understand, "asking ain't getting"]
managed is not the same as cured
Lifestyle has nothing to do with it
If you'd like to be part of Fred's fibro study, home-based pain self-management EMDR, which pays up to $160, contact Elaine Beun, RN, 855-221-4884

2014 IACFS/ME Conference -- Komaroff

There is biological evidence of CFS -- don't let anyone tell you it's psychological
We have evidence of:
Neuroendocrine dysfunction -- impairs multiple axes, including cortisol, prolactin, growth hormone, and serotonin
Cognition -- speed, memory, and attention
Autonomic dysfunction
MRI abnormalities
SPECT abnormalities
EEG abnormalities -- sharp/spike waves, even more so than with seizure disorders; distinct spectral coherence pattern
over half of the brain shows delta waves (sleep) even when the patient is awake, which means lower alpha waves -- need to wake up the brain -- conversely, there is intrusion of alpha (awake) waves when asleep.  Not enough deep delta wave sleep, which may be why there are delta waves during waking hours, brain fog
Leptin was the most distinctive difference -- it's made by fat cells, depresses appetite -- now found in all sorts of bioprocesses
Alan Light found relationship of gene expression after exercise to severity
autoantibodies -- increased B cells, ANA (autoimmune response), anti-cardiolipin, etc.
genes involved in inflammation
They've found an immune system activation in or near the brain and the nerves that lead to it
Various viruses: EBV, post-Q fever, Ross River virus, Lyme, Parvovirus, Enterovirus, HHV6 (Lipkin ruled out Borna virus and XMRV)
HHV6, like Epstein Barr, is ubiquitous, 95% of the population has it
There is now solid evidence that CFS can follow a new infection, cases are triggered by infection.  11% of EBV, Q fever and Ross River virus patients in rural Australia resulted in CFS.
Dysregulated immune response -- genetic -- rather than a single virus
still no approved treatment, but some small recent RCTs show promise: tricyclics, dual reuptake, gabapentin, Lyrica, etc.
Rituximab -- 67% versus 13% with placebo -- no adverse effects -- 25 weeks response -- small trial, only 15 patients
Montoya uses valganciclovir -- most but not all measurements improved
several different illnesses, or at least subgroups
No proven treatments -- can only be treated when its biology is understood
There is ROBUST EVIDENCE of biological processes: brain, autonomic nervous system, immune system, energy metabolism, oxidative and nitrosative stress
Q&A -- the manufacturer's Provigil for narcolepsy trial used the usual dose, not low dose -- 70% of the patients refused to complete the study because of the side effects
NK cell is not diagnostic -- not in 100% of patients -- very expensive
there are autoantibodies in many patients but not all -- can't say if it's autoimmune
antivirals -- he would not use them until trialled -- simpler herpes drugs like Valtrex have helped, but no justification for advocating them
more cortical/subcortical and fewer basal ganglia in Komaroff's studies, but others found the reverse -- in the same patient, location of the problem can move around in the brain

Conference: Translating Science into Clinical Care -- Lipkin

Lipkin notes that Montoya lets the data drive the research, rather than hypothesis.  Some researchers will tweak the data to prove what they want to prove, but not Montoya.  "We have people who are wedded to organisms", but Montoya is correct, to let the data lead.
Even when research fails, we ARE excluding causes.  Just by doing that we're getting closer to what it might be.  Every time we test and DON'T find something, it can be just as important as what we do find.
The cost of human genome sequencing is coming down.  It's now $1800 / 1400 euros.  Which means they're doing more of it.
Central nervous system auto-antibodies / bacterium-induced mental illness
Sometimes what looks like an infection is not -- it can be an "intoxication" that results in an autoimmune disorder.  He noted that in a slaughterhouse, the workers who were exposed to myelin had an autoimmune response.
Some people respond to carbohydrate reduction, some don't -- different body chemistry means different food reactions.  So just because your friend had success with dietary changes does not mean you will.
Absence of evidence of Borna virus in Swedish patients with CFS -- J.Neurobiology 1999
retrovirus 85%, annellovirus 75%
IL17 and IFNy in patients sick less than 3 years, higher; but Eotaxin in all patients
In the Q&A, Lipkin stopped seeing patients in 2001; he's now mostly the spokesman for the researchers.  But, in response to a specific question, "I'm pretty good on neuropathy"
70% of encephalitis is untestable -- only a post-mortem brain biopsy will find it
There is zero evidence that XMRV infects humans
There is 5x the risk of autism if the mother has a fever in early pregnancy
If there were a single agent, someone might have found it by now.
We need to look in other places.
The agent need not be replicating -- it could be something that acts one time and serves as a trigger for an autoimmune response.

March 2014, 11th Biennial IACFS/ME Conference -- Montoya

Montoya opened the conference with a brief welcome.  He is an infectious disease specialist.
His hope is to find a cure.  Stanford's mission statement is to become a Center of Excellence and "solve this mystery disease".
In the US alone, CFS costs $7B a year in medical expenses, $20B a year of lost productivity
He notes that cytokines are of interest:
50 cytokines increase with the severity of the CFS, but the one that helps inflammation is the only one that decreases -- "a perfect storm"
Montoya came back later in the day for a full presentation.  (N.B., the patient conference, which I attended, had 15-20 minute presentations on the same subjects that the professional conference at the other end of the hall had hour-long presentations on.  So, if you want more information on any of these topics, check Phoenix Rising's coverage of those in-depth presentations.)
AVOID AT ALL COSTS PUSH/CRASH SYNDROME -- this got a chuckle from many patients who knew we were push/crashing just to attend the conference.  "Biological destruction results from crashes."
"An infectious trigger and perpetuator is likely"
After verifying the patient really does have ME/CFS instead of a lookalike, he would try an anti-viral, but for now he's reserving IV antiviral until all else fails.  Valganciclovir -- start with the lowest dose and increase as tolerated.  Dramatic worsening with higher dosage.  Improved response with longer treatment (at least 4 months, up to a year).  The trial in the 1980s was only 5 weeks and therefore did not work.
Herpes types:
Herpes Simplex 1 and 2
HHV 3 -- Varicella/shingles
HHV 4 -- Epstein Barr
HHV 5 -- Cytomegalovirus
HHV 6 -- almost 100% of people have HHV6
HHV 7 -- rare
HHV 8 -- Kaposi's sarcoma, rare
Foscarnet decreases delta waves

Day Three conference summary

Phoenix Rising

Day Three, and 'Searcher' continued to deliver the goods. We hear about the
PANDORA national survey results, a very big familial case study from Spain,
results from the Canadian Community Health Survey, more results from
epidemiological studies (and a look at treatments and comorbidities), then
perhaps the key section of the day: the science of exercise testing and
post-exertional malaise...

Read more:

Day Four conference summary

Phoenix Rising:

It is Day Four and the final conference session from San Francisco. In this
review we hear from 'Searcher' about the neurosciences session, and PET and
EEG analysis, then a study on cognitive functioning, followed by a debate
on the revised 2014 IACFS/ME Primer, and then we wrap-up the conference
with a terrific summary from Dr. Antony Komaroff...

Read more:

Bioethics and ME tweet chat April 7

There will be a twitter chat open to all to participate on bioethics and ME early April thanks to the curiosity of Jennifer Chevinsky, a medical student who hosts weekly bioethics chat on Twitter on Monday evenings.

Following exchange of emails with a few patients and Jennifer we agreed to chat using the following questions:

1. Are there ethical or societal effects of calling the disease Myalgic Encephalomyelitis versus Chronic Fatigue Syndrome? How do disease names affect perceptions?

2a. Myalgic Encephalomyelitis is often misdiagnosed and/or mistreated. What additional harms can misdiagnosis and/or mistreatment expose individuals, healthcare professionals, and society to?

2b. A Patient with Myalgic Encephalomyelitis has been held in a Denmark psychiatric facility since February 2013 against her will. What conditions should be met to ethically commit a patient?

3a. Myalgic Encephalomyelitis is not 'rare,' but it can be considered unpopular. What makes (or should make) a disease more likely to get funding or research money?

3b What makes (or should make) a disease more likely to be taught in medical education? How does it affect the patient population if it is not taught?

T4 How can you, patients, health care professionals, and/or others help remove stigma from diseases such as myalgic encephalomyelitis? What's one thing you have learned tonight?

These chats attract health care professionals, ethicians, and the general public. You are welcome to join in the dialogue and share your ideas. All you need is a twitter account! It is an opportunity to raise awareness, and there are big chances that many will learn about ME and its devastation at the personal and societal levels.

In order to participate in the chat at forementioned time, all of your tweets need to include #bioethx in them.

A few website facilitate twitter chats including You will need a twitter account and log in information, enter the hashtag (bioethx) and enter the virtual room.

There are many Twitter Chats available as it related to health care. You can visit to look up the different chats and their schedule. I highly recommend you experience a tweet chat before April 7th. It is also a great opportunity to increase your contacts outside our patient community and speak out about your experiences as it related to the tweet chats. Sunday evening's #HCSM (health care social media) are usually fun and general in nature.

There are common sense rules when taking part to a tweet chat.
1) Answer the questions with their number A1, A2a, A2B etc
2) Stay on topic, and engage in the discussion. Have fun!
3) Make sure you have the #bioethx in your tweet otherwise it is not seen by others in the chat or recorded. Other hashtag of use are #mecfs #neuroME #CDC #HHS #NIH #meded #hcldr (health care leaders)

Twitter can be powerful as you can direct advocacy to interest groups, like the NIH and CDC for instance, Dr Frieden at the CDC has an account.  The Center for Infection and Immunity (@CII722) (Columbia university) has a twitter account and tweets about ME. We can increase awareness by engaging with different groups and people outside our community. Twitter does that.

The chat will be recorded and will be available afterwards if you missed it. I will update as available.

Share widely and join us on April 7th at 5:30 EST!

Feel free to add me on twitter @Katiissick

Changing Tactics by Jennie Spotila

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Occupy CFS
Occupyng CFS since 1994

Changing Tactics

March 24th, 2014

Jennie Spotila

For decades, ME/CFS research and clinical care has
been plagued by disagreement over the basic
classification of the illness.

Is ME/CFS a physical disease, as many patients and
researchers insist?

Or is it a mental health disorder perpetuated by
deconditioning, as argued by the psychosocial school?

There is growing rejection of the psychogenic
explanation for ME/CFS, but it is not disappearing. In my
view, the psychosocial school is simply changing tactics,
and this is a trap that we must avoid at all costs.

Transforming the Argument

The hypothesis that ME/CFS is a mental health issue has
been disproved by the data. For years, the psychosocial
school has claimed that CFS patients had poor coping
skills and were simply deconditioned.

All we needed to do was increase our physical activity
(GET) and ferret out our dysfunctional illness beliefs
(CBT), and we would recover.

While the PACE trial and other research has been based
on this premise, we have ample data that cuts the
theory off at the knees.

The two-day CPET (cardiopulmonary exercise testing) results cannot be faked, and distinguish ME/CFS patients from sedentary controls.

Gene expression studies have also shown a distinct pattern of response to exercise in ME/CFS patients compared with sedentary controls and patients with other illnesses.

Evidence, including imaging, spinal fluid, and immunological testing, has mounted to the point where Dr. Anthony Komaroff declared that the debate over back in 2006.

But the psychosocial school has not relented and I now
see a change in their tactics. Instead of insisting that
the illness is psychological, they are waving their hands
and saying that the psychological v. physical debate is

I offer two recent examples:

First, there is the systematic review of ME/CFS case
definitions by Brurberg, et al. (,
which I reviewed in detail in my post Systematic
Overreaching (

The authors stated:

       It is likely that all CFS/ME case definitions capture
       conditions with different or multifactorial
       pathogenesis and varying prognosis. The futile
       dichotomy of 'organic' versus 'psychic' disorder
       should be abandoned.

       Most medical disorders have a complex aetiology.
       Psychological treatments are often helpful also for
       clear-cut somatic disorders.

       Unfortunately, patient groups and researchers with
       vested interests in the belief that ME is a distinct
       somatic disease seem unwilling to leave the
       position that ME is an organic disease only.
       This position has damaged the research and
       practice for patients suffering from CFS/ME.

As I said in my comment on the article published on BMJ
Open (

"The authors presented no evidence to support their
accusation that the organic disease -only position has
damaged research and clinical practice.

Furthermore, they completely ignored the very real and
logical possibility that the reverse is true.

In other words, it is equally possible that the people with
vested interests in the belief that ME/CFS has
psychosocial causes are unwilling to leave that position,
and have damaged the research and practice for
patients suffering from the disease."

Second, the recent report on the case definition for Gulf
War Illness ( included the following
discussion of the mental v. physical debate:

       Like CMI and many other symptom-based illnesses,
       ME/CFS is not without controversy, particularly
       regarding whether they are mental disorders or
       physical health disorders [cite to IACFS/ME

       The committee notes that this either-or approach
       is not useful, for several reasons. The distinction
       between mental and physical disorders is often
       arbitrary, and most patients' experiences of any
       illness are influenced by biologic, psychologic, and
       social factors.

       Either-or thinking leads too often to a presumption
       that medically unexplained symptoms must be

       In addition, psychiatric [sic] symptoms may not be
       fully evaluated if a patient's symptoms are
       psychogenic. Although physical and psychologic
       stress can exacerbate many chronic conditions –
       including chronic pain, headache, respiratory, and
       gastrointestinal symptoms – there is an inherent
       risk in assuming that medically unexplained
       symptoms assume a "stress-induced" etiology.

As in Brurberg, et al., there is no rejection of the
psychogenic theory of ME/CFS. Instead, we're told to
abandon the debate.

It's not either-or, it's both. Let's stop arguing about the
evidence, and go with a holistic view (that still includes
the psychogenic theory).

It's A Trap

Do you see what's happening here?

The ME/CFS psychogenic school is wrong – as shown by
all the data that indicates biological abnormalities that
are not seen in sedentary controls or people with
depression or anxiety.

But instead of admitting the error, they are simply
changing tactics. Now they are saying that it's
psychological AND physical, and the distinction does not
matter anyway.

Contrary to this new angle on psychosocial explanations,
I believe it matters a great deal whether ME/CFS (or
GWI) is a mental or physical disorder.

The distinction between mental and physical is not
"arbitrary," but can be drawn based on signs and

I readily admit that my emotional state and coping skills
have had an impact on my experience of this disease,
but I completely reject the premise that therefore the
distinction between mental and physical does not
matter. It does.

People with mental health issues are primarily treated by
psychologists, and in ME/CFS that usually means CBT
and GET.

We know that GET can have serious and long-lasting
negative effects on ME/CFS patients.
For decades, ME/CFS patients have endured dismissal and worse because of the psychogenic view of the disease.

To say the distinction does not matter is foolish, at

The practice of medicine is structured around that
duology. There are medical diseases treated by
physicians, and there are psychological diseases
diagnosed with the DSM-IV (soon to be DSM-V) by

In the middle are psychiatric diseases like schizophrenia
which are known to be biological, but are treated in the
mental health setting because the symptoms of disease
are behavioral.

Mental health diagnoses are treated differently by health
and disability insurance.

There is a difference between the physical and
psychological attributions of illness: in health care, in
benefits, and in social views.

If the mental-physical duology no longer applies,
shouldn't that be true of all diseases?

If "patients' experiences of any illness are influenced by
biologic, psychologic, and social factors," then I suppose
we are abandoning the dichotomy in cancer, heart
disease, and multiple sclerosis too?

I don't know about anyone else, but I don't hear anyone
suggesting that those diseases are psychogenic in any
way. I have family members who have endured MS, cancer and heart disease.

Stress can make those diseases harder to manage, and even exacerbate the underlying disease process.

But no one would ever say "let's abandon the either-or thinking and agree it's biologic and psychologic."

No way.

Those diseases are accepted as physical in origin, with
implications for behavior and coping. I believe that I
deserve the same respect.

Bias and Decision Making

I've described the psychosocial school as changing their
tactics, but I don't necessarily believe there is a
smoke-filled room where a cabal of psychologists sat
down and said:

"We're losing the argument so let's use these talking
points instead."

I think the shift may be the result of cognitive bias and
the difficulty humans have with admitting they're wrong.

If I am a psychologist and I've invested 10 or 15 years in
the theory that CFS is the result of poor coping skills
and deconditioning, it's going to be hard to change my

Despite mounting evidence that my theory is wrong, it
will be hard to let it go. An easier step is to say that I'm
not completely right but also not completely wrong.

It's not either/or, it's both.

ME/CFS patients have gone through this process
themselves. When the XMRV paper was published in
2009, many patients seized on the results.

We had very good reasons to do so, and at first, the
science and scientists seemed to support that position.
But as contrary data emerged, and hard questions were
asked, some scientists and patients found it very
difficult to follow that data.

They continued to insist that it was XMRV, and when
that was disproved they claimed it was HGRVs. And
when that was disproved, they claimed the science
hadn't been done right or there was a conspiracy or
there were unidentified retroviruses at work.

And it was three years before Dr. Mikovits finally took
the courageous step of publicly admitting her
conclusions had been wrong.

Nobody likes to admit a mistake, and the more you have
invested in that mistake the harder it is to admit it.
The psychogenic explanation of ME/CFS is wrong, but
instead of admitting the mistake, some scientists are
shifting gears and saying that it's not completely wrong
because the physical-psychological divide doesn't
actually matter.

They are not following the data, and they are
attempting to twist the dialogue so they don't have to
admit they are wrong.

Drawing the Line

The divide matters, and I will not be drawn into a
compromise view.

ME/CFS is a physical disease with physical causes. My
emotions are relevant to my ability to cope with this
physical disease, just as emotions are relevant to coping
with cancer or AIDS.

But I reject any hypothesis that leaves the psychogenic
view on the table.

Not because I don't want to face up to having a mental
illness. Not because I want my disease to be physical.
Not because I am personally prejudiced against mental
illness and not because I don't see the relevance of
emotions in physical health.

I reject the psychogenic hypothesis because the data is
not there.

I had a happy childhood. I had a satisfying career and personal life. I enjoyed being physically active. Then I got sick. And despite my strong desire to continue in that career, that personal life, and that physical activity, I have not been able to do so for almost twenty years.

The reasons why my life was destroyed matter.

The cause of that destruction matters.

To say that the distinction between physical and
psychological causes is arbitrary and irrelevant is to
dismiss my experiences.

It may save face for the psychogenic school, but it is a
slap in mine.

I challenge the researchers and decision makers to admit
their errors, and get on with the business of finding the
answers that will repair my body and my life.

Copyright © 2012-2014 Occupy CFS

PEM, NOT Chronic Fatigue, is why patients
  are bedridden, homebound, unemployed,
         and unable to walk a block.

Neuroinflammation in CFS

J Nucl Med. 2014 Mar 24. [Epub ahead of print]
Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic
Encephalomyelitis: An 11C-(R)-PK11195 PET Study.
Nakatomi Y1, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K,
Fukuda S, Kawabe J, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K,
Inaba M, Kuratsune H, Watanabe Y.

Author information

1Department of Metabolism, Endocrinology and Molecular Medicine, Osaka
City University Graduate School of Medicine, Osaka, Japan.


Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a
disease characterized by chronic, profound, disabling, and unexplained
fatigue. Although it is hypothesized that brain inflammation is
involved in the pathophysiology of CFS/ME, there is no direct evidence
of neuroinflammation in patients with CFS/ME. Activation of microglia
or astrocytes is related to neuroinflammation.
(11C-(R)-PK11195) is a ligand of PET for a translocator protein that
is expressed by activated microglia or astrocytes. We used
11C-(R)-PK11195 and PET to investigate the existence of
neuroinflammation in CFS/ME patients.

METHODS: Nine CFS/ME patients and 10 healthy controls underwent
11C-(R)-PK11195 PET and completed questionnaires about fatigue,
fatigue sensation, cognitive impairments, pain, and depression. To
measure the density of translocator protein, nondisplaceable binding
potential (BPND) values were determined using linear graphical
analysis with the cerebellum as a reference region.

RESULTS: The BPND values of 11C-(R)-PK11195 in the cingulate cortex,
hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199%
higher in CFS/ME patients than in healthy controls. In CFS/ME
patients, the BPND values of 11C-(R)-PK11195 in the amygdala,
thalamus, and midbrain positively correlated with cognitive impairment
score, the BPND values in the cingulate cortex and thalamus positively
correlated with pain score, and the BPND value in the hippocampus
positively correlated with depression score.

CONCLUSION: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

KEYWORDS: 11C-(R)-PK11195, chronic fatigue syndrome (CFS), myalgic
encephalomyelitis (ME), neuroinflammation, positron emission
tomography (PET)

PMID: 24665088 [PubMed - as supplied by publisher]

SF Chronicle article about IACFS Conference

Doctors, drugs slowly coming around to chronic fatigue
Erin Allday
Published 4:39 pm, Tuesday, March 25, 2014

In a conference room at San Francisco's Parc 55 Hotel, a hundred or so
people, most of them patients with chronic fatigue syndrome, were
listening to a panel of doctors talk about treatment options.

Eventually, panelists would talk about the potential of antiviral and
immune-modulator drugs. But first came Dr. Charles Lapp, who runs a
treatment center in North Carolina focused on chronic fatigue and
diseases thought to be related to it.

"We have no known cause, no cure," Lapp told the crowd. "I feel
patients do best when they accept the illness - when they accept that
they're a new person, with new energy levels and new limitations."

There were a few nods around the room, but not much reaction
otherwise. One woman lay sprawled across two chairs, her eyes closed.
Another propped her feet on a chair and rested her head against a

The patients attending last week's conference - a biennial meeting of
the International Association of Chronic Fatigue Syndrome/Myalgic
Encephalomyelitis - had heard it before. Their condition, despite
being recognized by global and national health agencies for several
decades, is still largely misunderstood and often very difficult to

Chronic fatigue syndrome - also known as myalgic encephalomyelitis, or
ME - is thought to afflict up to a million people in the United States
with a broad range of symptoms, the most notable of which is intense,
debilitating fatigue.

Other symptoms are varied and often associated with more common, and
more easily diagnosed, diseases. Patients may suffer muscle and joint
pain, overall weakness, insomnia, and cognitive impairments that are
commonly described as a "brain fog."

Struggle for diagnosis

For decades, chronic fatigue syndrome was at best ignored by doctors
and scientists alike. Many doctors refused to believe it was an actual
disease, and those who did buy it were convinced it was a mental
illness, not something with a biological basis.

The medical field has come around slowly, but patients say they still
struggle to be diagnosed, because there are no simple test results or
exams to identify the disease. And once they get a diagnosis, there's
not much that medicine can do for them.

Doctors don't know what causes chronic fatigue syndrome - it could be
triggered by an infectious agent like a virus or be due to an
overactive immune reaction. Some people may be genetically predisposed
to getting sick. There may be environmental factors too.

"People want to define this illness better, but research is pointing
us in different directions. It hasn't coalesced around a certain
theme," said Fred Friedberg, a researcher based in New York's Stony
Brook University who is president of the international chronic fatigue

"I think it must be multifaceted," Friedberg said. "I don't think
we're going to get a smoking gun."

Lacking treatments

No federally approved treatments exist for chronic fatigue syndrome,
and there have been few trials looking into drug therapies. When drugs
show some promise in small studies, the results have proved difficult
to reproduce in larger trials.

So most patients get by with coping strategies - like learning to pace
themselves to maintain stable energy levels - or dietary changes.
Patients and the handful of doctors specializing in the disease have
been clamoring for money for research and support, but the condition
is still largely ignored by many of the largest funding agencies and
research institutions.

Resistance lessening

"For a long time institutions have been infected by this view that CFS
wasn't to be taken seriously," said Dr. Jose Montoya, an infectious
disease specialist who helped establish a chronic fatigue syndrome
team at Stanford School of Medicine almost a decade ago. "In the
beginning, when I started my research in this, the reaction was people
rolling their eyes, laughing at me. People would say I was committing
career suicide."

That's changing, but slowly, Montoya said. Just last week, after a
daylong meeting of scientists and patients at Stanford, Montoya said a
dean in the medical school took him aside and said, "Jose, what you're
doing is valid, it's important."

"They're not giving us the resources, the money yet," Montoya said.
"But just having that support is a big deal. At least we're not
getting active resistance."

Montoya is the lead investigator for a study that opened this year
looking at a combination treatment of the drug Ritalin and a nutrient
supplement. The treatment was developed by a Mill Valley physician,
Dr. Jon Kaiser.

Double-blind trial

The trial, which will enroll about 100 patients, is placebo-controlled
and double-blind, so patients and doctors won't know who's getting the
drugs and who isn't. Kaiser, whose company K-Pax Inc. is supplying the
nutrient supplement and funding the trial, hopes to have results early
next year.

Kaiser said he's given the drug therapy to some of his own patients,
who were positive enough about the medication that he was encouraged
to put money into a formal trial.

One of Kaiser's patients, Lisa Geiszler of Santa Cruz, started taking
the Ritalin-combination therapy a year ago and said she's noticed
significant improvements in her energy level and her ability to think

Geiszler was a serious cyclist and teacher specializing in literacy
training before she became sick in 1997. She eventually had to quit
her job and was frequently bedridden for days or weeks at a time. Just
a walk down the street was beyond her ability.

"Now I've noticed some cognitive improvements. It's easier to
comprehend what I'm reading. I'm able to remember more things," said
Geiszler, 47. "I can walk eight minutes a day. I no longer need any
help with the shopping, the cooking, washing.

"My life was very restricted and very small for a long time, and it's
radically changed," she said.

They've seen it before

But other doctors and patients remain skeptical. They've seen other
drugs show promise in the past. It's not unusual, patient advocates
said, for a drug or other treatment to appear beneficial based on
mostly anecdotal reports, but fail in clinical trials.

Last year, the U.S. Food and Drug Administration rejected one drug,
called Ampligen, over protests from many patients who said their
condition had improved while on the medication. The FDA said it needed
more proof.

"If you could offer up any treatment, at least to a subset of
patients, that would be so helpful. Even if you could help somebody
just 20 percent, give them a little bit more energy, that would be
huge," said Susan Kreutzer, a Danville woman with chronic fatigue
syndrome who has gone to Washington, D.C., multiple times to request
more funding for research.

'I have to pace myself'

For the most part, what's worked for her are coping strategies - or as
Dr. Charles Lapp said at the meeting last week, learning ways to live
with her illness.

"I have to pace myself. I have to rest a lot," Kreutzer said. "My
friends would say I'm doing much better these days. But I still have a
lot of the cognitive problems when I'm tired.

"You wouldn't want to put me in charge of anything," she said with a laugh.

Erin Allday is a San Francisco Chronicle staff writer. E-mail:

Sunday, March 23, 2014

Biotech company could be on verge of finding a cure, treatment for fibro

Dr. William "Skip" Pridgen has done research on fibromyalgia for about 15 years while working full-time in his surgical practice, Tuscaloosa Surgical Associates PC. His research has led to a possible new drug and treatment that might someday provide a cure for fibromyalgia.
Pridgen and Carol Duffy, who has a doctorate in virology and is an assistant professor in biological sciences at the University of Alabama, have developed a drug and treatment they believe might cure the problem.

Two trial phases to test their drug and treatment have shown some promising results, said Pridgen ... Phase 3 will not be cheap and will take two to three years to complete

... they theorized that the pain could be caused by a herpes virus that weakens the immune system.