You are here: Simmaron ResearchConferencesME/CFS Physicians Roundtable I: ME/CFS Docs Talk Diagnostics and More at the Simmaron Foundation Roundtable

ME/CFS Physicians Roundtable I: ME/CFS Docs Talk Diagnostics and More at the Simmaron Foundation Roundtable

June 18, 2013

Listen in on the field’s top experts at your own pace here!

(Thanks to Anita Patton for her notes from the Roundtable talk)

FDA-Stakeholders-MeetingSimmaron likes to get people talking.  At just about every conference I’ve been to recently, the Simmaron Foundation has rented a room, brought in some food and got patients, doctors and researchers talking.  This time at the FDA Stakeholder’s Meeting they pitched Dr. Peterson, Dr. Klimas, Dr. Lapp and Dr. Enlander questions around a physician roundtable and took questions from the patients present.  We learned a lot in the off-the-cuff wide-ranging discussion that followed.  In this blog we’re going to look at how these doctors diagnose their patients and next up we’ll look at treatment.

Redefining ME/CFS

PetersonPhoto right

“We are on the verge of better diagnostics.” Dr. Peterson

Diagnostics always come first. Before you can treat you must be able to diagnose. Unfortunately the diagnostics in chronic fatigue syndrome have been shrouded, vague, symptom-based definitions. From the myalgic encephalomyelitis to the Holmes to the Fukuda to the Canadian Consensus Criteria,  the chronic fatigue syndrome field has been grasping for definitions for as long as it’s been around.

Problems on the macro level (the definition), of course, lead to problems at the micro level ( the doctor’s office) where  ME/CFS doctors are deluged with all different kinds of ‘chronic fatigue syndrome’ patients. That uncertainty – not knowing just who might step in the door –surely makes for an interesting job.  The qualifications for a good chronic fatigue syndrome physician may look something like this…. good listener, not daunted by complexity, loves to problem-solve, has a wide range of knowledge and is flexible and  willing to try new things…

As Bernard Munos pointed out at the FDA Workshop, in a disorder like this which has few clinical trials, the physicians, more than anyone else are the innovators. Not able to rely on clinical trials, their offices are an ongoing clinical trial.

How Dr. Peterson, Dr. Klimas and Dr. Enlander made sense of their ME/CFS patients was what the first part of the Simmaron Foundation’s Physician Roundtable was all about.  Listening to how the different doctors approached ME/CFS was fascinating.

“I am very concerned about random drug trials that take the first 100 patients who sign up.  It would be a disaster.” Dr. Peterson

Given the many different types of patients Dr. Peterson sees, the idea of drug trials that don’t subset first is simply appalling. The idea that this complex mix of patients are ever going to respond similarly to a drug is nonsense.

For Dr. Peterson, who sees the complexity of the illness daily, diagnosis, whether in a research study, clinical trial or a doctor’s office, always comes first. Since the same symptoms can be produced by many different factors, symptom definitions, while helpful, will always have flaws. What’s needed is to ‘scientifically redefine ME/CFS’; that’s the Simmaron Foundation’s stated goal and each of these physician/researchers is working towards that.

Now onto diagnosing ME/CFS.

Immune System

Dr Enlander

“Like Dan and Nancy, we look at the patient as an immune system problem in order to develop idea of diagnosis.”  Dr. Derek Enlander

Dr. Peterson started off by stating that after screening for the ‘obvious stuff’ he goes after immune markers, primarily focusing on the NK, T and B cells.

Over time he found consistent patterns began to emerge with natural killer (NK) cells playing a major role. (These cells, which play a major role in the early, innate immune response, appear to be ground zero for the immune problems in ME/CFS.  Unfortunately, they’re not particularly well known in the medical community.  Dr. Peterson’s poll of his colleagues in his area a couple of years ago found that few knew anything about them.)

It doesn’t help that natural killer cells are tricky to work with and need to be assessed within four-six hours of sample collection. In an attempt to make them more user friendly, Dr. Peterson is experimenting with freezing live cells in liquid nitrogen.Nancy Klimas

“We are the Gold Standard” Dr. Klimas

Being an immunologist it wasn’t surprising to see Dr. Klimas’s strong focus on the immune system. With one of the top immune labs in the country, Dr. Klimas is at the center of a lot of immune work.

Immune factors are one lab measure you’ve got to get right; tweak the powerful immune system the wrong way and you can cause a lot of trouble. If you’re  using immune altering drugs, and both Dr. Peterson and Dr. Klimas do, the ability to trust your lab is critical. Dr. Klimas said her immune lab is the ‘gold standard’ and Dr. Peterson gets all his cytokine arrays done at Dr. Klimas’s lab.

Dr. Klimas will dig into IGG subclasses if she sees bacterial infections. Dr. Enlander focused on much the same factors;  CD4 and 8 ratios, NK cells and function, (IL2, IL4, IL10) and uses bacterial cultures to rule out other disease entities, like Lyme, etc.

Pathogens

Pathogens were discussed briefly. All three physicians were testing for them (eg; EBV, HHV6, CMV, Parvovirus, Coxsackie and bacteria)  but there were some differences. Dr Enlander did not see a relationship between viral load and disease severity, something that Dr. Peterson, as we’ll see later has found, at least with one group of patients. Dr. Klimas has not found HHV6 to be a good marker either as patients don’t test positive consistently; in fact, she called ME/CFS a ‘good day, bad day viral disease’ as patients may test negative on a good day and positive on a bad one. That’s helpful for her as a physician but is not good enough for the FDA to test treatments against. The FDA needs a test that’s consistently positive.

InfectionsWhat does Dr. Klimas find that tracks with severity?  Natural killer cell functioning and IL-5 levels  might be two markers the FDA could use to assess treatment effectiveness.

We don’t hear alot about IL-5 cells but they boost two immune factors of interest in ME/CFS; mast cells and B-cells.  Overactive B-cells cause autoimmune disorders and, of course, also  harbor EBV as well.

Dr. Enlander will be seeking to confirm/deny Dr. Chia’s enterovirus findings in his exercise study (see below.)

Autonomic Nervous System

With Dr. Peterson stating the amount of autonomic nervous system dysfunction in ME/CFS was ‘huge’ the stage was set  for the autonomic discussion. All three doctors do blood pressure and pulse testing with Dr. Peterson and Dr. Enlander doing 24-hour BP and heart testing, and Dr. Enlander and Dr. Klimas use tilt table testing. Dr. Klimas noted that an autonomic nervous system dysfunction appears to trigger immune dysfunction. She asserted that the sympathetic nervous system a major, major symptom generator in this disorder and she rattled off problems with standing, respiration, poor digestion, etc. that could all be caused by SNS overactivation.

Nervous-SystemIt’s not clear how many of the physicians were measuring blood volume; it may be that they all simply assume blood volume is low, but Dr. Klimas noted the astounding fact that most patients are about a liter of blood low, or about 20% down from normal. With that little blood running through your blood vessels those blood vessels are going to have to squeeze hard  to get it out to the tissues and brain, and right there you have a good reason for the sympathetic nervous system activation Dr. Klimas talked about earlier.

Dr. Klimas gives blood volume a boost with electrolytes and then puts the patients back on the tilt table to see if they’ve improved.

Dr. Enlander is using Dr. Cheney’s cardiac protocols to measure cardiac output, stroke volume, etc. He does it, interestingly enough in a variety of positions (lying down, standing) giving him a great deal of data on cardiovascular functioning.

With the ANS playing a huge role in exercise, onto to exercise testing we go.

Aerobic Testing

“You do better diagnostics when you do exercise challenges.” Dr.Nancy Klimas.

You probably couldn’t get three ME/CFS physicians more knowledgeable or committed to exercise testing in one room than you had at the Roundtable.

The first ME/CFS physician to embrace VO2 max testing, Dr. Peterson made a strong plug for Staci Steven’s test-retest, two day exercise protocol (the Stevens Protocol. This exercise test grew out of the work she did in Dr. Peterson’s office).

Dr. Peterson uses the most rigorous test of all; the aerobic exercise test to determine how well his interventions are working.   At the FDA Ampligen hearing, Dr. Bateman, noted that the VO2 max test, which measures the amount of energy a person can produce, is the hardest to budge of all ME/CFS tests . Since Dr. Peterson finds that low VO2 max scores are often correlated with poor cognition, abnormalities on MRI’s and spinal fluid as well as autonomic problems, bumping up those VO2 max scores even moderately can mean a significant improvement in functionality and well-being.

Exercise-test-cfs

All three practitioners use exercise testing in for research, disability and/or to assess the effectiveness of their interventions

( I asked Staci Stevens if she knew of any  ME/CFS patients who had returned to full VO2 max functioning and she said yes, some patients on antivirals and Ampligen –coming out of, no doubt given her longstanding connection with him, Dr. Peterson’s office.)

Dr. Klimas has been digging deep into exercise in her research, lately, which, in turn is informing her diagnostic work.  (That’s  ‘translational medicine’).  Earlier this year she reported gene expression studies indicated that the autonomic nervous system tanks first during exercise and then drags the immune system down with it.

This major finding, if validated, suggests breakdowns in the ANS, which is ever so tightly intertwined with the immune system, could be at the core of the disorder.

“Now let me tell you what we are really doing at Mt Sinai…” Dr. Enlander

And then there was Dr. Enlander who’s committing  a big chunk of money to a sophisticated exercise testing study at the Mt Sinai Research Center. He’s got a geneticist, an immunologist and a pulmonologist all working together.

After exercise Enlander’s team will be looking at RNA (genes), blood (immune factors, a stool sample, RNA, DNA genome, enteroviruses), brain MRI and SPECT scan. Amongst other things Enlander will be looking to confirm or deny Dr. Chia’s findings of enteroviruse of seven, yes, seven years ago. That’s seven years without a confirmatory study of a virus that was first linked to ME/CFS decades ago…

Spinal Taps and Brain Imaging

Dr. Peterson does spinal taps  to figure out what’s going on with his most cognitively challenged and neurologically impaired patients. (After decades of gathering spinal fluid, Dr. Peterson easily has the greatest store of ME/CFS spinal fluid on the planet. Dr. Mady Hornig has referred to Dr.Peterson’s spinal fluid as a precious resource).

spinal fluid

Dr. Peterson examines the spinal fluid of his more neurologically and cognitively challenged patients

Spinal taps are where Dr. Peterson, Dr. Klimas and Dr. Enlander part ways to some extent. Both Klimas and Enlander do them at times, but Dr. Peterson does them routinely in patients with neurological and brain issues (and he does them himself).  Dr. Klimas said she was astounded that Dr. Peterson found 17% of his patients’ spinal fluid tested positive for a virus.

Both Drs. Klimas and Enlander may be doing them more in the future. Dr. Klimas is waiting on finding the right neurologist, and Dr. Enlander said he was closely following Peterson’s ideas.  If the CFI and PHANU studies using Dr. Peterson’s spinal fluid are positive, we may see more and more doctors turning to spinal fluid to assist with their diagnoses.

Future -Dr. Peterson looked forward to future medical advances that will help him fine-tune his diagnostic protocols.  Genetic technologies are indicating, for instance, that a genetic predisposition to the NK dysfunction may be present in ME/CFS. On the other hand he also finds ‘acquired’ (ie non-genetic) NK cell dysfunction as well. He believes insights gathered from miRNA’s in the spinal fluid of ME/CFS patients, for instance, and the more rigorous pathogen detection techniques will continue to open up this field and inform his diagnostics.

Similarly, Dr. Klimas’ exercise studies are causing her to focus more on improving autonomic dysfunction, and Dr. Enlander will use his big exercise study to inform his understand of his patients. Each of these three physician/researchers is eager to translate their research findings into their diagnostic protocols.

Undefining ME/CFS?

“There is an entire school of thought in the medical profession that if anyone with chronic fatigue has anything objectively wrong with them – they don’t have chronic fatigue syndrome.” Dr. Dan Peterson

After all the talk about how to diagnose ME/CFS, Dr. Peterson brought up a trend towards ‘undefining’ that he found troubling. Undefining ME/CFS consists of putting ME/CFS patients in a different box as soon as something concrete is found.   Stating that this attitude is more forceful than he ever thought, Dr. Peterson explained that a person with ME/CFS with HHV6A in their spinal fluid will be labeled as having HHV6A encephalitis and be determined to never have had ME/CFS.

ME-CFSDr. Klimas acknowledged that while getting a diagnosis that can be treated is great, as a field winnowing large numbers of patients out of the ME/CFS basket could be devastating. For one it condemns ‘ME/CFS’ to be a  a mere placeholder of an illness.

Dr. Klimas noted Dr. Peterson’s finding that 17% of his cognitively dysfunctional patients were culture positive for viruses in their spinal fluid was a clear subset.  (She was reminded of former CDC CFS chief Bill Reeves response “you don’t know that doesn’t belong there” and she laughed and said “Wait a minute . Would it be ok for you to have your cognitively dysfunctional child culture have positive spinal fluid test? I don’t think so”). What a dilemma it was, she said when every time we start to get clarity, part of this disorder gets shuffled off into another column.

The Hidden Epidemic

“The bedridden patients – It’s the hidden epidemic within another epidemic..It’s scary” Dr. Dan Peterson

And then there’s the missing patients; the bed-ridden ones that rarely get to doctors clinics and certainly aren’t in research studies.  How do you define a disease without access to all the patients?  The most severely ill usually get the most attention in most disorders but the opposite is true in ME/CFS.  (Check out the astonishment from a former ICU nurse working with Dr. Kogelnik at the degree of disability she sees in ME/CFS. These patients, she thought, should be in a hospital, not at home.)

“Talk about a forgotten, ignored group of people.” Dr. Peterson

Dr. Peterson noted that we don’t an accurate count of how many people are in this situation. He didn’t have answers. He noted that you needed staff to get to these people and you needed to find them in the first place. Dr. Klimas answer suggested that funds were at the heart of the problem. Ads for an online CBT study did bring in bedbound patients who were unable to make it to the clinic and funding for the ‘good-day/bad-day’study did allow them to make house-calls on the patients bad days. Both Dr. Klimas and Dr. Enlander said they do do house-calls from time to time. (One of Dr. Enlanders house-calls is now up and working…he said there is hope for the severely ill.)

Listen to audio of the Roundtable in 7 parts here, and stay tuned for a blog summarizing the Roundtable discussion about treatments.

Print Friendly

13 Comments

  • John

    June 18, 2013 at 12:25 pm - Reply

    Is there a link to the transcript? Thanks.

  • Tom Kindlon

    June 18, 2013 at 2:18 pm - Reply

    “(Thanks to Anita Patton for transcribing the Roundtable talk)”
    If there was a transcript available, it’d be great if it could be posted at some stage. If I watch/listen to something, I have a tendency to want to make lots of notes, as I know my memory isn’t the best (this tendency started when I was studying when ill). But taking lots of notes is exhausting. So I love when transcripts are available for talks.

    • Cort Johnson

      June 20, 2013 at 5:51 pm - Reply

      I hope so…I should have called them note, though…

  • Jeanie Pochatko

    June 20, 2013 at 4:24 pm - Reply

    So much great information here. Thanks.

  • Chris Heppner

    June 20, 2013 at 4:30 pm - Reply

    Cort, thanks for another good and useful account–interesting to see Klimas’s focus on the primacy of the ANS confirmed here! Fits in with Julia Newton’s work in Newcastle… good stuff. Chris

  • Marg

    June 20, 2013 at 4:35 pm - Reply

    I love it that these experts are working together. We have always needed this hope more doctors will do this.
    Thanks Cort!

    • Cort Johnson

      June 20, 2013 at 5:50 pm - Reply

      It’s great to bring these docs together. Hopefully we’ll have a big Physician Roundtable at the IACFS/ME meeting next year. I hope Simmaron is thinking how they can build on this…How about Simmaron, OMI, Mt Sinai, CAA, etc all sponsoring a big Roundtable at that meeting…and invite other doctors in the area to attend…Get it videotaped and then get it out as much as possible…I love it :)

  • jimmy

    June 20, 2013 at 5:45 pm - Reply

    Perfect. This is what I was posting to the other day. Front line docs who have been in the trenches with a realistic and solid issues that they see in real patients that are now identifiable through new testing. I see the issues that these Docs are discussing and from my perspective they are right on. Great to see no egos involved and a great collaboration amongst Top Docs. here are the hopes for biomarkers and potential therapies that are real. Thanks cort

  • Questus

    June 20, 2013 at 6:29 pm - Reply

    Good information, the only Dr. I would have liked to see added to the mix is Dr. Cheney!

    Dr. Peterson makes some great points about research, and not vetting participants. (The first 100 who sign up…)

    Also, his point about ‘The Hidden Epidemic’, referring to those patients who are the sickest and yet unable to be seen by a CFS doctor. Such a strong true point! In his words…Talk about a forgotten, ignored group of people.

    I admit to not reading message boards much, but when I have over the years, I’m saddened most by those who are having to depend on the internet and message boards as their primary source of understanding CFS.

    Wishing everyone could see one on the top experts, or at a least a doctor who was interested enough/ cared enough to educate themselves so they could dx patients and try to treat.

    Cort, your new format is a great way for people to get solid CFS information. Keep up the good work.

    Best,
    Questus

  • Katherine

    June 20, 2013 at 10:42 pm - Reply

    Thank you for taking the time to summarize this for all of. This is helpful and hopeful information.

  • Kym

    June 21, 2013 at 1:15 am - Reply

    Are any of these doctors taking new patients? I called Dr. Klimas’ office this week and was told “no.”

    I don’t have a lot of resources but would like to invest my health with any one of these physicians.

    Any suggestions?

    Thanks, Kym

  • Sarah L

    June 23, 2013 at 6:08 am - Reply

    Both Dr. Klimas and Dr. Enlander said they do do house-calls from time to time. (One of Dr. Enlanders house-calls is no up and working…he said there is hope for the severely ill.) – See more at: http://simmaronresearch.com/2013/06/physicians-roundtable-i-diagnostics/#sthash.sPeuluHU.dpuf

    In the above excerpt from the end of the post — is that “no up and working” meant to be ^now^ or *not*?

    Thanks for the post.

  • Leave a Reply