USA: National Institutes of Health (NIH) intramural ME/CFS study

[duncan]

I'm the only one of 16 patients to have oligoclonal bands in spinal fluid,

How weird is it that my first inclination was to congratulate you on the oligoclonal hit?

How were your CSF protein levels? Any pleocytosis? What pathogens did they test for in blood vs CSF?

Did they do neuro-cognitive testing yet? Were you able to review results and write-up?

I also wonder who they are outsourcing stuff to, but you may be indifferent to that.

Sorry, don't mean to pry, just very curious.

ETA: Do you have balance issues? Are they looking at that (ENT)? Have they done the MRI yet?

 

[MErmaid]

Yes, they provide online access to all of the standard test results. The research stuff is not accessible - much of it will be run after samples from all the volunteers are collected and pooled, e.g. the immune analysis of spinal fluid (they're looking at a few thousand proteins in CSF). They are running a few specialized tests for me to see if they can ID an antibody that showed up in my blood and spinal fluid. So far, I'm the only one of 16 patients to have oligoclonal bands in spinal fluid, so Ibappreciste the extra steps they are taking to figure out what my immune system is attacking. One advantage to being in the study: If weird stuff shows up, NIH will chase it down and bring in other experts to help. I had a consult with a muscle specialist and a dermatologist that weren't originally involved in the study.

It’s great to hear the inside scoop re the study dynamics and also excellent to know, that at the same time, they are following up with your abnormal test results.

 

[duncan]

also excellent to know, that at the same time, they are following up with your abnormal test results.

The cynic in me might suggest that every disease/condition they can identify in a subject that is not ME/CFS, is one that they can demonstrate is not a discreet illness otherwise known as ME/CFS. That would hopefully benefit B.V. and the other subjects from whom they can remove the ME/CFS label, though.

 

[MErmaid]

The cynic in me might suggest that every disease/condition they can identify in a subject that is not ME/CFS, is one that they can demonstrate is not a discreet illness otherwise known as ME/CFS. That would hopefully benefit B.V. and the other subjects from whom they can remove the ME/CFS label, though.

I have comorbid diseases that are well known and can be managed (but not cured) with daily medications. I feel if the NIH can identify more comorbid disease, that offer treatments, these findings may help many of us to lead better lives.

Were you expecting the NIH, in this phase of the study, to find homogeneity? I have no expectation of this or in any major study published in my lifetime. Hopefully you are younger than I, and will benefit from future developments.

For now, I simply want to learn as much as I can from all sources and data points.

 

[duncan]

I have comorbid diseases that are well known and can be managed (but not cured) with daily medications.

Me, too. I'd wager many of us do.

I feel if the NIH can identify more comorbid disease, that offer treatments, these findings may help many of us to lead better lives.

Sure, if that is what they are trying to do. Even if it isn't.

Were you expecting the NIH, in this phase of the study, to find homogeneity? I have no expectation of this or in any major study published in my lifetime.

I am expecting very little of the NIH, and homogeneity was not high on that very short list.

Hopefully you are younger than I, and will benefit from future developments.

I doubt both. But both are nice thoughts.

For now, I simply want to learn as much as I can from all sources and data points.

Agreed. The question for some is, does the NIH want to? It may, and I hope that is the case.

B.V. brings a very important set of data because of his willingness to try, and I am curious to visit some of that data should he wish to share, hence my questions.

 

[MErmaid]

Me, too. I'd wager many of us do.


Sure, if that is what they are trying to do. Even if it isn't.


I am expecting very little of the NIH, and homogeneity was not high on that very short list.


I doubt both. But both are nice thoughts.


Agreed. The question for some is, does the NIH want to? It may, and I hope that is the case.

B.V. brings a very important set of data because of his willingness to try, and I am curious to visit some of that data should he wish to share, hence my questions.

Okay, then we are on the same page, and also in the same ME boat. We don’t have a course plotted, nor a captain, but I do enjoy the company.

 

[B_V]

How weird is it that my first inclination was to congratulate you on the oligoclonal hit?

It's ok. The banding pattern was type 4, which is not diagnostic of any specific illness but it does happen in neurodegenerative diseases. So that finding is quite worrisome. Does anyone know if other ME patients have had oligoclonal bands in spinal fluid?

How were your CSF protein levels? Any pleocytosis? What pathogens did they test for in blood vs CSF?

Protein looked fine. One white blood cell in the sample, which is clinically fairly meaningless. New in the protocol recently: Spinal fluid will be examined for every known and most unknown viruses (unless they're from Venus or something). The viral discovery technology they are using is pretty cool. It can find new viruses by comparing DNA and RNA to viral databanks. Anything unknown will show up as related to such-and-such known virus.

Did they do neuro-cognitive testing yet? Were you able to review results and write-up?

Yes, study participants have three rounds of neuro-cognitive testing. Once during the phenotyping visit (the first visit, which I did last year), and then twice during the second visit: Once before the exercise challenge and then a repeat after exercise. That's how most of the tests for visit two are structured, with pre- and post-exercise testing. I have not seen any of those results, and didn't ask about it because, frankly, I'm not all that interested in it. I know what cognitive deficits I have and where my brain is relative to when I was healthy. I don't think the testing is going to tell me anything I don't already know. The before-and-after exercise tests could be interesting I guess.

I also wonder who they are outsourcing stuff to, but you may be indifferent to that.

Almost everything is being done on the NIH campus. The only substudy I know about going out of NIH are the skin biopsies. Those are going to Johns Hopkins for small-fiber studies. And I heard some of my blood stem cells went to Singapore, where a former fellow of principal investigator Avi Nath now works. This scientist has a microfluidics device and makes neurons out of blood stem cells. He then does a battery of experiments with the neurons inside the device. But the viral discovery, the extensive immunology, the mouse model work, the genetics, and the muscle biopsy analysis are all being done at NIH. It's a big place with lots of experts, and about 40 scientists are involved in the study.

ETA: Do you have balance issues? Are they looking at that (ENT)? Have they done the MRI yet?

I don't really have balance issues, so I'm not sure what kind of work-up they would do for someone who does. I've had three MRIs. The first was a structural MRI during my first visit. I reviewed it with a physician. This second visit includes two functional MRIs, pre- and post-exercise. I was also wearing an EEG cap during these scans, so they generated a boat-load of data. During the scan, I had to do simple math problems for about 20 minutes (comparing two simple equations) and grip a force bar. The fMRI results are research and I probably won't get to see any individual data from them.

 

[Hutan]

I inquired about my son and/or I participating. Us living overseas wasn't a problem.

But we just passed the 5 year anniversary of our illness a month ago and that was a problem. So, it's definitely a 'less than 5 years' criterion, not '5 years or less'. Damn.

 

[B_V]

The question for some is, does the NIH want to? It may, and I hope that is the case.

Yes, the scientists working on the study have already learned a ton and they are going to learn much more when they compare the controls versus the patients. They are investing years of their career in this study. Their motivation is to learn, and it's ignorant to suggest otherwise.

 

[B_V]

I inquired about my son and/or I participating. Us living overseas wasn't a problem.

But we just passed the 5 year anniversary of our illness a month ago and that was a problem. So, it's definitely a 'less than 5 years' criterion, not '5 years or less'. Damn.

Yes, thanks for clarifying. They want patients in for visit one before their 5-year illiversary.

 

[MErmaid]

Yes, the scientists working on the study have already learned a ton and they are going to learn much more when they compare the controls versus the patients. They are investing years of their career in this study. Their motivation is to learn, and it's ignorant to suggest otherwise.

How can we thank the scientists involved? If many are investing years of their career, then I want to keep them as highly motivated as possible.

 

[duncan]

Their motivation is to learn, and it's ignorant to suggest otherwise.

Fair enough. I've been trying to learn for close to 20 years because I have been appallingly ignorant. Hopefully, I am chipping away that flaw. But I've also seen examples of researchers not being properly motivated, so, you know, once bitten, twice shy and all that. So please bear with me.

 

[B_V]

How can we thank the scientists involved? If many are investing years of their career, then I want to keep them as highly motivated as possible.

Avindra Nath, principal investigator: https://irp.nih.gov/pi/avindra-nath
Building 10-CRC, Room 7C103
10 Center Drive
Bethesda, MD 20814
301-496-1561
natha@mail.nih.gov

Brian Walitt, lead clinical investigator:
Building 10, Room 2-1341
10 Center Drive
Bethesda, MD 20892
301-827-0117
brian.walitt@nih.gov

If you want to thank the staff working full-time on the study - including a patient coordinator, two nurses, and two post-bachelor's fellows - you can send mail to:

Angelique Gavin
NIH/NINDS Patient Care Coordinator
National Institutes of Health
10 Center Drive
Building 10, Room 3B19, MSC 1251
Bethesda, MD 20814-9692
(301) 402-0880 (office)
(301) 451-7352 (fax)
angelique.gavin@nih.gov

 

[duncan]

Does anyone know if other ME patients have had oligoclonal bands in spinal fluid?

I did not.

Protein looked fine. One white blood cell in the sample, which is clinically fairly meaningless. New in the protocol recently: Spinal fluid will be examined for every known and most unknown viruses

So that suggests no acute infection. I am sorry, but which pathogens will be included? Viruses AND bacteria AND parasites? Or perhaps I should ask, are there any ones that are excluded?

The viral discovery technology they are using is pretty cool. It can find new viruses by comparing DNA and RNA to viral databanks. Anything unknown will show up as related to such-and-such known virus.

That does sound cool.

I have not seen any of those results, and didn't ask about it because, frankly, I'm not all that interested in it. I know what cognitive deficits I have and where my brain is relative to when I was healthy. I don't think the testing is going to tell me anything I don't already know.

You may wish to rethink this approach. How you feel vs how you perform on the testing may not jibe. Also, it might not hurt to see what the appraisals say.

Almost everything is being done on the NIH campus. The only substudy I know about going out of NIH are the skin biopsies. Those are going to Johns Hopkins for small-fiber studies. And I heard some of my blood stem cells went to Singapore, where a former fellow of principal investigator Avi Nath now works. This scientist has a microfluidics device and makes neurons out of blood stem cells. He then does a battery of experiments with the neurons inside the device. But the viral discovery, the extensive immunology, the mouse model work, the genetics, and the muscle biopsy analysis are all being done at NIH. It's a big place with lots of experts, and about 40 scientists are involved in the study.

Ok. I'm a bit surprised at that, i,e, not outsourcing. But that is a good thing.

I don't really have balance issues, so I'm not sure what kind of work-up they would do for someone who does.

Understood. It becomes a moot point of balance/gait/dizziness aren't issues.

 

[B_V]

Fair enough. I've been trying to learn for close to 20 years because I have been appallingly ignorant. Hopefully, I am chipping away that flaw. But I've also seen examples of researchers not being properly motivated, so, you know, once bitten, twice shy and all that. So please bear with me.

If I had any hint this study was not being done in good faith, I would have quit the study and raised holy hell. I used to work at NIH and know a lot of people around the place. Francis Collins visited me last year. I have many avenues with which to raise concerns and I would use them if I felt I needed to. The people working on the study are dedicated, they're career researchers, and they have a mandate from the director of the NIH to run a solid study. Very few NIH studies start with the director of the entire $30 billion, 20,000 person agency calling a meeting and ordering the head of an institute to make something happen.

 

[MErmaid]

Fair enough. I've been trying to learn for close to 20 years because I have been appallingly ignorant. Hopefully, I am chipping away that flaw. But I've also seen examples of researchers not being properly motivated, so, you know, once bitten, twice shy and all that. So please bear with me.

I have learned that I need to be my own advocate/researcher. Even if one has access to an amazing doctor, or choose to rally behind a top scientist, he/she will eventually retire at some point. So it’s better to learn to be self sufficient while sifting out the noise, because unfortunately most of it is has been noise.

I try to stay open minded, as possible, until I have a clear reason not to be. So far, Nath, has impressed me with his openness and humility. Nath has not spinned the science, which is a refreshing break.

 

[duncan]

If I had any hint this study was not being done in good faith, I would have quit the study and raised holy hell.

Sometimes it's only in the rear-view mirror that we see everything, but your point is taken. I applaud your efforts and spirit.

 

[Milo]

Does anyone know if other ME patients have had oligoclonal bands in spinal fluid?

I wish I had my spinal fluid tested. I am all about providing data including cerebrospinal fluid sample, but my health care system stubbornly does not want to gain any information or knowledge about my disease, they simply want us to attend CBT classes and learn more about pacing and eating, proper mental health.

Same for MRI.

 

[B_V]

One more thing I want to say about my time at NIH. The PI, Avi Nath, and other senior people at NINDS and in Building 1 (the NIH director's office) know about the history in the 1980s of Stephen Strauss squashing NIH research on ME. They have acknowledged to me and others that he was a bad actor in this regard. None of the current ME investigators or the administrators overseeing the study had any role in those events 30 years ago. It's always good to be aware of the past, but it's never a good idea to live there.

 

[Forbin]

Does anyone know if other ME patients have had oligoclonal bands in spinal fluid?

I came across this from "A Hummingbird's Guide to M.E." (2006)

From Professor Malcolm Hooper: In M.E. there is evidence of inflammation of the central nervous system (CNS). In some cases of ME, as in multiple sclerosis, there is evidence of oligoclonal bands in the cerebrospinal fluid. It is accepted by the most experienced ME clinicians that some degree of encephalitis has occurred both in patients with M.E. and in those with post-polio syndrome: the areas chiefly affected include the upper spinal motor and sensory nerve roots and the spinal nerve networks traversing the adjacent brain stem (which is always damaged).
http://www.name-us.org/MECFSExplainPages/ME_The_Medical_Facts.pdf

[ About 35 years ago, I had spinal fluid drawn about a month after onset. I'm guessing they didn't do tests for oligoclonal bands back then since there was no "box" for it on the lab report.
There was a mildly elevated protein level - which is something I've occasionally seen reported in ME/CFS - ex. below: ]

"Ten of the [43] patients had increased protein values ranging from 46–93 mg/dl (with a median of 59 mg/dl)..." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017287