From none to too many biomarkers for CFS?

[ramakentesh]

In the last few years there seems to be a flood of studies regarding CFS and or related conditions each emphasising their own unique take of the condition and the possible biomarkers that their specific research have identified.

As some examples:

- elevated cerebral lactate levels from impaired cerebral glucose metabolism
- XMRV serum studies
- elevated inflammatory markers such as interluekin/Tumor Necrosis factor alpha
- RNase fragmentation
- positive tilt table tests
- amyloid protein markers in CNS spinal fluid
- reduced cerebral autoregulation buffering
- reduced orthostatic brain perfusion

Im almost thinking this sudden influx of information has kept things confused - no one universal or accepted biomarker and perhaps groups of advocates for poorer science that are refusing to budge on their own mechanism theories?

 

[goldiland]

Another benchmark that is actually seen in a large majority of CFS patients.... low natural killer cell mediated toxiciity (poor NK function).

I was involved in a study at U of M through Klimas called a good/day bad/day study. Every six months over a period of two years, I had blood drawn, filled out some detailed questionnaires regarding my recent health and was tested cognitively through a series of spatial and analytical exercises. The idea is to identify cellular biomarkers and see how those potential biomarkers change when patient is having a "good day" or a "bad day". Based on the results, the researchers hope to identify the right biomarkers.... the ones that indicate active illness.

Klimas believes genomes are ultimately going to have a big impact on treatment protocols... much like many illnesses today. Find the right markers, figure out which gene is expressing and figure out how to target it.

 

[ukxmrv]

I'm not sure how this could be confusing? Many other illnesses have multiple biomarkers.

One of the problems for some doctors is the lack of a unique biomarker (i.e. they claim that the same test results are seen in other patients)

It's not really a sudden inflex either. Not a "few years" but more like decades for some.

Tilt table tests and have been around for a long time. It was well over 10 years since that was suggest to me. RnaseL in about 2001.

TNF-a test over 5 years ago. Cytokine tests back in the late 80's for me and then added to over time.

Brain hyproperfusion years ago as well.

 

[Hope123]

A lot of these biomarkers and findings are not new as ukxmrv says but have been around for a long time. Problem is that powerful entities like the US federal government via the CDC have not paid much attention to them and your primary care physicians are not educated about them as the tests are not yet well validated in large multiple studies. Primary care docs are too busy to read the research literature and even if they did, few would rely on one or two studies (appropriate as many studies do not pan out).

If you just go by what some CFS sites/ advocates say, they sometimes makes some tests to have a better evidence base than they do and lament why healthcare staff do not use them. If you go just by what the CDC says (or doesn't say), you would conclude that there were no tests available at all. The picture as I see it is more grey than either stance. Many diagnostic tests advanced have been based on small numbers of patients, have not been replicated, have not had tight cohort selection (that is, some patients might have had depression or other illness rather than CFS).

This latter part is extremely detrimental as it might account for why inconsistent results are seen in the studies then; imagine one study with 0% depressed patients vs. another mixed with 30% depressed patients. The former might find a biomarker but the latter might not. Someone looking at both studies will conclude there is no biomarker. Healthcare staff base decisions on multiple studies, not one or two. This is why so many people are concerned about how CFS is defined. (I haven't gone through all the articles over the last 25 years but have read enough to come to this conclusion.)

Also, there is not enough research funding or research staff interested in doing integrative work -- i.e. let's take a group of people with CFS and run them through a multitude of tests -- e.g. cytokines. viral titers, tilt table, etc. and see what patterns emerge. Perhaps there are subgroups within CFS.

A true comparison cannot be made with illnesses with multiple biomarkers though as usually those have been found in a large percentage (if not 100%) of people with disease X over multiple studies and treatments found in the interim are able to modify those biomarkers along with improvement in illness. (If we're lucky, maybe the latter will happen to us soon.)

 

[ramakentesh]

I'm not sure how this could be confusing? Many other illnesses have multiple biomarkers.

I think you missed my point. Each of these biomarkers arent exactly complemenatory of each other or suggestive of the ultimate etiology. Im sure in time they may be, but if the average doctor read three studies with totally contradictory information (CFS is a disorder of circulatory control or CFS is an immunodeficiency or CFS is related to oxidise stress) the average doctor is going to just shrug and suggest the studies are meaningless.

For years when they hasnt been an accepted pathophysiology a lot of dubious science and view points have been contended to explain the condition and I cant see the supporters of any of these view points just suddenly changing their opinions - because a lot of it is already based on belief rather than science any way. So for many years CFS has been largely caught in that pseudoscience area where doctors arent that interested anymore because what they have heard previously has been equivocal.

There is some intergrative work going on right now between the doctors being funded by CFIDS - marvin medows on blood flow, some other guy on brain lactate, etc.

But when its all done and dusted we will ned concensus and a clear message before the wider medical community will be interested or adopt it.

BTW there are undoubtedly subgroups in CFS - there has to be - its a catch all mechanism.

 

[richvank]

Hi, ramakentesh and the group.

For what it's worth, I suggest that the fundamental marker for CFS is the partial methylation cycle block, which is intimately linked to glutathione depletion and draining of folate metabolites from the cells. I suggest that the other biochemical abnormalities and the resulting symptoms all result from this fundamental issue in the biochemistry. I have described the connections in my 2007 pathogenesis paper, which can be found at www.cfsresearch.org by clicking on cfs/M.E. and then on my name. I think this suggestion is well supported by known biochemistry and physiology and by the fact that treating to lift the partial methylation cycle block improves a broad range of symptoms, as shown in the clinical study done by Dr. Nathan and myself, a report on which can also be found on this site.

Best regards,

Rich