Schutzer, Natelson study of XMRV in CSF article

[ixchelkali]

Here's another article about the Annals of Neurology study by Schutzer, Natelson, el al that didn't find XMRV in spinal fluid of ME/CFS patients. According to the article, it was the same group of samples in which they reported finding unique proteins in ME/CFS patients.

http://www.healthcanal.com/brain-ne...e-Probes-for-XMRV-Central-Nervous-System.html

And the actual study is now available on the Annals of Neurology website:
http://onlinelibrary.wiley.com/doi/10.1002/ana.22389/abstract

 

[toddm1960]

Does anyone know if he was able to find known positive samples of XMRV with the type of PCR he's using? Does anyone know if he even tried to test a known positive? Most of these negitive studies THAT GET PUBLISHED have never even tested a known positive sample to prove their PCR process works.

 

[kday]

Isn't Natelson that quack neurologist at the recent workshop?

I wouldn't trust a study from him (positive or negative). What an idiot.

Sorry, I don't usually like that term since I consider it derogatory, but I think it's appropriate.

 

[ukxmrv]

The thing I found signifigent here was not the XMRV finding (after all it's not a validated test) but that they "did not find XMRV or multiple other common viruses"

So what went wrong here. Is spinal fluid the wrong place to look for viri or something else?

 

[kday]

The thing I found signifigent here was not the XMRV finding (after all it's not a validated test) but that they "did not find XMRV or multiple other common viruses"

So what went wrong here. Is spinal fluid the wrong place to look for viri or something else?

The study is crap. It's from 2 samples. Means absolutely nothing. And Natelson is an ostrich anyway.

 

[ukxmrv]

Kday, the abstract says that 43 samples were examined. I still think it is significant that they couldn't find any viri - let alone XMRV. That's why I was just wondering if this was the best method to use to look for them (i.e. any).

I'm not sure what Dr Mikovits was referring to by the 2 samples. Someone said that only 2 had been sent to her for testing?

 

[ixchelkali]

I have no idea if the PCR method they used was a good one. From some of studies done so far it seems as though it's fairly easy to miss XMRV by PCR. But at the very least, it tells us that testing spinal fluid isn't going to make it easy to find XMRV. Since everyone seems to find it hard to find XMRV in blood, it would be nice if we could find somewhere else where it's easier to find...somewhere relatively simple to get at, like saliva, sputum, urine, or spinal fluid. So even these negative results may be useful.

I looked back at the reports of the macaque monkey study, and didn't see any mention of them finding XMRV in spinal fluid. It was the immune system (lymph noded, spleen) and reproductive systems that seemed to be the respositories. Unfortunately, those aren't so easy to test. It would be interesting to know what the results would be of doing a PAP-type smear of people whose blood has tested positive, to see if it would find XMRV in higher copy numbers.

I'm reminded of Dr Chia and his enteroviruses: they weren't present in sufficient number to test in the blood. It wasn't until he did GI biopsies that he found real signs of infection.

 

[omegaman]

The thing I found signifigent here was not the XMRV finding (after all it's not a validated test) but that they "did not find XMRV or multiple other common viruses"

So what went wrong here. Is spinal fluid the wrong place to look for viri or something else?

Does anybody else find it odd they did not test the CSF for Lyme also to make sure the CFS patients did not have Lyme and or the Lyme patients did not actually have CFS. Given the overlap of sympomology between the two I would hope they would have done this. Lyme blood tests are notoriously unreliable and many Lyme diagnosis's are now made clinically.

 

[ixchelkali]

Does anybody else find it odd they did not test the CSF for Lyme also to make sure the CFS patients did not have Lyme and or the Lyme patients did not actually have CFS. Given the overlap of sympomology between the two I would hope they would have done this. Lyme blood tests are notoriously unreliable and many Lyme diagnosis's are now made clinically.

Omegaman, were you able to access the whole article? Or how did you know they didn't test for Lyme? Can you share with us anything else about what viruses they tested for?

 

[ukxmrv]

I didn't mean if it was a good PCR test for XMRV (as it's not a standard test and may never work as far as we know).

It was the "other viruses" part that got me.

When the WPI rang a microarray on CFS patients they picked up a whole lots of viruses.

So why didn't this paper pick up the common viruses patients seem to be infected with ?

 

[Enid]

Quite agree ukxmrv - WPI/K de M/Chia are finding "other viruses" requiring treatment so is everybody else not looking hard enough.

 

[Nielk]

Quite agree ukxmrv - WPI/K de M/Chia are finding "other viruses" requiring treatment so is everybody else not looking hard enough.

I think it just means that it's not present in the spinal fluid. The study doesn't negate the fact that XMRV or other viruses are present in other parts of the body. This group did a study on the spinal fluid because they are Neurologists.

Why don't we give them credit for the fact that they also tested for proteins and found an amazing abundance in CFS patients.

I happen to know Dr. Natelson. I had gone to him a few years ago for treatment for my CFS and was very impressed with his knowledge and came across as a very nice, caring doctor. I stopped going to him because I couldn't take the commute anymore. He doesn't think that CFS is in the mind. He very much believes that it's a biological disease that also affects the brain/nervous system.

We should be thankful that he is part of a group who are doing hard core studies to find some answers for us.

Instead, we put him down because he didn't find the results we WANTED.
Maybe XMTV just doesn't pass the barrier of the nervous system?

To be honest, I am disturbed by the tunnel vision of many people who just want to see all studies pointing to XMRV or else they feel the studies are not legitimate.

 

[floydguy]

I think it just means that it's not present in the spinal fluid. The study doesn't negate the fact that XMRV or other viruses are present in other parts of the body. This group did a study on the spinal fluid because they are Neurologists.

Why don't we give them credit for the fact that they also tested for proteins and found an amazing abundance in CFS patients.

I happen to know Dr. Natelson. I had gone to him a few years ago for treatment for my CFS and was very impressed with his knowledge and came across as a very nice, caring doctor. I stopped going to him because I couldn't take the commute anymore. He doesn't think that CFS is in the mind. He very much believes that it's a biological disease that also affects the brain/nervous system.

We should be thankful that he is part of a group who are doing hard core studies to find some answers for us.

Instead, we put him down because he didn't find the results we WANTED.
Maybe XMTV just doesn't pass the barrier of the nervous system?

To be honest, I am disturbed by the tunnel vision of many people who just want to see all studies pointing to XMRV or else they feel the studies are not legitimate.

I agree with you to some extent. However, the reason I wasn't that thrilled with Natelson is that he seemed to be very dismissive of immune system issues. So, speaking of tunnel vision I thought Natelson was a pretty good example of that from the researcher side. This isn't going to be solved by just focusing on the immune system or the brain or probably even XMRV. I was frustrated by many like Natelson who seemed imprisoned by their silos.

 

[ixchelkali]

I didn't mean if it was a good PCR test for XMRV (as it's not a standard test and may never work as far as we know).

It was the "other viruses" part that got me.

When the WPI rang a microarray on CFS patients they picked up a whole lots of viruses.

So why didn't this paper pick up the common viruses patients seem to be infected with ?

Quite agree ukxmrv - WPI/K de M/Chia are finding "other viruses" requiring treatment so is everybody else not looking hard enough.

What other viruses have ever been found in the spinal fluid of ME/CFS patients? I looked in PubMed back to 1995 and couldn't find any published studies of anyone finding pathogens in the spinal fluid of ME/CFS patients.

Most infections don't get into the spinal fluid, so it's very possible they didn't find any viruses there because they aren't there, not because they are "not looking hard enough." Not every negative study is automatically junk science or out to prove ME/CFS is psychogenic. Since I haven't read anything but the abstract on this one, I don't know if it was well designed or not.

 

[ukxmrv]

NielK,

I have no gripe with Dr Natalson or any gripe with his study. I don't know much about him. My question/concern was solely over whether this test was a good way to find any virus in the spinal fluid of a CFS patient and nothing to do with XMRV. If you look back on my postings that I was have been asking.

I didn't expect him to find XMRV as it's not a validated test.

If it's not normal or reliable to use this method to detect viri in patients then so be it. Someone had to try and see. I'm just asking.

Did you see/hear his comments at the SOK? Did you agree with his exchange with Dr Mikovits? My guess is that is why some people are commenting.

 

[Nielk]

NielK,

I have no gripe with Dr Natalson or any gripe with his study. I don't know much about him. My question/concern was solely over whether this test was a good way to find any virus in the spinal fluid of a CFS patient and nothing to do with XMRV. If you look back on my postings that I was have been asking.

I didn't expect him to find XMRV as it's not a validated test.

If it's not normal or reliable to use this method to detect viri in patients then so be it. Someone had to try and see. I'm just asking.

Did you see/hear his comments at the SOK? Did you agree with his exchange with Dr Mikovits? My guess is that is why some people are commenting.

I did not hear his comments at the SOK. I did read the comments from forum members that he was rude and interrupted other speakers and I wasn't happy to hear that. There is no excuse for inappropriate behavior. It seems that people were also upset about the rashness of Dr. Mikovitz. I understand people getting upset about such behavior. I guess when you have a strong personality and want to make sure you are heard and understood, you might lose your cool. It shouldn't happen though especially at such a professional meeting.

As far as why look for XMRV in spinal fluid of CFS patients. My guess is that since they already had the samples they took for the study of proteins, they tried to see if XMRV is present. This does not negate Mikovitz' findings at all.

 

[ukxmrv]

Thanks ixchelkali,

For looking. I agree not all negative studies are other than that. Probably not saying that very well. Bad brain day.

 

[August59]

I am very curious to see if Dr. Bariniuk looked for viruses in his latest spinal fluid study?? I thought I had seen on here where the spinal fluid was a very sterile environment and my impression was that it would be much harder to find viruses or bacteria in the spinal fluid as opposed to blood.

I thought the WPI did the test for XMRV on the original spinal fluid study by Dr. Natelson and others?? It seemed that the sample sizes were very small and had been frozen and thawed more than once. This is just vaguely in my mind, but is the original study available in full now (not an abstract)?

These spinal fluid studies (Dr. Bariniuk and Dr. Natelson) could contain extremely valuable information and I really wish this information could be freely accessible to all researchers.

Imagine if all the information from blood, spinal fluid, autopsy and gastrointestinal studies, including all the papers that are not being published (I don't think it is just Dr. Mikovits that are being shunned) were combined and made available for all researchers. I would be willing to bet that we would have much better treatments available and possibly living a life that is somewhat enjoyable instead of feeling like being condemned to torture for the rest of our lives.

There is too much freaking POLITICS where it doesn't belong. I'm not sure what is going on between Dr. Natelson and Dr. Mikovits, but neither one of them should have taken that tone in a public meeting. It just was not the place. Again, I think the politics that has fractured research environment for ME/CFS is to blame for researchers being so defensive and "hair triggered". Not a conspiracy, just political stupidity!!

Thanks, as that was my rant for the week! Hope everyone has a good weekend!

 

[Snow Leopard]

Note that this this study states "We used VIP Dx in the capacity of a service laboratory". - The VIPDx results were also negative. The rest of the testing appears to have been done by Ibis Biosciences.

As far as other viruses go,

Broad Viral Detection by RT-PCR/ESI Assay

All 43 individual CSF samples (based on available volumes) from CFS patients analyzed with the broad range RT-PCR/ESI-MS8 were negative for human adenoviruses, alpha viruses, herpes viruses (HHV 1, 2, 3, 4, 5, 8), human parvovirus B19, dengue viruses 1 to 4, WNV, JEV, SLE, enteroviruses A to D, and coxsackieviruses. Limit of detection LOD95 experiments for these viruses in RT-PCR/ESI-MS were determined in genome copy number compared to internally calibrated competitive PCR, and ranged from 15 to 125 genome copies per PCR reaction as follows: human adenovirus, 15; HHV 1, 30; HHV 4, 60; HHV 5, 30; coxsackievirus, 30; dengue, 60; human parvovirus B19, 125. The genome copy numbers of the viral stocks determined by internally calibrated competitive PCR were shown to be within 10-fold of real time PCR reactions for each individual virus stock. In the present experiment, 100?l of CSF was extracted to yield 100?l of eluted volume, from which 3?l was put into each PCR reaction.

The technique they used is described here:
http://www.ncbi.nlm.nih.gov/pubmed/18521073
http://www.ibisbiosciences.com/technology/how-it-works/biosensortechnology.html (this site has an interesting "Not for use in Diagnostic Procedures" disclaimer which you have to agree to when you visit.)
It is possible that this (newly developed) technique has poor sensitivity for the CSF quantities used.

As far as the effects of CSF vs serum goes, there are plenty of studies, starting with this one: http://www.ncbi.nlm.nih.gov/pubmed/2994792 (that was the first google result I got)

 

[acer2000]

According to his paper, he didn't find XMRV in the spinal fluid samples with the test that he used. Thats pretty much all that can be gathered from the paper. It says nothing as to if XMRV is implicated in CFS, or if the test he used could even find XMRV if it was in the spinal fluid to begin with.

I think people were upset at the Natelson study not because of what the actual study said, but because of what he seemed to imply the results meant in the SOK meeting. He seemed to be saying that because he didn't find XMRV in the spinal fluid, that it couldn't be the cause of CFS. His logic seemed to be that because so many symptoms of CFS are "brain" symptoms, if a virus were to cause CFS, it would certainly be picked up readily in the spinal fluid. I think thats probably too narrow of a conclusion to come to.

A virus doesn't have to show in the spinal fluid to cause CNS symptoms. There isn't always such an obvious direct link like that. The virus could be causing other pathogens to infect the CNS, it could be giving off a toxin that effects the CNS, it could be altering blood flow in the CNS, effecting oxygen permeability into the CNS, mitochondrial function, effecting the metabolism of the neurotransmitters, etc.. All of these things could cause "brain" symptoms and could secondary effects of an infection that could exist outside of the spinal fluid.

And it could have been that XMRV was there, but the test he used was calibrated to find it in blood, not CSF. There really hasn't been any research on XMRV in CSF to be able to compare his study to.

A recent pattern seems to be that scientists overstate the meaning of their results when giving talks or interviews. Its pretty troubling.