Research: biomarkers in the spinal fluid

R
Komori M et al. Proteomic pattern analysis discriminates among multiple sclerosis-related disorders. Ann Neurol. 2012 May;71(5):614-23.


OBJECTIVE: To use a new biomarker (marker of a biological process) discovery strategy to obtain and assess proteins from  the cerebrospinal fluid (CSF) of MSers.

METHODS: CSF protein profiles were analyzed from 107 people with either MS-related disorders (including RRMS, PPMS, anti-aquaporin-4 antibody seropositive-neuromyelitis optica spectrum disorder [SP-NMOSD], and seronegative-NMOSD with long spinal cord lesions on spinal magnetic resonance imaging [SN-NMOSD]), amyotrophic lateral sclerosis (ALS or motor neurone disease), or other inflammatory neurological diseases (used as controls). 

RESULTS: MS-related disorders differed considerably in terms of CSF protein profiles. SP-NMOSD and SN-NMOSD, both of which fit within the NMO spectrum, were distinguishable from RRMS, especially in the relapse phases. Some proteins derived from samples of relapsed SP-NMOSD could discriminate RRMS and this was reproduced on the second cohort. The similarity of proteomic patterns between selected neurological diseases were demonstrated by pattern matching analysis. To their surprise, the spectral or protein differences between RRMS and PPMS were much larger than those of PPMS and ALS.

INTERPRETATION: These findings suggest that CSF protein pattern analysis can increase the accuracy of disease diagnosis of MS-related disorders and will aid physicians in appropriate therapeutic decision-making.



“I disagree with this interpretation. At present we define MS clinically therefore differences in CSF protein profile will not aid in the diagnosis. These investigators should flip the coin and characterise these study subjects based on their CSF protein profile; if these correspond to the clinical phenotypes (subtype of MS and NMO based on clinical observations) bingo, they may have found a diagnostic biomarker.”


“The reality of this type of research is that it is seldom replicated. Hoepfully, the investigators will have identified specific proteins that can be taken forward in further validation studies.”


“Of interest is the differences noted between RRMS and PPMS; this is not surprising as they differ so much clinically. In other words it is not unexpected that they would differ in their spinal fluid protein profiles.”


“What does this mean to you clinically? Not much at present except the CSF studies show that RRMS and PPMS differ and  that NMO and MS also differ. Any critic would say “big deal we know this already from treatment responses”; I would say yes we know this but difference in protein profiles may lead to new diagnostic tests and may uncover novel molecular pathways that could lead to a treatment for MSers with PPMS; this is something we all want.”

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About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

23 comments

  • "At present we define MS clinically"

    Maybe its time we discussed the disease definition process. Many would agree that the current definition of MS is a weak one.

  • mutiple=alot sclerosis =scars. ms makes alot of scars in the nerve. Not a good definition? What do you suggest?
    Maybe we should call it BS.
    Matt does, and has some great logos and T shirts to prove it.

  • Re: "Maybe its time we discussed the disease definition process. Many would agree that the current definition of MS is a weak one."

    I agree; the community keep changing the definition with each new version of the diagnostic criteria. I am not sure it is the name we need to change, what we need is a diagnostic biomarker.

  • Of course, name doesn't matter. What matters is the diagnostic criteria. Unfortunately, in MS they are very much relied upon unclear entities like "lesion" and "relapse". There is nothing MS-specific in the current definition of MS although there are aspects of MS seen in NO other neurological disease.

    You once mentioned the Popper criteria of disease definition, if i am correct. Do they apply in MS?

  • Re: "You once mentioned the Popper criteria of disease definition, if i am correct. Do they apply in MS?"

    Not Popper, but Wittgenstein!

  • Vasilis Vasilopoulos said:

    "Not Popper, but Wittgenstein!" Sorry. So, what makes MS a distinct disease entity, according to modern neurology and/or your personal opinion?

  • Re: "Sorry. So, what makes MS a distinct disease entity, according to modern neurology and/or your personal opinion?"

    Please read this article it explains everything.

    Flier, F. J., & de Vries Robbé, P. F. (1999). Nosology and causal necessity; the relation between defining a disease and discovering its necessary cause. Theoretical medicine and bioethics, 20(6), 577-88. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10765492

  • That was a very enlightening article.

    Using its terminology, MS is a natural kind term, pretheoretically defined by the McDonald criteria. The problem is that these criteria use the hardly tangible terms "lesion" and "relapse". Different definitions of these two terms lead to totally different definitions of MS. Moreover, the term "lesion", as part of each criterion, is not evaluated by its essence, but by the multiplicity of its existence, aka the lesion number. Thus, MS diagnosis entails counting entities of unknown, or at best conjectured, origin.

    In that way, the accidental characteristics with which MS is empirically correlated are totally arbitrary, balanced only by the judgement of experienced neurologists that formulate-revise McDonald criteria. Certain MS specific findings are not taken into account. Most prominent of them, Dawson's fingers and the numerous differences between cerebral and spinal lesions.

  • What finding is MS specific?

    Different definitions of lesion and relapse lead to totally different definitions of MS. Please explain.

  • Re: "n that way, the accidental characteristics with which MS is empirically correlated are totally arbitrary, balanced only by the judgement of experienced neurologists that formulate-revise McDonald criteria. Certain MS specific findings are not taken into account. Most prominent of them, Dawson's fingers and the numerous differences between cerebral and spinal lesions."

    VV this is why medicine is not a science but an art. An experienced clinician is worth his/her weight in gold. Dr Charles Kaplan, my mentor , taught me that the first, second and third best investigation in neurology was the history and examination. Neurology is a clinical speciality and neurologists get the diagnosis of MS correct 95-98% of the time. These figure are 75% and 80% for Parkinson's and Alzheimer's disease. I think we do quite well.

  • Vasilis Vasilopolus wrote 2.14pm

    "A good clinical neurologist may diagnose MS accurately, but in terms of treating is as helpful as a student in medicine.

    This a hint that McDonald criteria do not capture the MS-essence|

  • VV I think your Post was deleted by mistake but

    but not one from a very good philosopher. Otherwise you would think before you write

  • Truth hurts MD. Show me a neurologist that cured MS and i'll take my comment back asking for forgiveness. Unless you call discussing, advising and prescribing a form of treatment.

  • Unless you call discussing, advising and prescribing a form of treatment.

    Yes I do, because some of those prescribed drugs do some good.

    Truth Hurts….Sometimes, you don't half talk a load of old rubbish….Does that hurt 🙂

  • "Yes I do, because some of those prescribed drugs do some good."

    If even drugs did anything, prescribing them would need no effort. Your students could do it too. No extra skills needed once the diagnosis is made. So is there something extra a clinical neurologist can do? Show me a cured patient, just one.

    "Yes I do, because some of those prescribed drugs do some good."

    SOME…do SOME good. That's light years away from a cure and a neurological cliché. Projections of an imaginary future are just mushroom food for hopeless patients.

    "Yes I do, because some of those prescribed drugs do some good."

    Who says so? Trials for licensed drugs were made by their manufacturers, not some independent research team. Tobacco industry used to produce its own trials showing that smoking is harmless.

    "Does that hurt :-)"

    It would, if you had cured at least one patient. You haven't, so it doesn't.

  • 'If even drugs did anything, prescribing them would need no effort. Your students could do it too. No extra skills needed once the diagnosis is made.'

    VV thinks a physician's job doesn't require any skills!!!

  • Trials are made from pharma…..

    Some are some aren't. Do your research

    "Who says so….."

    I think if you care to read posts from the Blog. THE READERS DO…Some drugs are anti symptomatics, it is not all about DMT.

    These are not cures..accepted, but is CCSVI? The trials and follow up will tell us that. Are some people who have taken some of the new DMT cured…possibly. The follow up will tell.

    If you are not hopeless then it should not be mushroom food.

    PS No blog site still, You are full of boloney/hot air or you are hiding your identify or left feld ideas. I can respect the former.
    However we have no way of knowing that you are not some CCSV-salesman.

    If you are still in the closet it is a shame that many of the comments belong in the water version.

    http://multiple-sclerosis-research.blogspot.co.uk/2012/01/what-is-your-story.html

  • "Are some people who have taken some of the new DMT cured…possibly."

    Now this is from a parallel universe.
    Are you talking about natalizumab (Tysabri)? I think not, because curing all 2.500.000 patients worldwide would require inducing PML to 3000 of them at least and then killing 1000.
    Are you talking about fingolimod (Gilenya)? The failed anti-transplant-rejection drug? I think not, it's even less effective than Tysabri in clearing MRIs.
    So you must be talking about alemtuzumab (Campath, Lemtrada). This is so good that needs more than one trade name. Well, who cares if it causes permanent damage to the immune system or destroys thyroid gland? It doesn't even matter if MS is only suspected to be autoimmune. That is execution based on suspicion. Highly scientific and humane.

    "However we have no way of knowing that you are not some CCSV-salesman."

    With an intuition like that, MS research is in secure hands.

    "If you are still in the closet it is a shame that many of the comments belong in the water version. "

    We have all understood your obsession with fitting human excretions in every metaphor. Must be useful in the lab.

  • Re: "Need this to be done in MS!"

    Yes, I suggest the NHS does a large head-2-head trial of generic or cheap cladribine vs. the new generation DMTs.

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