Research: Proteins analysis of spinal fluid

Background: MS is a chronic disease, but in rare fulminant cases rapid
progression may lead to death shortly after diagnosis. Currently there
is no diagnostic test to predict disease course. The aim of this study
was to identify potential biomarkers/proteins related to rapid

Methods: The investigators present the case history of a 15-year-old male MSer. Cerebrospinal fluid (CSF) was taken at diagnosis and at the
time of rapid progression leading to the subject’s death. They quantitatively analyzed the protein content of two CSF
samples from the MSer with fulminant MS as well as one
with RRMS and one control subject with a headache,
whose CSF analysis was normal. 

Results: 78 proteins were identified
and 7 proteins were found to be more abundant in both fulminant MS
samples but not in the RRMS sample compared to the control. These
proteins are involved in the immune response, blood coagulation, cell
proliferation and cell adhesion. 

Conclusion: This pilot study showed differences in the CSF proteome of a rapidly
progressing MSer compared to a more typical clinical form of MS
and a control subject.

Spinal fluid collected from a lumbar puncture!

“Firstly, I want to point out that rapidly progressive fulminant MS is very rare. I haven’t seen a case in more than 10 years. Why? Because we now have more effective treatments that MSers respond to; before we had these treatments MSers used to die from their disease. I have never thought about this, but this could be an outcome measure we could use to show that DMTs work; i.e. the number of MSers dieing of fulminant MS (within 2 or 5 years of disease onset) has decreased.”

“This study identified 7 proteins in the CSF of the MSer who died of fulminant disease that were not seen in a RRMSer who had a more benign course. Are these proteins predictive of a more severe course? This will need to be studied in other MSers using a longitudinal study design to assess whether or not the detection of these proteins predicts a poor outcome. How long do these follow-on studies need to be? It will depend on the number or subjects studied and how good the assays are at detecting these proteins. I would predict that after proper power calculations we would need to study over 240 subjects and follow them up for more at least 3 years to get an answer. Even then some cynics would say we would need longer studies to be confident. As you can see there are no easy answers to studying biomarkers in MS.”

5 thoughts on “Research: Proteins analysis of spinal fluid”

  1. Prof G, Your comment about changes in your patient outcomes is interesting. It seems a lot of MS societies still quote disease outcomes from studies that either predate new DMTs or overlap. The fundamental question is this: do new DMTs prevent the shift from RRMS to SPMS? Do they impact progression? Some studies suggest disease progression is linked to he age of the patient. Some to the duration of the is ease. Some to the burden of lesions. Can you suggest an article tat might show the efficacy in DMTs on these outcomes?

  2. As a person who has had Acute Disseminated Encephalomyelitis or ADEM and seems to be transitioning to MS (RDEM), I wonder if there is any difference in rapidly progressive MS and ADEM? Since both cases are extremely rare, it seems like it would be difficult to distinguish between the two.

  3. Re: "Would the proteins be affected by any DMT's the MSers took whilst on the follow up study?"Almost certainly, which is why this data needs to be reproduced.

  4. Re: "Can you suggest an article tat might show the efficacy in DMTs on these outcomes."Goodin et al. Relationship between early clinical characteristics and long term disability outcomes: 16 year cohort study (follow-up) of the pivotal interferon β-1b trial in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):282-7. Epub 2011 Dec 21.

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