Research: Proteins analysis of spinal fluid

Füvesi et al. Proteomic analysis of cerebrospinal fluid in a fulminant case of multiple sclerosis. Int J Mol Sci. 2012;13:7676-93.


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 progression. 

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."

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