Prognostic value of CSF analysis

 

REPORT FROM THE EUROPEAN CHARCOT FOUNDATION ANNUAL MEETING – BAVENO, ITALY, NOVEMBER 28-30, 2013 – Lumbar puncture was once part of the routine work-up of MS patients but the usefulness of CSF oligoclonal bands (OCB) in the diagnosis of MS was de-emphasized following the publication of the revised McDonald criteria (Polman et al. Ann Neurol 2005;58:840-846).

However, in recent years, OCBs have been shown to have prognostic value in CIS and MS (Giovannoni G. ECF 2013). A recent meta-analysis of 71 studies found that 87.7% of MS patients (n=12,253) and 68.6% of CIS patients (n=2,685) were OCB-positive (Dobson et al. J Neurol Neurosurg Psychiatry 2013;84:909-914). OCB positivity was prognostic of future disability (odds ratio 1.96) in MS patients. In CIS patients, OCB positivity was a strong predictor (OR 9.88) of conversion to MS. Moreover, the presence of oligoclonal IgM bands against myelin lipids has been shown to be associated with an especially aggressive disease course, which may be due to an increase in CD5+ B cells and higher levels of CXCL13 and TNF-alpha in CSF (Villar et al. Clin Immunol 2010;137:51-59).

An emerging prognostic marker is neurofilaments (NfL), structural axonal proteins that are released into the interstitial fluid when axons are acutely transected or during chronic neurodegeneration. NfL values have been shown to be higher in CIS and MS patients compared to controls; and NfL levels are correlated with EDSS score in patients with relapsing MS (Kuhle et al. Mult Scler 2013;19:1597-1603). Thus, NfL has the potential to serve as a quantitative marker of neurodegeneration, and as a surrogate of neuroprotection in treatment trials

Preliminary studies have reported that NfL levels are normalized or markedly reduced during treatment with natalizumab or fingolimod (Kuhle et al. Acta Neurol Scand 2013;128:e33-36; Kuhle et al. ECTRIMS 2013, abstract 233), suggesting that anti-inflammatory therapies may reduce ongoing axonal injury. Studies are now incorporating NfL assessments to determine a possible neuroprotective effect of therapies in MS and Alzheimer’s disease.

Reviewer: Dr. Daniel Selchen. Head of Neurology, St. Michael’s Hospital, Toronto, Canada.

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