While the majority of individuals who experience clinically isolated syndrome (CIS) go on to develop multiple sclerosis (MS), 20-40% do not. New research presented at the 2017 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting indicates that a test of cerebrospinal fluid could identify those patients at greatest risk of progression more accurately than current methods (P832).

Cerebrospinal fluid. (Source: Creative Commons)

According to the researchers, clinicians need to know which patients who present with a single neurologic sign or symptom, such as optic neuritis, or have a single episode with multiple symptoms will progress to MS so that those at highest risk can begin a disease-modifying therapy. This is to prevent or slow the appearance of a subsequent episode and the definitive onset of MS. The presence of old brain lesions on magnetic resonance imaging (MRI) can confirm MS at the time of an apparent first episode and detection of current lesions increases the risk of developing MS to 60-80%.

The researchers found that high levels of homeobox protein HoxB3 in cerebrospinal fluid (CSF) more accurately predicts MS conversion. Their study analyzed data from 42 consecutive patients with CIS who were followed for at least 60 months. CSF samples taken at initial diagnosis were kept frozen. Controls included 36 patients with non-inflammatory neurological disease. During the 5 years of follow up, 20 patients met the criteria for MS.

Mass spectrometry analysis found 5 proteins that were higher in patients with CIS. Of those, only HoxB3 levels were significant in elevated in those who went on to develop MS. Regression analysis found that HoxB3 levels greater than 3 ng/ml had a 83% sensitivity and 62% sensitivity for conversion. Of the patients who had elevated HoxB3 levels along with oligoclonal bands, 85% developed MS in 5 years.