A Potential New Diagnostic Test for Multiple Sclerosis, the My…

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. Its cause is elusive, and there is no cure. Additionally, there is no singular diagnostic test available. Rather, a diagnosis is made by deduction and the sum of a set of criteria.^1,2

Cerebrospinal fluid (CSF) has been used to look for abnormalities in proteins related to MS since 1922. The most commonly used biomarkers are oligoclonal antibodies; however, even this is not entirely accurate, as about 5% to 10% of patients diagnosed with MS are not positive for oligoclonal markers. Additionally, oligoclonal markers are present in other diseases as well and, therefore, cannot be relied upon as a complete diagnostic test.³

In a recent investigation, Dhaunchak et al.⁴ challenges traditional concepts of MS pathogenesis by suggesting that it is, in fact, the nodes of Ranvier and axoglial apparatus that are involved in early events in MS. Findings further suggested that this perturbation in the axoglial apparatus is responsible for the release of axoglial apparatus molecules, triggering a targeted immune response and demyelination.

Dhaunchak et al. collected CSF samples from 19 children with acquired CNS demyelinating syndrome (ADS). The aim was to find potential biomarkers at the time of ADS onset that could define a test to distinguish patients who would later go on to develop MS from those with a monophasic presentation.

Peptides of interest were analysed by a linear ion-trap mass spectrometer (Thermo Scientific). Elevated levels of CSF immunoglobulin were evident when ADS was initially diagnosed in children who later went on to be diagnosed with MS as compared to children with monophasic disease. However, there was also a 10.6-fold increase of differentially expressed axoglial apparatus molecules in the children later diagnosed with MS.

Here, we have the discovery of a completely new indicative test for MS, identifying expression of axoglial apparatus molecules in the CSF as hallmarks of early pathogenesis.

MS is a debilitating disease that can strike early in life and affects more than 2.5 million people in North America and Europe,¹ and it is irreversible. Its effects on the individual are physically and emotionally significant as it progresses and more function is lost. To have a single test to accurately diagnose MS has the potential to reduce the time from diagnosis to commencing treatment to impede progression.

References

1. Trapp, B.D. and Nave, K.A. (2008) ‘Multiple sclerosis: an immune or neurodegenerative disorder?‘, Annual Reviews of Neuroscience, 31, (pp. 247-269)

2. MS Australia, http://www.msaustralia.org.au/aboutms.asp

3. Awad, A., et al. (2010) ‘Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis‘, Journal of Neuroimmunology, 219 (1-2), (pp. 1-7)

4. Dhaunchak, A.S., et al. (2012) ‘Implication of Perturbed Axoglial Apparatus in Early Pediatric Multiple Sclerosis‘, Annals of Neurology, 71 (5), (pp. 601-613)