Revealing underlying differences of NAWM from primary and secondary progressive MS (P4.404)

Objective: To investigate the underlying differences between normal-appearing white matter (NAWM) of primary and secondary progressive MS using Raman spectroscopy. Background: The underlying mechanisms of disease progression in MS are still poorly understood. In recent years, Raman spectroscopy has emerged as a powerful biomedical tool. It is based on the light scattering phenomenon which provides a unique biochemical fingerprint of the analysed sample, allowing for earlier detection of disease states. We previously reported that Raman spectroscopy differentiated NAWM from MS patients and healthy controls without staining or damaging the samples. Design/Methods: Snap-frozen post-mortem WM tissue sections (10μm) were analysed by Raman micro-spectroscopy. Using a Thermo Nicolet DXR™ Raman Microscope operating with a 532nm laser, 80 points were analysed from each sample. Spectral data was then subjected to multivariate analysis. Parallel tissue sections were subjected to histology and immunohistochemistry in order to guarantee similar level of tissue preservation and disease activity (no visible demyelination, low levels of inflammation and microglia activation) amongst all samples. Samples were also closely matched to brain location, post-mortem interval, age and gender. Results: It was possible to separate NAWM from primary and secondary progressive MS samples based on their Raman spectroscopic profiles despite no visible differences in overall demyelination, inflammation and/or microglia activation levels. This separation was dominated by differences in C-H bonding assignments of lipids, which are suggested to be more asymmetrical in primary progressive disease. These findings are supportive of an underlying difference in the lipid intramolecular packaging between primary and secondary forms of disease progression. Conclusions: To our knowledge this is the first time different profiles are reported between NAWM of primary and secondary progressive MS. We demonstrated the ability of Raman spectroscopy to identify significant differences mainly at lipid level suggesting different pathology mechanisms might take place. We are currently investigating these differences further. Disclosure: Dr. Ramos has nothing to disclose. Dr. U Rehman has nothing to disclose. Dr. Sharrack has nothing to disclose. Dr. Woodroofe has nothing to disclose.