Abstract

Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative disease of central nervous system. Here, we aimed to develop a method for differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated syndrome (CIS) patients, as well as to identify CIS patients who will progress to RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and multivariate analysis. Spectral analyses demonstrated significant differences in the molecular contents, especially in the lipids and Z conformation of DNA of CSF from CIS, CIS to RRMS transformed (TCIS) and RRMS groups. These changes enables the discrimination of diseased groups and controls (individuals with no neurological disease) from each other using hierarchical cluster and principal component analysis. Some CIS samples were consistently clustered in RRMS class, which may indicate that these CIS patients potentially will transform to RRMS over time. Z-DNA band at 795 cm−1 that is existent only in diseased groups and significant increase in carbonyl amount, decrease in amideI/amide II and lipid/protein ratios observed only for RRMS groups can be used as diagnostic biomarkers. The results of the present study shed light on the early diagnosis of RRMS by IR spectroscopy complemented with multivariate analysis tools.

Highlights

  • Multiple sclerosis (MS) affects approximately 2.5 million people worldwide, ranking as one of the most prevalent neurodegenerative disease, and is the cause of disability among young adults especially in Europe and North America[1]

  • Fourier transform infrared (FTIR) spectroscopy has had an important role in the field of disease diagnostics in recent years[16,17,18,19], especially when complemented with Attenuated Total Reflectance (ATR) due to its rapidity and ease to put into clinical practice

  • Different chemometric methods such as Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) together with FTIR spectral measurements have been successfully used in screening and diagnosis[20], providing highly sensitive and specific discrimination of diseases based on spectral differences

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Summary

Introduction

Multiple sclerosis (MS) affects approximately 2.5 million people worldwide, ranking as one of the most prevalent neurodegenerative disease, and is the cause of disability among young adults especially in Europe and North America[1]. A clear discrimination between the bipolar, schizophrenic and control groups’ blood samples was obtained by FTIR spectroscopy and multivariate analysis methods[33]. During the course of the disease progression, subtle biochemical and structural alterations throughout the cerebellum and spinal cords of EAE not detected by conventional histological methods were observed by FTIR spectroscopy as an early indication of the clinical signs of EAE28. All these studies are limited to tissue sampling. It is eminent to discover new methods that better discriminate MS from other CNS diseases

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