Development of biomarkers for multiple sclerosis as a neurodegenerative disorder |
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Authors: | Ziemann Ulf Wahl Mathias Hattingen Elke Tumani Hayrettin |
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Affiliation: | Department of Neurology, Goethe-University, Frankfurt am Main, Germany. u.ziemann@em.uni-frankfurt.de |
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Abstract: | Multiple sclerosis (MS) is the most common neurological disorder leading to permanent disability in young adults in the developed world. While traditionally conceived as an autoimmune inflammatory disease it is becoming increasingly evident that axonal and neuronal degeneration occur, at least partly independent of inflammation, and already at the earliest stages of the disease. In addition, it is the progressive neurodegeneration which determines the amount of accumulating clinical disability. Therefore, MS should be considered as a neurodegenerative disorder. Development of disease-modifying drugs to treat MS is currently highly dynamic. Already, several drugs have shown short-term efficacy to delay progression of clinical disability, but the ultimate aim is to halt disease progression. In this context, the development of sensitive, reliable and valid biomarkers to measure neurodegeneration is an indispensible need to facilitate successful informative clinical trials. While no such biomarker is currently fully established, several promising candidate biomarkers obtained with multimodal techniques, including cerebrospinal fluid and serum analysis, neuroimaging and neurophysiology, are presently developed and evaluated. This paper compiles an up-to-date critical review of the available knowledge of candidate biomarkers of neurodegenerative processes in MS. |
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Keywords: | CDMS, clinically definite multiple sclerosis CIS, clinically isolated syndrome CMCT, central motor conduction time CNS, central nervous system CSF, cerebrospinal fluid DMD, disease-modifying drug DTI, diffusion tensor imaging DWI, diffusion weighted imaging EDSS, expanded disability status scale EEG, electroencephalography EP, evoked potential FA, fractional anisotropy fMRI, functional magnetic resonance imaging GFAP, glial fibrillary acidic protein INF, interferon MBP, myelin basic protein MD, mean diffusivity MEG, magnetoencephalography MEP, motor evoked potential MMP, metalloproteinase MOG, myelin oligodendrocyte glycoprotein MRI, magnetic resonance imaging MRS, magnetic resonance spectroscopy MS, multiple sclerosis MTR, magnetization transfer ratio NAA, N-acetyl-aspartate NAGM, normal appearing gray matter NAWM, normal appearing white matter OCB, oligoclonal band OCT, optical coherence tomography PET, positron emission tomography PLP, proteolipid protein PPMS, primary progressive multiple sclerosis RCT, randomized clinical trial RNFL, retinal nerve fiber layer RRMS, relapsing-remitting multiple sclerosis sICAM, soluble intercellular adhesion molecule SPMS, secondary progressive multiple sclerosis TMS, transcranial magnetic stimulation TNF-α, tumor necrosis factor alpha TST, triple-stimulation technique UCCA, upper cervical cord area VEP, visual evoked potential |
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