Biological Markers of Prognostic Value in Multiple Sclerosis

Biological Markers of Prognostic Value in Multiple Sclerosis

Berger Thomas, Di Pauli Franziska, Reindl Markus
Published: European Neurology - Volume 3 Issue 2
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Multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system (CNS), is the most common neurological disease among young adults, and carries the potential risk of permanent disability. The pathological hallmarks of the disease are multifocal white (and, most recently, also grey) matter lesions, which are characterised by variable extents of inflammation, demyelination, axonal loss, gliosis and atrophy.1 MS has variable clinical presentations and highly heterogeneous disease courses, ranging from rare acute fulminate forms to benign MS without substantial disability. Eighty-five per cent of patients initially present with a clinically isolated syndrome (CIS); most of these patients go on to develop relapsing–remitting (RR) MS, with acute relapses alternating with periods of clinical remission or stability.2 Ultimately, more than half of (untreated) RRMS patients convert to secondary chronic progressive (SP) MS, which is characterised by accumulating neurological disability with or without superimposed relapses.3 The clinical outcome of MS is largely unpredictable for individual patients. The great variability of this complex disease highlights the need for reliable biological markers with high sensitivity and specificity that are able to predict the future disease course and treatment response. Furthermore, stratification of MS patients with regard to their dominating pathological processes would allow individualised differential therapeutic concepts. In this review, we discuss the prognostic value of biological markers that are currently under debate, including magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) parameters and antibodies.

Markers to Predict Disease Progression

Magnetic Resonance Imaging as a Prognostic Marker
MRI is a well established tool for the diagnosis4 and management of MS that allows disease activity and progression to be monitored. The lesions detected on T2-weighted and gadolinium (Gd)-contrast-enhanced T1-weighted MRI reflect the pathological hallmark of the disease: the T2 lesion burden seems to be correlated with the number of preceding relapses5 and the use of Gd enables visualisation of blood–brain barrier disruption and therefore inflammatory disease activity.6 Thus, MRI has become a relevant surrogate outcome marker in MS clinical trials. Doubtless, MRI has its greatest relevance in patients with a CIS: evidence of dissemination of MS lesions in space and time and the extent of MRI activity are robust predictors of a first relapse.7,8 However, since commonly used MRI techniques show only a weak association with future disability,9 their prognostic value is limited and they are not useful for predicting clinical outcome in individual patients.10 Poor clinicoradiological correlations may be due to either insensitive clinical rating scales or methodological difficulties in the detection of pathological alterations, especially axonal damage, within the normal-appearing white (NAWM) and grey matter (NAGM).10,11 Neuropathology demonstrates that axonal loss, which seems to be the substrate of accumulating disability, occurs not only in classic MS plaques but also in NAWM and the cortex. Imaging of axonal loss and further brain atrophy is not sufficiently reflected by conventional MRI techniques. Although it has been suggested that the degree of disability depends mainly on the extent of brain atrophy,13 until now it has not been commonly agreed upon as a prognostic marker. Newly emerging and innovative MRI techniques, such as higher-resolution imaging, brain volumetry, magnetisation transfer imaging and magnetic resonance spectroscopy, and the combination of these different imaging parameters, will be more predictive for disease progression in MS patients in the future.

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