Biological Markers of Prognostic Value in Multiple Sclerosis

Abstract

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 MarkerMRI is a well established tool for the diagnosis 4 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 relapses 5 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 t...

Freezing influences, the exposure of IgG glycans in sera from multiple sclerosis patients

“…The marker used most often is oligoclonal IgG bands in cerebrospinal fluid with sensitivity of >90%, but low specificity of ~35% and the need for cerebrospinal fluid samples [16,17]. The most reliable serum markers of MS are antibodies to myelin oligodendrocyte glycoprotein (MOG) or myelin basic protein (MBP) that provide specificity and sensitivity in the range of 60 to 85% [18,19]. The combination of antibody testing towards MOG, MBP and α-βcrystallin, with the diagnostic criteria being the presence of 2 out of 3 parameters, provides a specificity of 80-95% and sensitivity of 40-60% [20].…”