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Multiple Sclerosis
Biological Markers of Prognostic Value in Multiple Sclerosis
a report by
Franziska Di Pauli, Markus Reindl and Thomas Berger
Neuroimmunological and Multiple Sclerosis Clinic and Research Unit, Clinical Department of Neurology, Innsbruck Medical University
Multiple sclerosis (MS), a chronic inflammatory disorder of the central debate, including magnetic resonance imaging (MRI), cerebrospinal fluid
nervous system (CNS), is the most common neurological disease among (CSF) parameters and antibodies.
young adults, and carries the potential risk of permanent disability. The
pathological hallmarks of the disease are multifocal white (and, most Markers to Predict Disease Progression
recently, also grey) matter lesions, which are characterised by variable
extents of inflammation, demyelination, axonal loss, gliosis and atrophy.
1
Magnetic Resonance Imaging as a Prognostic Marker
MS has variable clinical presentations and highly heterogeneous disease MRI is a well established tool for the diagnosis
4
and management of MS
courses, ranging from rare acute fulminate forms to benign MS without that allows disease activity and progression to be monitored. The lesions
substantial disability. Eighty-five per cent of patients initially present with detected on T2-weighted and gadolinium (Gd)-contrast-enhanced
a clinically isolated syndrome (CIS); most of these patients go on to T1-weighted MRI reflect the pathological hallmark of the disease: the T2
develop relapsing–remitting (RR) MS, with acute relapses alternating with lesion burden seems to be correlated with the number of preceding
periods of clinical remission or stability.
2
Ultimately, more than half of relapses
5
and the use of Gd enables visualisation of blood–brain barrier
(untreated) RRMS patients convert to secondary chronic progressive (SP) disruption and therefore inflammatory disease activity.
6
Thus, MRI has
MS, which is characterised by accumulating neurological disability with or become a relevant surrogate outcome marker in MS clinical trials.
without superimposed relapses.
3
The clinical outcome of MS is largely Doubtless, MRI has its greatest relevance in patients with a CIS: evidence
unpredictable for individual patients. The great variability of this complex of dissemination of MS lesions in space and time and the extent of MRI
disease highlights the need for reliable biological markers with high activity are robust predictors of a first relapse.
7,8
However, since
sensitivity and specificity that are able to predict the future disease course commonly used MRI techniques show only a weak association with
and treatment response. Furthermore, stratification of MS patients with future disability,
9
their prognostic value is limited and they are not useful
regard to their dominating pathological processes would allow for predicting clinical outcome in individual patients.
10
Poor clinico-
individualised differential therapeutic concepts. In this review, we discuss radiological correlations may be due to either insensitive clinical rating
the prognostic value of biological markers that are currently under 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
Franziska Di Pauli is a staff member of the
Neuroimmunological and Multiple Sclerosis Clinic and
that axonal loss, which seems to be the substrate of accumulating
Research Unit in the Clinical Department of Neurology, disability, occurs not only in classic MS plaques but also in NAWM and
Innsbruck Medical University, where she is enrolled in the
the cortex. Imaging of axonal loss and further brain atrophy is not
PhD programme in neurosciences. Her main research
interests in multiple sclerosis are biological markers with their
sufficiently reflected by conventional MRI techniques. Although it has
neuroimmunological, clinical and magnetic resonance
been suggested that the degree of disability depends mainly on the
imaging correlations and the impact of environmental factors.
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,
Markus Reindl is an Associate Professor of Neuroscience and
Head of the Neurological Research Laboratory in the Clinical
magnetisation transfer imaging and magnetic resonance spectroscopy,
Department of Neurology at Innsbruck Medical University. and the combination of these different imaging parameters, will be more
His main interest is clinical immunology of multiple sclerosis,
predictive for disease progression in MS patients in the future.
with a strong research focus on antibodies and B cells.
Oligoclonal Bands
The qualitative and quantitative measurement of elevated
immunoglobulins (IgG) in the CSF of MS patients is the only laboratory
Thomas Berger is an Associate Professor of Neurology and
Head of the Neuroimmunological and Multiple Sclerosis
biomarker included in MS diagnostic criteria. Isoelectric focusing (IEF) is
Clinic and Research Unit in the Clinical Department of the best qualitative method for detection of oligoclonal bands (OCBs),
14
Neurology at Innsbruck Medical University. His main
and has a sensitivity higher than 95% in MS
15
and a specificity generally
scientific interests regard immunopathogenetic heterogeneity
of multiple sclerosis and the identification and
considered to be more than 86%.
14
The value of the presence of OCBs
characterisation of diagnostic/prognostic biological markers
to predict future disability remains controversial.
16,17
in multiple sclerosis.
E:
thomas.berger@i-med.ac.at
IEF also allows the detection of oligoclonal IgM bands,
18
which seem to
be predictive for a more severe disease course with a shorter time period
94 © TOUCH BRIEFINGS 2008
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