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Multiple Sclerosis
Management of Early Multiple Sclerosis
a report by
Andrew Chan
Department of Neurology, Ruhr University Bochum, St Josef Hospital
Relapsing remitting multiple sclerosis (RRMS) accounts for Surrogate Parameters – Initial Cranial Magnetic Resonance
approximately 90% of MS cases and first presents with a Imaging Identifies Clinically Isolated Syndrome Patients
demyelinating neurological attack, the clinically isolated syndrome Who Are ‘At Risk’
(CIS). Despite full clinical recovery from CIS in most patients, subclinical While the majority of CIS patients experience further relapses, defining
tissue damage may persist and accumulate over time. Supported by MS, the disease remains monophasic in a proportion of patients. Given
histopathological and radiological data demonstrating active disease this population on the one hand, but early irreversible tissue damage in
with potentially irreversible damage even at early disease stages, the other patients, a major aim is to identify parameters that can predict
beneficial impact of early immunomodulatory intervention on risk of further relapses and accrual of disability after CIS. Currently,
subsequent disease evolution can now be demonstrated. Here I will cranial (c)MRI is the best validated method of identifying CIS patients
review the pathological, radiological and clinical data supporting early with a high risk of experiencing further relapses. Long-term observation
therapy of MS and also the ongoing controversy on early of a CIS cohort reported by the group from the National Hospital for
immunomodulatory treatment. Neurology and Neurosurgery (NHNN) at Queen’s Square, London
corrobated the predictive value of the initial cMRI. Here, the risk of
Histopathological and Radiological Studies – suffering further relapses is related to the initial cMRI lesion load, which
Early Multiple Sclerosis Is Not Silent may also be associated with the degree of long-term disability.
4
Axonal pathology in MS was described as early as the 19th century.
However, it was only in the late 1990s that methodologically advanced Similar findings have been reported for other cohorts. Thus far, no
histopathological studies led to a reappraisal of the concept of other biological markers characterising CIS patients who are ‘at risk’
irreversible axonal damage underlying persistent disability. have been unequivocally identified. Initial high expectations after a
report on the value of serum antibodies against components of central
A series of elegant studies demonstrated that axonal transection myelin to predict the risk of suffering further relapses after CIS were
occurs early during the disease and is at least initially associated with not met due to lack of reproduction of these findings in other
ongoing tissue inflammation.
1
Using different non-conventional cohorts.
5,6
However, the role of antimyelin antibodies as surrogate
magnetic resonance (MR) techniques, such as magnetisation transfer parameters and optimal detection methods and their potential
and MR spectroscopy, widespread tissue damage and axonal pathogenetic implications are currently still under investigation.
dysfunction can also be identified radiologically during early MS, even
in areas without overt lesions on conventional MR imaging (MRI). Clinical Studies – Evidence in Favour of Early
Immunomodulatory Treatment
Functional re-organisation of neuronal networks and/or compensation Given the data demonstrating highly active disease even at early
by redundant mechanisms are thought to contribute to rapid clinical stages, it was soon suggested that immunotherapy initiated
recovery after CIS, again emphasising widespread alterations during immediately after disease onset could have an impact on subsequent
this early disease phase.
2
This initially subclinical tissue damage can clinical course. Three phase III randomised, placebo-controlled trials
accumulate over time and pose a substantial risk for disease have investigated the effects of initiating immunomodulatory therapy
progression and disability during later disease stages. Clinically, this in CIS patients with abnormal cranial MRI, thus selecting for patients
may be reflected by the impact of the early course of established MS at risk of undergoing further relapses. One major end-point common
on long-term prognosis. Thus, several longitudinal natural history to all studies was the conversion to ‘clinically definite multiple
studies demonstrate that the number of relapses during the first two sclerosis’ (CDMS) according to the Poser criteria, with the
to five years is associated with the rate of accrual of permanent demonstration of clinical temporospatial dissemination, e.g. a second
disability, with greater numbers of early episodes leading to a shorter relapse affecting a different site in the central nervous system.
interval to reach disability landmarks.
3
The Controlled High-Risk Subjects Avonex
®
Multiple Sclerosis
Prevention Study (CHAMPS) demonstrated that interferon-beta (IFN-β)
Andrew Chan is a consultant in neurology and currently serves as the Deputy Head of the
1a (30µg intramuscular once weekly; Avonex) was efficacious in
Department of Neurology, Ruhr University Bochum, St Josef-Hospital, Germany. He focuses on
neuroimmunological disorders, in particular multiple sclerosis, with major interests in the
delaying the development of a second relapse in 383 CIS patients with
immunobiology of glial cells and the mechanisms of action of immune therapeutics. He serves
at least two lesions on T2-weighted cMRI suggestive of MS.
7
While for
as a reviewer for neuroimmunological and neurobiological journals.
the placebo group the risk of developing CDMS at three years was
50%, IFN-β1a treatment reduced the risk to 35%.
32 © TOUCH BRIEFINGS 2007
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