Investigacion

Horakova et al. BMC Neurology 2012, 12:10 http://www.biomedcentral.com/1471-2377/12/10

REVIEW

Open Access

Clinical correlates of grey matter pathology in multiple sclerosis
Dana Horakova*†, Tomas Kalincik†, Jana Blahova Dusankova and Ondrej Dolezal
Abstract Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has latelybeen subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals withmultiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improvethe prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect. Review Multiple sclerosis (MS) is known for the great variability of its clinical presentations, spanning the relapsingremitting course with a subsequent secondary progressive phase, primary progressive course andrelapsingprogressive course. The rate of disability accumulation varies from a lack of disease activity (benign MS) to rapidly progressing (malignant) MS [1] with a range of possible neurological manifestations. Therefore, the view of MS as a heterogeneous entity resulting from a number of inter-related etiopathogenetic cascades has been receiving increasing scientific attention [2-4]. The role of the immunesystem is likely to be pivotal in the disease pathogenesis, however, direct causality is yet to be established [5,6]. Surrogate markers such as magnetic resonance imaging (MRI), optic coherent tomography and susceptibility genes may elucidate the great clinical variability arising from the complex etiopathogenesis. On the diagnostic level, these might help to identify the specific subtypes of diseasein individual patients, predict the future MS course, and develop individually tailored therapeutic regimens [7,8].
* Correspondence: dana.horakova@vfn.cz † Contributed equally Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic

The currently availabletherapies, which are based mainly on their anti-inflammatory properties, are imperfect, with a number of patients showing only sub-optimal control over the MS activity [9]. It is therefore important that clinicians are able to predict the future response to treatment in individual patients early after disease onset in order to allow for the most appropriate treatment to be chosen [10]. Furthermore,the treatment, once administered, needs to be monitored to verify its efficacy. In both instances, surrogate markers may play significant roles [11,12]. Among different surrogate markers, MRI has been the only one used routinely in clinical practice. The traditional view of MS as a disease affecting predominantly white matter (WM) was driven by the higher sensitivity of the conventional MRItechniques to the WM changes [13-15]. However, these changes proved to be insufficient to explain the broad spectrum of neurological and psychological manifestations of MS satisfactorily [16-22]. Novel MRI techniques with improved sensitivity to grey matter (GM) changes [23-28] have shown that the GM damage is more prevalent than first estimated [29-34], that it may even precede development of the WM...