Article

Clinical correlates of grey matter pathology in multiple sclerosis

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.
BMC Neurology (Impact Factor: 2.49). 03/2012; 12:10. DOI: 10.1186/1471-2377-12-10
Source: PubMed

ABSTRACT Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been 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 with multiple 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 improve the 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.

Download full-text

Full-text

Available from: Ondrej Dolezal, Jun 17, 2015
0 Followers
 · 
261 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Decision-making is an essential function of everyday life. Decision making under explicit risk requires developing advantageous decision strategies based on known outcomes (e.g., probabilities of winning or losing a bet). Decision making and its neural substrates have been rarely studied in MS. We expected performance in decision making under risk to be lowered in MS patients, and negatively correlated with disease-related disability, cognition, and ventricular width. Three groups were included: 32 MS patients and 20 healthy controls were examined with conventional neuropsychological tests and the Game-of-Dice Task (GDT) assessing decision-making under explicit risk. Linear 2-D ventricular width was assessed on MS patients' clinical MRIs and compared to a third group, 20 non-MS neurological control patients. Compared to healthy controls, MS patients showed impaired GDT and neuropsychological performance, depending on the MS-subtype (relapsing-remitting (RR), n = 22; secondary progressive, n = 10) and disability severity among RR-MS patients. In MS patients, GDT performance correlated with processing speed, intercaudate ratio, and third ventricle ratio (p's < 0.05). Mediation analysis showed that the link between GDT performance and processing speed was fully explained by ventricular size. Decision-making under explicit risk was reduced in MS patients, but only those with more pronounced disability. Independent of processing speed, decision-making under explicit risk correlates inversely with central atrophy in MS.
    BMC Neurology 04/2015; 15(1):61. DOI:10.1186/s12883-015-0318-0 · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: From 1868, when Charcot first described the clinical features and the pathologic correlates, up till the present day, multiple sclerosis (MS) has commonly been characterized by the symptoms caused by inflammatory plaques in the white matter of the brain and spinal cord. Early use of magnetic resonance imaging (MRI) to diagnose MS focused on detecting these white matter lesions. By the 1990s, researchers recognized that many patients with MS have cognitive deficits that can cause severe disability, and also determined the associated pathology; these findings shed more light on both the pathogenesis and progression. Since 2004, several lines of evidence have shown that the extent of white matter plaques identified on MRI does not correlate well with cognitive deficits. High-resolution MRI and advances in immunohistochemical techniques have enabled detection of cortical demyelination early in the course, correlating with cognitive deficits. Late in the course, pathologic changes in normal-looking white and gray matter correlate more closely with progressive cognitive deficits than with visual, sensory, and motor symptoms. This finding implies the need to redefine the disease and its progression. In this review, we discuss the histopathologic studies of cortical plaques in MS and early indications about their role in disease definition and progression, describe the role of high-resolution MRI in staging and determining progression of cognitive symptoms, and discuss how advances in these areas are forcing us to rethink diagnosis and determination of progression.
    Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 03/2014; 27(1):1-7. DOI:10.1097/WNN.0000000000000023 · 1.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple sclerosis (MS) has traditionally been considered to be primarily an inflammatory demyelinating disorder affecting the white matter. Nowadays it is recognized as both an inflammatory and a neurodegenerative condition involving the white and grey matter. Grey matter atrophy occurs in the earliest stages of MS, progresses faster than in healthy individuals, and shows significant correlations with cognitive function and physical disability; indeed, brain atrophy is the best predictor of subsequent disability and can be measured using magnetic resonance imaging (MRI). There are a number of MRI methods for measuring global or regional brain volume, including cross-sectional and longitudinal techniques. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article summarizes the knowledge on brain volume in MS.