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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values (r = 0.479, P = 0.004). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF- α . Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability.
    Multiple sclerosis international. 01/2013; 2013:265259.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS). Objectives To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS). Methods This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons. Results SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes. Conclusions Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.
    NeuroImage: Clinical. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Fingolimod (FTY) is a new oral drug for multiple sclerosis. It acts as a functional antagonist for sphingosine 1-phosphate receptor (S1PR). After phosphorylateion by sphingosine kinase in vivo, FTY binds to S1PR on lymphocytes to downregulate S1PR, thereby preventing lymphocyte egress from lymphoid tissues to reduce infiltration of autoreactive lymphocytes into the central nervous system. FTY easily passes through the blood–brain barrier and directly affects cells in the central nervous system. Recently, we have shown that FTY exerts neuroprotective effects by suppressing pro-inflammatory functions of glial cells and by upregulating neuroprotective functions of neuronal and glial cells in vitro. In the present study, we examined whether FTY exerts neuroprotective effects in vivo in the chronic phase of experimental autoimmune encephalomyelitis (EAE).Methods Myelin oligodendrocyte glycoprotein-induced EAE mice were orally treated with FTY (1 mg/kg/day) or vehicle (water) once a day starting at the disease peak (15 days after immunization). To evaluate gliosis and axonal damage, the lumbar spinal cords were examined immunohistochemically at 28 days after immunization.ResultsFTY treatment starting at disease peak improved the severity of symptoms, and reduced gliosis and axonal damage in the spinal cord, as assessed by glial staining and formation of neuritic bead/spheroid.ConclusionsFTY exerts protective effects on axonal impairments during the chronic phase of EAE. The neuroprotective effect of FTY could synergistically suppress pathology of multiple sclerosis with its immunosuppressive effect.
    Clinical and Experimental Neuroimmunology. 06/2014;

Full-text (2 Sources)

Available from
May 23, 2014