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: 2.56). 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.

0 Bookmarks
 · 
231 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple sclerosis (MS) and epilepsy are common disorders, the co-occurrence of which has been of considerable interest. This study aimed to evaluate the prevalence and clinical features of epileptic seizures in patients with definite MS including those with pediatric onset (≤16 years of age). Out of 2,300 patients with definite MS followed in our outpatient clinic, 36 with epileptic seizures were identified. In this cohort, 8 out of 146 pediatric cases had seizures. The clinical and demographic features of the patients were recorded. Multiple logistic regression model with the occurence of seizures as the dependent variable was performed to identify the risk factors for seizure occurrence in MS patients. The prevalence of epileptic seizures was 1.5 % in definite MS patients, 1.3 % in adult-onset (comparable to seizure prevalence in the general population) and 5.5 % in pediatric MS patients (≤16 years old). Twenty-six of 36 (72 %) patients with MS and epilepsy developed recurrent seizures after the first epileptic seizure. Mean annual relapse rate (p ≤ 0.001), mean expanded disability status scale (EDSS) score (p = 0.004) and the ratio of patients with pediatric onset (p = 0.01) were higher in MS patients with seizures. In the multiple logistic regression analysis, age at MS onset and EDSS at the last examination were found to be predictors of seizure occurrence. Occurrence of seizures during the clinical course of MS appears to be associated with early-onset and increased disease severity and might be coincidental in adults.
    Acta neurologica Belgica. 05/2013;
  • [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: Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS.
    PLoS ONE 01/2013; 8(12):e82848. · 3.53 Impact Factor

Full-text (2 Sources)

View
55 Downloads
Available from
May 23, 2014