Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS

Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 10/2010; 82(4):423-8. DOI: 10.1136/jnnp.2010.209890
Source: PubMed


To investigate whether T2 lesion load and magnetisation transfer ratio (MTR) in the normal-appearing white matter (NAWM) and grey matter (GM) at study entry are independent predictors of progression and whether their changes correlate with the accrual of disability, over 5 years in early primary progressive multiple sclerosis (PPMS).
Forty-seven patients with early PPMS and 18 healthy controls were recruited at baseline and invited to attend clinical 6-monthly assessments for 3 years, and after 5 years. Patients were scored on the Expanded Disability Status Scale and multiple sclerosis functional composite subtests (25-foot timed walk test (TWT), nine-hole peg test and paced auditory serial addition test). At each time point, all subjects underwent brain MRI including T2-weighted, magnetisation transfer and volumetric sequences. T2 lesion load (T2LL), MTR histogram parameters and volumes for NAWM and GM were calculated. Statistical analyses identified predictors of progression and correlations between MRI changes and clinical changes over time.
Baseline T2LL and GM peak location and peak height MTR were independent predictors of progression, as measured by TWT; a model including these three predictors explained 91% of the variance of the progression on TWT, a significantly higher percentage than that obtained when the predictors were modelled individually (80%, 74% and 68%, respectively). A greater progression rate correlated with a steeper increase in T2LL and a faster decline in GM mean and peak location MTR.
The combined assessment of both visible white matter damage and GM involvement is useful in predicting progression in PPMS.

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Available from: Mara Cercignani,
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    • "Several studies have demonstrated MTR reductions in MS CGM (Cercignani et al., 2001; Khaleeli et al., 2007; Tur et al., 2011; Hayton et al., 2009), but to the best of our knowledge none have investigated sulcal or gyral crown localisation of abnormalities within the cortical ribbon, or directly compared CGM MTR values in RRMS, SPMS, PPMS and healthy controls. "
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    ABSTRACT: Abstract Background: Histopathology has demonstrated extensive cortical grey matter (GM) demyeli- nation in multiple sclerosis (MS), and suggests that sulcal folds may be preferentially affected, particularly in progressive MS. This has not been confirmed in vivo, and it is not known if it is relevant to clinical status. Objectives: To determine sulcal and gyral crown magnetisation transfer ratio (MTR) in MS cortical GM, and the MTR associations with clinical status. Methods: We measured sulcal and gyral crown cortical GM MTR values in 61 MS patients and 32 healthy controls. Disability was measured using Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores. Results: MTR values were reduced in sulcal and gyral crown regions in all MS subtypes, more so in secondary progressive (SP) MS than relapsing remitting (RR) MS, and similarly in primary progressive (PP) MS and RRMS. Sulcal MTR was lower than gyral crown MTR in controls, PPMS and RRMS patients, but not in SPMS. MTR correlated with clinical status in RRMS and SPMS, but not PPMS. Conclusions: Cortical pathology, as reflected by MTR, is present in all MS subtypes and most pronounced in SPMS. A preferential disease effect on sulcal cortical regions was not observed. Cortical MTR abnormalities appear to be more clinically relevant in relapse-onset rather than progressive-onset MS. & 2013 Elsevier B.V. All rights reserved.
    Multiple Sclerosis and Related Disorders 01/2013; 2(3). DOI:10.1016/j.msard.2013.01.001 · 0.88 Impact Factor
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    • "The mechanisms responsible for the inter-individual variation in the extent of GM and WM pathology are largely unknown, and their identification will significantly contribute to the understanding of the MS etiopathogenesis. On the diagnostic level, GM atrophy and lesions provide information complementary to the conventional MRI variables and further improve correlation between the radiological and clinical variables [118,183]. Thus, GM pathology may not only serve as a new marker for the existing immunomodulatory therapies but may also provide a potential target for novel therapies. "
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    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.
    BMC Neurology 03/2012; 12(1):10. DOI:10.1186/1471-2377-12-10 · 2.04 Impact Factor
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    ABSTRACT: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.
    Multiple Sclerosis 07/2011; 17(11):1324-32. DOI:10.1177/1352458511410341 · 4.82 Impact Factor
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