Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis.
ABSTRACT While there is now evidence for thalamic abnormality in established secondary progressive and relapsing-remitting multiple sclerosis (MS), it remains unclear when such abnormality begins. This study investigated the emergence of thalamic abnormality in relapsing-remitting MS by assessing the thalamic magnetization transfer ratio (MTR) in a cohort with clinically early disease. Twenty-three patients with early relapsing-remitting MS (mean age 37; mean disease duration 1.9 years; Expanded Disability Status Scale (EDSS) range 0-3) and 19 healthy controls (mean age 34) were imaged yearly with a magnetization transfer imaging sequence. Twenty-two MS patients and 14 controls completed two-year follow-up. Regions of interest were placed in both thalami and mean thalamic MTR calculated. At baseline, significant differences between patient and control thalamic MTR were not observed. However, at years one and two, the thalamic MTR in patients was significantly lower than control MTR. Although baseline lesion volume did not correlate with baseline thalamic MTR, at year one, an association between baseline lesion volume and year one thalamic MTR emerged. There was also a significant inverse correlation between EDSS and thalamic MTR (r = -0.47, P = 0.02). The study suggests that thalamic involvement occurs within the first five years of MS onset, when most patients are still minimally disabled.
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ABSTRACT: We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures. To assess the relevance of gray matter changes over time to changes in cognition in RRMS. A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. Two university MS clinics. Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5). We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving. We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.JAMA Neurology 08/2007; 64(8):1157-61. · 7.58 Impact Factor
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ABSTRACT: Magnetization transfer (MT) magnetic resonance imaging (MRI) can provide in vivo quantitative estimates of microscopic tissue damage in normal-appearing white matter (NAWM) and gray matter (GM) from patients with multiple sclerosis (MS). To determine whether a one-time MT MRI can provide markers of short-term disease evolution in patients with relapsing-remitting MS. Eighteen-month observational study. Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele. Twenty-two patients with untreated relapsing-remitting MS. Relapse rate; disability according to the Expanded Disability Status Scale (EDSS); dual-echo, 2-dimensional gradient echo with and without a saturation MT pulse and T1-weighted MRIs of the brain; and MT ratio (MTR) histograms for NAWM and GM. During the study period, 13 patients (59%) experienced 25 relapses. The median EDSS score was 1.25 (range, 0-3.5) at study entry and 1.75 (range, 0-3) at study exit. Significant, although moderate, correlations were found between average GM MTR values at baseline and EDSS changes during the study period (r = -0.44; P = .04). A trend was observed for the correlation between NAWM MTR values at baseline and the EDSS changes throughout 18 months (r = -0.42; P = .05). For the relation between EDSS changes and baseline GM MTR, the slope of the regression line was -0.5 (95% confidence interval, -1.0 to 0.0), indicating that a decrease in the baseline GM MTR of 1% predicted an increase in the EDSS score of 0.5 point throughout the 18 months. This study indicates that a "snapshot" MT MRI assessment detects subtle brain tissue changes that are associated with short-term disability accumulation in patients with relapsing-remitting MS.JAMA Neurology 06/2006; 63(5):736-40. · 7.58 Impact Factor
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ABSTRACT: Despite a strong correlation to outcome, the measurement of gray matter (GM) atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS). This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meaning of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy (TA) with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the “yearly rate of Relative Thalamic Atrophy” (yrRTA). In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.Frontiers in Aging Neuroscience 08/2014; · 5.20 Impact Factor