Vaithianathar L, Tench CR, Morgan PS, Constantinescu CS
J Neurol 2003 Mar;250(3):307-15
University Hospital, Queens Medical Centre, Faculty of Medicine, Division of Clinical Neurology, Nottingham, NG7 2 UH, UK
The Spinal Cord is a common site of involvement in Multiple Sclerosis (MS) where pathology contributes substantially to locomotor disability.
Previous studies have demonstrated significant correlations between clinical disability and Cervical Cord Atrophy, but not with Cord T2 lesion load.
We evaluate Cervical Cord pathology using, for the first time, quantitative T1 relaxation time (T1), which shows HistoPathological specificity for tissue damage in the Cerebral White Matter.
Cervical Cord T1 was compared in 15 MS patients [8 Relapsing/Remitting (RR), 7 Secondary/Progressive (SP)] and 6 healthy controls.
And related to normalized Upper Cervical Cord Area (UCCA), Cerebral White Matter T1, T2 lesion load and disability measures including the Expanded Disability Status Scale (EDSS), Ambulation Index (AI) and timed 25-foot walk.
T1 maps of the Brain and Cervical Cord were acquired using a high-resolution, 3-dimensional fast low-angle shot sequence. Dual-echo sequences were also obtained.
Median Cervical Cord T1 [mean (standard deviation)] was significantly greater in RR [854  ms] (p = 0.0006) and SP patients [927  ms] (p < 0.0001) compared with controls [888  ms], and in SP vs. RR patients (p = 0.002).
In the overall patient cohort, it correlated significantly with median Cerebral White Matter T1 (r = 0.7, p = 0.0046), UCCA (r = -0.87, p < 0.0001), but not T2 lesion loads.
Both median Cervical Cord T1 and UCCA (respectively) correlated significantly with the EDSS (r = 0.55, p = 0.03; r = -0.54, p = 0.04), AI (r = 0.77, p = 0.001; r = -0.60, p = 0.02) and timed 25-foot walk (r = 0.56, p = 0.03; r = -0.55, p = 0.04).
Cervical Cord T1 distinguishes between MS subgroups and could also prove a useful surrogate outcome measure in MS.
The relation of Cervical Cord T1 to Cerebral White Matter T1 suggests that Cord pathology may be influenced by tissue damage upstream.
De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi ML, Guidi L, Ghezzi A, Montanari E, Cifelli A, Federico A, Smith SM
Neurology 2003 Apr 8;60(7):1157-62
Institute of Neurological Sciences, University of Siena, Italy
To assess Cortical Gray Matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of White Matter (WM) in patients with the Relapsing/Remitting (RR) and Primary/Progressive (PP) forms of the disease.
Conventional MRI examinations were obtained in patients with Definite MS who had either the RR or the PP form of the disease.
An automated analysis tool was used with conventional T1-weighted MR images to obtain total and Cortical Brain Volumes normalized for head size.
Total Brain lesion load was estimated on conventional proton density and T1-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed.
Normalized Cortical Volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5).
NCV decreases in both patients groups were detected even in those patients with short disease duration (< 5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal Brain lesion volume (< 5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS).
Measures of NCV in individual patients were negatively correlated with T1-weighted lesion volume (r = -0.47, p < 0.001) and disease duration (r = -0.25, p < 0.05) only in the patients with RR MS.
NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = -0.64, p < 0.0001) than for RR (r = -0.27, p = 0.04) MS patients.
These data confirm substantial NeoCortical volume loss in MS patients and suggest that NeoCortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to Neurologic impairment.
Although a proportion of this NeoCortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent NeuroDegenerative process also is active.
Brain Tissue Volume Changes In Relapsing/Remitting Multiple Sclerosis: Correlation With Lesion Load
Quarantelli M, Ciarmiello A, Morra VB, Orefice G, Larobina M, Lanzillo R, Schiavone V, Salvatore E, Alfano B, Brunetti A
NeuroImage 2003 Feb;18(2):360-6
National Council for Research, BioStructure and BioImaging Institute, Building 10, Via Pansini 5, 80131 Naples, Italy
The aim of this study was to simultaneously measure in vivo volumes of Gray Matter (GM), normal White Matter (WM), Abnormal White Matter (aWM), and CerebroSpinal Fluid (CSF).
And to assess their relationship in 50 patients with Relapsing/Remitting Multiple Sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to Brain MR studies.
Tissue volumes were normalized to total IntraCranial Volume providing corresponding Fractional Volumes (fGM, faWM, fWM, and fCSF).
Subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70).
In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001).
No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%).
faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM.
There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and Fractional Volumes.
Brain Atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.