Gonen O, Oberndorfer TA, Inglese M, Babb JS, Herbert J, Grossman RI
AJNR Am J NeuroRadiol 2007 Feb;28(2):267-71
New York University School of Medicine, Department of Radiology, New York, NY
Background And Purpose
The cross-sectional rate of Whole-Brain N-AcetylAspartate (NAA, a Neuronal cell marker) loss in clinically similar Relapsing/Remitting Multiple Sclerosis (RRMS) patients has recently been shown to fall into 3 distinct decline rate strata.
Our goal was to test the reproducibility of this observation in a new cohort of RRMS patients.
Materials And Methods
Sixteen serial patients (12 women, 4 men, median age 38 [27-55] years) with clinically definite RRMS for an average of 5 (0.3-18) years' disease duration and a mean Expanded Disability Status Score of 2.0 (0-6) were studied, once each.
Their Whole-Brain NAA (WBNAA) amounts, obtained with proton MR Spectroscopy, were divided by Brain Volumes (segmented from MR imaging) to yield concentrations suitable for cross-sectional comparisons.
Three distinct strata of cross-sectional NAA decline rates were found: -0.031, -0.32, and -1.71 mmol/L/y when disease duration was estimated from confirmed diagnosis, or -0.057, -0.20, and -1.38 mmol/L/y when measured from the first clinical symptom.
These rates and their corresponding fractions of the study population were indistinguishable from those reported previously in a different group of 49 clinically similar (mean Expanded Disability Status Score also 2.0) RRMS patients.
Reproducing the previous cohort's cross-sectional WBNAA decline characteristics in this new group of clinically similar RRMS patients indicates that 3 WBNAA loss strata may be a general attribute of MS.
Consequently, WBNAA could serve as a surrogate marker for the global load of Neuronal and Axonal dysfunction and damage in this disease.
Lin F, Yu C, Jiang T, Li K, Chan P
AJNR Am J NeuroRadiol 2007 Feb;28(2):278-282
Chinese Academy of Sciences, National Laboratory of Pattern Recognition, Institute of Automation, Beijing, People's Republic of China
Background And Purpose
Many studies have reported abnormal changes in Relapsing/Remitting Multiple Sclerosis (RRMS) by Histogram and region-of-interest-based methods by using Diffusion Tensor Imaging.
However, there are few studies on specific White Matter fiber tracts of RRMS.
Our study sought to use Diffusion Tensor Tractography-based group mapping to investigate the presence of abnormal Diffusion in the Normal-Appearing Pyramidal Tract (PYT) of RRMS and its possible mechanism.
A PYT probability map was first constructed from data on 20 healthy patients based on the deterministic-based Tractography method.
The PYT probability map was then applied to 29 RRMS patients to calculate Diffusion indices of the PYT.
In this study, 4 quantitative indices were used to characterize the abnormal Diffusion:
- Fractional Anisotropy (FA)
- Directionally averaged Diffusion Coefficient (D(av))
- Axial Diffusion coefficient (lambda(1))
- Radial Diffusion Coefficient (lambda(23))
Compared with healthy controls, RRMS patients had a significantly higher D(av)) and lambda(23) but a lower FA and a trend toward a lower lambda(1) in the Normal-Appearing PYT.
In RRMS patients, PYT lesions had a significantly higher lambda(23) and a lower FA, but there were no differences for D(av) and lambda(1) when compared with the Normal-Appearing PYT.
Moreover, the Diffusion indices derived from the Normal-Appearing PYT were significantly correlated with PYT lesion volumes by using the Spearman correlation analysis.
Our findings confirm the presence of abnormal Diffusion in the Normal-Appearing PYT of RRMS patients and suggest that Wallerian Degeneration might be its mechanism.
Triosephosphate Isomerase- And Glyceraldehyde-3-Phosphate Dehydrogenase-Reactive AutoAntiBodies In The Cerebrospinal Fluid Of Patients With Multiple Sclerosis
Kolln J, Ren HM, Da RR, Zhang Y, Spillner E, Olek M, Hermanowicz N, Hilgenberg LG, Smith MA, van den Noort S, Qin Y
J Immunol 2006 Oct 15;177(8):5652-8
University of California, Department of Neurology, Irvine, CA 92697, USA
Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B-Cells in the CerebroSpinal Fluid (CSF) from patients with Multiple Sclerosis (MS) bind to Axons in MS Brains.
To study the Axonal Ags involved in MS, we identified the glycolytic enzymes, Triosephosphate Isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs generated from clonal B-Cells in the CSF and in lesions from MS patients.
Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%), Clinically Isolated Syndrome (CIS) suggestive of MS (40%), Other Inflammatory Neurological Diseases (OIND; 29%), and Other NonInflammatory Neurological Diseases (ONIND; 31%).
Levels of GAPDH-reactive Abs were elevated in MS patients (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%).
The coexistence of both AutoAntiBodies was detected in 10 MS patients (29%), and 1 CIS patient (3%), but not in patients with OIND/ONIND.
Two scFv-Abs generated from the CSF and from lesions of a MS Brain showed ImmunoReactivity to TPI and GAPDH, respectively.
The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to Neurons and Axons in MS.
Marrie RA, Cutter G, Tyry T, Vollmer T, Campagnolo D
Neurology 2006 Apr 25;66(8):1235-40
Cleveland Clinic Foundation, Department of Neurology, Cleveland, OH 44195, USA
To investigate differences in disability between African American and Caucasian patients with Multiple Sclerosis (MS) by comparing the relationship between current age and disability between races.
And by assessing the effect of adjustment for SocioEconomic Status (SES) on the associations.
The authors selected US participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry with an age at symptom onset of 10 to 60 years, who reported their race as Caucasian or African American (n = 21,557).
They classified participants as having mild, moderate, or severe disability in the domains of Mobility, Hand function, Cognition, and Vision.
Using Patient Determined Disease Steps and Performance Scales and assessed the association of disability with race using polytomous logistic regression.
Disability increased more rapidly with increasing disease duration in older patients, but there was no interaction between race and age.
African Americans had increased odds of severe vs mild disability in all four domains dds ratio OR [95% CI]:
- Hand 1.35 [1.10 to 1.64]
- Vision 1.75 [1.37 to 2.27]
- Cognition 1.32 [1.04 to 1.67]
- Mobility 1.32 [1.11 to 1.56]
Adjustment for all covariates, including SES, attenuated these associations OR [95% CI]:
- Hand 1.27 [1.00 to 1.61]
- Vision 1.59 [1.19 to 2.08]
- Cognition 0.98 [0.74 to 1.30]
- Mobility 1.37 [1.11 to 1.67]
Lack of adjustment for SES produced stronger associations. After enrollment in NARCOMS, disability progression did not differ between the groups.
African Americans experience greater Multiple Sclerosis-associated disability than Caucasians.
Failure to account for SocioEconomic Status leads to overestimation of these differences. Disease progression is similar in African Americans and Caucasians after diagnosis.
The Patient Knows Best; Significant Change In The Physical Component Of The Multiple Sclerosis Impact Scale (MSIS-29 Physical)
Costelloe L, O'rourke K, Kearney H, McGuigan C, Gribbin L, Duggan M, Tubridy N, Daly L, Hutchinson M
J Neurol NeuroSurg Psychiatry 2007 Mar 1
St Vincent's University Hospital, Republic of Ireland
Introduction And Aims
The aims of this study were to determine the reliability, responsiveness and minimally important change score of the MSIS-29 physical using the EDSS as an anchor measure.
214 MS patients (EDSS 0- 8.5) had concurrent MSIS-29 and EDSS assessments at baseline and at up to four years of follow-up.
Stable patients. 116 patients had unchanged EDSS scores.
Stability of the MSIS-29 physical (mean change 0.1 points) was better in the 85 patients with EDSS 0 to 5.0 than in the 31 patients with EDSS 5.5 to 8.5.
In whom the MSIS-29 physical score fell by eight points, a response shift phenomenon. A floor effect for the MSIS-29 was observed in 5% of stable patients at both time points. Changed Patients.
98 patients experienced EDSS change with moderately strong statistically significant correlations between change scores in the EDSS and the MSIS-29 physical (r = 0.523, p< 0.0001).
Effect sizes for MSIS-29 physical change were moderate to large. Using ROC curves, the MSIS-29 change score which produced a combination of optimal sensitivity and specificity was chosen for both EDSS ranges.
For EDSS range 5.5- 8, a change score of eight had a sensitivity of 87% and specificity of 67%. For EDSS 0- 5.0, a change score of seven had a sensitivity of 78% and a specificity of 51%.
The MSIS-29 physical performs well over time, and is suitable for use in trials; a minimal change score of eight points in the MSIS-29 is clinically significant.
Gray Matter Involvement In Multiple Sclerosis
Pirko I, Lucchinetti CF, Sriram S, Bakshi R
Neurology 2007 Feb 27;68(9):634-42
University of Cincinnati, Department of Neurology, OH, USA
Gray Matter (GM) involvement is detected even in the earliest stages of Multiple Sclerosis (MS), and GM Atrophy occurs at a faster rate than White Matter (WM) Atrophy early in the disease course.
Studies published to date establish that:
- GM involvement and in particular Cortical DeMyelination can be extensive in MS;
- GM pathology may occur in part independently of WM lesion formation;
- A primarily GM-related process may be the earliest manifestation of MS;
- GM involvement is associated with Physical Disability, Fatigue, and Cognitive Impairment in MS; and
- GM disease might help explain the observed dissociation between markers of inflammatory DeMyelination (relapses, WM Gadolinium enhancement, WM lesion burden) and disease progression.
It remains likely that GM damage is related to WM damage.
However, continued studies of GM pathology as well as Neuronal and Axonal involvement in MS and related experimental models are necessary to better understand the etiology and pathogenesis of the degenerative components.
A Secondary/Progressive Clinical Course Is Uncommon In NeuroMyelitis Optica
Wingerchuk DM, Pittock SJ, Lucchinetti CF, Lennon VA, Weinshenker BG
Neurology 2007 Feb 20;68(8):603-5
Mayo Clinic College of Medicine, Department of Neurology, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
We compared the clinical course of 96 patients with NeuroMyelitis Optica (NMO) to Multiple Sclerosis (MS) natural history data.
Based on the distribution of follow-up data (median 6.1 year), we estimated that 21 NMO patients would convert to a Secondary/Progressive course, but we observed only two conversions (p = 0.00002; relative risk = 0.08).
The disparate natural histories of MS and NMO suggest dissociation between relapses and clinical progression in CNS DeMyelinating Diseases.