#6
A Serial Study Of White Matter And New
Multiple Sclerosis Lesions
Goodkin DE, Rooney WD, Sloan R, Bacchetti P, Gee L, Vermathen M, Waubant E, Abundo M, Majumdar S, Nelson S, Weiner MW
Neurology 1998 Dec;51(6):1689-97
Univ of California, Dept of Neurology, San Francisco 94115, USA
PMID# 9855524; UI# 99071166
Abstract
Objective
To compare MS Normal-Appearing White Matter (NAWM) where new Gadolinium-enhancing (Gd+) lesions do and do not arise.
Methods
A total of 22 Relapsing/Remitting MS patients and 11 healthy control subjects completed as many as 12 monthly Brain MRI sessions.
Quantitative measures of Gadolinium Enhancement (GDR), water Proton Density (PDN), water proton T2 relaxation time constants (T2), Magnetization Transfer Ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM.
Results
A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM.
NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with ContraLateral homologous NAWM regions in which no new Gd+ lesions arose.
Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N.
Conclusions
Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise.
After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.
#7
Clinical Outcome Measures And Rating Scales
In Multiple Sclerosis Trials
Wingerchuk DM, Noseworthy JH, Weinshenker BG
Mayo Clin Proc 1997 Nov; 72(11): 1070-1079
Mayo Clinic Rochester, Dept of Neurology, Minnesota 55905, USA
UI# 98042417
Abstract
In this review, we analyzed clinical outcome measures used in Multiple Sclerosis (MS) clinical trials in which the primary goal is to slow or arrest progression of disease.
In addition, we examined rating scales that quantify symptomatic complications of MS (for example, Spasticity) and the current role of Magnetic Resonance Imaging in MS treatment trials.
Each proposed scale has advantages and deficiencies, and none meets all the criteria for an ideal outcome measure.
The validity of trial design may be improved by using combinations of selected components of current scales as well as new instruments targeted to specific variables (such as motor strength).
Symptom-specific rating scales are most appropriately used in trials of symptomatic therapeutic strategies for MS.
Until serial Magnetic Resonance Imaging changes are definitely known to predict long-term Impairment and Disability in patients with MS, clinical outcome measures will remain the primary means of assessing therapeutic efficacy in Phase III Clinical Trials.
#8
European Validation Of A Standardized Clinical Description Of Multiple Sclerosis
Amato MP, Grimaud J, Achiti I, Bartolozzi ML, Adeleine P, Hartung HP, Kappos L, Thompson A, Trojano M, Vukusic S, Confavreux C
J Neurol 2004 Dec;251(12):1472-80
University of Florence, Department of Neurological Sciences, Viale Morgagni, 85, 50134, Florence, Italy
PMID# 15645346
Abstract
Objectives
The EDMUS system is a clinical database specifically tailored to the description of Multiple Sclerosis (MS).
The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives:
1) to assess the inter-examiner reliability of the whole EDMUS system;
2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS).
Methods
The protocol included 12 Neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Wurzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms.
The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification.
The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate.
Results
The study included 180 patients with Definite or Probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2.
The disease course was Relapsing/Remitting in 67%, Secondary/Progressive in 22%, and Progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent.
Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p < 0.0001) between both scales demonstrated EGS's construct validity.
Conclusion
The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.
#9
Outcome Measures For Multiple Sclerosis Clinical Trials: Relative Measurement Precision Of The Expanded Disability Status Scale And Multiple Sclerosis Functional Composite
Hobart J, Kalkers N, Barkhof F, Uitdehaag B, Polman C, Thompson A
Mult Scler 2004 Feb;10(1):41-6
Peninsula Medical School, Derriford Hospital, Plymouth, Devon, UK
PMID# 14760951
Abstract
We compared the Relative Measurement Precision (RMP) of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC).
For discriminating between groups of patients known to differ in their extent of Multiple Sclerosis (MS). A total of 133 patients were rated with the EDSS and MSFC and had Magnetic Resonance Imaging (MRI) scans.
Patients were grouped on the basis of MRI appearances (T1- and T2-weighted lesion loads, Parenchymal and Ventricular Fractions - T1 LL, T2 LL, PF, VF, respectively) and RMP was determined using the method of Group Differences.
For each MRI parameter, the total sample was arranged in ascending order of magnitude and divided into two, three, four and five similar sized groups.
For each division (two, three, four or five groups), EDSS and MSFC scores for the groups were compared using parametric (paired samples t-tests, one-way ANOVA) and nonparametric (Wilcoxon's rank-sum test, Kruskal-Wallis analysis of variance) statistical methods and RMP was estimated.
The EDSS and MSFC were correlated substantially (r = -0.64). Relative to the MSFC, the EDSS had inferior measurement precision regardless of the number of groups into which the total sample was divided, or the statistical method.
However, the RMP of the EDSS compared with the MSFC varied from 2% to 86%. Results suggest the MSFC is better than the EDSS for detecting differences between groups of patients, defined by these MRI markers of MS.
However, the finding that both scales correlated weakly with MRI markers, indicated that they are limited as predictors of MS pathology as defined by MRI.
An explanation for this well-established clinical-MRI paradox is that rating scales and MRI measure fundamentally different manifestations of MS.
#10
Outcome Measures For Multiple Sclerosis Clinical Trials: Relative Measurement Precision Of The Expanded Disability Status Scale And Multiple Sclerosis Functional Composite
Hobart J, Kalkers N, Barkhof F, Uitdehaag B, Polman C, Thompson A
Mult Scler 2004 Feb;10(1):41-6
Peninsula Medical School, Derriford Hospital, Plymouth, Devon, UK
PMID# 14760951
Abstract
We compared the Relative Measurement Precision (RMP) of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC).
For discriminating between groups of patients known to differ in their extent of Multiple Sclerosis (MS).
A total of 133 patients were rated with the EDSS and MSFC and had Magnetic Resonance Imaging (MRI) scans.
Patients were grouped on the basis of MRI appearances (T1- and T2-weighted Lesion Loads, Parenchymal and Ventricular Fractions - T1LL, T2LL, PF, VF, respectively) and RMP was determined using the method of group differences.
For each MRI parameter, the total sample was arranged in ascending order of magnitude and divided into two, three, four and five similar sized groups.
For each division (two, three, four or five groups), EDSS and MSFC scores for the groups were compared using Parametric (paired samples t-tests, one-way ANOVA).
And NonParametric (Wilcoxon's Rank-Sum Test, Kruskal-Wallis analysis of variance) statistical methods and RMP was estimated.
The EDSS and MSFC were correlated substantially (r = -0.64).
Relative to the MSFC, the EDSS had inferior measurement precision regardless of the number of groups into which the total sample was divided, or the statistical method.
However, the RMP of the EDSS compared with the MSFC varied from 2% to 86%.
Results suggest the MSFC is better than the EDSS for detecting differences between groups of patients, defined by these MRI markers of MS.
However, the finding that both scales correlated weakly with MRI markers, indicated that they are limited as predictors of MS pathology as defined by MRI.
An explanation for this well-established clinical-MRI paradox is that rating scales and MRI measure fundamentally different manifestations of MS.
#11
Multiple Sclerosis Severity Score: Using Disability And Disease Duration To Rate Disease Severity
Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA
Neurology 2005 Apr 12;64(7):1144-51
Cambridge University, Neurology Department, UK
PMID# 15824338
Abstract
Background
There is no consensus method for determining progression of disability in patients with Multiple Sclerosis (MS) when each patient has had only a single assessment in the course of the disease.
Methods
Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole.
An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS.
In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability.
Results
Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression.
Conclusion
The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data.
The Global MSSS can be used as a reference table for future disability comparisons.
While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.
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