Serial Magnetic Resonance Imaging In Multiple Sclerosis: Correlation With Attacks, Disability, And Disease Stage
Weiner HL, Guttmann CR, Khoury SJ, Orav EJ, Hohol MJ, Kikinis R, Jolesz FA
J NeuroImmunol 2000 May 1;104(2):164-73
Brigham and Women's and Massachusetts General Hospitals, Center for Neurologic Diseases, Partners Multiple Sclerosis Center, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115-5817, USA
PMID# 10713356; UI# 20183743
Serial MRI and clinical testing was performed on 45 well-defined untreated Multiple Sclerosis patients in different categories of disease (Relapsing/Remitting, Progressive, stable).
Up to 24 MRIs were scheduled over a 1-year period for each patient. Clinical evaluation was performed monthly and at times of attacks using the Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI).
MRI scans were performed both with and without Gadolinium enhancement. MRI lesion volume was determined by computerized analysis and Gadolinium-enhancing lesions were counted by Radiologists.
We observed an increase in lesion volume over 1 year in all patient groups except those classified clinically as stable.
In Relapsing/Remitting patients there were correlations between increases in the number of gadolinium enhancing lesions and increases in EDSS and the occurrence of attacks.
In Chronic/Progressive patients, increases in lesion volume were correlated with both increases in EDSS and AI.
These results demonstrate a linkage between MRI and clinical disease that depends both on the stage of MS and the MRI measures used and support the use of MRI as a surrogate marker of clinical disability in the study of Multiple Sclerosis.
Linomide In The Treatment Of Multiple Sclerosis: MRI Results From Prematurely Terminated Phase-III Trials
Tan IL, Lycklama A Nijeholt GJ, Polman CH, Ader HJ, Barkhof F
Mult Scler 2000 Apr;6(2):99-104
Univ Hospital Vrije Universteit, Dept of Radiology, Amsterdam, The Netherlands
PMID# 10789987; UI# 20248898
Due to an unexpected increase in serious CardioVascular events in MS patients treated with Linomide, a synthetic ImmunoModulator, two Phase-III multinational Relapsing/Remitting (RR) and Secondary/Progressive (SP) MS trials had to be discontinued.
MRI results of 413 patients who participated for at least 3 months were analyzed. Patients received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated.
At month 3, the decrease in the number of enhancing lesions in the placebo group was 11%, compared with 15% in the 2.5 mg group (P=0.027) and 23% in the 5 mg group (P=0.057).
Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2.5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.01).
Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effects, it seems to have a modest effect on MS disease activity, as measured by MRI.
Multiple Sclerosis (2000) 6, 99 - 104
Kurtzke Scales Revisited: The Application Of Psychometric Methods To Clinical Intuition
Hobart J, Freeman J, Thompson A
Brain 2000 May;123(Pt 5):1027-1040
Institute of Neurology, Neurological Outcome Measures Unit, London, UK
PMID# 10789987; UI# 20248898
When developing his disability scales for Multiple Sclerosis, Kurtzke demonstrated perception and insight. However, 45 years later, the evaluation of his clinically derived scales remains limited, particularly for more disabled patients.
Indeed, many of Kurtzke's assumptions underpinning the development of the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) are untested.
This study aims to build on previous work and provide a more detailed examination using psychometric methods of the EDSS and FS.
There are three study objectives:
- To examine comprehensively the psychometric properties of the EDSS in more disabled people with Multiple Sclerosis undergoing in-patient rehabilitation;
- To examine the reliability of the FS and test Kurtzke's assumptions that they measure different aspects of the Neurological Examination and measure different constructs from that measured by the EDSS; and
- To examine whether the FS can be summed to generate a summary score.
The EDSS was examined for its acceptability (score distributions), reliability (inter- and intra-rater reproducibility, standard error of measurement), validity (convergent and discriminant validity, measurement precision, discrimination between individuals) and responsiveness (effect size).
The FS were examined for their reliability (inter- and intra-rater reproducibility), intercorrelations, correlations with the EDSS and the extent to which they satisfy Likert's criteria as a summed rating scale.
In this more disabled sample of people with Multiple Sclerosis, the EDSS is an acceptable measure but demonstrates limited variability.
Inter-rater reproducibility (intraclass correlation coefficient; ICC = 0.78) is adequate for group comparison studies, but intra-rater reproducibility is variable (ICC = 0.62-0.94).
Convergent and discriminant validity for the EDSS is supported, but its measurement precision relative to the Functional Independence Measure is limited (56%).
Also, the EDSS has a limited ability to distinguish between individuals in terms of their disability and its responsiveness is poor (effect size = 0.10).
Results indicate that the FS measure constructs distinct from each other (intercorrelations = -0.23 to +0.52) and from the EDSS (correlations = -0.10 to +0.59).
Intra-rater, but not inter-rater reproducibility is adequate for group comparison studies. The FS do not satisfy criteria as an eight-, seven- or six-item summed rating scale.
Despite being based on sound clinical intuition, the lack of psychometric input into the development of the EDSS and FS has limited their usefulness as evaluative outcome measures in Multiple Sclerosis.