MR in Monitoring the Natural History Of
Multiple Sclerosis & The Effects Of Treatment
Filippi M, Rovaris M, Comi G
Ital J Neurol Sci 1996 Dec;17(6):385-91
Universita di Milano, Dept of Neurology,
IRCCS Ospedale San Raffaele, Italy
UI # 97133085
In this review the main contributions of Magnetic Resonance (MR) techniques in the monitoring of Multiple Sclerosis (MS) course, both natural or modified by treatments, are presented.
MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments.
In contrast, the correlation between MR measures and long-term clinical evolution in Clinically Definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials.
The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed.
Clinical & Magnetic Resonance Imaging Predictors Of Disability in Primary & Secondary/Progressive Multiple Sclerosis
Losseff NA, Kingsley DP, McDonald WI, Miller DH, Thompson AJ
Mult Scler 1996 Feb;1(4):218-22
NMR Research Unit,
Institute of Neurology,
UI # 98005298
The role of Magnetic Resonance Imaging (MRI) in predicting disability in Multiple Sclerosis (MS) remains unclear.
In this study 21 patients with Primary and Secondary/Progressive MS were reviewed 5 years following a serial MRI study of 6 months duration.
In the Secondary/Progressive group (n = 11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in disability 5 years later.
For both groups change in disability over the initial study period was predictive of outcome.
These results suggest that the presence and frequency of Gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in Progressive patients.
Magnetic Resonance Imaging In Monitoring the Treatment of Multiple Sclerosis
Statistical power of parallel-groups and crossover designs
Nauta JJ, Thompson AJ, Barkhof F, Miller DH
J Neurol Sci 1994 Mar;122(1):6-14
Free Univ Hospital, Dept of Theory of Medicine,
Biostatistics and Epidemiology,
Amsterdam, The Netherlands
UI # 94253836
Serial Brain Magnetic Resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early Relapsing/Remitting and Secondary Progressive Multiple Sclerosis (MS).
Based on monthly unenhanced and Gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome.
It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months.
Short to medium term studies of new experimental treatments in MS, using MRI as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time.
The Treatment of Multiple Sclerosis
Current & Future
Polman CH, Hartung HP
Curr Opin Neurol 1995 Jun;8(3):200-9
Free Univ Hospital, Dept of Neurology,
Amsterdam, The Netherlands
UI # 96023837
During the past year observations have been published that might lead to further improvement in the design of future clinical trials.
At the same time, results of clinical trials have become available that suggest that a number of treatments could be of benefit in the care of patients in the various phases of Multiple Sclerosis.
Future Multiple Sclerosis clinical trials should involve a blinded investigator restricted to assessing the clinical outcome variables, and because current evidence suggests that MRI gives an objective and sensitive reflection of the biological evolution of the disease, such scanning should also be included.
The use of a composite outcome variable in a trial of Chronic Progressive Multiple Sclerosis should also be considered in order to increase the percentage of patients reaching the clinical endpoint.
In 1994 recommendations were published for the selection of Relapsing/Remitting patients for treatment with Interferon-ß-1b.
Furthermore, large and well performed clinical trials demonstrated that Interferon-ß-1a and Copolymer-1 are also partially effective, though not curative, for these patients.
Two smaller studies suggested that low-dose Methotrexate and Cladribine might have a beneficial effect on the course of the disease in patients with Secondary Chronic Progressive Multiple Sclerosis, the former drug probably being less toxic.
Unfortunately, therapeutic perspectives for patients with Primary/Progressive Multiple Sclerosis are less promising at present.
Several studies suggest that 4-Aminopyridine and Tizanidine have therapeutic potential for symptomatic treatment; the former by improving Neurological Deficits, the latter by relieving troublesome Spasticity.