New T2 Lesions Enable An Earlier Diagnosis Of Multiple Sclerosis In Clinically Isolated Syndromes
Dalton CM, Brex PA, Miszkiel KA, Fernando K, MacManus DG, Plant GT, Thompson AJ, Miller DH
Ann Neurol 2003 May;53(5):673-6
National Hospital for Neurology and NeuroSurgery, Institute of Neurology, NMR Research Unit, United Kingdom
In Clinically Isolated Syndromes (CIS), the new McDonald Criteria for Multiple Sclerosis diagnosis require new Gadolinium-enhancing lesions for dissemination in time at a 3-month follow-up Magnetic Resonance Imaging scan.
In a cohort of 56 patients, these Criteria were specific (95%) but less sensitive (58%) for Clinically Definite Multiple Sclerosis at 3 years.
If new T2 lesions were allowed as an alternative for dissemination in time, sensitivity increased (74%) with maintained specificity (92%), enabling an accurate diagnosis of Multiple Sclerosis in more patients.
AntiMyelin AntiBodies As A Predictor Of Clinically Definite Multiple Sclerosis After A First DeMyelinating Event
Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M
N Engl J Med 2003 Jul 10;349(2):139-45
University of Innsbruck, Department of Neurology, Innsbruck, Austria
Most patients with Multiple Sclerosis initially present with a Clinically Isolated Syndrome.
Despite the fact that Clinically Definite Multiple Sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated Magnetic Resonance Imaging (MRI).
We investigated whether the presence of Serum AntiBodies against Myelin Oligodendrocyte Glycoprotein (MOG) and Myelin Basic Protein (MBP) in patients with a Clinically Isolated Syndrome predicts the interval to conversion to Clinically Definite Multiple Sclerosis.
A total of 103 patients with a Clinically Isolated Syndrome, positive findings on cerebral MRI, and OligoClonal Bands in the CerebroSpinal Fluid were studied.
At base line, serum samples were collected to test for anti-MOG and anti-MBP AntiBodies with Western blot analysis, and the lesions detected by Cerebral MRI were quantified.
Neurologic Examinations for relapse or disease progression (defined as conversion to Clinically Definite Multiple Sclerosis) were performed at base line and subsequently every three months.
Patients with Anti-MOG and Anti-MBP AntiBodies had relapses more often and earlier than patients without these AntiBodies. Only 9 of 39 AntiBody-SeroNegativ patients (23 percent) had a relapse, and the mean (+/-SD) time to relapse was 45.1+/-13.7 months.
In contrast, 21 of 22 patients (95 percent) with AntiBodies against both MOG and MBP had a relapse within a mean of 7.5+/-4.4 months, and 35 of 42 patients (83 percent) with only Anti-MOG AntiBodies had a relapse within 14.6+/-9.6 months (P < 0.001 for both comparisons with AntiBody-SeroNegative patients).
The adjusted hazard ratio for the development of Clinically Definite Multiple Sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6).
Among the patients who were SeroPositive for both AntiBodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were SeroPositive only for Anti-MOG AntiBodies, as compared with the SeroNegativ patients.
Analysis of AntiBodies against MOG and MBP in patients with a Clinically Isolated Syndrome (CIS) is a rapid, inexpensive, and precise method for the prediction of early conversion to Clinically Definite Multiple Sclerosis.
This finding may be important for the counseling and care of patients with a first DeMyelinating event suggestive of Multiple Sclerosis.
Copyright 2003 Massachusetts Medical Society
Baseline MRI Characteristics Of Patients At High Risk For Multiple Sclerosis
Results From The CHAMPS Trial
Mult Scler 2002 Aug;8(4):330-8
Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study
The baseline MRI studies from the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial, a randomized, longitudinal, double-blind trial of 383 patients with a first acute clinical DeMyelinating event.
And, evidence of prior SubClinical DeMyelination on Magnetic Resonance Imaging (MRI) of the Brain, provides a large MRI database for patients likely in the earliest stages of Multiple Sclerosis (MS).
High-resolution baseline MRIs revealed a median of 13 T2 lesions (maximum = 103 lesions) and 2.05 cm3 of T2 lesion volume (maximum 35.04 cm3), with 30% of patients having one or more enhancing lesions despite receiving a standardized high-dose course of IntraVenous CorticoSteroids.
PeriVentricular, discrete, and JuxtaCortical T2 lesions were present in 99%, 92% and 67% of the patients, respectively. Large (> 6 mm), T1-HypoIntense, InfraTentorial, and Corpus Callosum lesions were present in 69%, 50%, 55% and 58%, respectively.
Clinical presentation groups showed differences in T2 lesion volume, and enhancing lesion number and volume. At baseline, 97%, 81% and 72% of the patients met 'Paty', 'Fazekas', and 'Barkhof' research Criteria for MS, respectively, with the percentages similar according to clinical presentation group.
These results support and extend those of smaller and/or retrospective series, which have shown substantial SubClinical injury, based on Brain MRI, at the earliest identifiable stages of disease.
Interferon-beta-1a For Early Multiple Sclerosis: CHAMPS Trial Subgroup Analyzes
Beck RW, Chandler DL, Cole SR, Simon JH, Jacobs LD, Kinkel RP, Selhorst JB, Rose JW, Cooper JA, Rice G, Murray TJ, Sandrock AW
Ann Neurol 2002 Apr;51(4):481-90
CHAMPS Analysis Center, Jaeb Center for Health Research, Tampa, FL 33613, USA
The objective of this work was to assess the effect of Interferon-ß-1a (Avonex) on the rate of development of Clinically Definite Multiple Sclerosis and Brain Magnetic Resonance Imaging changes in subgroups.
Based on type of presenting event, baseline Brain Magnetic Resonance Imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial.
After the onset of a first DeMyelinating event, 383 patients with Brain Magnetic Resonance Imaging evidence of SubClinical DeMyelination were treated with CorticoSteroids and randomly assigned to receive weekly intramuscular injections of 30 microg Interferon-ß-1a or placebo.
The treatment effect within subgroups was assessed in proportional hazards models both for the development of Clinically Definite Multiple Sclerosis and for a combined outcome of development of Clinically Definite Multiple Sclerosis or >1 new or enlarging T2 lesions on Brain Magnetic Resonance Imaging.
A beneficial effect of treatment was noted in all subgroups evaluated.
Adjusted rate ratios for the development of Clinically Definite Multiple Sclerosis in the Optic Neuritis, BrainStem-Cerebellar, and Spinal Cord Syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01).
And, for the development of the combined Clinically Definite Multiple Sclerosis/Magnetic Resonance Imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively.
A treatment benefit on both outcome measures also was seen in subgroups based on baseline Brain Magnetic Resonance Imaging parameters, gender, and age.
Interferon-ß-1a is beneficial when initiated at the first clinical DeMyelinating event (CIS) in patients with Brain Magnetic Resonance Imaging evidence of SubClinical DeMyelination.
The beneficial effect is present for Optic Neuritis, BrainStem-Cerebellar Syndromes, and Spinal Cord Syndromes.