ObjectiveTo assess the ability of baseline MRI characteristics to predict the early development of clinically definite MS (CDMS) and combined CDMS/MRI outcomes in 190 patients with a positive MRI at the time of their first demyelinating event. Methods Based on individual and sets of baseline MRI characteristics, the authors evaluated the percentage of patients meeting outcomes of CDMS and various combined CDMS/MRI outcomes by 18 months. They also optimized a cutpoint for dichotomizing each baseline MRI characteristic and evaluated these variables using logistic regression to determine which MRI characteristics best predicted CDMS by 18 months. Results The presence of two or more gadolinium-enhancing lesions better predicted the development of CDMS and combined CDMS/MRI outcomes by 18 months than any other individual MRI characteristic or set of MRI characteristics. Among patients with two or more gadolinium-enhancing lesions, 52% developed CDMS compared with 24% of patients with fewer than two lesions. For those meeting the criteria of Barkhof et al., 32% of patients developed CDMS compared with 16% of those not meeting these criteria. Irrespective of individual or sets of criteria, however, the majority of patients developed either CDMS or demonstrated disease activity on brain MRI by 18 months. Conclusions For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging (MRI) outcomes in patients with a first clinical demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and subclinical demyelination on brain MRI. The two study outcomes were 1) development of clinically definite multiple sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging brain MRI T2 lesions. The presence of godolinium (Gd)-enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p=0.003 and <0.001, respectively). The only demographic or clinical characteristic associated with an increased risk of these outcomes was younger age (p<0.001 for both outcomes). The lowest risk subgroups we could define had a 30% risk of CDMS and a 65% risk of the combined clinical/MRI outcome. Our results indicate that all patients presenting with a first demyelinating event who also have brain MRI evidence of subclinical demyelination have at least a moderate risk of short-term disease activity. This finding provides support for initiating disease-modifying therapy at the time of the first demyelinating event in patients meeting the CHAMPS enrollment criteria.

PURPOSE: To evaluate the effect of treatment with interferon beta -1a (Avonex) initiated at the time of a first episode of optic neuritis in patients at high risk for multiple sclerosis (MS). DESIGN: Randomized clinical trial METHODS: Prospective. SETTING: Fifty clinical centers throughout the US and Canada. STUDY POPULATION: After the onset of a first episode of optic neuritis treated with intravenous and oral corticosteroids, 192 patients with brain magnetic resonance imaging (MRI) evidence of subclinical demyelination were randomly assigned to receive weekly intramuscular injections of 30 mug interferon beta -1a or placebo. MAIN OUTCOME MEASURE: The study outcomes were the development of clinically definite MS within 3 years of follow,up and brain MRI changes at 6, 12, and 18 months. RESULTS: The rates of clinically definite MS and of a combined MS/MRI outcome were lower in the interferon beta -1a group than in the placebo group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50, 95% confidence interval 0.34 to 0.73, respectively). Compared with the placebo group, on the 18,month brain MRI the interferon beta -1a group had a smaller change from baseline in T2 lesion volume (P = .02), fewer new or enlarging T2 lesions (P < .001), and a lower frequency of Gd-enhancing lesions (P < .001). CONCLUSION: The clinical and brain MRI results of this trial support initiating interferon beta -1a treatment at the time of a first episode of optic neuritis occurring in patients at high risk for MS based on the presence of subclinical brain MRI lesions. (C) 2001 by Elsevier Science Inc. All rights reserved.

Background: Multiple sclerosis (MS) is a common neurologic disease in young and middle-aged adults affecting approximately 35,000 Canadians, The objectives of this study were to estimate the annual and lifetime costs of MS from the Canadian societal perspective. Methods: Patients were consecutively recruited by neurologists in 14 MS outpatient clinics across Canada. They were classified according to the Expanded Disability Status Scale (EDSS) into three groups: mild (EDSS less than or equal to 2.5), moderate (EDSS = 3.0-6.0) and severe (EDSS greater than or equal to 6.5), Sociodemographic, clinical and resource utilization data were collected retrospectively for the three months prior to patient inclusion, Costing of resources was performed from Ministry of Health, private third party payers, patient and societal perspectives, Average Canadian costs ($CDN 1995) were valued from available provincial data, Results: A total of 198 patients were included in the analysis (mild: n = 62, moderate: n = 68 and severe: n = 68), Costs increased with increasing EDSS scores, from all perspectives, The annualized societal costs per patient were $CDN14,523, $CDN21,698 and $CDN37,024 for the mild, moderate and severe groups, respectively, In all severity groups, most of the financial burden is borne by patients, from 74% to 88%, Indirect costs, namely lost daily activity/leisure time and lost productivity, were the major societal cost drivers. The lifetime cost of MS, including patient institutionalization, was estimated to be $CDN1,608,000 per patient. Conclusions: In Canada, MS is associated with enormous direct and indirect costs, Patients carry most of the economic burden of this disease. The results of this burden of illness study provide a basis for cost-effectiveness analyses of new therapeutic interventions for MS.

Objective: To measure the quality of life (QoL) of multiple sclerosis (MS) patients in Canada using a generic QoL instrument, the SF-36. Methods: QoL was assessed in 198 MS patients, recruited from 14 MS Clinics in Canada, and stratified into three levels of disease severity, based on their Expanded Disability Status Scale (EDSS) score, Statistical tests were used to compare QoL scores between severity groups and to identify possible relationships between QoL and patient sociodemographic, clinical and economic parameters, Results: QoL scores for all eight ca!es of the SF-36 were substantially reduced early in the disease, Compared to the normal population, QoL scores for patients with mild MS were on average 30% lower for all SF-36 scales, With EDSS progression a statistically significant decrease in three of the SF-36 domains (physical function, role-physical, and social function) was observed, There were no significant correlations between patient parameters considered and QoL scores, Conclusions: QoL of MS patients collapses early in the disease. With EDSS progression, physical functioning scales show further decreases in QoL, The absence of further changes in the mental SF-36 scales may be a reflection of patient adaptation to the disease and/or effective support care, However, the SF-36 instrument may be insensitive to some of the QoL changes in MS and a disease-specific instrument may provide additional information on QoL, particularly at later stages of the disease, This study provides a basis for future research aimed at improving management of MS.

Disturbances of hearing in multiple sclerosis patients have been variably reported, likely because standard audiologic testing emphasizes assessment of peripheral, rather than central, auditory function. This study investigated a group of patients with multiple sclerosis (MS), prospectively selected on the basis of magnetic resonance imaging (MRI) scans. Five of these patients had demyelinating lesions that included the rostral auditory fibre tracts, while another seven patients had lesions restricted to brainstem auditory sites. A further four had no lesions in the distribution of their auditory pathways. A comprehensive battery of audiometric tests, including standard audiometry and retrocochlear testing, was performed. In addition, their findings on electrophysiologic testing, including auditory brainstem responses (ABR) and middle latency responses (MLR), were studied. Finally, their performances in gap detection and speech recognition in continuous and interrupted background noise were examined to assess their auditory temporal resolution. The MS patients were found to be selectively impaired under the interrupted masker of this speech-in-noise paradigm, confirming a temporal processing defect. Furthermore, these patients' performances suggested a predominant role of forebrain pathways in mediating auditory temporal resolution.

Previous studies have reported variable prevalence of pain in multiple sclerosis (MS) and have not documented the impact of pain on daily living. In this consecutive series, we report on data collected from structured interviews with 85 patients seen within a 16-month period at a regional referral clinic. The prevalence of pain for the month preceding assessment was 53%. There were no significant differences between patients who did and those who did not report pain on the basis of patient demographics (age, gender) and disease characteristics (disease subtype, duration and neurologic symptom severity). Disease duration and neurologic symptom severity were significantly correlated with the number of hours of pain per week but were not correlated with pain severity, the number of pain sites or pain-related distress. There was wide variability in the number of pain hours/week reported with 17.6% of the sample reporting continuous pain for the month preceding assessment. Sixty-five percent of patients with pain reported taking medications for pain and 90% of these patients evaluated their medication(s) as 50% effective or better. Nevertheless, patients with pain reported poorer mental health and more social-role handicap. Discussion focuses on the need for routine assessment of pain and the comprehensive evaluation of the effectiveness of pain interventions in the therapeutic management of patients with MS.