O.R. Hommes

Background: The PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-beta -1a, 22 and 44 meg thrice weekly (tiw), compared with placebo in relapsing-remitting MS. Years 3 and 4 extension study results are reported. Methods: Patients initially receiving placebo were randomized to blinded interferon-beta -1a, 22 or 44 meg tiw (n = 172; crossover group); others continued blinded treatment with their originally assigned dose, 22 meg (Rx22 group) or 44 meg (Rx44 group) tiw (n = 167 per group). Patients had 3- to 6-month clinical and annual MRI assessments. Results: Relapse rates for 4 years were 1.02 (crossover), 0.80 (Rx22, p < 0.001), and 0.72 (Rx44, p < 0.001); the dose effect approached significance (p = 0.069; risk ratio, 0.88; 95% CI, 0.76-1.01). Crossover groups showed reductions in relapse count, MRI activity, and lesion-burden accumulation with interferon-p-la compared with their placebo period (p < 0.001 both doses). Time to sustained disability progression was prolonged by 18 months in the Rx44 group compared with the crossover group (p = 0.047). Rx22 and Rx44 reduced new T2 lesion number and lesion burden compared with crossover (p < 0.001); Rx44 was superior to Rx22 on several clinical and MRI outcomes. Persistent neutralizing antibodies developed in 14.3% (Rx44) and 23.7% (Rx22) of patients and were associated with reduced efficacy. Conclusions: Clinical and MRI benefit continued for both doses up to 4 years, with evidence of dose response. Outcomes were consistently better for patients treated for 4 years than for patients in crossover groups. Efficacy decreased with neutralizing antibody formation.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

We followed two women with MS during pregnancy by means of serial unenhanced MR imaging. On each follow-up image, we assessed the number of new or enlarging lesions. Both women showed a decrease in MR disease activity during the second half of pregnancy and a return of MR disease activity to prepregnancy levels in the first months postpartum. These findings support the view that pregnancy reduces disease activity in MS.

In a prospective study, we compared the number of gadolinium-DTPA (Gd-DTPA) enhancing lesions on MRI with the CSF and clinical findings before and after a total of 20 courses of high-dose intravenous methylprednisolone in relapsing multiple sclerosis patients. Before treatment, there was a significant correlation of Gd-DTPA enhancement (seen on 16 of 20 scans) and CSF myelin basic protein (MBP). If enhancement with Gd-DTPA represents inflammation and CSF-MBP indicates myelin breakdown, the amount of inflamed tissue should correlate with the amount of myelin being damaged. Clinical improvement occurred following 15 of 20 courses, and decrease of Gd-DTPA enhancement in 12 of 16 scans; the mean CSF-MBP level was the only CSF variable to return to reference values. There was a significant correlative triad of decrease in CSF-MBP, Gd-DTPA enhancement, and clinical disability. Thus, the clinical effect of methylprednisolone might be accompanied by a reduction of inflammation and myelin breakdown.