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While the diagnosis of multiple sclerosis is accomplished on the basis of clinical symptoms, magnetic resonance imaging (MRI) may be far superior for observing the underlying disease process itself. This is especially true for the observation of many multiple sclerosis white matter lesions that do not produce any detectable symptoms at all. In addition, multiple sclerosis is often a fluctuating disease, and both symptoms and lesions wax and wane with time. A study was undertaken to determine if monthly MRI could provide insight into the dynamic pathological processes of multiple sclerosis. The brains of four patients with multiple sclerosis were imaged monthly for a total of four months. In addition to the standard unenhanced MRI, the patients were also imaged using gadolinium-DTPA enhancement. The paramagnetic properties of the metallic element gadolinium can sometimes reveal lesions on the final image that would be difficult to visualize otherwise. The gadolinium-DTPA is administered intravenously, and it is believed that gadolinium enhancement within the brain represents regions where the substance passes easily from the blood into the brain. The blood-brain barrier, which normally restricts the entrance of many substances into the brain, is apparently less effective at these regions; the pathologic process of multiple sclerosis may be tied to alterations in this blood-brain barrier. When the patients' brains were examined, enhancement was observed in new lesions in the white matter and lesions that were enlarging. Enhancement could also be seen in some pre-existing lesions. When images from the succeeding month were compared, only about 30 percent of the enhancing lesions from the previous month continued to enhance. While all of the lesions could be observed without enhancement, it is thought that enhancement indicates pathological activity. Since enhancement was visible in some older lesions, as well as in all new lesions, it seems that MRI without enhancement may underestimate disease activity in the brains of patients with multiple sclerosis. Gadolinium enhancement suggests that even old lesions, which are not obviously changing on unenhanced MRI, may indeed pass through periods of pathological activity. (Consumer Summary produced by Reliance Medical Information, Inc.)

Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. Tovalidate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19–74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0–9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS<4.5 (n = 46) and >4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by + 0.5 steps and + 1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether recombinant human interferon-beta-1a significantly affects disease activity as measured by a reduction in the number and volume of Gd enhancing lesions on monthly MRI. The study also evaluated the effect on six-monthly T2 weighted abnormality and relapse frequency.Methods: After a baseline scan and a six month pretreatment period, 68 patients were randomly assigned to receive either 3 MIU or 9 MIU of interferon-beta-1a by subcutaneous injection three times a week for six months. All patients were examined by Gd enhanced MRI every month in both pretreatment and treatment periods. The evaluation of Gd enhancing lesions was performed blind at the end of the study.Results: The mean number of Gd enhancing lesions was higher during the pretreatment period than during treatment. This difference was statistically significant for the two different dose subgroups (3.5 v 1.8, P < 0.001 for the 3 MIU group and 2.4 v 0.9, P < 0.001 for the 9 MIU group, corresponding to a reduction of 49% and 64% respectively). The mean volume of Gd enhancing lesions also significantly decreased by 61% (3 MIU group) and 73% (9 MIU group). These reductions were evident only after the first month of treatment. The six-monthly rate of new lesions as seen in T2 weighted images showed a similar trend of reduction with treatment (65% and 70% respectively). Lesion volume on T2 scans significantly increased during the pretreatment period whereas it remained almost stable during the treatment period in both groups. Clinical relapse rate was significantly reduced by treatment (53% for the 3 MIU group, P < 0.001; 69% for the 9 MIU group, P < 0.001).Conclusion: Interferon-beta-1a seemed effective in reducing disease activity in relapsing-remitting multiple sclerosis at both the doses used. [ABSTRACT FROM AUTHOR]

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their ability to produce interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin-2 (IL-2) and interleukin-4 (IL-4). The CSF-T clones were compared for their ability to produce cytokines with autologous peripheral T clones and with liver-infiltrating T cell clones from patients with chronic active hepatitis. IL-4 production was also compared with that by peripheral T clones derived from atopic patients. All the CSF-T clones (both CD4+ and CD8+) produced large amounts of IFN-γ and particularly of TNF-α. These cytokines were synthesized in significantly larger amounts by CSF T clones than by reference clones. Moreover, they were capable of secreting IL-2, but not IL-4. We conclude that the CSF-CD4+ T clones could constitute a subset with functional properties similar to those of T helper 1 (Th1)/inflammatory cells of the mouse; and that the large amounts of TNF produced by CSF T cell clones strongly suggest a significant role for this cytokine in MS immunopathogenesis. [ABSTRACT FROM AUTHOR]

A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study. Eighty nine consecutive patients with clinically definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age, sex, and degree of disability, who did not experience clinical exacerbations during the same period. Only potential risk factors occurring in the three months preceding the interview were considered patients. Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group. These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors. [ABSTRACT FROM AUTHOR]