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Background: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated. Objective: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS. Design: Open-label treatment vs baseline study. Setting: Outpatient MS clinical center at a university hospital. Patients: Fourteen patients with relapsing-remitting MS ofshortdurationandatleast3gadolinium-enhancing(Gdϩ) brain lesions observed within 6 months before treatment. Intervention: Azathioprine, up to 3 mg/kg daily, individually adjusted according to blood lymphocyte number and the occurrence of adverse events. Main Outcome Measures: Brain Gdϩ lesions evaluated by monthly magnetic resonance imaging for 6 months before and 6 months during treatment and new T2 lesions evaluated during the same periods and after an additional 6 months. Results: The treatment reduced to 0 the median Gdϩ lesion number and volume per magnetic resonance image (PϽ.001 for both), resulting in a Gdϩ lesion number reduction of 50% or more in 12 of 14 patients (PϽ.01). An equivalent reduction in the new T2 lesion number was observed (PϽ.02); this activity also persisted during the additional treatment period evaluated using this outcome measure (PϽ.01). The median azathioprine dose administered (2.6-2.8 mg/kg daily) reduced the mean blood lymphocyte count to 57% of the baseline value. Adverse events were transient or reversible with dose adjustment. Conclusions: This study indicates for the first time that azathioprine, administered at lymphocyte-suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated.

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T cells reactive to self-antigens are present in the peripheral blood of patients with autoimmune diseases as well as in healthy subjects. Although T cell-response to the self-myelin antigen myelin basic protein (MBP) has been widely investigated in multiple sclerosis (MS) patients, very little is known about the evolution over time of this response and its correlation with the disease activity. In recent years magnetic resonance imaging (MRI) techniques have provided new tools for following the inflammatory activity in the central nervous system (CNS) of MS patients. In the present study the T cell response to MBP was longitudinally investigated in terms of frequency, epitope specificity, and cytokine production profile in four patients with relapsing-remitting MS enrolled in a gadolinium-enhanced MRI serial study. In spite of different profiles of inflammatory activity within the CNS, all the patients examined showed major changes in their reactivity to MBP during the follow-up period in terms of both frequency and epitope specificity. Episodic expansions of MBP-specific T cell populations were observed in each patient, and overall they did not correlate with disease activity. In these patients the expansions: 1) occurred in the context of a steady level of disease activity, 2) correlated with a burst of CNS inflammation, 3) followed the appearance of a new active lesion, and 4) were observed even in the absence of detectable signs of CNS inflammation during the entire follow-up period. These results suggest that the evolution over time of the T cell response to a self-antigen such as MBP is more complex than previously expected. The short-term repertoire dynamics of autoreactive T cells in MS underscore the importance of longitudinal studies for evaluating autoreactivity to myelin antigens and probably to any self-antigen in other autoimmune diseases.

Oxcarbazepine (OXC) is a new anti‐epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinicai side‐effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth‐pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double‐blind cross‐over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth‐pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p<0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11‐epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study.