This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.

The impact of relapses on long-term disability in multiple sclerosis remains unclear; however some evidence suggests that relapses play an important role in determining subsequent prognosis. We report on outcome, prognostic factors for recovery and the contribution of relapses to the accumulation of fixed disability in a large series of patients with documented relapses. Two hundred and seventy-nine relapses in 182 patients were assessed before, during and after relapse by expanded disability status scale and data analysed to assess degree of recovery. Factors affecting outcome were considered including sex, age and site of relapse. Mean EDSS prior to relapse was 3.73, during relapse 5.18 and post relapse 4.23. Mean interval to post relapse assessment was 127 days post relapse. Mean residual change in EDSS score (pre to post relapse) was 0.50 points. Overall 49.4 % of patients had a residual increase in disability post relapse of at least 0.5 EDSS points and 32.7 % had an increase of at least 1 point. No significant difference was observed in mean residual EDSS for sex, site of relapse or age at relapse or in the proportion of patients with a residual increase in disability of > or = 1 EDSS point post relapse. 14.4 % of patients had no increase in EDSS score during relapse compared to pre relapse. These results suggest that acute relapses are commonly associated with an objective worsening of disability in the majority of patients with MS and that recovery is incomplete in approximately half and not influenced by gender, age or site of lesion. Therapies which reduce relapse frequency and/or severity might therefore be expected to slow or prevent worsening of disability if initiated prior to the onset of more permanent damage.

These results confirm a continuing trend of premature death in patients with MS. Relying on data derived from death certificates will underestimate disease prevalence. Differences were identified between those dying from MS-related causes and those dying from other causes.

Recent change in disease incidence and prevalence in this population is likely to be the result of environmental factors that have been operative in the past few decades in women alone and infers avoidable risk factors. Modelling of current overall incidence suggests a further increase in prevalence to 260 per 100 000 population within the next 20-40 years. Further studies are needed in order to identify recent changes in sex specific environment and lifestyle that confer susceptibility.

5.4% of patients with MS have POMS (2.7% <16 years; 0.3% <10 years) and have distinct phenotypic characteristics in early disease. Furthermore, while patients with POMS take longer to reach disability milestones, they do so at a younger age than their adult counterparts and could be considered to have a poorer prognosis. Management strategies for these patients should take account of these data.