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Sustained disability improvement was observed in about 30% of patients with multiple sclerosis (MS) treated with natalizumab (Tysabri, Biogen Idec, Cambridge, Massachusetts, USA), thus suggesting the occurrence of reversal of neurological dysfunction.1 In addition to its striking effect in suppressing contrast-enhancing lesions and new or enlarged T2-hyperintense lesions on MRI by 92% and 83%, respectively,2 natalizumab was also reported to induce a decrease in lesion volumes on T2-weighted and T1-weighted images by 9.4% and 23.5%, respectively, over a 24-month follow-up.3 Nevertheless, the relationship between sustained disability improvement and reduction in MRI lesion burden during treatment with natalizumab has not been elucidated yet. We collected clinical and MRI data from 88 patients (58 women, 30 men) treated with natalizumab at the MS Center of S Andrea Hospital in Rome (Italy). Brain MRI scans were acquired using a 1.5T magnet (GE Signa Excite) within 4 weeks before natalizumab start (baseline) and after 6 and 24 months (±4 weeks) of treatment. Hyperintense lesion volume on post-gadolinium T1-weighted images (GD-LV), T2-weighted images (T2-LV), and hypointense lesion volumes on T1-weighted images (T1-LV), were measured using a local thresholding segmentation technique (Jim 5.0, Xinapse Systems, Leicester, UK). Regions of interest were identified by the agreement of two trained operators (FDA and RDA) unaware of clinical data. Patients were divided into three groups according to changes in their disability status at the end of the 24-month follow-up versus baseline, as follows: (1) 6-month sustained reduction of ≥1-point in Expanded Disability Status Scale (EDSS) score; (2) stable or …