The authors measured brain atrophy in nine patients undergoing immunoablation and autologous hematopoietic stem cell transplantation for multiple sclerosis. From baseline to 1 month after treatment, atrophy was 10 times faster than before treatment. A patient with non-CNS lymphoma showed comparable acute brain atrophy after analogous therapy. These observations suggest that brain atrophy after immunoablation may not be due entirely to the resolution of edema but may be related to chemotoxicity. the Canadian MS BMT Study Group Brain atrophy occurs at a faster rate than normal in patients with multiple sclerosis (MS) and may be accelerated in the year after initiation of immuno-modulatory therapy 1-a phenomenon that is often attributed to the resolution of edema. To explore the nature of the changes in brain volume after anti-inflammatory therapy, we measured global brain volume changes on MRI scans of patients with aggressive MS being treated with immu-noablation and autologous hematopoietic stem cell transplantation (AHSCT). We also measured brain volume changes on MRI scans of a patient with lym-phoma that did not involve the CNS and who was undergoing a similar treatment. Methods. We studied nine secondary progressive (SP) MS patients with active disease who were participating in a tricenter phase II trial of immunoablation followed by AHSCT. 2 Stem cell mobilization was achieved with IV cyclophosphamide (4.5 g/m 2) and 10 days of granulocyte colony-stimulating factor (10 g/kg/day). Immunoablation was accomplished using IV cyclo-phosphamide (200 mg/kg), dose-adjusted oral busulfan (maximum 16 mg/kg) and rabbit antithymocyte globulin (5 mg/kg). 2 Solu-Medrol was administered for 4 days during the conditioning regimen. A 54-year-old man with non-Hodgkin lymphoma and no CNS involvement was followed up after chemotherapy (IV busulfan: 12.8 mg/kg [total 845 mg]; IV cyclophosphamide: 120 mg/kg [total 7,920 mg]; dose-adjusted IV methotrexate: 45 mg/m 2 [to-tal 76 mg]; cyclosporine: 1.5 mg/kg every 12 hours from day 1) and allogeneic bone marrow transplantation (BMT). MRI scans included T1-weighted and dual spin-echo (PD/T2-weighted) sequences acquired at baseline and serially after treatment as previously described. 3 In two cases, the earliest baseline scans were performed more than 12 months before the last base-line scan because of delays in the study. The rate of brain atrophy was calculated using SIENA 4 (http:// www.fmrib.ox.ac.uk/fsl). Gadolinium-enhancing lesions were segmented manually, and T2-weighted lesion volume (T2LV) was quantified automatically using a Bayesian classifier followed by manual correction. A simplified estimation of T2-relaxation maps were calculated based on a single-exponential fit of the image intensities of the dual spin-echo sequence. Results. The patient demographics and rates of atrophy at baseline and 1 month after AHSCT are shown in the table. Atrophy (brain volume loss) is reported as a positive percentage change. The entire therapy (stem cell mobilization , immunoablation, and ...

There were two aims to this study. First, to explore how the reduction in the volume of abnormal T2-signal intensity associated with white matter (WM) lesions in multiple sclerosis (MS) relates to tissue loss resulting from focal pathology inside lesions. Second, to demonstrate that this volume of abnormal T2-signal intensity underestimates the actual size of the region to which the direct effects of lesion activity extend. For these purposes, we used deformation field analysis to quantify the evolution of local atrophy associated with a chronic peri-ventricular lesion in a patient with secondary progressive MS. This subject had particular features that may not necessarily co-exist in a group of unselected patients, which enabled interesting observations to be made. We show, quantitatively, that the focal WM lesion was associated with adjacent regional WM volume loss, which was disproportionate to concurrent diffuse atrophy in the rest of the normal appearing brain tissue, and that the loss of volume associated with the lesion was partially reciprocated by local ventricular expansion. Our observations re-emphasise the complex relationship between the change in the volume of abnormal signal intensity on magnetic resonance images and the tissue volume change directly related to lesion pathology.

At a conference held in October 2005, participants presented studies on high dose immunosuppression with hematopoietic cell transplant (HCT) for multiple sclerosis (MS), including neuroimmunological and magnetic resonance imaging (MRI) mechanistic approaches, clinical registry reports, and ongoing or newly-designed protocols. A discussion panel considered questions on how to define success, timing of controlled clinical trials, difficulty in patient recruitment, and future direction of high dose therapy.