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Summary Interferon beta (IFN-β) is among the first-line treatment options for patients with multiple sclerosis (MS). A potential caveat of therapy, however, is the development of neutralizing antibodies (NAb) and/or neutralizing activity (NA) non-antibody mediated, although debate is still ongoing as to whether NAb significantly hampers the efficacy of the drug or rather represents an immunologically irrelevant epiphenomenon. In the present study, we describe the effect of NAb on IFN-β-1b through clinical and magnetic resonance imaging (MRI) outcome measures of five relapsing–remitting multiple sclerosis (RRMS) patients who were treated with 250 μg of subcutaneously administered IFN-β-1b every other day and developed NAb at varying titres and times during the course of therapy. Despite the small number of NAb+ patients, heterogeneity in MRI/clinical response to IFN-β-1b was identified. Response to IFN-β-1b therapy was observed in the absence or presence of NAb. Also observed was failure to IFN-β-1b coincident with high and sustained NAb titres, but also before NAb development or in the presence of low NAb titres. Multiple MRI and NAb measurements performed within the same individual allow for a better description of the complex heterogeneous response to IFN-β-1b with respect to NAb occurrence.

Objectives To investigate the heterogeneity in magnetic resonance image (MRI) patterns of response to interferon beta across patients with multiple sclerosis or within an individual patient over time. Design, Setting, and Patients Fifteen patients with relapsing-remitting multiple sclerosis underwent monthly MRIs and clinical examinations (6-month pretherapy phase and 36-month therapy phase) and bimonthly neutralizing antibody tests. On each MRI, the total number of contrast-enhancing lesions was noted. Therapy MRI responders were defined as those with a reduction of 60% or more in the total number of contrast-enhancing lesions during each semester of therapy. Intervention Subcutaneous administration of interferon beta-1b, 250 μg, every other day for 3 years. Main Outcome Measure Reduction in the number of contrast-enhancing lesions. Results Eight patients (53.3%) were MRI responders and 7 (46.7%) were nonresponders. Of those 7, 3 (20.0%) had only an initial optimal reduction of the total number of contrast-enhancing lesions, 2 (13.3%) never reached an optimal response, and 2 (13.3%) had a delayed optimal response. No clear association between neutralizing antibody profile and MRI response was evident. Conclusions Multiple MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure. Published online November 10, 2008 (doi:10.1001/archneur.66.1.noc80047).

Human T-cell lymphotropic virus (HTLV)-1 is associated with a chronic progressive neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) that affects 0.2% to 3% of HTLV-1-infected people. The authors aimed at exploring, in vivo, whether brain volume reduction occurs in patients with HAM/TSP through the use of magnetic resonance imaging (MRI). T1 pre/postcontrast spin echo-weighted images (WIs) and T2WIs of the brain were obtained in 19 HAM/TSP patients and 14 age- and sex-matched healthy volunteers. Both patients and healthy individuals were imaged at a 1.5-Tesla magnet by employing a conventional head coil. Focal T1 and T2 abnormalities were calculated and two measurements of brain parenchyma fraction (BPF) were obtained by using SIENAx (Structural Image Evaluation,using Normalisation, of Atrophy; University of Oxford, Oxford, UK) and MIPAV (Medical Image Processing, Analysis, and Visualization; National Institutes of Health, Bethesda, USA) from T1WIs. No significant differences in BPF were found between patients and healthy subjects when using either SIENAx or MIPAV. Analysis of individual patients detected that BPF was lower by 1 standard deviation (SD) relative to patients’ average BPF in one patient. The authors conclude that reductions in BPF do not occur frequently in patients with HAM/TSP. However, the authors believe that one individual case of significant brain atrophy raises the question as to whether atrophy selectively targets the spinal cord of HAM/TSP patients or may involve the brain as well. A larger patient population analyzing regional brain volume changes could be helpful in determining whether brain atrophy is a marker of disease in patients with HAM/TSP.