Active Magnetic Resonance Imaging Lesions Research Articles

Definition of responder: introduction

Availability of multiple disease modifying treatments in multiple sclerosis requires the definition of criteria to classify the response to individual treatments, to open the possibility to substitute a drug with another potentially effective drugs in case of treatment failure or to add a second treatment if the first is classified as partially effective. Because of the large inter and intra-individual variability of the disease evolution such a classification is frequently difficult. Different clinical and magnetic resonance imaging (MRI) parameters have been proposed. Measures of disease activity, attacks and active MRI lesions, are ore suitable, particularly in the remitting phase of the disease.

Relationship between MRI lesion activity and response to IFN-β in relapsing–remitting multiple sclerosis patients

Objective Our objective in this study is to evaluate whether brain magnetic resonance imaging (MRI) performed at interferon-beta (IFN-β) onset and after 12 months allow us to identify relapsing–remitting multiple sclerosis (RRMS) patients with a disability increase in the first 2 years of therapy. Methods This is a prospective and longitudinal study of patients with RRMS treated with IFN-β. All patients included underwent brain MRI before the onset of therapy with IFN-β and 12 months after. MRI measures (T2, unenhanced T1-weighted and gadolinium-enhancing T1-weighted brain lesion load, brain parenchymal fraction) were undertaken at baseline and after 12 months. The number of active lesions (new or enlarging T2 plus gadolinium-enhancing brain lesions) was also assessed on the 12 months MRI scan. Expanded Disability Status Scale (EDSS) was scored every 3 months. We defined an increase in disability as an increase of at least 1 EDSS point confirmed and sustained during the first 2 years of therapy with IFN-β. Regression analysis was performed in order to identify MRI variables of response. Results We included 152 patients who were followed-up for at least 2 years. After 2 years of therapy, 24 patients (16%) had an increase in disability. The logistic regression model showed that active lesions in the scan performed at 12 months were the most important factor related with the increase of disability after 2 years of therapy (odds ratio 8.3, 95% confidence interval 3.1–21.9; p < 0.0001). Conclusions In RRMS patients treated with IFN-β the MRI changes occurring during the first year may have a prognostic value for identifying patients with a confirmed increase of disability after 2 years of therapy.

Effect of early interferon beta-1a therapy on conversion to multiple sclerosis in Iranian patients with a first demyelinating event

A new treatment approach to multiple sclerosis (MS) is the initiation of interferon therapy in the early phase of the disease when a patient presents with clinically isolated syndrome. The goal of this study was to assess the effect of early treatment on the risk of conversion to clinically definite MS in Iranian patients. Eligible patients had presented with a first episode of neurological dysfunction suggesting MS within the previous 3 months and had abnormal brain magnetic resonance imaging (MRI). Patients were randomly assigned to receive intramuscular interferon beta 1a 30 mug or placebo once a week for 3 years. Of the 217 patients randomized, 202 patients completed the study; 104 received Avonex and 98 received placebo. Fewer patients converted to clinically definite multiple sclerosis in the treated group than in the placebo group during the study (36.6% vs 58.2%, P < 0.003). The number of active T2-weighted MRI lesions was significantly lower in the treated group. The results of our study, which are consistent with those from western studies, show that treatment at an early stage of MS delays conversion to definite MS and has positive effects on MRI outcomes.

Randomized study of once-weekly interferon β-1a therapy in relapsing multiple sclerosis: three-year data from the OWIMS study

Once weekly interferon beta-1a for multiple sclerosis (OWIMS) demonstrated modest, but significant, magnetic resonance imaging (MRI) benefit of once-weekly (qw) interferon (IFN) beta-1a at 48 weeks, but no significant effect on relapses. An OWIMS extension permitted assessment of longer-term efficacy/safety of qw IFN beta-1a in relapsing-remitting multiple sclerosis (RRMS). Placebo patients were rerandomized to IFN beta-1a, 22 or 44 mcg qw, for two additional 48-week intervals. Primary outcome was MRI lesion activity. Relapse rate and other MRI measures were secondary outcomes. After three years, median (mean) T2 lesion count/patient/scan was 1.3 (2.6) for 44 mcg, 1.7 (3.3) for 22 mcg, 1.7 (3.4) for placebo/22 mcg, 2.0 (3.6) for placebo/44 mcg (all differences not significant). Annualized relapse rates were lowest for 44 mcg (0.77) versus other groups (0.83-0.86, not significant). Persistent neutralizing antibodies did not affect relapse rates, but MRI active lesions were increased in antibody-positive patients receiving 44 mcg compared to antibody negative patients. In RRMS, once weekly IFN beta-1a, particularly 44 mcg, can induce a significant MRI, but not relapse, effect, compared with placebo. No significant dose effect was seen. In contrast to the significant effect observed with three-times-weekly dosing of subcutaneous IFN beta-1a compared with placebo, this study confirms the lack of meaningful clinical benefit with once-weekly dosing.

A new approach for evaluating antigen-specific T cell responses to myelin antigens during the course of multiple sclerosis

We used a flow cytometry assay to measure proliferation and cytokine production of self-antigen-specific T cells in individual patients during the clinical course of multiple sclerosis (MS). Myelin-associated oligodendrocytic basic protein (MOBP) was selected for proof of principles in the assay, along with myelin basic protein (MBP) to assess specific activated T cells in 10 MS patients over an 18-month period, in parallel with brain magnetic resonance imaging (MRI) scans and clinical rating scale. A positive correlation occurred between antigen-specific T cell proliferation and interferon-γ production with clinical relapses and MRI lesion activity that was absent when the same patients were in remission.

Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis.

Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI. We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined. A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively. Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.

Increased percentage of IL-12+ monocytes in the blood correlates with the presence of active MRI lesions in MS

Interleukin (IL)-12 is a cytokine thought to play a major role in the pathogenesis of multiple sclerosis (MS). We have previously shown that patients with progressive MS have a high percentage of IL-12-producing monocytes in the blood compared to normal individuals. We analyzed 269 blood samples from 189 MS patients for the percentage of IL-12-producing monocytes. We found that the increased IL-12 expression correlates with disability, as measured by the Expanded Disability Status Scale (EDSS), and with disease activity, measured by the presence of gadolinium-enhancing magnetic resonance imaging (MRI) lesions.

Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis.

To determine if sex hormones play a role in the pathogenesis of multiple sclerosis (MS) by correlating serum estradiol and progesterone levels with gadolinium (Gd) enhancing lesions on magnetic resonance imaging (MRI) in MS. Thirty patients with MS were studied with Gd enhanced brain MRI and simultaneous serum estradiol and progesterone levels either during the early follicular, late follicular or luteal phases of their menstrual cycle. Correlation between hormone levels and number of Gd enhancing lesions was determined. Patients with high estradiol and low progesterone levels had a significantly greater number of Gd enhancing lesions than those with low levels of both these hormones. Patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio. Estradiol and progesterone may influence disease activity in MS. If further studies confirm these results, it may be possible to develop therapy by altering levels of these hormones.