Assessment of automatic decision-support systems for detecting active T2 lesions in multiple sclerosis patients

Background: Active (new/enlarging) T2 lesion counts are routinely used in the clinical management of multiple sclerosis. Thus, automated tools able to accurately identify active T2 lesions would be of high interest to neuroradiologists for assisting in their clinical activity. Objective: To compare the accuracy in detecting active T2 lesions and of radiologically active patients based on different visual and automated methods. Methods: One hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months. Four approaches were assessed for detecting active T2 lesions: (1) conventional neuroradiological reports; (2) prospective visual analyses performed by an expert; (3) automated unsupervised tool; and (4) supervised convolutional neural network. As a gold standard, a reference outcome was created by the consensus of two observers. Results: The automated methods detected a higher number of active T2 lesions, and a higher number of active patients, but a higher number of false-positive active patients than visual methods. The convolutional neural network model was more sensitive in detecting active T2 lesions and active patients than the other automated method. Conclusion: Automated convolutional neural network models show potential as an aid to neuroradiological assessment in clinical practice, although visual supervision of the outcomes is still required.

Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

Objective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI

Background Myelin-oligodendrocyte-glycoprotein (MOG)-IgG-positivity in patients with typical MS lesions on MRI may lead to diagnostic/therapeutic uncertainty. Objective and Methods We reviewed reports of cases with MS phenotype on MRI and MOG-IgG-positivity published in Pubmed between 01/2012–06/2021. Results Sixteen patients were included (median age [range], 37,5 [25–66] years; 60% female). Three patients initially tested negative for MOG-IgG. Disease course was: relapsing-remitting, 10; or progressive, 6. Intrathecal IgG-synthesis was common (79%). Low and high-efficacy MS-targeted agents prevented relapses in 30% and 100%, respectively. None of the patients showed resolution of MRI T2-lesions over time. Conclusions MOG-IgG-positivity is unlikely to alter the expected treatment response and outcomes in patients with otherwise typical MS phenotype on MRI.

Thalamus Atrophy in the Peri-Pregnancy Period in Clinically Stable Multiple Sclerosis Patients: Preliminary Results

Radiological activity in the post-partum period in MS patients is a well-known phenomenon, but there is no data concerning the influence of pregnancy on regional brain atrophy. The aim of this article was to investigate local brain atrophy in the peri-pregnancy period (PPP) in patients with MS. Thalamic volume (TV); corpus callosum volume (CCV) and classical MRI activity (new gadolinium enhancing lesions (Gd+), new T2 lesions, T1 lesions volume (T1LV) and T2 lesions volume (T2LV)) were analyzed in 12 clinically stable women with relapsing–remitting MS and with MRI performed in the PPP. We showed that there was a significant decrease in TV (p = 0.021) in the PPP. We also observed a significant increase in the T1 lesion volume (p = 0.028), new gadolinium-enhanced and new T2 lesions (in 46% and 77% of the scans, respectively) in the post-partum period. Our results suggest that the PPP in MS may be associated not only with classical MRI activity but, also, with regional brain atrophy.

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients

Recent studies estimated an incidence of 4–25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11–3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses.

Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population ( n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

Background and ObjectivesTo estimate the proportions of patients with relapsing-remitting multiple sclerosis who despite achieving the no evidence of disease activity-3 (NEDA-3) status in the first 2 treatment years experienced relapse-associated worsening (RAW) or progression independent from relapse activity (PIRA) in the following years.MethodsWe selected patients with NEDA-3—defined as no relapse, no disability worsening, and no MRI activity—in the first 2 years of either glatiramer acetate or interferon beta as initial treatment. We estimated the long-term probability of subsequent RAW and PIRA (considered as 2 contrasting outcomes) by cumulative incidence functions. Competing risk regressions were used to identify the baseline (i.e., at treatment start) predictors of RAW and PIRA.ResultsOf 687 patients, 224 (32.6%) had NEDA-3 in the first 2 treatment years. After a median follow-up time of 12 years from treatment start, 58 patients (26%) experienced disability accrual: 31 (14%) had RAW and 27 (12%) had PIRA. RAW was predicted by the presence of >9 T2 lesions (subdistribution hazard ratio [SHR] = 3.92, p = 0.012) and contrast-enhancing lesions (SHR = 2.38, p = 0.047) on baseline MRI scan and either temporary or permanent discontinuation of the initial treatment (SHR = 1.11, p = 0.015). PIRA was predicted by advancing age (SHR = 1.05, p = 0.036 for each year increase) and presence of ≥1 spinal cord lesion on baseline MRI scan (SHR = 4.08, p = 0.016).DiscussionThe adoption of NEDA-3 criteria led to prognostic misclassification in 1 of 4 patients. Different risk factors were associated with RAW and PIRA, suggesting alternative mechanisms for disability accrual.Classification of EvidenceThis study provides Class II evidence that in patients with RRMS who attained NEDA-3 status, subsequent RAW was associated with baseline MRI activity and discontinuation of treatment and PIRA was associated with age and the presence of baseline spinal cord lesions.

MRI brain volume loss, lesion burden, and clinical outcome in secondary progressive multiple sclerosis

Background: Magnetic resonance imaging (MRI) of brain volume measures are widely used outcomes in secondary progressive multiple sclerosis (SPMS), but it is unclear whether they are associated with physical and cognitive disability. Objective: To investigate the association between MRI outcomes and physical and cognitive disability worsening in people with SPMS. Methods: We used data from ASCEND, a large randomized controlled trial ( n = 889). We investigated the association of change in whole brain and gray matter volume, contrast enhancing lesions, and T2 lesions with significant worsening on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT) with logistic regression models. Results: We found no association between MRI measures and EDSS or SDMT worsening. T25FW worsening at 48 and 96 weeks, and NHPT worsening at 96 weeks were associated with cumulative new or newly enlarging T2 lesions at 96 weeks. NHPT worsening at 48 and 96 weeks was associated with normalized brain volume loss at 48 weeks, but not with other MRI outcomes. Conclusion: The association of standard MRI outcomes and disability was noticeably weak and inconsistent over 2 years of follow-up. These MRI outcomes may not be useful surrogates of disability measures in SPMS.

Іmpact of pathogenic therapy of multiple sclerosis on clinical and neuroimaging factors of its activity

The article presents the experience of the Kiev Center of Multiple Sclerosis in using pathogenic first-line and second-line therapy to treat patients with relapsing-remitting multiple sclerosis (RRMS). We have analyzed clinical and neuroimaging factors of disease activity (relapse rate, changes in T2 lesions, Gd+ lesions) to assess the efficacy of the treatment during 24 months. Based on the NAA/Cr ratio we determined the neuroprotective effect of the therapy. The significant effect of pathogenic treatment is associated with both decrease in relapse frequency and with a slowdown in the emergence of new T2 and Gd+ lesions.