Abstract

BACKGROUND:
Available data suggest that pregnancy exposure to interferon-beta might result in lower mean birth weight and preterm birth.

OBJECTIVE:
To determine the effect of interferon-beta exposure during pregnancy on pregnancy outcomes in multiple sclerosis patients.

METHODS:
We compared the pregnancy outcomes of women exposed to interferon-beta with pregnancies unexposed to disease-modifying therapies. Women were enrolled into the German Multiple Sclerosis and Pregnancy Registry. A standardized questionnaire was administered during pregnancy and postpartum. Detailed information on course of multiple sclerosis and pregnancy, concomitant medications, delivery, and outcome of pregnancy was obtained.

RESULTS:
We collected data on 251 pregnancies exposed to interferon-beta and 194 unexposed to disease-modifying therapies. In all, 246 (98.01%) women discontinued interferon-beta treatment during first trimester. No differences regarding mean birth weight (exposed: 3272.28 ± 563.61 g; unexposed: 3267.46 ± 609.81 g), mean birth length (exposed: 50.73 ± 3.30 cm; unexposed: 50.88 ± 3.45 cm), preterm birth (p = 0.187), spontaneous abortion (p = 0.304), and congenital anomalies (p = 0.197) were observed between the two groups.

CONCLUSIONS:
Interferon-beta exposure during early pregnancy does not influence the mean birth weight, risk of preterm birth, or other adverse pregnancy outcomes. Our study provides further reassurance that interferon-beta treatment can be safely continued up until women become pregnant.

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This study suggests that extended interval dosing up to 8 weeks can be safe and effective. Longer follow-up will be mandatory to evaluate if this kind of strategy can decrease the risk of PML

Abstract

Background
Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days.

Methods
A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks.

Results
17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort.

Conclusions
Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.

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A study evaluating serum cytokine profiel to assess therapeutic response to beta interferon in RRMS

Abstract

Objective: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)–β treatment in patients with multiple sclerosis (MS).

Methods: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays. Baseline cytokine profiles were grouped by hierarchical clustering analysis. Demographic features, changes in cytokines, and clinical outcome were then assessed in the clustered patient groups.

Results: A total of 157 patients were included in the study and clustered into 6 distinct subsets by baseline cytokine profiles. These subsets differed significantly in their clinical and biological response to IFN-β therapy. Two subsets were associated with patients who responded poorly to therapy. Two other subsets, associated with a good response to therapy, showed a significant reduction in relapse rates and no worsening of disability. Each subset also had differential changes in cytokine levels after 3 months of IFN-β treatment.

Conclusions: There is heterogeneity in the immunologic pathways of the RRMS population, which correlates with IFN-β response.

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This study suggests that samrtphone and tablet apps based on Ishihara plates for detection of dyschromatopsia are efficient and reliable, particularly in optic neuritis patients.

Abstract

Optic neuritis (ON) is a common and important cause of vision loss or vision disturbances in the community, particularly amongst the young, and it is often associated with a persistent dyschromatopsia. Traditionally screening for dyschromatopsia has been carried out using pseudo-isochromatic Ishihara plates. These colour plates were originally developed for testing of colour blindness, and indeed have only more recently been applied to ON. As the Ishihara plate books used for testing are expensive, unwieldy, and are not commonly available in many clinics or wards, many neurologists and ophthalmologists have taken to using untested and unstudied downloadable software packages on portable electronic devices for testing. This study compared the efficacy of printed and iPad (Apple, Cupertino, CA, USA) versions of the Ishihara plates in screening for dyschromatopsia in patients who were suspected of having ON. The main finding was that dyschromatopsia testing using a commercially available application on an iPad was comparable to using the current pragmatic clinical benchmark, the pseudo-isochromatic plates of Ishihara. These findings provide support for the increasingly common practice of screening for dyschromatopsia using the iPad.

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Two recent articles were recently published in the New England Journal of Medicine about management of neurovascular diseases.

The first one is about a randomized study assessing senting versus surgery for the treatment of asymptomatic carotid stenosis, showing equivalent efficacy for both techniques in patients who were not at high risk for surgical complications.

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The second one demonstrates the efficacy of pioglitazone in patients who present with stroke or TIA and who have insuln resistance without diabetes.

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