This open access article assessed the efficacy and safety of bevacizumab in the treatment of NMO relapses as an add on therapy to high dose corticosteroids.

Abstract

Objectives
Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood–brain barrier.

Methods
We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused 10 mg/kg of bevacizumab intravenously on day 1 of treatment. The primary outcome measure was safety and the secondary outcome measure was efficacy.

Results
Of the 10 participants enrolled, five presented with acute transverse myelitis, four with acute optic neuritis and one with a brainstem lesion. Bevacizumab was safe in all 10 participants, with only one serious adverse event within the 90-day follow up that was not attributed to the medication. Three patients recovered to pre-attack neurological function or better, and no patients required escalation to plasmapheresis.

Conclusions
Bevacizumab is a safe add-on therapy to high-dose corticosteroids for NMO/NMO spectrum disease patients presenting with an acute relapse.

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This article published in the latest issue of Neurology, NeuroImmunology & Neuroinflammation shows the evolution of JC serology and index in French an German patients treated with natalizumab.

Abstract

OBJECTIVE:
The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment.

METHODS:
German (n = 1,921; 525 longitudinally) and French (n = 1,259; 711 longitudinally) patients were assessed for JCV serology alongside their therapy with natalizumab.

RESULTS:
JCV serostatus changed in 69 of 525 longitudinally followed German patients (13.1%) over 14.8 months. Seroconversion according to serostatus was seen in 43 of 339 initially JCV- German patients (12.7% in 14.8 months; 10.3% per year) and 41 of 243 initially JCV- French patients (16.9% in 24 months; 8.5% per year). JCV index values could be reproduced (R (2) = 0.89) with the caveat of 8 of 50 samples (16%) being set into different risk categories between 2 assessments. Index values of JCV+ patients rose over time (p = 0.009) but not because of aging. Treatment with natalizumab was associated with a 15.9% increase of value in JCV+ patients in 14.8 months (12.9% per year).

CONCLUSIONS:
JCV seroconversion and index values may be influenced by treatment with natalizumab. It is therefore important to monitor patients' JCV serology but also to incorporate additional risk factors into the progressive multifocal leukoencephalopathy risk stratification.

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A recently published article demonstrates the feasability and efficacy of treadmill training combined with virtual reality to improve gait in patients with MS.

Abstract

Gait and cognitive deficits are common in multiple sclerosis (MS) and are negatively affected during dual-task walking. Treadmill (TM) training has been previously used to preserve locomotor activity in MS. Virtual reality (VR) engages the user in cognitive and motor activities simultaneously. A training combining TM and VR has been successfully adopted in several neurological diseases, but not in MS. This study aims at investigating the feasibility of a VR-based TM training program on gait of subjects with MS.

Eight persons with relapsing–remitting MS were recruited to participate in a six-week VR-based TM training program. Gait analysis was performed both in single and dual task conditions. Clinical tests were used to assess walking endurance and obstacle negotiation. All the evaluations were performed before, immediately and one month after the training.

Gait speed and stride length improved in dual task post-intervention and were retained at follow-up. An improved ability in negotiating obstacles was found across the evaluations. VR-based TM training program is feasible and safe for MS subjects with moderate disabilities and may positively affect gait under complex conditions, such as dual tasking and obstacle negotiation.

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This article was published in the latest issue of The Lancet Neurology

Article summary

In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.

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A recent review published in the Journal on Neurology

Introduction

There is no consensus about short-term suboptimal response to first-line treatments in relapsing-remitting multiple sclerosis.

Methods

We searched studies with interferon beta or glatiramer acetate in which a long-term (≥ 2 years (y)) outcome could be predicted using short-term (≤ 1 y) suboptimal response criteria (EDSS-, imaging- and/or relapse-based). We obtained pooled diagnostic accuracy parameters for the 1-y criteria used to predict disability progression between 2–5 y.

Results

We selected 45 articles. Eight studies allowed calculating pooled estimates of 16 criteria. The three criteria with best accuracy were: new or enlarging T2-weighted lesions (newT2) ≥ 1 (pooled sensitivity: 85.5%; specificity:70.2%; positive predictive value:48.0%; negative predictive value:93.8%), newT2 ≥ 2 (62.4%, 83.6%, 55.0% and 87.3%, respectively) and RIO score ≥ 2 (55.8%, 84.4%, 47.8% and 88.2%). Pooled percentages of suboptimal responders were 43.3%, 27.6% and 23.7%, respectively. Pooled diagnostic odds ratios were 14.6 (95% confidence interval: 1.4–155), 9.2 (1.4–59.0) and 8.2 (3.5–19.2).

Conclusions

All criteria had a limited predictive value. RIO score ≥ 2 at 1-y combined fair accuracy and consistency, limiting the probability of disability progression in the next years to 1 in 8 optimal responders. NewT2 ≥ 1 at 1-y had similar positive predictive value, but diminished the false negatives to 1 in 16 patients. More sensitive measures of treatment failure at short term are needed.

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