Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE

Fewer accidents and better maintenance with active wheelchair check-ups: a randomized controlled clinical trial

Objective: To investigate whether active intervention using a compiled checklist for wheelchair check-ups increases user satisfaction and/or decreases accidents, near accidents and pressure sores.\ud \ud Design: A randomized controlled trial comparing active intervention versus standard intervention for prescribed, manually propelled wheelchairs.\ud \ud Setting: Patients within primary health care of Bora's and Bollebygd municipalities, a mixed urban and rural population.\ud \ud Subjects: Users of manually propelled wheelchairs over 16 years of age.\ud \ud Interventions: The accident rate, extent of pressure sores, number and extent of repairs, reconditioning, adjustments as well as user satisfaction were measured initially and at one year. In the standard intervention, the user and carer were encouraged to initiate contact when necessary. In the active intervention, an occupational therapist performed a scheduled, thorough check-up of the wheelchair, following a compiled checklist for safety, comfort and positioning, manoeuvrability and transportation.\ud \ud Results: Of 253 registered wheelchair users, 216 were suitable and randomized. In the active intervention group, 99% (95% confidence interval 96 / 100%) of the inspected wheelchairs required maintenance. The incidence of accidents was unchanged in the standard intervention group, but decreased to 'no accidents' in the active intervention group (p / 0.03). User satisfaction was not affected by the active intervention.\ud \ud Conclusion: Most wheelchair users are unable to determine on their own when adjustments are needed. An active check-up on manually propelled wheelchairs seems to reduce accidents

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study.

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appearing brain tissue (NABT) may play an important role in explaining the pathogenesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by pathologic changes. Using DW-MRI we investigated diffusion in the NABT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (ADCav) was measured in 10 regions of interest located in the normal-appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the ADCav in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The ADCav in frontal NAWM was associated with disability as measured by the MS Functional Composite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. Our preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant