Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial.

Background: Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis.

Methods: MESEMS is a randomised phase 2 trial done at 15 sites in nine countries.

Association of a Marker of N-Acetylglucosamine With Progressive Multiple Sclerosis and Neurodegeneration.

Importance: N-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration. N-acetylglucosamine (GlcNAc) is a rate-limiting substrate for N-glycan branching, but, to our knowledge, endogenous serum levels in patients with multiple sclerosis (MS) are unknown.

Objective: To investigate a marker of endogenous serum GlcNAc levels in patients with MS.

MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis.

Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS.

Methods/design: This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS.

Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans.

Based on our previous data on the presence of very small superparamagnetic iron oxide nanoparticles (VSOP) on brain endothelial structures during experimental autoimmune encephalomyelitis (EAE), we investigated the mechanisms of VSOP binding on inflamed brain endothelial cells in vivo and in vitro. After intravenous application, VSOP were detected in brain endothelial cells of EAE animals at peak disease and prior to clinical onset. In vitro, inflammatory stimuli increased VSOP uptake by brain endothelial bEnd.

Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder.

Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field.

Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Background: The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention.

Methods: Forty patients with anti-NMDAR encephalitis after the acute disease stage and 25 healthy control subjects underwent multimodal structural imaging that combined volumetry of hippocampal subfields with analysis of hippocampal microstructural integrity.

Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation.

Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood-brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in MRI.

Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations.

Background: Retinal nerve fibre layer (RNFL) thinning is associated with brain atrophy in multiple sclerosis (MS). An influence of optic neuritis is well documented but sparsely investigated. Recently, the retinal ganglion cell layer (GCL) has been shown to provide superior information regarding visual function and retinal neurodegeneration as compared with RNFL.

Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis.

Objective: To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients' clinical symptoms concerning the visual pathway.

Design, Subjects And Methods: Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter.

Results: RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA.

Association of retinal and macular damage with brain atrophy in multiple sclerosis.

Neuroaxonal degeneration in the central nervous system contributes substantially to the long term disability in multiple sclerosis (MS) patients. However, in vivo determination and monitoring of neurodegeneration remain difficult. As the widely used MRI-based approaches, including the brain parenchymal fraction (BPF) have some limitations, complementary in vivo measures for neurodegeneration are necessary.

Gadofluorine M-enhanced MRI shows involvement of circumventricular organs in neuroinflammation.

Background: Circumventricular organs (CVO) are cerebral areas with incomplete endothelial blood-brain barrier (BBB) and therefore regarded as "gates to the brain". During inflammation, they may exert an active role in determining immune cell recruitment into the brain.

Methods: In a longitudinal study we investigated in vivo alterations of CVO during neuroinflammation, applying Gadofluorine M- (Gf) enhanced magnetic resonance imaging (MRI) in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Development of ulcerative colitis in a patient with multiple sclerosis following treatment with interferon beta 1a.

To alert clinicians to a potential novel adverse drug effect of interferon beta 1a, we herein report a patient with relapsing-remitting multiple sclerosis who developed ulcerative colitis following treatment with interferon beta 1a. Ulcerative colitis persisted despite discontinuation of interferon beta 1a treatment and switching the patient to glatiramer acetate. Tacrolimus (FK506), 6-mercaptopurine, and prednisolone were required to induce remission.