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.

Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis.

Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.

Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.

Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis.

Magnetization transfer ratio (MTR) is a semi-quantitative measure that seems to correlate with the degree of myelin loss and generally tissue destruction in multiple sclerosis (MS). Our objective was to comprehensively assess the MTR of lesions and normal appearing (NA) tissue separately in the white matter (WM), the cortex, the thalamus and the basal ganglia (BG) and determine their relative contribution to disability. In this cross-sectional study 71 patients were included (59 with relapsing-remitting MS, 12 with secondary progressive MS).

MRI characteristics of periaqueductal lesions in multiple sclerosis.

Background: In multiple sclerosis (MS), periaqueductal lesions (PAL) have been described histopathologically.

Objectives: We sought to investigate the frequency and characteristics of PAL on magnetic resonance images (MRIs) in patients with MS or clinically isolated syndrome (CIS).

Methods: We analyzed proton density (PD)-weighted MRIs of 247 MS and 10 CIS patients.

Cervical spinal cord volume loss is related to clinical disability progression in multiple sclerosis.

Objective: To examine the temporal evolution of spinal cord (SC) atrophy in multiple sclerosis (MS), and its association with clinical progression in a large MS cohort.

Methods: A total of 352 patients from two centres with MS (relapsing remitting MS (RRMS): 256, secondary progressive MS (SPMS): 73, primary progressive MS (PPMS): 23) were included. Clinical and MRI parameters were obtained at baseline, after 12 months and 24 months of follow-up.

Head motion parameters in fMRI differ between patients with mild cognitive impairment and Alzheimer disease versus elderly control subjects.

Motion artifacts are a well-known and frequent limitation during neuroimaging workup of cognitive decline. While head motion typically deteriorates image quality, we test the hypothesis that head motion differs systematically between healthy controls (HC), amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) and consequently might contain diagnostic information. This prospective study was approved by the local ethics committee and includes 28 HC (age 71.

Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years.

Background: The development of predictors of multiple sclerosis (MS) disability is difficult due to the complex interplay of pathophysiological and adaptive processes.

Objective: The purpose of this study was to investigate whether combined evoked potential (EP)-measures allow prediction of MS disability after 20 years.

Methods: We examined 28 patients with clinically definite MS according to Poser's criteria with Expanded Disability Status Scale (EDSS) scores, combined visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a cranial magnetic resonance imaging (MRI) scan at T0 and T2.

Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis.

Background: Cortical lesions (CLs) have been reported to be a better predictor for cognitive impairment than white matter (WM) lesions in relapsing-remitting multiple sclerosis (RRMS).

Objectives: The objectives of this article are to investigate the contribution of CLs and WM lesions to cognitive impairment in 91 patients with MS and clinically isolated syndrome, and to test potential associations of CLs and WM lesions with fatigue and depression.

Methods: Lesions were scored and segmented on 3D double inversion recovery sequences, according to their location (cortical, WM).

Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study.

Background: Fingolimod 0·5 mg once daily is approved for treatment of relapsing multiple sclerosis (MS). In the phase 3, 2-year FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in MS) study, fingolimod significantly reduced annualised relapse rates (ARRs) and the risk of confirmed disability progression compared with placebo. We aimed to investigate whether the beneficial treatment effect reported for the overall population is consistent in subgroups of patients with different baseline characteristics.

Evolution of MS lesions to black holes under DNA vaccine treatment.

Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.

MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials.

Over the past 15 years, MRI lesion activity has become the accepted surrogate primary outcome measure in proof-of-concept placebo-controlled clinical trials of new immunomodulating therapies in relapse-onset multiple sclerosis (MS). In parallel, the number of patients that are available for the placebo arm of trials has declined, and more-aggressive drugs are being developed. A critical review is warranted to ensure efficient MRI--and patient--resource utilization.

Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability.

Background: Although grey matter damage in multiple sclerosis is currently recognized, determinants of grey matter volume and its relationship with disability are not yet clear.

Objectives: The objectives of the study were to measure grey and white matter volumes across different disease phenotypes; identify MRI parameters associated with grey matter volume; and study grey and white matter volume as explanatory variables for clinical impairment.

Methods: This is a cross-sectional study in which MRI data of 95 clinically isolated syndrome, 657 relapsing-remitting, 125 secondary-progressive and 50 primary-progressive multiple sclerosis patients from three centres were acquired.

Can cortical thickness asymmetry analysis contribute to detection of at-risk mental state and first-episode psychosis? A pilot study.

Purpose: To investigate whether cortical thickness analysis in individuals with an at-risk mental state (ARMS) might contribute to early detection of psychosis.

Materials And Methods: Ethics committee approval and written informed consent were obtained. Cortical thickness was analyzed because early disease-related morphometric changes were expected to be most pronounced in the cerebral cortex.

Spatial and temporal analysis of fMRI data on word and sentence reading.

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions.

Neural activation associated with corrective saccades during tasks with fixation, pursuit and saccades.

Corrective saccades are small eye movements that redirect gaze whenever the actual eye position differs from the desired eye position. In contrast to various forms of saccades including pro-saccades, recentering-saccades or memory guided saccades, corrective saccades have been widely neglected so far. The fMRI correlates of corrective saccades were studied that spontaneously occurred during fixation, pursuit or saccadic tasks.

Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring.

Natalizumab is a new treatment option for patients with active relapsing-remitting multiple sclerosis. In phase III studies, natalizumab was highly effective and well tolerated; however, three cases of progressive multifocal leucoencephalopathy (PML) were identified (estimated incidence of one per 1000; 95% CI 0.2-2.

Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF.

Objective: We investigated the correlation of antimyelin oligodendrocyte glycoprotein-(anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested,the incidence of more frequent and rapid progression to clinically definite MS (CDMS).

Methods: 133CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed.

Mapping continuous neuronal activation without an ON-OFF paradigm: initial results of BOLD ceiling fMRI.

Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON-OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation.

Oral fingolimod (FTY720) for relapsing multiple sclerosis.

Background: Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.

Methods: We randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.

Effect of fMRI acoustic noise on non-auditory working memory task: comparison between continuous and pulsed sound emitting EPI.

Conventional blood oxygenation level-dependent (BOLD) based functional magnetic resonance imaging (fMRI) is accompanied by substantial acoustic gradient noise. This noise can influence the performance as well as neuronal activations. Conventional fMRI typically has a pulsed noise component, which is a particularly efficient auditory stimulus.

Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors.

Objective: The aim of this study was to evaluate the characteristics of an ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain tumors and to correlate changes on MRI with histopathologic data collected systematically in all patients.

Subjects And Methods: Nine patients with brain tumors were imaged before and 24 hr after administration of a USPIO at a dose of 2.6 mg Fe/kg.

What is different about a radiologist's brain?

Purpose: To investigate neuronal activations during processing of radiologic and nonradiologic images by experienced radiologists and nonradiologist subjects by using event-related functional magnetic resonance (MR) imaging.

Materials And Methods: Study was approved by local ethics committee, and informed consent was obtained. Radiologic and control images were presented to 12 experienced radiologists (mean age, 35.

Atrophy is detectable within a 3-month period in untreated patients with active relapsing remitting multiple sclerosis.

Background: Atrophy is recognized as a measure of destructive changes in multiple sclerosis (MS). The time course and pathologic mechanisms of atrophy development are not well understood. Significant atrophy was reported to occur within 9 to 12 months in relapsing remitting MS.

Differential sex-independent amygdala response to infant crying and laughing in parents versus nonparents.

Background: Animal and human studies implicate forebrain neural circuits in maternal behavior. Here, we hypothesized that human brain response to emotional stimuli relevant for social interactions between infants and adults are modulated by sex- and experience-dependent factors.

Methods: We used functional magnetic resonance imaging and examined brain response to infant crying and laughing in mothers and fathers of young children and in women and men without children.