A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis.

Objective: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS).

Methods: In the randomized, double-blind, placebo-controlled, phase 2 study, ARPEGGIO (A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes), eligible patients with PPMS were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.

Defining responders to therapies by a statistical modeling approach applied to randomized clinical trial data.

Background: Personalized medicine is the tailoring of treatment to the individual characteristics of patients. Once a treatment has been tested in a clinical trial and its effect overall quantified, it would be of great value to be able to use the baseline patients' characteristics to identify patients with larger/lower benefits from treatment, for a more personalized approach to therapy.

Methods: We show here a previously published statistical method, aimed at identifying patients' profiles associated to larger treatment benefits applied to three identical randomized clinical trials in multiple sclerosis, testing laquinimod vs placebo (ALLEGRO, BRAVO, and CONCERTO).

Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas.

Using placebo data from 3 randomized multiple sclerosis (MS) trials with uniform inclusion criteria, we investigated heterogeneity of Expanded Disability Status Scale (EDSS) progression by geographical areas. Our analysis revealed a significantly lower EDSS progression in Eastern European countries (10.8%) compared with Western Europe (13.

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Recent successful endovascular stroke trials have provided unequivocal support for these therapies in selected patients with large-vessel occlusive acute ischemic stroke. In this piece, we briefly review these trials and their utilization of advanced neuroimaging techniques that played a pivotal role in their success through targeted patient selection. In this context, the unique challenges and opportunity for advancement in current stroke networks' routine delivery of care created by these trials are discussed and recommendations to change current national stroke system guidelines are proposed.

Imaging Acute Ischemic Stroke: Mapping Present and Future Clinical Practice.

Imaging is an increasingly key component of advances in stroke care. Its role in the success of multiple recently reported trials that have now driven new standards of practice highlights its expanding importance in acute stroke management. With significant gains already realized, routine practice only stands to benefit further from additional advances in imaging in the future.

The goldilocks dilemma in acute ischemic stroke.

Despite the advent of and exciting advances in novel endovascular therapies, t-PA remains the only proven treatment for acute ischemic stroke to date. Although a variety of reasons likely underlie why past trials of endovascular strategies have been unsuccessful, we address in this perspective piece one critical unknown for which a solution is undoubtedly necessary if future ones are to meet with success: determination and selection of patients that are "just right" for endovascular treatments, or the Goldilocks dilemma. Key clinical criteria highlighted in past trials may help provide a solution to this critical problem.

Use of perfusion imaging and other imaging techniques to assess risks/benefits of acute stroke interventions.

The advent of multimodal neuroimaging has provided acute stroke care providers with an armamentarium of sophisticated imaging options to utilize for guidance in clinical decision-making and management of acute ischemic stroke patients. Here, we propose a framework and potential algorithm-based methodology for imaging modality selection and utilization for the purpose of achieving optimal stroke clinical care. We first review imaging options that may best inform decision-making regarding revascularization eligibility, with a focus on the imaging modalities that best identify critical inclusion and exclusion criteria.

A functional MRI study of preparatory signals for spatial location and objects.

We investigated preparatory signals for spatial location and objects in normal observers using functional magnetic resonance imaging (fMRI). Activity for attention-directing cues was separated from activity for subsequent test arrays containing the target stimulus. Subjects were more accurate in discriminating a target face among distracters when they knew in advance its location (spatial directional cue), as compared to when the target could randomly appear at one of two locations (spatial neutral cue), indicating that the spatial cue was used.

Quantitative analysis of attention and detection signals during visual search.

Prior work has distinguished regions in the intraparietal sulcus (IPs) and frontal eye field (FEF) involved in the voluntary control of attention, from more ventral regions in the temporoparietal junction (TPJ) involved in target detection. The present results show that when subjects search for and detect a visual target stimulus among nontargets, these regions show sensory-, search-, and detection-related signals that both confirm and refine these functional distinctions. The different signals were isolated by an additive model that accounted for a large fraction of BOLD (blood oxygenation level-dependent) signal modulation over the brain.

Two attentional processes in the parietal lobe.

We report fMRI evidence for two attentional processes in parietal cortex. Subjects matched a feature, cued by a word, to a test display of moving colored dots. Either color (red, green) or motion direction (left, right) was cued on mixed scans while only one dimension was cued on blocked scans.

Word retrieval learning modulates right frontal cortex in patients with left frontal damage.

Previous studies have suggested that recovery or compensation of language function after a lesion in the left hemisphere may depend on mechanisms in the right hemisphere. However, a direct relationship between performance and right hemisphere activity has not been established. Here, we show that patients with left frontal lesions and partially recovered aphasia learn, at a normal rate, a novel word retrieval task that requires the damaged cortex.

Reactivation of networks involved in preparatory states.

We report an endogenous signal that has a widespread cortical distribution and is time-locked to the termination of a sustained state of task-readiness. In three event-related functional magnetic resonance imaging (fMRI) experiments, subjects saw an arrow cue that predicted either the direction of motion or the location of a subsequent test stimulus. A reactivation of the BOLD (blood oxygenation level-dependent) signal occurred at the termination of the state of readiness in occipital regions that were transiently activated by the cue and in frontal-parietal regions that maintained an attentional set over the trial.