Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies.Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access.

Although multiple sclerosis (MS) has traditionally been considered a white matter disease, extensive research documents the presence and importance of gray matter injury including cortical and deep regions. The deep gray matter (DGM) exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in MS using magnetic resonance techniques. DGM injury has been associated with clinical and cognitive disability. Recently, MRI characterization of DGM properties, such as thalamic volume, have been tested as potential clinical trial endpoints associated with neurodegenerative aspects of MS. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in MS (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to the DGM. Herein, we review current knowledge regarding DGM injury in MS from an imaging perspective, including insights from histopathology, image acquisition and post-processing for DGM. We discuss the clinical relevance of DGM injury and specific regions of interest within the DGM. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.

Highlights Approximately one in five patients with MS do not have the disease. The central vein differentiates multiple sclerosis from other white matter lesions. The central vein sign has not been evaluated in multi-center prospective studies. CAVS-MS is a prospective multicenter study to validate the central vein. CAVS-MS will useT2*-weighted, high-isotropic-resolution, segmented echo-planar MRI.

Despite improvements in nutritional management, preterm infants continue to face high rates of postnatal growth restriction. Because variability in breast milk composition may result in protein and energy deficits, targeted fortification has been advocated. We conducted an interventional study to compare body composition and growth outcomes of very low birth weight infants fed targeted protein-fortified human milk (HM) with those fed standard fortified HM. If mother’s own milk was not available, donor milk was used. Weekly analysis of HM with mid-infrared spectroscopy was conducted and additional protein was added to the fortified HM to ensure a protein intake of 4 g/kg/day. Weekly anthropometric measurements were done. Prior to discharge or at 37 weeks, corrected age skinfold thickness (SFT) measurements as well as body composition measurement using air displacement plethysmography were done. Among 36 preterm infants enrolled, those in the targeted group (n = 17) received more protein and had a larger flank SFT at study end than those in the standard group (n = 19). A pilot post-hoc analysis of subjects having at least 30 intervention days showed a 3% higher fat-free mass in the targeted group. Use of a targeted fortification strategy resulted in a higher protein intake and fat-free mass among those receiving longer intervention.