Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Tracking insulin- and glucagon-expressing cells in vitro and in vivo using a double reporter human embryonic stem cell line.

Human embryonic stem cell (hESC)-derived pancreatic alpha and beta cells can be used to develop cell replacement therapies to treat diabetes. However, recent published differentiation protocols yield varying amounts of alpha and beta cells amidst heterogeneous cell populations. To visualize and isolate hESC-derived alpha and beta cells, we generated a GLUCAGON-2AmScarlet and INSULIN-2A-EGFP dual fluorescent reporter (INSEGFPGCGmScarlet) hESC line using CRISPR/Cas9.

Characteristics and predictors of disease course in children initially presenting with ADEM.

ADEM is an inflammatory disease, with new onset polyfocal neurologic symptoms, encephalopathy and multifocal demyelination, typically in childhood. Initial diagnosis of ADEM is challenging and up to 20 % of children with MS or NMOSD are initially diagnosed with ADEM. We describe characteristics of patients with monophasic ADEM vs.

Patient and family views on research priorities and design of clinical trials and research studies in pediatric multiple sclerosis.

Background And Objectives: This survey study aimed to (1) identify patient/family research priorities in pediatric-onset multiple sclerosis (POMS), and (2) delineate optimized methods for research study/clinical trials design, engagement, and implementation.

Methods: Participants were as follows: (1) parents of a child (<18 years) with POMS enrolled in a national registry, (2) adolescents (13-17 years) with POMS in the registry, and (3) adults (18-40 years) with POMS receiving care at a registry affiliated clinic. Of 293 eligible participants, 192 completed surveys.

Distinct plasma lipids predict axonal injury and multiple sclerosis activity.

Background: Lipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this study, we performed an in-depth lipidomics analysis to identify lipids associated with injury and disease activity.

Methods: Plasma samples were collected from paediatric-onset multiple sclerosis (MS) cases within 4 years of disease onset from 17 sites.

A single-center retrospective series of OCT and MRI findings in pediatric MOGAD optic neuritis patients.

Background: Whether optical computed tomography (OCT) and magnetic resonance imaging (MRI) findings are associated with final visual acuity in children with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) optic neuritis is unclear.

Methods: We retrospectively reviewed the charts of pediatric patients with MOGAD optic neuritis seen at St. Louis Children's Hospital/Barnes Jewish Hospital since 2016.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Background And Objectives: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.

Methods: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study.

Comparison of CT-Guided needle biopsy versus percutaneous endoscopic debridement and drainage in pathogen identification and pain outcomes for spondylodiscitis patients: A systematic review and literature review.

Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%-48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis.

Increased intraindividual variability (IIV) in reaction time is the earliest indicator of cognitive change in MS: A two-year observational study.

Background: Cognitive decline in multiple sclerosis (MS) is common, but unpredictable, and increases with disease duration. As such, early detection of cognitive decline may improve the effectiveness of interventions. To that end, the Symbol Digit Modalities Test (SDMT) is effective in detecting slow processing speed as it relates to cognitive impairment, and intraindividual variability (IIV) observed in trials assessing continuous reaction time (RT) may be a useful indicator of early cognitive changes.

Association of nutritional intake with clinical and imaging activity in pediatric multiple sclerosis.

Background: Understanding nutrition's role in multiple sclerosis (MS) can guide recommendations and intervention-based studies.

Objective: Evaluate the association between nutrition and pediatric-onset MS outcomes.

Methods: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers.

Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.

Endogenous opioids facilitate stress-induced binge eating via an insular cortex-claustrum pathway.

Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well established to be a crucial mediator of the anhedonic component of stress.

Clinical and magnetic resonance imaging outcomes in pediatric-onset MS patients on fingolimod and ocrelizumab.

Background: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials.

Objective: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age.

Methods: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18.

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

Objective: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored.

Design: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n  = 15), ART-naive ( n  = 15), and adolescents without HIV (AWOH; n  = 10)] and Myanmar [AWH on ART ( n  = 54) and AWOH ( n  = 22)] were studied.

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

Background: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown.

Objective: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests.

Gene-environment interactions: Epstein-Barr virus infection and risk of pediatric-onset multiple sclerosis.

Background And Objective: Prior Epstein-Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS.

Mexican consensus on cow's milk protein allergy.

Background: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico.

Material And Methods: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire.

Assessing Needs and Perceptions of Research Participation in Pediatric-Onset Multiple Sclerosis: A Multistakeholder Survey.

Background: Patient-powered research networks (PPRNs) for autoimmune disease are widely used in the adult population to recruit patients and drive patient-centered research, but few have included pediatric patients. We aimed to characterize viewpoints regarding research needs and participation in pediatric-onset multiple sclerosis (POMS) via a PPRN-disseminated survey.

Methods: This is an exploratory, cross-sectional study.

Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors.

Background: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk.

Methods: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02).

Pearls & Oy-sters: MOG-AD Meningoencephalitis With Holocord Gray Matter Predominant Myelitis.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been implicated in a wide range of CNS encephalitis and myelitis presentations. We present a previously healthy 16-year-old girl who presented with acute onset headaches that rapidly progressed to encephalopathy, flaccid paraparesis, lower extremity hyperreflexia, and urinary retention. Serial MRI brain and total spine imaging demonstrated evolving diffuse supratentorial leptomeningeal enhancement and holocord gray matter restricted T2 bright lesion without enhancement.

Central Vein Sign in Pediatric Multiple Sclerosis and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background: The central vein sign (CVS) on brain magnetic resonance imaging (MRI) is a promising diagnostic marker for distinguishing adult multiple sclerosis (MS) from other demyelinating conditions, but its prevalence is not well-established in pediatric-onset multiple sclerosis (POMS) versus myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD can mimic MS radiologically. This study seeks to determine the utility of CVS, together with other radiological findings, in distinguishing POMS from MOGAD in children.