The Long‑Term Outcomes (LTO) Project aims to characterize long‑range trajectories in pediatric‑onset MS by examining social, clinical, and behavioral measures of wellbeing over time. Launched in early 2024, the study evaluates both baseline and longitudinal clinical and biological predictors of long‑term outcomes in children and adolescents with MS, with particular attention to the impact of early environmental exposures and the types of MS therapies used within the first two years after diagnosis. By integrating these data, the project seeks to identify factors that meaningfully influence disease progression, functioning, and quality of life, ultimately informing more precise, evidence‑based approaches to long‑term care in pediatric MS.

The CARE in MS project is a multicenter, NIH‑funded study designed to examine how childhood adversity influences clinical outcomes in pediatric‑onset MS. Focused on high‑risk groups—including Black, Hispanic, and socioeconomically disadvantaged populations—the study integrates focus groups, questionnaires, socioeconomic indicators, and brain imaging to evaluate how modifiable social and environmental factors contribute to disparities in disease severity, age of onset, and quality of life. With a target enrollment of approximately 300 participants, CARE in MS aims to generate evidence that can inform targeted interventions and reduce inequities in pediatric MS outcomes.

The Family Caregiving Project examines the caregiving experiences, burdens, and support needs of families following a child’s diagnosis of pediatric‑onset MS. Launched in January 2025, the study aims to characterize the types of care provided, the challenges families face, and how these experiences vary based on clinical features, timing of diagnosis, and socioeconomic context. By capturing a detailed picture of family‑level impacts, the project seeks to identify modifiable factors that may improve support systems and reduce disparities in caregiving strain.

The MOGAD Real‑World Evidence Study, launched in March 2024, examines real‑world clinical patterns in pediatric patients with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). This ongoing project evaluates relapsing disease behavior, treatment strategies, and cognitive and psychosocial outcomes across participating U.S. centers. By integrating longitudinal clinical data with functional and psychosocial measures, the study aims to clarify how children with MOGAD experience and respond to care in everyday practice—providing critical insights that can guide earlier diagnosis, more targeted treatment decisions, and improved long‑term support for affected youth.

The Avonex vs. Plegridy Project evaluates real‑world relapse outcomes in pediatric patients treated with two interferon‑based therapies: intramuscular interferon beta‑1a (Avonex) and subcutaneous peginterferon beta‑1a (Plegridy). Using data from 250 participants in the PeMSDD registry, the analysis compares time to first relapse between the two treatment groups, providing valuable evidence on how these commonly used disease‑modifying therapies perform in routine clinical practice. Findings from this study have been disseminated through both an abstract and a published manuscript, contributing to a more informed understanding of therapeutic effectiveness in pediatric MS.

The Roche Real‑World Data Project analyzes PeMSDD registry data to better understand treatment patterns and outcomes in pediatric‑onset relapsing‑remitting MS. Focusing on individuals ages 10–17, the study evaluates demographics, medication use, relapse rates, and MRI measures across real‑world clinical settings. This collaboration has already produced multiple abstracts and manuscripts, contributing important evidence on how current therapies perform in practice and helping to guide more effective, data‑driven care for youth with MS.

The CANDI Study examines long‑term clinical and developmental trajectories in individuals with pediatric‑onset demyelinating disease. Although active follow‑up for this cohort concluded in March 2022, the dataset continues to support important analyses, including a recently submitted manuscript focused on outcomes in the adult cohort. Ongoing work leverages these longitudinal data to deepen understanding of how early demyelinating events shape health and functioning into adulthood, providing a critical foundation for future research across the Network.

The Diet and Relapses Study investigates how dietary patterns and nutritional factors may influence relapse activity in pediatric‑onset MS. Enrollment for this project concluded in October 2022, with strong questionnaire completion rates across participating sites. The primary manuscript has already been submitted, with additional analyses in development. This study continues to provide valuable insight into the potential role of modifiable lifestyle factors in shaping disease activity, helping guide future research on nutrition‑based interventions for children with MS.

The Metabolic Correlates Study explores how lipid profiles and fatty acid metabolism relate to disease activity and underlying biology in pediatric‑onset MS. Using previously collected biospecimens, researchers are conducting detailed analyses of lipid and fatty acid markers to identify metabolic patterns associated with MS risk and progression. The primary manuscript has already been submitted, and additional analyses are underway, making this project an important contributor to understanding metabolic pathways that may influence pediatric MS.

This Network study, funded by the National Institute of Neurological Disorders and Stroke (NINDS), investigates whether established adult MS risk factors also contribute to pediatric‑onset MS. The study evaluates key exposures—including HLA‑DRB1*1501/1503, Epstein–Barr virus (EBV), vitamin D insufficiency, and cigarette smoke exposure—and examines how these factors may interact to influence disease susceptibility. Conducted as a large prospective study of 640 early pediatric‑onset MS cases and 1,280 matched controls, it also incorporates a comprehensive Environmental Assessment developed at UCSF and UC Berkeley to explore a wide range of additional environmental influences. This work provides critical insight into the biological and environmental pathways that may shape MS risk in children and informs future prevention‑focused research.

The Microbiomes Study investigates how commensal bacteria may influence the development and course of pediatric‑onset MS. Funded by the National MS Society, this project examines whether the composition of the nasal, oral, and gut microbiota differs between children with MS and matched healthy controls—and how these microbial differences might contribute to disease mechanisms. By collecting nasal, oral, and stool samples from 70 pediatric MS cases and 70 controls, the study leverages the unique advantage of working with a pediatric population, minimizing the confounding effects of long‑term environmental exposures seen in adults. The long‑term goal is to determine whether microbiome‑based pathways affect MS susceptibility or progression and to inform future preventive or therapeutic strategies targeting the microbiota.

The NMO Study, funded by the Guthy‑Jackson Charitable Foundation, examines how pediatric‑onset neuromyelitis optica spectrum disorders differ from other demyelinating diseases in both clinical presentation and radiological features. Using data from the PeMSDD registry, researchers compare disease course, diagnostic characteristics, and outcomes to improve recognition and early diagnosis of NMO in children. An additional goal of the project is to summarize and evaluate the available biological samples collected from pediatric NMO participants, supporting future investigations into disease mechanisms and potential therapeutic targets. This work aims to advance clinical understanding and enhance the care of children affected by this rare but serious condition.

The CRISS Study aims to establish a cohort of children with pediatric‑onset radiologically isolated syndrome (RIS) to better understand which individuals may go on to develop multiple sclerosis. By examining clinical outcomes and identifying potential risk factors for MS development, this project helps clarify how RIS presents in children and how it differs from other early demyelinating conditions. Insights from this study will support clinicians in making more informed monitoring and management decisions for youth identified with RIS. The project is funded by the National MS Society and continues to contribute valuable data to the Network’s broader efforts to understand early disease mechanisms in pediatric MS.

The NEDA Study, funded by the Cleveland Clinic, examines how many children with pediatric‑onset MS achieve No Evidence of Disease Activity (NEDA) at six‑month intervals following diagnosis. By comparing individuals who do and do not reach NEDA, the project aims to identify demographic and clinical factors—such as age, race, disease duration, and treatment type—that influence the likelihood of maintaining disease stability. These insights will help clinicians better predict which patients are most likely to achieve NEDA and guide more personalized treatment strategies for pediatric MS.