Clinical Advances Are Transforming Care for Children with MOGAD and Multiple Sclerosis

Not long ago, a child who presented with optic neuritis, transverse myelitis or inflammatory brain lesions was often diagnosed under the broad umbrella of multiple sclerosis. Physicians could see that these patients didn’t all follow the same clinical course, but they lacked the disease-specific biomarkers to explain why.

That is changing. New antibody testing now enables physicians to distinguish myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from MS with greater accuracy. Physicians such as Linda Nguyen, M.D., Ph.D., an Assistant Professor of Child Neurology at UT Southwestern, are helping lead that shift, caring for patients in one of the region’s few dedicated pediatric neuroimmunology programs to translate these discoveries into care.

“Now we recognize MOGAD and MS as distinct diseases with different biology, prognosis, relapse risk, and treatment strategies,” said Dr. Nguyen, who treats children in the pediatric neuroimmunology clinic. “Making the correct diagnosis at disease onset is essential to providing the most appropriate care.”

A Diagnosis Refined by Biology

MOGAD is an immune-mediated disease of the optic nerves, spinal cord and brain, and its symptoms overlap heavily with pediatric MS, making accurate diagnosis difficult, especially at a child’s first attack.

The discovery of the aquaporin-4 antibody, and later the myelin oligodendrocyte glycoprotein (MOG) antibody, gave physicians the first biologic evidence to separate these conditions. Before commercial MOG antibody testing arrived in the U.S. in 2017, physicians had no reliable way to distinguish MOGAD from other inflammatory diseases, and children with recurrent attacks were often diagnosed with MS because it was the closest fit. Today, that testing is standard for any child with a suspected inflammatory demyelinating disorder.

Diagnostic precision has sharpened on the MS side, too. The revised 2024 McDonald criteria, published in The Lancet Neurology in 2025, added the optic nerve as a fifth anatomical location, so children now need only two of five typical regions involved, rather than two of four. A UT Southwestern study currently under peer review applied the new criteria to its pediatric cohort and found it substantially improved diagnostic sensitivity for MS, so children could start treatment at their very first visit instead of waiting under a “clinically isolated syndrome” label.

Dr. Nguyen has seen what a correct diagnosis can do. One patient began relapsing as a toddler, years before MOG testing existed, and was diagnosed with MS for lack of any other explanation. She kept relapsing despite treatment. After MOG testing became available, her diagnosis was corrected to MOGAD, and she switched to a therapy better suited to MOGAD. She hasn’t relapsed since.

Different Diagnosis, Different Treatment

Children with MS tend to have a higher inflammatory burden at onset and more frequent early relapses, so clinicians typically start disease-modifying therapy early, often right after the first attack. MOGAD is different. Many children remain monophasic, experiencing only one inflammatory episode for life, and roughly 30% to 70% go on to develop relapsing disease, compared with 80% or more in MS, a gap that reshapes how physicians approach long-term therapy.

“We generally avoid long-term immunosuppression after the first attack in MOGAD,” Dr. Nguyen said. “Reliable biomarkers that can predict relapse risk could help personalize treatment decisions while sparing many children unnecessary therapy.”

Long-term immunosuppressive therapies can raise infection risk, blunt vaccine responses and interfere with a still-developing immune system, which is why most clinicians wait for a second attack before starting chronic immunotherapy. The challenge, Dr. Nguyen said, is figuring out sooner which children truly need it.

Predicting Relapse

Researchers increasingly believe the next generation of biomarkers will predict what these diseases do in the future. Using blood samples donated by patients and families, Dr. Nguyen’s research applies advanced immune profiling to find the biologic signatures tied to disease activity.

“The goal is always precision medicine,” Dr. Nguyen said. “We’re trying to understand why some children relapse while others don’t, so we can identify biological signatures that predict future disease activity.”

If it works, this research could move MOGAD management beyond reactive medicine, estimating relapse risk shortly after diagnosis and sparing lower-risk children years of unnecessary immunosuppression. Making that possible requires continued partnership with patients and families who contribute blood samples for research.

“I’ve encountered several instances where the MOG antibody wasn’t tested or the incorrect assay was ordered,” Dr. Nguyen said. “Patients weren’t diagnosed appropriately simply because the right test wasn’t performed. Early referral matters. These disorders can be challenging to diagnose, even for specialists.”

A Pipeline of Targeted Therapies

“This field is booming,” Dr. Nguyen said. “We have far more effective therapies for pediatric MS, and we’re seeing promising targeted therapies for MOGAD.”

No medication is FDA-approved specifically for MOGAD, but Dr. Nguyen said that gap is closing as clinical trials expand. Researchers are also exploring next-generation technologies, including engineered immune-cell therapies, such as CAR T-cells, that have the potential to fundamentally reshape the treatment of autoimmune neurologic diseases.

A Multidisciplinary Approach to Care

At UT Southwestern, children with MOGAD or pediatric MS are evaluated through a dedicated multidisciplinary neuroimmunology clinic, a model still rare among major academic centers and a destination clinic for the Dallas-Fort Worth area.

Beyond neurology, patients have access to rehabilitation medicine specialists who help maximize physical recovery, neuropsychologists who evaluate subtle cognitive changes, and social workers and school specialists who coordinate classroom accommodations. Patients also undergo specialized optic nerve imaging, with specialists in areas such as epilepsy and urology looped in as needs arise.

“Our multidisciplinary approach has improved the care and the long-term outcomes of our patient population,” Dr. Nguyen said, pointing to the clinic’s strong patient retention as one indicator of its impact.

Looking Toward Precision Medicine

Despite recent advances, important questions remain. In MS, current therapies effectively suppress inflammation and prevent new relapses but don’t yet address the progressive neuronal injury behind long-term disability. In MOGAD, predicting who will relapse remains the field’s central unanswered question. Across both diseases, an equally important goal is promoting remyelination to restore function rather than just preventing future attacks.

For Dr. Nguyen, the future is about understanding each child’s disease at the biological level and using that information to guide every treatment decision, so physicians can intervene earlier, treat more thoughtfully, and improve outcomes for every child in their care.