MOGAD takes center stage in childhood neuroinflammatory disease

Acquired demyelinating syndromes are immune-mediated disorders that strip myelin from the central nervous system, and in children they are rare but increasingly recognized. A newly published open-access review in Pediatric Radiology by Jessie Aw-Zoretic distills a decade of rapid evolution in this field, spanning pediatric-onset multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease, formally defined by international consensus in 2023. The review arrives at a moment when advances in imaging techniques, consensus statements, and detection of CNS-specific autoantibodies have made prompt, precise diagnosis achievable in both community and specialized pediatric practice. Population-based data from the western United States report higher acquired demyelinating syndrome risk among Black children compared with White and Hispanic peers, a pattern that may reflect improved detection, environmental drivers, or both.

The clinical spectrum is heterogeneous, and classification hinges on lesion location, whether presentation is monofocal or polyfocal, and whether the disease course is monophasic or multiphasic. Monophasic events include clinically isolated syndrome, optic neuritis, transverse myelitis, and brainstem encephalitis. Clinically isolated syndrome denotes a single demyelinating event that may precede multiple sclerosis, while radiologically isolated syndrome refers to incidentally detected MRI lesions with demyelinating features in asymptomatic individuals. In children, radiologically isolated syndrome may include clinically silent spinal cord lesions, and when accompanied by cerebrospinal fluid oligoclonal bands, the risk of subsequent multiple sclerosis is further increased. Notably, diagnostic practices vary by age and sex: children under 12 years and boys are less likely to undergo CSF analysis, reinforcing MRI’s central role in detecting subclinical disease and informing early treatment, which is linked to slower disease progression and improved outcomes.

Optic neuritis deserves particular attention in pediatric cohorts because its phenotype differs sharply from the adult disease. Bilateral optic neuritis predominates in children and typically presents with acute visual disturbance, often following febrile illness, commonly upper respiratory infections. Pain is reported in approximately one-third of early pediatric cohorts and about half in more recent series, whereas adults more frequently report periocular pain during attacks. Conversion to multiple sclerosis appears lower than in adults. Early, intensive therapy is critical to limit inflammation, reduce relapse risk, and prevent optic nerve atrophy. Yet standard brain MRI frequently under-assesses the intra-orbital optic nerves in acute optic neuritis. A 2021 study by Schroeder and colleagues demonstrated that dedicated orbital MRI, using fat-suppressed, high-resolution T1- and T2-weighted sequences with gadolinium, is significantly more sensitive than standard brain MRI for detecting active optic neuritis, a finding that has reshaped imaging practice.

Transverse myelitis, usually a monophasic cord syndrome, is characterized by acute motor, sensory, and autonomic deficits below the neurological level of the lesion. The Transverse Myelitis Consortium working group published a diagnostic framework in 2022 to reduce diagnostic confusion. Because spinal cord biopsy is not a realistic option in routine evaluation, spinal MRI, with or without CSF analysis, is the main tool for confirming inflammation and extent of involvement, and it is essential to exclude compressive etiology. MRI typically shows long-segment T2 hyperintensity with cord expansion and variable, patchy, or longitudinal enhancement. Whole-spine coverage and axial imaging at lesion levels are essential for assessing lesion length, morphology, and enhancement pattern. Although pediatric-specific data remain limited compared with adult cohorts, a 2024 study showed that longitudinally extensive transverse myelitis, defined as a T2-hyperintense lesion spanning more than three vertebral body segments, is the strongest predictor of relapse in pediatric idiopathic transverse myelitis.

Acute disseminated encephalomyelitis is classically a monophasic inflammatory demyelinating disorder with encephalopathy not explained by fever, most common in children under 10 years, and characterized by multifocal neurologic deficits involving the brain and spine. MRI of the entire neuroaxis is recommended in the acute phase and is typically abnormal. Most cases are self-limited within approximately three months, but recurrent and multiphasic subtypes occur, with recurrence denoting a second event more than three months after onset. Pathogenesis is thought to involve post-infectious or post-vaccination autoimmunity in genetically susceptible hosts. ADEM is the most common first presentation of pediatric acquired demyelinating syndrome, but it often overlaps with other entities, with subsequent follow-up leading to reclassification as other demyelinating disorders. Classic MRI features include diffuse, poorly marginated, large lesions exceeding two centimeters in the subcortical and deep cerebral white matter, as well as bilateral, relatively symmetric lesions in the thalami and basal ganglia. Brainstem encephalitis, an uncommon inflammatory disorder of the brainstem, is most strongly associated with ADEM and MOG antibody-associated disease within this spectrum.

Chronic demyelinating disease involves inflammation and myelin loss that persist or recur over the long term, often with a relapsing or progressive course. Recurrent and repeated attacks are associated with incomplete remyelination, leading to cumulative axonal injury. On MRI, patients with progressive clinical courses demonstrate chronic gliosis, white-matter volume loss, cortical or subcortical atrophy, and T2 hyperintensities without contrast enhancement. Serial longitudinal MRI allows clinicians to distinguish true disease progression, evidenced by new or enlarging T2 lesions, accelerating brain volume loss, and atrophy, from a stable or resolved monophasic presentation, guiding timely escalation of therapy. In the pediatric population with multiple sclerosis and MOG antibody-associated disease, brain atrophy manifests as variable deep gray matter involvement with a predilection for the thalamus, a pattern that, unlike in adult cohorts, cannot be attributed to normal aging given the short disease duration.

Imaging protocols form the technical backbone of the review. A standard MRI protocol for demyelination should include T2-FLAIR and T1-weighted sequences with gadolinium contrast, with a two-orthogonal-plane T2-weighted acquisition for brain imaging; axial and sagittal T2-FLAIR combined is optimal, especially for interrogating juxtacortical regions and assessing the midline and corpus callosum. Single-slab, isotropic 3D T2-FLAIR provides high spatial resolution for multiplanar reformations, avoids gaps or misregistration between slabs, and allows high-quality 3D reconstruction, though at the cost of increased scan time. Double inversion recovery, designed to suppress CSF and white matter, improves cortical and juxtacortical lesion conspicuity, while susceptibility-weighted imaging is considered when microhemorrhage is a concern. The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations provide updated guidance on MRI protocols for diagnosis and monitoring of demyelinating diseases. Pediatric imaging demands trade-offs between minimizing scan time and maximizing diagnostic yield, addressed through child-appropriate coils, feed-and-wrap techniques, audiovisual distraction, or sedation when necessary. A 16-channel design suits infants between 0 and 18 months, while older children aged 1 to 10 years benefit from high-density flex coils typically offering 12 to 48 channels.

Advanced sequences and contrast agents are pushing pediatric MRI forward. 3D T2 and 3D T2 STIR acquisitions, known by vendor names including SPACE, CUBE, and VISTA, produce isotropic or near-isotropic T2-weighted volumes with voxels of approximately 0.8 to 1.2 millimeters, enabling excellent delineation of the optic nerves and spinal cord and more reliable assessment of lesion length, particularly relevant to longitudinally extensive transverse myelitis. STIR-based fat suppression is more robust than chemical fat saturation because it is less sensitive to B0 and B1 inhomogeneity, an advantage most apparent at the cervicothoracic junction and in the orbits. Limitations include longer acquisition times, greater sensitivity to motion, and higher specific absorption rate when inversion pulses are used, mitigated with parallel imaging and compressed sensing. On the contrast front, gadopiclenol, a new next-generation, high-relaxivity macrocyclic gadolinium-based agent designed with dual water-exchange sites, has been approved for use in children aged 0 years and older in North America, following European approval. It delivers diagnostic performance comparable to gadobutrol at half the conventional gadolinium dose, with no major safety concerns identified, a key advantage for children who may require multiple imaging studies over their lifetime.

MOG antibody-associated disease now occupies center stage. It affects the brain, spinal cord, and optic nerves, is pathologically distinct but can clinically mimic multiple sclerosis and AQP4-positive neuromyelitis optica spectrum disorder, and equally affects females and males, unlike either comparator. In 2023, an international consensus panel established formal diagnostic criteria requiring MOG-IgG seropositivity and a core clinical demyelinating event, namely ADEM, optic neuritis, transverse myelitis, cerebral cortical encephalitis, or brainstem and cerebellar syndrome. Live cell-based assays using MOG-transfected cells are critical for diagnostic confirmation, as solid-phase assays lack specificity. Brain lesions in MOGAD tend to be large, poorly marginated, bilateral, somewhat expansile, and relatively symmetric, best seen on T2/FLAIR sequences, in contrast to the ovoid, periventricular, and juxtacortical lesions typically seen in multiple sclerosis. A 2025 study categorized six distinct radiological phenotypes in children, with the ADEM-like pattern most common at 71 percent. Younger children had more ADEM-like imaging phenotypes, while older children were more likely to present with optic neuritis and cortical encephalitis. Pediatric populations have lesions more commonly in the thalamus or thalamus plus additional structures, while adults have more frequent lesions in the corpus callosum and subcortical white matter, consistent with previous studies finding the corpus callosum rarely involved in children with MOGAD.

Two newly recognized clinico-radiological phenotypes are expanding the MOGAD spectrum. Budhram and colleagues identified a subset of patients with seizures, headaches, and fevers with meningo-cortical manifestations on MRI, proposing the term FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures, or FLAMES. FLAMES is characterized by cortical T2/FLAIR hyperintensity, typically unilateral and affecting one or more lobes, most commonly the frontal and parietal lobes, with occipital lobes least common. There is associated cortical diffusion restriction reflecting cytotoxic edema secondary to encephalitis, and the cortical hyperintensity may be subtle, warranting careful review. A subset of FLAMES patients exhibit unilateral leptomeningeal enhancement, for which Budhram coined the term FLAIR-variable Unilateral Enhancement of the Leptomeninges, or FUEL, with sulcal enhancement best seen on post-contrast FLAIR, which is more sensitive for leptomeningeal disease than standard post-contrast T1. Optic neuritis in MOGAD is frequently bilateral at 80 percent and often involves the intra-orbital segments at 77.4 percent, distinguishing it from AQP4-IgG-positive NMOSD and multiple sclerosis. Spinal involvement is variable: myelitis can affect both gray and white matter or gray matter alone, manifesting as a distinct H sign on axial T2-weighted sequences due to selective central gray matter inflammation. Lesions extending to or involving the conus medullaris are considered highly specific for MOGAD and are seen more frequently than in AQP4-IgG-positive NMOSD. MOGAD is now an established, distinct CNS inflammatory disease, but the boundaries of its clinical and radiological phenotype are still evolving, and greater recognition of this spectrum may improve diagnostic accuracy and inform best clinical practice.

Subject of Research: Pediatric neuroinflammatory and demyelinating disorders with a focus on myelin oligodendrocyte glycoprotein antibody-associated disease

Article Title: Neuroinflammatory and demyelinating disorders in children: demystifying and updating with a focus on myelin oligodendrocyte glycoprotein antibody-associated disease

Article References: Aw-Zoretic, J. (2026). Neuroinflammatory and demyelinating disorders in children: demystifying and updating with a focus on myelin oligodendrocyte glycoprotein antibody-associated disease. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06800-1

Image Credits: AI Generated

DOI: 10.1007/s00247-026-06800-1

Keywords: MOGAD, pediatric multiple sclerosis, ADEM, neuromyelitis optica spectrum disorder, optic neuritis, transverse myelitis, MRI, FLAMES, autoantibodies, demyelination, gadopiclenol, children