Natalizumab Escalation Early in the Disease Course of Pediatric-Onset Multiple Sclerosis: Two Japanese Cases

Pediatric-onset multiple sclerosis is characterized by high inflammatory disease activity. Although high-efficacy therapies are effective, the optimal timing and clinical markers for escalation remain to be fully established, particularly in Asian populations.

We report two Japanese children with pediatric-onset multiple sclerosis who presented with distinct clinical courses but shared poor prognostic features. Both patients underwent integrated assessments using advanced brain magnetic resonance imaging metrics, including the central vein sign, double inversion recovery imaging, and corpus callosum index.

Patient 1, a 14-year-old boy, exhibited a rapidly progressive course involving the brainstem and cerebellum, resulting in severe neurological disability (peak Expanded Disability Status Scale score 9.0) refractory to standard acute immunotherapies. Patient 2, a 13-year-old girl, initially presented with a first demyelinating episode consistent with clinically isolated syndrome, followed by a clinical relapse with radiologic progression that fulfilled the 2024 revised McDonald criteria for multiple sclerosis. In both cases, the presence of central vein sign-positive lesions and the corpus callosum index findings were interpreted as supportive features of disease severity, although pediatric thresholds and clinical actionability remain unvalidated. Natalizumab with extended-interval dosing was followed by sustained clinical and radiologic stability over a 2-year follow-up.

These cases illustrate that natalizumab may be a reasonable option early in the disease course for selected pediatric patients with aggressive clinicoradiologic features.