The unseen majority: Characterizing seronegative MOGAD beyond traditional diagnostic criteria

Myelin oligodendrocyte glycoprotein antibody- associated disease (MOGAD) presents with optic neuritis, transverse myelitis, acute encephalitis or acute disseminated encephalomyelitis (ADEM). Less commonly it may manifest as aseptic meningitis, seizures and fever of unknown origin. We describe a paediatric case of seronegative MOGAD with an unusual clinical and neuroimaging profile. Despite negative serum MOG antibody testing, the patient exhibited features consistent with MOGAD and showed response to pulse methylprednisolone, expanding the known phenotypic spectrum of the disease. Recent studies have reported patients with CSF MOG-IgG but without detectable serum MOG-IgG challenging existing diagnostic criteria and need for further research on utility of CSF MOG antibody testing. • Seronegative MOGAD Challenges traditional diagnosis highlights the existence of seronegative MOGAD , suggesting that current antibody testing may miss some cases, possibly due to delayed testing or low antibody titters . • Atypical Clinical and Radiological features including non-encephalopathic seizures, dystonia, and prominent basal ganglia involvement, which are not typical of classic MOGAD. • Despite seronegative serum MOG-IgG, diagnosis relied on CSF lymphocytosis, steroid response, and MRI evolution. This recommends CSF MOG-IgG testing in suspected seronegative cases. • The patient showed significant improvement with high-dose methylprednisolone, reinforcing that early immunotherapy can be effective even in seronegative cases. • The case underscores the heterogeneity of MOGAD , including seronegative forms, atypical neuroimaging patterns which advocate for revised diagnostic criteria to include antibody-negative cases with supportive clinical/MRI findings and role of CSF testing in seronegative cases.