Clinical presentation and course of three pediatric Neuromyelitis Optica Spectrum Disorder (NMOSD) cases with negative aquaporin-4 (AQP4) IgG antibodies (seronegative).

NMOSD is an autoimmune disorder characterized by chronic, relapsing episodes of inflammation primarily affecting the spinal cord, optic nerves, and brainstem. Less than 5% of cases occur in pediatric patients, with almost all being AQP4-IgG positive. Diagnosis of the few seronegative cases relies heavily on clinical presentation. Myelin oligodendrocyte (MOG) IgG is often positive in this patient group; double seronegative (AQP4-IgG and MOG-IgG) cases are not well described.

Chart review identified three cases of seronegative NMOSD diagnosed between 2018-2023.

Patients 1 and 2 presented before three years of age and patient 3 at 15 years of age. Patient 1 exhibited typical NMOSD optico-spinal disease with relapses over five years of follow up; MRI showed lumbar spinal root enhancement. Patient 2 presented with altered sensorium, vision loss, and left leg weakness; MRI demonstrated diencephalic and central spinal cord lesions suggestive of NMOSD. Patient 3 presented with area postrema syndrome and had subsequent relapses of brainstem syndrome manifesting as trigeminal neuralgia and cranial nerve palsies. AQP4-IgG was negative in all patients. MOG-IgG was positive in patient 2 (1:40) and 3 (1:20); patient 3 tested negative three months later, as expected with low titers.

Pediatric NMOSD has typical features and a course that parallels adult NMOSD. Lumbar root enhancement in NMOSD is an atypical feature without MOG-IgG positivity. Low titers of MOG-IgG should not rule out NMOSD, (demonstrated by patient 3), which is a more aggressive disease with higher relapse risk and incomplete relapse recovery. Differentiating between negative and possibly false positive (low titer) MOG-IgG in NMOSD can difficult early on, (as shown by patient 2), but is needed for expeditious initiation of immunomodulatory therapy to prevent further relapses and permanent neurological deficits.