Pediatric neuromyelitis optica-beyond the optic nerve and spinal cord

Aims: Neuromyelitis Optica (NMO) is no longer considered to be a disease limited to the optic nerves and spinal cord. Coexisting systemic autoimmunity has been described in children with NMO and NMO spectrum disorders (NMO-SD). It is unknown whether children with coexisting evidence for systemic autoimmune disease have a distinct central nervous system phenotype.

Methods: This is a retrospective analysis of 409 consecutive patients who were prospectively enrolled in the pediatric demyelinating disease registry of a tertiary children's hospital from 1999 to 2012. Included were all children who met the criteria for NMO or NMO-SD according to the Wingerchuk criteria (1999, 2006) or who were NMO-IgG positive in the context of a symptomatic NMO specific brain lesion. Coexisting systemic autoimmunity was defined by specific or persistent autoantibodies.

Results: Eight children (four female) met the inclusion criteria. Average age at first attack was 13.8 years (range 10.3 to 16.9 years). Median follow up time was 3.2 years (range 0.5 to 7.8 years). Presenting phenotype consisted of optic neuritis (3), symptomatic brainstem lesion (4), and encephalopathy (1). NMO IgG was positive in seven children. Five children were diagnosed with NMO, two with NMO-SD, and one child was NMO-IgG positive in the context of a symptomatic area postrema lesion. Coexisting (SA) was found in three out of eight children; one with antiphospholipid antibody syndrome, one with mixed connective tissue disorder (ANA 1:640, rheumatoid factor 1:32, anti Ro 81 U/mL [< 8 U/mL], anti LA 98 U/mL [< 8 U/mL]) and one with a variety of auto antibodies (ANA [1:320],anti Ro [55 U/mL], anti La [11 U/ml], anti cardiolipin antibodies [28 U/mL, < 5 U/mL], and anti TPO [565 U/mL, < 35 U/mL]). Two of these children presented with brainstem lesions, and one with optic neuritis.

Conclusion: In summary, 62.5% of our NMO and NMO-SD patients had a first attack localizing outside the optic nerve and spinal cord. Coexisting systemic autoimmunity was found in 37.5% of the children. The majority of those presented with brainstem lesions. Larger, multicenter prospective studies are needed to confirm these findings.