Neuromyelitis optica spectrum disorders

Abstract

Background: Neuromyelitis Optica (NMO) is a demyelinating disease of the CNS in which presence of autoantibody NMO-IgG, supports distinction from other inflammatory and autoimmune disorders of the CNS. Even with modern assays, there are up to 25% of “seronegative NMO”. The concept of NMO spectrum disorders (NMOSD) was created to include patients displaying a NMO-similar clinical spectrum but not fulfilling its diagnostic criteria. Family aggregation of NMO occurs in up to 3% of cases. Case Report: A 4 years old girl developed severe bilateral optical neuritis and 6 months after presented with tetra-paresis. Neuroaxis MRI showed subcortical, diencephalic and pons lesions, together with a longitudinally extensive cervicothoracic lesion. CSF analysis showed no oligoclonal bands (OCB) and infectious, immune, metabolic and vascular study were negative. She recovered partly after corticotherapy and started immunosuppression with azathioprine, keeping clinically stable. Four years later she tested positive for NMO-IgG, so the diagnosis of NMO as assumed and the immunosuppressive regimen was kept. In the following years she developed several brainstem, spinal and ocular relapses with cumulative disability. Systemic evaluation revealed sinoatrial disease and bilateral lung nodules suggestive of sarcoidosis. In subsequent chest CT and scintigraphy the lung nodules resolved and there was no inflammatory activity compatible with sarcoidosis. Her last relapse was last year and she is actually on azathioprine plus corticosteroids. Her 6 years older brother had a left optical neuritis at the age of 14. One year later he developed paraparesis. Neuroaxis MRI showed a longitudinally extensive cervico-thoracic lesion but no signal change on the cerebral parenchyma. He was put on azathioprine and corticosteroids and recovered completely. Two years later he tested negative for NMO-IgG and, with the diagnosis of seronegative NMO, kept on immunosuppression with clinical stability thereafter. Systemic evaluation revealed positive antinuclear antibodies, normal chest CT and a scintigraphy with inflammatory activity in thoracic ganglia, compatible with possible sarcoidosis. He remains clinical asymptomatic on immunosuppressive therapy for the last 10 years. Discussion: In up to 20-30% patients with NMOSD there is association with autoimmune disorders. There is only one report of NMOSD associated with sarcoidosis, but up to 40% of patients show autoantibodies without disease evidence. We report two sibling diagnosed with NMO with two completely different clinical courses. They both show some evidence of a systemic inflammatory disease, suggesting sarcoidosis, but without supporting diagnostic criteria. This exemplifies the challenge of diagnosis and management of NMOSD and the autoimmune associated disorders.