Development of Neuromyelitis Optica Spectrum Disorder with Tumefactive Demyelination after Treatment with Monoclonal Anti-Tumor Necrosis Factor Alpha Antibodies

Background: The range of clinical syndromes related to antibody positive NMOSD continues to expand with better diagnostic recognition and serologic testing. Tumefactive lesions have previously been reported in NMOSD. Infliximab is a chimeric anti-tumor necrosis factor alpha monoclonal antibody used in a number of autoimmune disorders. Monoclonal anti-TNF alpha antibodies have previously been described with clinical exacerbations in Multiple Sclerosis, but the occurrence of clinical exacerbations associated with this therapy have not been reported in NMO

Objectives: To report a case of Neuromyelitis Optica Spectrum Disorder (NMOSD) that presented as a tumefactive demyelinating lesion after a initiation of infliximab.

Methods: Case report and literature review.

Results: A 66-year-old right handed woman presented with one day of progressive confusion, neglect, and left sided hemiplegia two months after starting infliximab for seronegative rheumatoid arthritis. Magnetic resonance imaging (MRI) showed extensive T2 signal change in the right frontal and temporal lobes with areas of restricted diffusion in portions the right cortical spinal tract but minimal contrast enhancement. The imaging features were felt to be most consistent with either an infiltrating non-enhancing tumor such as gliomatosis cerebri or an infection such as progressive multifocal leukoencephalopathy given her immunosuppression. CSF showed a pleocytosis with 710 WBC (neutrophil predominant), 0 RBC, normal glucose, and protein. No oligoclonal bands were detected and IgG index was within normal limits. CSF JCV PCR was negative. Her clinical course rapidly deteriorated and repeat MRI on hospital day six revealed significant progression of the lesion to involve the parietal and occipital lobes. A stereotactic lesional biopsy was performed. Pathology demonstrated mildly hypercellular white matter with perivascular clusters of foamy macrophages and perivascular zones of demyelination. Aquaporin-4 antibody was sent from CSF and serum, both returning positive. A diagnosis of Neuromyelitis Optica Spectrum disorder was established and the patient was treated with steroids and plasmapheresis with clinical improvement.

Review of literature demonstrates cases where Multiple Sclerosis (MS) was either triggered or worsened following initiation of infliximab or similar therapies but no such case of Neuromyelitis Optica Spectrum Disorder has yet to be indentified.  TNF is major controbibutor to the inflammatory immune response and it has previously been hypothesized that TNF inhibition may lead to increased levels of activated T lymphocytes which would influence inflammatory neurologic diseases.

Conclusions: Our patient represents an atypical case of NMOSD that was either quiescent and unmasked by infliximab or induced by the therapy.