Objective:

To highlight a rare case of brain lymphoproliferative disease in a patient treated with mycophenolate for aquaporin-4-IgG positive Neuromyelitis Optica Spectrum Disorder (AQP4+NMOSD).

Background:

AQP4+NMOSD is an autoimmune demyelinating disease that can manifest with attacks of optic neuritis, transverse myelitis, area postrema syndrome, or other brainstem or cerebellar deficits. Treatment with older generation immunosuppressive agents may increase the risk of lymphoproliferative disease.

Design/Methods:

Results:

A 75-year-old female presented with new onset imbalance and cognitive changes. She has a history of AQP4+NMOSD, first manifesting at age 50 with a longitudinally extensive transverse myelitis. She was initially treated as multiple sclerosis with interferon beta-1a but 13 years later tested positive for aquaporin-4-IgG. She was treated with 1000 mg of oral mycophenolate mofetil twice daily. She was stable until 11 years later when she developed recurrent myelitis and oral prednisone 20 mg every other day was added. A few months later, she developed ataxia and cognitive dysfunction, and brain MRI demonstrated multifocal T2-hyperintense lesions within the cerebral white matter bilaterally. Cerebral involvement of AQP4+NMOSD or complications of immunosuppression (progressive multifocal leukoencephalopathy or lymphoproliferative disorder) were considered among the differential diagnoses. Cerebrospinal fluid showed a mildly elevated white blood cell count but negative cytology and flow cytometry, negative JC virus PCR but positive Epstein Barr Virus (EBV) PCR. Peripheral blood EBV PCR was also positive. Brain biopsy was performed and revealed polymorphous lymphoproliferative infiltrate with kappa light chain restricted plasma cells and 50% positive for EBV on in situ hybridization. Central nervous system restricted iatrogenic immunodeficiency–associated lymphoproliferative disorder was diagnosed. Mycophenolate was discontinued and rituximab was administered with improvement in symptoms and MRI findings 3 months later. 

Conclusions:

Treatment of AQP4+NMOSD with long-term oral immunosuppressive agents may increase the risk of lymphoproliferative disease, including those that involve the brain.