An MRI of her brain with MRA/MRV (see Figure 1) demonstrated “increased FLAIR signal in the optic chiasm and bilateral intracranial optic nerves and proximal optic radiations, without enhancement. There was possible enlargement of the intracranial optic nerves and optic chiasm.” The MRV of the brain and an MRI of the spine were unremarkable.
During her early hospital course, she remained afebrile and continued on empiric treatment for bacterial meningitis while culture results were monitored. Methotrexate was held. Her headache and nausea completely resolved, but the visual loss persisted. After three days of negative cultures, an infection was felt to be less likely, and she was treated with solumedrol 1,000 mg IV for three days. A repeat lumbar puncture demonstrated an opening pressure of 29 cm CSF, 9 nucleated cells/uL with 84% lymphocytes, glucose of 68 mg/dL and protein 22 mg/dL. Bacterial cultures from blood and CSF remained negative. Viral and fungal studies including enterovirus, cryptococcal, varicella zoster, cytomegalovirus, herpes simplex and others were negative.
Diagnosis & Treatment
Testing for IgG to Aquaporin-4 in both the serum and CSF was positive, leading to a diagnosis of neuromyelitis optica (NMO).
She subsequently received five courses of plasmapheresis followed by rituximab 500 mg IV given once. Antibiotics were discontinued. It was decided to replace methotrexate with mycophenolate mofetil. By discharge, she felt that her vision was improving, albeit very slowly. She could track objects and people in the room, but she was still unable to read any letters on a Snellen chart. She was continued on hydroxychloroquine and discharged on a dose of prednisone 60 mg daily with a prolonged taper.
Discussion
Neuromyelitis optica spectrum disorders (NMOSDs), also known as Devic disease, are autoinflammatory, demyelinating conditions affecting the central nervous system. The pathogenesis is thought to be directly linked to the highly specific Aquaporin-4 antibody (AQP4-IgG), which targets the water channel most common in astrocytes. With the discovery of this antibody, it is now evident that NMOSD is not simply a subtype of multiple sclerosis (MS), but rather a distinct entity. Typical symptoms include blindness or weakness, depending on the location of the demyelinating lesion. The primary cause of mortality is severe ascending cervical myelitis or respiratory failure from brainstem lesions.
This rare disorder is estimated to affect fewer than 1 to 4.4 of 100,000 individuals in Europe and North America.1 It typically affects individuals between the ages of 35 and 45 and more commonly affects women, particularly patients who are seropositive for AQP4-IgG (10:1 female preponderance) vs. seronegative patients (approximately 2:1). There appears to be a distinct presentation with those who are seropositive exhibiting a chronic relapsing course, whereas seronegative patients often experience a monophasic episode.