Multiple sclerosis: pathology and pathogenesis
Monday, May 30, 2011, 17:15 – 18:15
The pathology of fulminant neuromyelitis optica with extremely high level of serum anti aquaporin 4 antibody
K. Maruyama, M. Kobayashi, Y. Shimizu, T. Takeda, S. Uchiyama (Tokyo, JP)
We report a patient of fulminant form of neuromyelitis optica (NMO) with extremely high level of serum anti aquaporin 4 (AQP4) antibody and discuss the pathological features with the review of the past literature.
CLINICAL COURSE: The patient was a 14 year-old female when she had first attack with retrobulbar optic neuritis. Despite multiple treatments with steroid pulse therapy, immunosuppressive agents, IFN-beta, and IVIg, the disease progressed and she had become blind and paraplegic until 25 years of age. At the age of 26, she often had epileptic attacks, and serum anti-AQP4 antibody was measured for the first time, which was positive, thus she was diagnosed as NMO. At the age of 30, large cystic lesions appeared in the brain on MRI, and she became unconscious and required respirator. The cerebrospinal fluid showed elevated cell count and protein level, and anti-AQP4 antibody in the serum was extremely high as 524,288 times. The anti-AQP4 antibody level elevated up to 4,190,000 times at the highest level in her clinical course. The patient died of multiple organ failure with sepsis at the age of 32.
PATHOLOGY: The brain was atrophic, soft and 980 grams in weight. The optic nerve was significantly demyelinated with infiltration of lymphocytes and macrophages. The white matter of the brain was diffusely destructed with demyelination and necrosis. Focal nodular macrophage infiltration was noticed in the cortex. There was necrosis in the cortex and the lymphocyte and macrophage infiltration was also noticed perivascular area in the cortex. In the spinal cord, severe demyelination and necrosis were evident from cervical to sacral cord predominantly in the antero-lateral funiculus and gray matter. Astrocytic proliferation was not apparent in the central part of these lesions.
CONCLUSION: NMO is caused by astrocyte impairment while multiple sclerosis is caused by demyelination. It has been reported that anti-AQP4 antibody level correlates with clinical features and clinical course. We reported a case of NMO with extremely high anti-AQP4 antibody level, and in the pathology, widespread necrosis with inflammation was noticed in the brain and spinal cord. A case with very high anti-AQP4 antibody level such as this patient may have refractory and fulminant clinical course.