Innocent until Proven Guilty

Post-mortem histopathologic examination of the brain stem/cerebellar lesion revealed extensive, focally necrotizing inflammation, primarily composed of neutrophils but with a significant number of CD68-positive macrophages and a smaller number of CD3-positive T-cells. CD20-positive B-cells were rarely detected. There was vascular and perivascular deposition of eosinophilic material. GFAP staining highlighted extensive fragmentation of astrocytic processes in perivascular areas. There was perivascular loss of aquaporin 4 immunoreactivity. Luxol fast blue-PAS special staining and neurofilament immunostaining indicated no selective loss of myelin. Immunofluorescence demonstrated perivascular reactivity for C3/C4, and IgG without reactivity for IgM, C1q, Kappa and Lambda. Lower spinal cord and left parietal lesion sections demonstrated atrophy and extensive multifocal cavitation associated with macrophagic infiltrates. There was significant myelin loss, axon loss and extensive gliosis. Eye and optic nerve sections demonstrated multifocal predominantly chronic but focally acute inflammatory infiltrates in the subarachnoid space around atrophic optic nerves. There was marked loss of retinal ganglion cells in the retina bilaterally. Special stains, immunostains, electron microscopy and postmortem cultures did not show evidence for infectious organisms. The clinical, radiographic and pathologic distinction of diseases on the demyelinating spectrum is challenging and evolving. At presentation, a diagnosis of acute hemorrhagic leukoencephalitis was favored. NMO was diagnosed based on disease progression and relapse. The pathologic findings of perivascular deposition of IgG, complement, neutrophilic infiltrates, loss of AQP4 and destruction of perivascular astrocytes support this. The mechanism of tissue injury in NMO including the relative timing of astrocytic injury versus demyelination due to secondary oligodendrocyte injury remains incompletely understood. It has been proposed that in a subset of NMO cases oligodendrocyte apoptosis and selective loss of minor myelin proteins occurs simultaneously with astrocyte pathology. Our case demonstrates extensive astrocytic pathology without significant selective demyelination and provides support for reports indicating that astrocyte injury predates demyelination in NMO.