Optic Nerve Axon Loss and Neuropsychological Impairment in HIV Encephalitis

Abstract

Purpose:: To quantify optic nerve axon loss in patients with HIV associated encephalopathy and variable neuropsychological impairment

Methods:: 16 optic nerves, collected at autopsy from 8 patients previously established to have HIV associated encephalopathy. All patients underwent extensive pre-mortem neuropsychological testing, quantifying cognitive impairment. Optic nerves were immersion fixed and embedded into epon blocks. 1µm sections were obtained and stained with p-phenylenediamine (PPD). Images were digitally captured in 32 distinct and regularly distributed sectors of each optic nerve. Myelinated axon counts for each optic nerve were obtained from each of these images.

Results:: Quantification analysis demonstrates a significant loss of myelinated axons in optic nerves of patients with HIV associated encephalitis when compared to age matched historical HIV-negative patient controls. Among patients with HIV associated encephalopathy, axon count decreased linearly with increased neuropsychological impairment as determined by global cognitive ratings from pre-mortem patient testing. Within this group of HIV associated encephalitis patients those with an equivalent degree of cognitive impairment demonstrated a decrease in total axon count proportional to increased patient age.

Conclusions:: While previous studies have been able to correlate neuronal damage in the neocortex to neurocognitive diagnosis, our findings suggest a correlation between optic nerve axonal degeneration and severity of dementia in patients with HIV associated encephalopathy.

Keywords: neuro-ophthalmology: optic nerve • AIDS/HIV • pathology: human