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Background:  HIV sensory neuropathy (HIV⁺SN) is now the most common neurological complication found in patients with AIDS. HIV⁺SN presents as a distal form of neuropathy attributed to “dying-back” neuropathic mechanisms. The purpose of this study was to evaluate the magnitude of neuropathological abnormalities in sensory pathways, spinal cord, and dorsal root ganglia of patients affected by HIV⁺SN as compared with those with HIV infection without history of neuropathy (HIV⁺ controls).

Methods:  Lumbar spinal cord segments and dorsal root ganglia were studied by immunocytochemistry in 13 cases of HIV⁺SN and compared with 13 HIV⁺ controls. Neuroglial reactions were assessed by immunocytochemistry with markers for MHC class II (activated microglia), CD68 (macrophages/activated monocytes), and GFAP (astrocytes). Presence of HIVp24 viral antigen was detected by immunocytochemistry and used as an indicator of tissue viral load. An unbiased assessment of the area fraction of immunoreactivity was used to quantify the magnitude of neuroglial reactions in the spinal cord compartments associated with sensory pathways such as posterior column and dorsal horn as well as other compartments (e.g., anterior horn, lateral and anterior columns). Group comparisons were carried out using 2 sample t-tests.

Results:  In patients with HIV⁺SN, a significant increase in the area fraction of immunoreactivity for macrophages/monocytes was the most consistent neuroglial reaction observed as compared with HIV⁺ controls (p < 0.01). The increase in macrophage infiltration was seen in the perineuronal and interstitial compartment of the dorsal root ganglia. In few cases, HIVp24 antigen was seen localized in macrophages but no evidence of Schwann or neuronal immunoreactivity was observed. There was no difference in microglial or astroglial reactions in the dorsal horn or posterior columns in HIV⁺SN cases as compared with HIV⁺ controls. The magnitude of neuroglial reactions was similar between all regions of the spinal cord involved in motor function, such as the corticospinal tract.

Conclusions:  The findings of this study support the view that the dorsal root ganglia is the main site of dysfunction in sensory pathways of patients with HIV⁺SN. The presence of marked increase in macrophage activation and infiltration of the perineuronal compartment in the dorsal root ganglia may play a role in neuronal dysfunction and explain some of the features of painful sensory symptomatology in HIV⁺SN.

Keywords: Dorsal root; Spinal cord; sensory neuropathy