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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Neuropathology

Three salient pathological changes observed in HIV encephalitis, both in adults and children, are (1) the presence of multinucleated giant cells or viral antigen, (2) white matter pallor, and (3) microglial nodules [75, 76]. The disruption of the BBB permits egress and deposition of serum proteins into the CNS, which is linked to the white matter pallor. In children, there is also mineralization adjacent to blood vessels. Postmortem examination has demonstrated a number of distinct arrays of neuronal loss [77, 78]. While the larger pyramidal neurons within the cortex are more susceptible to cell death, other neurons expressing somatostatin are resistant to HIV injury.

Vacuolar myelopathy is neuropathologically described as intralaminar edema inside of the myelin sheaths with axonal preservation. Neuropathologically, vacuolar myelopathy of AIDS resembles subacute combined degeneration [13]. Macrophages also play a role as they are found in the posterior columns along with enhanced expression of activation markers. Studies have indicated a relationship of low levels of the protein negative regulatory factor (Nef) in oligodendrocytes with the development of vacuolar myelopathy.

The mechanisms for neuropathy in HIV patients are related to neuronal and axonal injury due to neurotoxicity of HIV and envelope glycoprotein gp120. HIV infection alone in the root ganglia leads to upregulation of IL-1p and TNF-a. As mentioned before, macrophages can play a role in the dorsal root ganglion neurons and Schwann cells. Gp120 is involved in direct toxicity by activation of the mitochondrial caspase pathway which leads to apoptosis and axonal degeneration. HIV patients also exhibit distal sensory polyneuropathy with reduction of epidermal nerve fibers in lower extremities related to macrophage infiltration and activation markers. Other agents like alcohol and illegal drugs in patients with HIV contribute to neuropathy. Nutritional factors like vitamin deficiencies should be addressed in this population. Neuropathy does not seem to be related to viral load or decreased CD4+ T lymphocyte count.

Mitochondrial toxicity has been suggested with the use of nucleoside reverse transcriptase inhibitors. L-carnitine levels are reduced which causes a disruption in the membrane energy balance and fatty acid oxidation. Low levels of L-carnitine are reported in patients with neuropathy likely from the accumulation of fatty acids. L-carnitine is important for peripheral nerve regeneration and its neuroprotective abilities.

HIV patients may develop inclusion body myositis or polymyositis, and histopathologic studies of these cases have revealed the upregulation of Toll-like receptor-3 mRNA [79].

 
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