Page 190 - AIDSBK23C

Page 190

Biopsy of peripheral nerve (typically sural nerve) rarely reveals an opportunistic infection
as a cause for neuropathy, but there may be lymphocytic infiltrates and demyelination in
peripheral nerve indicative of acute or chronic inflammatory demyelinating neuropathy. An
immunologic mechanism is suggested by improvement of patients with inflammatory
neuropathies undergoing plasmapheresis, corticosteroid, or intravenous immunoglobulin therapy.
There are several types of neuropathy seen with HIV infection. Either autoimmunity,
cytomegalovirus, or direct HIV infection may be an etiology for such peripheral
neuropathies.[810]
The most common HIV-associated neuropathy, which tends to occur with advanced HIV
infection with CD4 counts <200/µL, is distal sensory polyneuropathy (DSP). DSP clinically is
manifested mainly by sensory symptoms in the feet and legs that can include spontaneous or
evoked pain, but there can be loss of vibration and temperature sense. Though proprioception
remains intact, the pain may be so severe that the patient cannot walk. The soles of the feet may
be painful on palpation. Ankle reflexes may be reduced or absent. Examination of cerebrospinal
fluid may show a slightly elevated protein. The course of DSP is subacute to chronic. DSP
typically manifests late in the course of AIDS, though it may occur earlier. DSP is
predominantly an axonal neuropathy by electrophysiologic findings, but it may be difficult to
distinguish from a toxic neuropathy from antiretroviral therapy, and many patients will have
elements of both. The characteristic pathologic feature of DSP is axonal degeneration of long
axons in distal regions, with a “dying back” pattern of degeneration. The density of both small
and large myelinated fibers is reduced, but the density of unmyelinated fibers is reduced even
more. DSP may exhibit variable lymphocytic infiltration of the perineurium, but perivascular
inflammation is uncommon. Dorsal root ganglia often contain small numbers of degenerating
neurons with macrophage and lymphocyte activation.[811]
Inflammatory demyelinating polyneuropathy (polyradiculopathy) may occur in
association with moderately advanced HIV infection with CD4 counts between 200 and 500/µL.
There are two forms: chronic inflammatory demyelinating polyneuropathy (CIDP) and acute
inflammatory demyelinating polyneuropathy (AIDP), Both forms typically appear early in the
course of HIV, before the onset of AIDS. They are much less common than DSP. Both CIDP
and AIDP manifest with motor and sensory symptoms. Examination of the cerebrospinal fluid
may reveal an elevated protein and a lymphocytic pleocytosis. Electrophysiologic studies may
show slow conduction, delayed latencies, and conduction blocks. The initial pathologic finding
with CIDP is lymphocytic and macrophage infiltration with demyelination. More advanced
findings include remyelination, onion bulbs, minimal lymphocytic infiltration, and a reduced
density of both myelinated and unmyelinated fibers. The pathologic findings with AIDP are
more heterogeneous, resembling the findings of Guillain-Barré syndrome, with two forms. The
more common form manifests with demyelination with macrophage and CD4 cell infiltration.
The less common axonal form of AIDP shows minimal inflammation, no demyelination, and
mostly changes of Wallerian degeneration.[808,810]
Mononeuritis multiplex (MM) may also be seen with either early or advanced HIV
infection as a manifestation of a vasculitic neuropathy. When MM occurs early during the
course of HIV infection, it is often the result of a self-limited immune-mediated neuropathy or
vasculitis. Late in the course of HIV infection, it is often associated with cytomegalovirus
infection. There may be cranial nerve involvement. The usual clinical presentation is sensory
involvement, with numbness and tingling in distribution of one peripheral nerve trunk.