Page 191 - AIDSBK23C

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Sequential sensory and motor involvement of other noncontiguous nerves may evolve over days
and weeks. The initial multifocal and random neurologic features may progress to symmetrical
neuropathy. Biopsy of MM shows epineurial and endoneurial necrotizing vasculitis. This
vasculitis may be similar to the cryoglobulinemic vasculitis seen with hepatitis B and C
infections.[808,810]
Progressive radiculopathy appears to be related to cytomegalovirus infection, typically
late in the course of AIDS when CD4 counts are below 50/µL. Cytomegalovirus
polyradiculopathy typically manifests as a cauda equina syndrome developing over a few days or
weeks. There is mainly a motor deficit in an asymmetric distribution. A common initial finding
is low back pain with radiation to one leg. This may be followed by urinary incontinence, saddle
anesthesia, and progressive leg weakness. If the CMV infection is not treated,
polyradiculopathy then advances to flaccid paraplegia with bowel and bladder incontinence, with
death in a few weeks. Electrophysiologic studies show evidence of axonal loss in lumbosacral
roots with later denervation potentials in leg muscles. Examination of the cerebrospinal fluid
shows a low glucose, elevated protein, and a polymorphonuclear pleocytosis with 200 cells/µL.
CMV can be demonstrated by culture or PCR analysis. Pathologic findings include marked
inflammation with infiltrates of both neutrophils and mononuclear cells and necrosis of the
dorsal and ventral nerve roots with cytomegalic inclusions detectable in endothelial cells and
nerve parenchyma. In severe cases, vascular congestion, edema, and parenchymal necrosis may
be present,.[808,810]
A condition known as diffuse infiltrative lymphocytosis syndrome (DILS) that may
mimic lymphoma can rarely involve peripheral nerve. In this condition, there is a pronounced
angiocentric infiltration of peripheral nerve with CD8 lymphocytes and a vascular mural
necrosis. It is associated with massive HIV proviral load within nerve, as evidenced by
increased HIV p24 expression in macrophages infiltrating nerve.[581,808]
Autonomic neuropathies may appear late in the course of HIV infection, with or without
evidence of peripheral neuropathy, in up to 12% of patients. Parasympathetic failure may
present clinically as resting tachycardia, palpitation, and genitourinary dysfunction. Sympathetic
dysfunction may be manifested by orthostatic hypotension and syncope, anhidrosis, and
gastrointestinal disturbances.[808]
In early HIV infection, neuropathies may occur transiently. Cranial and peripheral
neuropathies, most often facial nerve palsy, may accompany primary HIV infection. Findings
resembling Guillain-Barré syndrome may occur. A mononeuropathy resembling Bell’s palsy has
been observed.[808]
Use of the antiretroviral drugs in the category of nucleoside analogue reverse
transcriptase inhibitors (NRTIs) including ddC (most common), ddI, and d4T, can be
complicated by neuropathy and/or myopathy. The NRTIs contain azido groups that compete
with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate
mitochondrial DNA synthesis. Zalcitabine (no longer used), didanosine, and lamivudine may
cause neuropathy; stavudine may cause either neuropathy or myopathy with lactic acidosis;
zidovudine may cause myopathy. The NRTI induced neuropathy may present with numbness,
tingling, and pain. The appearance is that of a painful sensory polyneuropathy. It can be similar
to neuropathies seen in relation to HIV infection, but may be distinguished by a temporal
relationship to drug therapy. HIV-associated neuropathy usually takes weeks to months to
develop, while a neuropathy associated with antiretroviral therapy evolves more rapidly, usually
after 16 to 20 weeks of treatment. This latter neuropathy appears to be dose-related, so lowering