Page 178 - AIDSBK23C

Page 178

stem, and cervical spinal cord may also be involved. The lesions are usually centered around
capillaries.[765]
Microscopically, PML involves mainly the myelin-producing oligodendrocytes. The
resulting cell lysis results in PML lesions that demonstrate demyelination with perivascular
monocytes, astrocytosis with bizarre or enlarged astrocytes (with occasional mitotic figures), and
central lipid-laden macrophages. At the periphery of the lesions there are large "ballooned"
oligodendrocytes infected with JC virus that have enlarged "ground glass" nuclei containing viral
antigen. The presence of JC virus can be confirmed by immunohistochemical staining or in situ
hybridization methods. Multinucleated giant cells containing HIV may also be present. A
marked perivascular mononuclear infiltrate composed predominantly of T-lymphocytes may be
present in some lesions. The JC virus can also be detected within peripheral blood lymphocytes
in most AIDS patients with PML.[746,765] JC virus can be detected using PCR. In addition,
bone marrow serves at a site of latency and of neurotropic transformation of JC virus.[766]
The prognosis with PML is not good, with a mortality of 30 to 50% within 3 months for
most AIDS patients. A CD4 lymphocyte count above 100/µL is a favorable prognostic
factor.[764] Overall mortality is reduced with higher CD4 counts and when patients receive
antiretroviral therapy.[767]

CNS-IRIS.-- In some patients beginning antiretroviral therapy (ART), an immune
reconstitution inflammatory syndrome (IRIS) can occur in the CNS within 3 to 6 months
following initiation of ART, but may occur 2 years later. The most severe cases involve
reactivation of JC virus with PML, with up to 42% mortality and neurologic impairment often
requiring long term care in survivors. Up to 1 in 5 HIV-infected persons with a history of PML
will develop PML-IRIS. With MR imaging, PML-IRIS is marked by absence of contrast
enhancement, compared with PML. Not only CD4 cells, but also CD8 cells are found in the
inflammatory infiltrates. Other viruses associated with CNS-IRIS include varicella-zoster virus,
Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and BK polyoma virus. The most
common fungal pathogen associated with CNS-IRIS is Cryptococcus neoformans. In the
absence of defined infection, fulminant HIV encephalitis may be the only manifestation of IRIS.
MR imaging may reveal diffuse multifocal white matter changes with associated cerebral edema.
Microscopically there are many CD8 lymphocytes with fewer macrophages, CD4 cells, and B
cells diffusely infiltrating white and gray matter, leptomeninges, and blood vessels.
Corticosteroid therapy may be of benefit.[768]

SPINAL CORD.-- HIV infection producing a myelitis is present in only about 8% of
AIDS cases. Vacuolar myelopathy of the spinal cord may be seen in one third of AIDS cases,
and though it is probably a consequence of HIV infection, it is not usually associated with HIV
myelitis. Vacuolar myelopathy is manifested only when vacuolization is severe, and it presents
with slowly progressive spastic paraparesis accompanied by loss of vibratory and position sense
and urinary frequency and urgency. In males, erectile dysfunction can be an early
manifestation.[769] Vacuolar myelopathy is characterized mainly by vacuolar intramyelinic
swellings of white matter, but also by infiltration with macrophages. Some vacuoles may appear
in macrophages and axons. The vacuoles, 10 to 50 microns in size, usually appear in the
posterior and lateral columns in a pattern similar to subacute combined degeneration. The
disease starts in the mid to low thoracic cord and extends rostrally as it becomes more severe.
The most severe lesions can also have clearing of macrophages from the centers of foci of