Second edition

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496 Infectious and related disorders
Etiology
In most cases there are widespread microglial nodules and
inclusion-positive cytomegalic cells (Morgello et al. 1987);
in those cases characterized by a fulminant delirium there
is marked periventricular inflammation, with, in some
cases, necrotic changes (Berman and Kim 1994; Kalayjian
et al. 1993).
Differential diagnosis
Both AIDS dementia and other opportunistic infections
must be considered; fulminant cases with brainstem signs
may mimic Wernicke’s encephalopathy.
Treatment
The general treatment of dementia and delirium are discussed
in Sections 5.1 and 5.3 respectively. Ganciclovir and
foscarnet are typically prescribed; however, in some cases
CMV encephalitis has occurred despite ongoing treatment
with these agents (Berman and Kim 1994).
14.3 PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
Progressive multifocal leukoencephalopathy occurs secondary
to an opportunistic infection of the central nervous
system by the JC virus (Padgett et al. 1971). Multifocal areas
of demyelinization occur, producing various focal signs
and, in some, a dementia. In almost all cases patients have
depressed cell-mediated immunity, most commonly due
to AIDS, in which 2–5 percent of patients are afflicted.
Clinical features
The onset is typically subacute, generally over approximately
2 weeks. In most cases, patients present with a slowly
progressive focal sign, such as hemianopia, aphasia, apraxia,
hemisensory loss, or hemiplegia (Astrom et al. 1958; Krupp
et al. 1985; Richardson 1961); rarer focal findings such
as Balint’s syndrome (Ayuso-Peralta et al. 1994) have
also been reported. Over time, these initially unilateral
deficits become bilateral, and many patients then go on
to develop a personality change, a dementia or, rarely, a
delirium. Seizures may occur in up to 20 percent of patients
and may be simple partial, complex partial, or grand mal
(Lima et al. 2006; Moulignier et al. 1995). Rarely, progressive
multifocal leukoencephalopathy may present with a
dementia (Sellal et al. 1996; Zunt et al. 1997), delirium
(Davies et al. 1973), or personality change (Astrom et al.
1958). Cerebellar signs may occur but are not common
(Parr et al. 1979). Other rare signs include quadriparesis
secondary to brainstem involvement (Kastrup et al. 2002),
and dystonia (Factor et al. 2003), chorea (Piccolo et al. 1999),
or parkinsonism (Bhatia et al. 1996).
The electroencephalogram (EEG) may show diffuse or
focal slowing.
Magnetic resonance scanning (Guilleux et al. 1986; Kuker
et al. 2006) will reveal one or more focal lesions, generally
in the subcortical white matter. On T1-weighted imaging
these display decreased signal intensity, and on FLAIR
or T2-weighted imaging, increased signal intensity is
seen. Diffusion-weighted imaging may demonstrate mild
increased signal intensity in some cases and, again, in some
cases there may be enhancement with gadolinium (Huang
et al. 2007).
The CSF, although characteristically normal, may occasionally
reveal a mild lymphocytic pleocytosis. The PCR
assay for JC virus is generally, but not always, positive
(Hensen et al. 1991; Koralnik et al. 1999). Serum testing for
antibodies to JC virus is not helpful, given, as noted below,
that most adults will be positive. In doubtful cases brain
biospy may be required.
Course
In the natural course of events the disease is generally
relentlessly progressive, with death occurring after about 4
months on average. Rarely the course may stretch out for
years, and even more rarely there may be spontaneous
remissions (Price et al. 1983).
Etiology
Approximately 80 percent of the adult population of
the United States has latent infection with the JC virus.
In a very small minority of patients with depressed cellmediated
immunity, this virus reactivates and spreads to
the brain. Although by far the most common cause of
immunoincompetence in these patients is AIDS, progressive
multifocal leukoencephalopathy has also been noted
in patients with Hodgkin’s disease, other lymphomas,
leukemia, other cancers, tuberculosis, sarcoidosis, systemic
lupus erythematosus (Krupp et al. 1985), and in patients
undergoing therapeutic immunosuppression after transplantation
(Sponzilli et al. 1975). Progressive multifocal
leukoencephalopathy may also, albeit rarely, occur in
patients treated with natalizumab (Yousry et al. 2006).
Finally, it also appears that, very rarely, progressive multifocal
leukoencephalopathy may occur in otherwise healthy
individuals (Fermaglich et al. 1970; Guillaume et al. 2000).
Within the central nervous system, oligodendrocytes
and, to a lesser degree, astrocytes are infected by the JC
virus. With destruction of oligodendrocytes, demyelinization
with only relative axonal sparing occurs, and foci of
demyelinization begin to appear. Within and surrounding
these foci there is a variable, and typically quite slight,