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AM Report May 4, 2009
Amy Auerbach
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Severe demyelinating disease of the central
nervous system caused by reactivation of the
polyomavirus JC
Occurs almost exclusively in
immunosuppressed patients
Normally remains latent in kidneys and
lymphoid organs
Can reactivate, spread to brain and induce
lytic infection of oligodendrocytes
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Seroprevalence studies demonstrate antibodies
in 60-80% of adults
Can be detected in tonsillar tissue and mucosa
of GI tract- unclear pattern of transmission
Likely initially associated with viremia- seeding
of kidney
Latent infection may be reactivated during
periods of immunosuppression (T cell
dysfunction)
JCV infects oligodendrocytes and astrocytes
once it reaches the CNS
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Almost exclusively in immunocompromised
patients
Initially described in lymphoproliferative
and myeloproliferative disease
Rare patients with solid organ malignancies,
granulomatous and inflammatory disease,
solid organ transplant recipients
Opportunistic infection in HIV patients
Observed in patients treated with
natalizumab- immunomodulatory drug
used in Crohn’s disease and multiple
sclerosis
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Altered mental status
Motor deficits (hemiparesis or monoparesis)
Limb ataxia, gait ataxia
Visual symptoms
Varied based on location of lesions in CNS
In HIV, pt’s with PML typically have CD4
count<200
Typically spares optic nerves and spinal cord
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Progressive disease course
Remyelination does not occur in affected
areas of brain
Median survival time is now 1.8 years- many
patients left with severe neurologic deficitsin patients with HIV infection
In patients without HIV infection- median
survival is only 2.6 months
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Believed to be secondary to immune
reconstitution therapy syndrome
Occurs after treatment with HAART in HIV
patients- inflammatory reaction of PML
lesions
Initial worsening but clinical outcome
ultimately more favorable
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JCV can cause lytic infection of cerebellar
granule cell neurons
Leads to ataxia and cerebellar atrophy
Separate disease process from white matter
lesions in cerebellum from PML
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Multifocal areas of
white matter
demyelination
Do not exhibit mass
effect
Lesions often
bilateral and localize
preferentially to
periventricular areas
and subcortical white
matter
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Reactive gliosis
with enlarged
astrocytes
Can confirm
presence of JCVinfected cells by
immunohistochemi
stry
Viral Inclusions in Oligodendrocytes
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PCR detection of JCV DNA in the CSF in
patients with appropriate neurologic and
neuroradiologic findings
“possible PML” if exclude primary CNS
lymphoma, infectious etiologies but do not
have JCV DNA in CSF
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In HIV infection: HIV encephalopathy
PML lesions typically asymmetric, well
demarcated, focal neurologic deficits
HIV lesions tend to be poorly demarcated,
associated with HIV CSF viral load
CNS Lymphoma: cortical involvement,
positive CSF cytology or EBV PCR can help
differentiate
Ischemic lesions, tumors
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HAART therapy in patients with HIV
Stop immunosuppressive therapy in patients
on immunosuppression (transplant patients,
inflammatory disorders)
Short term glucocorticoid therapy in patients
with inflammatory PML and edema
Other treatments under evaluation:
cytarabine, mirtazapine
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PML is an opportunistic infection associated
with impairment of cell-mediated immunity
New onset or clinical worsening may occur
after initiation of HAART due to immune
reconstitutions inflammatory syndrome
Primary differential includes HIV
encephalopathy and CNS lymphoma
Brain biopsy or detection of JCV DNA in CSF
needed for diagnosis
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Langer-Gould et. Al. Progressive Multifocal Leukoencephalopahty in
a Patient treated with Natalizumab. NEJM353:375; July 28, 2005.
Epker et.al. PML: a review and an extended report of five patients
with different immune compromised states. Eur J Intern Med. 2009
May; 20 (3) 261-7
Uptodate.com