Progressive Multifocal Leukoencephalopathy (PML)
Etiology:
-
Multifocal demyelinating lesions of CNS
- Due to
reactivation of JC virus (papovavirus)
- 90% of
general population have serological evidence of JC virus infection which is
benign / asymptomatic
- PML occurs
in association with immunosuppression (esp HIV / AIDS), leukemia, lymphoma
- The
incidence of PML dramatically rose in the 1980s with AIDs
- Up to
4% of patients with AIDs develop PML at some point during disease
- The incidence
of PML has NOT changed with introduction of HAART (highly active antiretroviral
therapy)
- JC virus infects oligodendrocytes, leading to lysis and demyelination
Clinical
Presentation:
- Insidious
subacute onset over months
- Confusion
/ cognitive dysfunction
- Behavioural
change and / or personality change
- Focal
neurological deficits depending on location of lesions which may include
hemiparesis, sensory disturbance, aphasia
- Usually
no headache or fever
Pathology:
- Multifocal
demyelination, patchy to confluent
- Hyperchromic
enlarged oligodendroglial nuclei containing characteristic viral intranuclear
inclusions by electron microscopy
- Bizarre
astrocytes with lobulated hyperchromatic nuclei, can simulate astrocytoma
Investigations
CT /
MRI
- White
matter lesions, may involve gray
-
"Scalloped" appearance, may affect U-fibres
-
Multiple, bilateral lesions or confluent
- No or
little mass effect / edema
-
Hypodense lesions on CT
-
Hypointense on T1, hyperintense on T2
- Usually
not enhancing (may get mild enhancement with immune reconstitution)
Cell
count
- Usually
severe cellular immunsuppression with CD4<200
- Subset (7-25%) may develop PML with CD4 >200
- WBC<20,
protein normal or <200, may have low glucose
- PCR for JC virus DNA 80% sensitivity, 95% specificity
Brain
Biopsy
- Definitive
diagnosis
- Note:
brain biopsy may be non-diagnostic in 4-36%
Prognosis:
- Fatal
with median 6 months
- 8-10%
survive > 12 mo. and have spontaneous recovery of neurological function
- Survival
may be ameliorated by HAART in PML associated with AIDs
-
Prognostic factors for longer survival:
HAART, high CD4 at diagnosis, increase of CD4, low HIV load, low JC
virus level, lack of progression at 2 months
Treatment:
- No
effective treatment
- Anedoctal
evidence that HAART treatment may prolong survival in PML associated with AIDs
- Experimental
treatments: ara-C, IFN-g, captothecin, antisense
nucleotides, cidofovir, topotecan
References:
J.
Neurovirol. 9:205-221, 2003
J.
Neurovirol. 8:158-167, 2002
CID 34:103-115, 2002
Semin. in
Neurol. 19:193-200, 1999
HIV
In-Site (http://hivinsite.ucsf.edu/)
Last
update: September 30,
2003
Reviewed
by: pending review
Neurological Medicine Pocketbook
© 2003-2004
UWO Neurology Residents
http://www.uwo.ca/cns/resident
All Rights
Reserved