Progressive Multifocal Leukoencephnlopathy
After Orthotopic liver Transplantation
David J. Bvonstev, * Miha W. Lidov, t David Wozfe, # Myron E. Schwavtz, §
and Charles M. Millev§
Six weeks after liver transplantation, a 51 -year-old
man developed a slowly progressive hemiparesis
with deteriorating mental status and seizures.
Successive computed tomography (CT) scans of
the brain revealed unilateral nonenhancing white
matter lucencies that gradually coalesced and
progressed to both hemispheres. Brain biopsy
results were consistent with progressive multifo-
cal leukoencephalopathy (PML). We believe this
is the first antemortem description of PML after
liver transplantation. Herein, we describe the case
and review the literature on PML after solid organ
transplantation. Early recognition of this central
nervous system disease may be important with
new advances in therapy of this viral infection of
the immunocompromised patient.
Copyright o 1995 by the American Association for
the Study of Liver Diseases
rogressive multifocal leukoencephalopathy (PML)
P results from infection of the brain by JC vims, a
papovavims. It is generally seen in the setting of
immunosuppression, particularly when cell-medi-
ated immunity is compromised. Cyclosporine inter-
feres with T-cell proliferation by blocking interleu-
PML has been observed after renal and cardiac
transplantation. Although two autopsied cases have
been reported in liver recipient^,^,^ we believe this is
the first antemortem description of PML after ortho-
topic liver transplantation (OLT).
A 51-year-old man, who tested negatively for human
immunodeficiency virus, underwent OLT for crypto-
genic cirrhosis. Immunosuppression included cyclos-
porine, azathioprine, solumedrol, and acyclovir. He
required a second transplantation 2 weeks later for
primary graft nonfunction. Six weeks after transplan-
tation, he became agitated and tearful, with a slowly
progressive right hemiparesis. He remained ventila-
tor dependent, precluding magnetic resonance imag-
ing (MRI) examination, but computed tomography
(CT) scan of the brain showed a low attenuation area
in the left posterior parietal region. Ten days later,
contrast CT showed extension of this nonenhancing
lesion into the frontal lobe (Fig 1).
During the 13th postoperative week, he had a
generalized seizure. Immunosuppression was with-
held and stereotactic brain biopsy results showed
Prom the Departments o f 'Neurology, ?Radiology, +Neuroputhof-
ogy, and §Surgery, The Mount Sinai Medical Center New Yorh, NY
Addresc repnnt requests to Charle, M Miller, MD, The Mount
Sinai Medical Center, BOX 1104, One Guctuve L L a y Place, New
York, NY 10029
Copyright 0 1995 by the Amencan Altociation for the Study of
Figure 1. PML: Axial CT with contrast. Low-
attenuation lesion in left parietal lobe extending
anteriorly to the white matter of the frontal lobe.
There is minimal effacement of adjacent sulci but
no shift of midline structures. No enhancement is
Liver Transplantation and Surgq, Vol1, No 6 (November), 1995: pp 371-372
Bvonster et al
Table 1. PML After Organ Transplantation
Martinez et , I 6
Worthman et a17
Saxton et all
Legrain et , I 3
Manz et , I 4
Egan et a12
Hall et a 1 5
Abbreviations: bx, biopsy; NA, not available.
*Interval from transplantation.
demyelinated white matter fragments containing git-
ter cells, reactive astrocytosis, and enlarged hyperchro-
matic oligodendrocyte nuclei containing opaque punc-
tate inclusions diagnostic of PML. Therapy with
cytarabine was initiated. Two weeks later, CT scan
showed a new lesion in the right hemisphere. The
patient became obtunded and died.
The clinical presentation of PML includes hemipare-
sis, aphasia, cortical blindness, encephalopathy, and
seizures, and it progresses slowly.
Results of neuroimaging show that lesions begin
as small and asymmetric in the paneto-occipital
white matter, eventually coalescing into a single
larger area, with high signal intensity on T2-weighted
MRI and low attenuation on CT scan. PML typically
lacks mass effect and enhancement,' unlike brain
abscesses and lymphomas; however, these latter may
be altered radiographically by steroids. PML is distin-
guished from cyclosporine neurotoxicity by its radio-
graphic and clinical progression.
Whether PML in transplant recipients represents
reactivation of latent virus or a new primary infection
remains The incidence of PML after OLT
may increase as more transplantations are performed
and as recipients survive longer. Antemortem recogni-
tion after organ transplantation is rare (Table 1) but
will assume greater importance as more successful
therapies are developed. Treatment with cytarabine
and acyclovir has been di~appointing,~
treatment using cytarabine and interferon alfa has
The early posttransplantation presentation in this
case suggests that when focal, progressive neurologi-
cal signs appear after the first postoperative month
accompanied by white matter changes on imaging
studies, brain biopsy is indicated.
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