Progressive multifocal leukoencephalopathy after orthotopic liver transplantation.
ABSTRACT 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 multifocal 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.
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ABSTRACT: Central nervous system (CNS) complications are relatively common after organ transplantation. A large autopsy series reported that the majority of organ transplant patients (n=500), including liver, heart, lung, heart-lung, kidney recipients, had sustained an insult to the CNS (1). Over half of patients had suffered cerebrovascular complications, and many had potentially treatable pathology such as infections, immunosuppression associated leukoencephalopathy, and lymphoproliferative disorders (1). Since neurological complications confer a higher rate of morbidity and mortality in both adult and pediatric transplant recipients than in patients without CNS abnormalities (2), it is of critical importance to be familiar with these entities. Many of the CNS complications encountered at our institution may be diagnosed with imaging, thus avoiding the need for biopsy and its attendant morbidity (3).
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ABSTRACT: Progressive multifocal leucoencephalopathy due to JC virus is a rare complication of liver transplantation. Only four cases have already been described in the literature. This disease is difficult to differentiate from leucoencephalopathy associated with immunosuppressive drugs such as cyclosporin or tacrolimus. Positive diagnosis of progressive multifocal leucoencephalopathy no longer requires cerebral biopsy. It must be confirmed by positive JC virus RNA amplification in the cerebrospinal fluid. We report a case of progressive multifocal leucoencephalopathy occurring 18 months after liver transplantation for hepatitis C-related cirrhosis.Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL. 01/2006; 30(3):473-475.
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ABSTRACT: Background: The polyomaviruses that infect humans, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40), typically establish subclinical persistent infections. However, reactivation of these viruses in immunocompromised hosts is associated with renal nephropathy and hemorrhagic cystitis (HC) caused by BKV and with progressive multifocal leukoencephalopathy (PML) caused by JCV. Additionally, SV40 is associated with several types of human cancers including primary brain and bone cancers, mesotheliomas, and non-Hodgkin's lymphoma. Advancements in detection of these viruses may contribute to improved diagnosis and treatment of affected patients. Objective: To develop sensitive and specific real time quantitative polymerase chain reaction (RQ-PCR) assays for the detection of T-antigen DNA sequences of the human polyomaviruses BKV, JCV, and SV40 using the ABI Prism 7000 Sequence Detection System. Study design: Assays for absolute quantification of the viral T-ag sequences were designed and the sensitivity and specificity were evaluated. A quantitative assay to measure the single copy human RNAse P gene was also developed and evaluated in order to normalize viral gene copy numbers to cell numbers. Results: Quantification of the target genes is sensitive and specific over a 7 log dynamic range. Ten copies each of the viral and cellular genes are reproducibly and accurately detected. The sensitivity of detection of the RQ-PCR assays is increased 10-to 100-fold compared to conventional PCR and agarose gel protocols. The primers and probes used to detect the viral genes are specific for each virus and there is no cross reactivity within the dynamic range of the standard dilutions. The sensitivity of detection for these assays is not reduced in human cellular extracts; however, different DNA extraction protocols may affect quantification. Conclusion: These assays provide a technique for rapid and specific quantification of polyomavirus genomes per cell in human samples.
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.
Saxton CR, Gailiunas P, Helderman JH, Farkas RA,
McCoy R, Diehl J, et al. Progressive multifocal leukoen-
cephalopathy in a renal transplant recipient: Increased
diagnostic sensitivity of computed tomographic scan-
ning by double-dose contrast with delayed films. Am J
Egan JD, Ring BL, Reding MJ, Wells IC, Shuman RM.
Reticulum cell sarcoma and progressive multifocal
leukoencephalopathy following renal transplantation.
Transplantation 1 980;29:84-86.
Legrain M, Graveleau J, Brion S, Mikol J, Kuss R.
Leuco-encephalopathie multifocale progressive apres
transplantation renale. J Neurol Sci 1974;23:49-62.
Manz HJ, Dinsdale HB, Morrin PAF. Progressive multifo-
cal leukoencephalopathy after renal transplantation.
Ann Intern Med 1971 ;75:77-81.
Hall WA, Martinez AJ, Dummer JS. Progressive multifo-
cal leukoencephalopathy after cardiac transplantation.
Martinez AJ, Ahdab-Barmada M. The neuropathology
of liver transplantation: Comparison of main complica-
tions in children and adults. Mod Pathol 1993;6:25-32.
Worthman F, Turker T, Muller AR, Patt S, Stoltenburg-
Didinger G. Progressive multifocal leukoencephalopa-
thy after orthotopic liver transplantation. Transplanta-
Hogan TF, Borden EC, McBain JA, Padgett BL, Walker
DL. Human polyomavirus infections with JC virus and
BK virus in renal transplant patients. Ann Intern Med
Rubin RH. Infection in the renal and liver transplant
patient. In: Rubin RH, Young LS (eds): Clinical ap-
proach to infection in the compromised host. Ed 2. New
York, Plenum Medical Book Co, 1988557-621.
Steiger MJ, Tarnesby G, Gabe S, McLaughlin J,
Schapira AHV. Successful outcome of progressive
multifocal leukoencephalopathy with cytarabine and
interferon. Ann Neurol 1993;33:407-411.