Progressive multifocal leukoencephalopathy after orthotopic liver transplantation

Department of Neurology, Mount Sinai Medical Center, New York, NY 10029, USA.
Liver transplantation and surgery: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 12/1995; 1(6):371-2. DOI: 10.1002/lt.500010606
Source: PubMed


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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    • "JCV lytically infects oligodendrocytes and destroys these myelin generating cells, causing lesions and eventual death of the patient (Berger, 2003). PML incidence has increased in recent years due to a larger number of immunocompromised patients, such as organ transplant recipients (Bronster et al., 1995; Berner et al., 1999; Osorio et al., 2002; Ouwens et al., 2000; Singh et al., 2000; Steurer et al., 2003), bone marrow transplant patients (Coppo et al., 1999; Osorio et al., 2002; Re et al., 1999; Seong et al., 1996; Steurer et al., 2003), and AIDS patients (Gordon and Khalili, 1998; Holman et al., 1991; Safak and Khalili, 2003). Recent molecular studies have revealed an association of SV40 with some human cancers. "
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    ABSTRACT: 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. 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. 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. 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. These assays provide a technique for rapid and specific quantification of polyomavirus genomes per cell in human samples.
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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: Despite the potential medical problems described here, the vast majority of liver transplant recipients report a remarkable improvement in the quality of their lives. Many, in fact, have normal lifestyles, in marked contrast to their disability before liver transplantation. Maintenance of this status, however, requires compliance with regular medical follow-up to implement preventive measures and early detection of complications. A basic knowledge of these issues should enable the internist, general practitioner, and gastroenterologist to diagnose and manage many of the problems unique to liver transplant recipients. The liver transplant center should encourage communication and be readily accessible to the primary care physician. This team approach is responsible for measuring the survival of liver transplant recipients in decades, rather than years.
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