Progressive Multifocal Encephalopathy in a Patient with Advanced Liver Cirrhosis

Abstract

Background: Progressive multifocal encephalopathy (PML) is a rare, often fatal, demyelinating disease of the central nervous system. Primary infection by JC Polyoma Virus (JCV) is asymptomatic in immunocompetent individuals, however depressed cellular immunity can lead to reactivation of the latent virus. PML is predominantly associated with marked immunosuppressed states such as cancer chemotherapy, Human Immunodeficiency Virus (HIV) infection, solid organ transplant and drugs like natalizumab. PML in occult immune deficiency states such as liver cirrhosis is extremely rare. Case Report: A 56 year-old male with a history of chronic kidney disease and advanced alcoholic cirrhosis presented with altered mental status, left-sided weakness, and a fall. He was on the wait-list for liver transplantation and had abstained from alcohol for 2 years. There was no history of HIV infection, immunosuppressant drugs or chemotherapy. His exam was notable for confusion, left-sided weakness, facial droop, and neglect. His labs were notable for a WBC of 7.3 x 1000/microL, CD4 of 180/mm and CD8 of 30/mm, creatinine of 1.28 mg/dL, and ammonia of 153 mg/dL. Magnetic resonance imaging of brain showed hyperintense T2 signal in bilateral occipital lobes, the splenium, and frontal gray-white matter junction consistent with a demyelinating process. Lumbar puncture performed was negative for bacterial infection, herpes simplex, Epstein Barr and Varicella Zoster viruses, and Cryptosporidium. Diagnosis of PML was confirmed with a positive PCR test for JCV in the serum and cerebrospinal fluid. Based on multiple co-morbidities and overall poor prognosis, no specific treatment was offered for PML. Patient died 10 weeks after initial presentation. Discussion: Liver cirrhosis as the primary risk factor for PML has only been described in four previous reports. Proposed mechanism involves depressed cellular immunity. Low CD4 T-cell counts (< 550/mm) are commonly seen in patients with liver cirrhosis. A subset of patients with liver cirrhosis was found to have CD4 counts less than 350/mm which can lead to opportunistic infections, such as PML. This has strong implications in liver transplantation (LT) where a mild or occult infection pre-LT can become life threatening due to high doses of immune suppressants after LT. Liver patients at risk for opportunistic infections can be identified and closely monitored by testing for parameters of cellular immunity such as CD4 and CD8 counts.