title: Changing picture of central nervous system complications in liver transplant recipients.
abstract: Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12-hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus-related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3-month patient survival (88.8% versus 95.4%) and 5-year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64-patient group with CNS complications and the asymptomatic group of 331 patients.
authors.affiliation: Mediterranean Institute for Transplantation and High Specialization Therapies, University of Pittsburgh Medical Center in Italy, Palermo, Italy. gvizzini@ismett.edu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vizzini
authors.forename: Monica
authors.initials: M
authors.lastname: Asaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Miraglia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gruttadauria
authors.forename: Daniela
authors.initials: D
authors.lastname: Filì
authors.forename: Adele
authors.initials: A
authors.lastname: D'Antoni
authors.forename: Ioannis
authors.initials: I
authors.lastname: Petridis
authors.forename: Gianluca
authors.initials: G
authors.lastname: Marrone
authors.forename: Duilio
authors.initials: D
authors.lastname: Pagano
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
mesh_terms: D000328:Adult; D002276:Carcinoid Tumor / Q000453:epidemiology / Q000601:surgery; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000601:surgery; D002493:Central Nervous System Diseases / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D019694:Hepatitis B, Chronic / Q000453:epidemiology; D019698:Hepatitis C, Chronic / Q000453:epidemiology; D019693:Hepatitis, Autoimmune / Q000453:epidemiology / Q000601:surgery; D006527:Hepatolenticular Degeneration / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000601:surgery / Q000821:virology; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology / Q000601:surgery; D008113:Liver Neoplasms / Q000453:epidemiology / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus