title: Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management.
abstract: BACKGROUND
  Precise diagnosis of central nervous system (CNS) lesions in liver transplant recipients remains problematic. Brain biopsies are often not feasible as a result of coagulopathy. We sought to determine whether selected clinical or radiologic characteristics can predict the likely etiology of CNS lesions in liver transplant recipients and thus obviate the need for diagnostic brain biopsies.
  
  
  METHODS
  A 4-year prospective, observational, cohort study was conducted at liver transplant centers at four geographically diverse medical institutions. A total of 1730 consecutive liver transplant recipients were evaluated for CNS lesions; 60 patients with radiologically documented CNS lesions comprised the study sample.
  
  
  RESULTS
  Vascular events (52%, 31/60), infections (181%, 11/60), immunosuppressive associated leukoencephalopathy (12%, 7/60), central pontine myelinolysis (8%, 5/60), and malignancy (3%, 2/60) were the predominant etiologies of CNS lesions. CNS lesions were most likely to occur within 30 days of transplantation (43%, 26/60); central pontine myelinolysis, subdural hematoma, acute infarcts, and Aspergillus brain abscesses were the predominant etiologies during this time. All brain abscesses were fungal; 73% (8/11) of these patients concurrently had documented extraneural (pulmonary) infection as a result of the same fungal pathogen. Thus, a diagnostic brain biopsy is not warranted in these patients. Patients on dialysis were more likely to have ischemic or infectious CNS lesions (P=0.03). Vascular events were more likely to occur in repeat transplant recipients (P=0.03). Twenty-five percent (15/60) of the CNS lesions occurred more than 1 year after transplantation; small vessel ischemic lesions, malignancy, or non-Aspergillus fungal brain abscesses accounted for all such lesions.
  
  
  CONCLUSIONS
  A presumptive etiologic diagnosis can be established in a vast majority of CNS lesions in liver transplant recipients based on identifiable presentation that includes time of onset, unique risk factors, and neuroimaging characteristics. Empiric therapy of brain abscesses in liver transplant recipients should include antifungal and not antibacterial agents.
authors.affiliation: University of Pittsburgh, Thomas E. Starzl Transplantation Institute, Pennsylvania, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Bonham
authors.forename: E A
authors.initials: EA
authors.lastname: Dominguez
authors.forename: M B
authors.initials: MB
authors.lastname: Fukui
authors.forename: D L
authors.initials: DL
authors.lastname: Paterson
authors.forename: G A
authors.initials: GA
authors.lastname: Pankey
authors.forename: M M
authors.initials: MM
authors.lastname: Wagener
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
authors.forename: N
authors.initials: N
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000209:etiology* / Q000628:therapy; D002545:Brain Ischemia / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000209:etiology; D002544:Cerebral Infarction / Q000209:etiology; D005260:Female; D006408:Hematoma, Subdural / Q000209:etiology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology; D017590:Myelinolysis, Central Pontine / Q000209:etiology; D011446:Prospective Studies