title: Leukoencephalopathy syndrome after living-donor liver transplantation.
abstract: OBJECTIVE
  Leukoencephalopathy syndrome is a neurologic complication after organ transplantation caused predominantly by the neurotoxic effects of immunosuppressive agents on cerebral white matter. We determined the incidence and features of leukoencephalopathy syndrome in recipients after living-donor liver transplantations.
  
  
  METHODS
  We retrospectively investigated 205 patients who had a living-donor liver transplantation performed at our institution between August 1998 and October 2008.
  
  
  RESULTS
  Leukoencephalopathy syndrome developed in 7 of 205 patients (3.9%) and in 4.7% of the 150 patients treated with tacrolimus-based immunosuppression after their living-donor liver transplantation. The underlying diseases were alcoholic cirrhosis in 3 cases, viral cirrhosis in 2, biliary atresia in 1, and Wilson disease in 1. Time to clinical onset after tacrolimus medication was 15.6 days (range, 6-30 days). The neurologic symptoms included headache, confusion, myoclonus, seizures, and visual disturbances. The mean serum trough level of tacrolimus at clinical onset was not very high (11.7 ng/mL [range, 6.0-14.2 ng/mL]). T2-weighted magnetic resonance imaging in all cases showed diffuse high signal in the white matter of the frontal, parieto-occipital, and temporal lobes. Treatment with antihypertensives, anticonvulsants, and withdrawal of tacrolimus resulted in amelioration of symptoms and magnetic resonance imaging abnormalities. Six patients showed complete recovery, while the seventh had residual rigidity and cognitive impairment caused by hypoxia during a convulsion.
  
  
  CONCLUSIONS
  Tacrolimus neurotoxicity can occur despite low trough levels; it depends on variations in pharmacokinetics, such as absorption and maximum concentration level. Early diagnosis and treatment of leukoencephalopathy syndrome should contribute to complete remission.
authors: Department of Gastroenterological Transplant Surgery, Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. y.umeda@d9.dion.ne.jp
authors: Yuzo
authors: Y
authors: Umeda
authors: Hiroaki
authors: H
authors: Matsuda
authors: Hiroshi
authors: H
authors: Sadamori
authors: Susumu
authors: S
authors: Shinoura
authors: Ryuichi
authors: R
authors: Yoshida
authors: Daisuke
authors: D
authors: Sato
authors: Masashi
authors: M
authors: Utsumi
authors: Takahito
authors: T
authors: Yagi
authors: Toshiyoshi
authors: T
authors: Fujiwara
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001656:Biliary Atresia / Q000601:surgery; D002648:Child; D000075202:Contraindications; D005260:Female; D006527:Hepatolenticular Degeneration / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D056784:Leukoencephalopathies / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy*; D008103:Liver Cirrhosis / Q000601:surgery; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012189:Retrospective Studies; D013577:Syndrome; D016559:Tacrolimus / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus