肝移植术后癫痫患者八例临床分析

Clinical analysis of seizures following liver transplantation: report of 8 cases

目的：探讨肝移植术后癫痫的发病原因及防治措施。方法回顾性分析2003年10月至2009年6月在中山大学附属第三医院器官移植中心接受肝移植术的772例患者中，术后随访期间发生癫痫的8例患者临床资料。所有患者均签署知情同意书，符合医学伦理学规定。其中男5例，女3例；年龄46～58岁，中位年龄54岁。术后定期复查血常规、肝功能、肾功能、电解质、免疫抑制剂的血药浓度、感染相关的病原学检查等。对可疑癫痫发作的患者，完善脑电图、CT或MRI等检查。分析患者发病原因、诊治和转归情况，包括发生率、发作时间、发作类型、病因分析、治疗方法和疾病转归。结果肝移植术后癫痫的发生率为1.0%（8/772），其中发生在术后1周1例、5～16周2例、16周以后5例，最长的1例发生在术后7年。全身强直-阵挛发作7例，其中2例发展为癫痫持续状态；复杂部分发作1例。病因分析显示，术前有癫痫发作史1例、肝性脑病2例；术后出现水、电解质紊乱6例，其中2例合并低血糖；术后出现脑卒中4例，其中1例合并术后他克莫司（FK506）血药浓度异常升高，1例合并术后颅内真菌和巨细胞病毒感染。8例患者均给予镇静及抗癫痫药物治疗，同时针对各种诱因进行治疗。经治疗后2例患者痊愈出院，6例死于多器官功能障碍综合征或脑出血。结论肝移植术后癫痫可能与术前癫痫发作史、肝性脑病以及术后免疫抑制剂毒性、水电解质紊乱、脑卒中、颅内感染等多种因素有关。一旦确诊，给予镇静及抗癫痫药物治疗，同时针对各种诱因进行治疗。患者预后较差。

Objective To investigate the causes, prevention and treatment of seizures following liver transplantation （LT）. Methods In the 772 patients undergoing LT in Organ Transplantation Center, the third Affiliated Hospital of Sun Yat-sen University from October 2003 to June 2009, clinical data of 8 patients who developed seizures during the follow-up after operation were analyzed retrospectively. The informed consents of all patients were obtained and the ethical committee approval was received. There were 5 males and 3 females with age ranging from 46 to 58 years old and median age of 54 years old. The patients received regular reexaminations of blood routine, liver function, renal function, electrolytes, blood concentration of immunosuppressant, infection related etiological examinations, etc. The examinations of electroencephalogram （EEG）, computed tomography （CT）, or magnetic resonance imaging （MRI） were＆amp;nbsp;completed for the suspicious patients of seizures. The causes of disease, diagnosis, treatments and outcome of the patients were analyzed, including the incidence, onset time, seizures types, etiological analysis, treatments and outcome. Results The incidence of seizures following LT was 1.0% （8/772）, in which 1 case occurred in 1 week after operation, 2 cases within 5 to 6 weeks, 5 cases over 16 weeks and the longest case over 7 years after operation. Generalized tonic-clonic seizure was observed in 7 cases, including 2 cases developed to status epilepticus and 1 case of complex partial seizure. The etiological analysis revealed that 1 case had a history of seizures and 2 cases had hepatic encephalopathy before operation. Water-electrolyte imbalance occurred in 6 cases after operation including 2 cases complicated with hypoglycemia. And cerebral apoplexy occurred in 4 cases after operation including 1 case complicated with abnormally elevating blood concentration of tacrolimus （FK506）, 1 case complicated with intracranial fungus and cytomegalovirus infections. Sedative and antiepileptic were given to all of 8 patients and various inducements were treated. Two cases recovered well and were discharged from hospital, and 6 cases died of multiple organ dysfunction syndrome or cerebral hemorrhage. Conclusions Seizures following LT may be related with many factors such as preoperative history of seizures and hepatic encephalopathy, immunosuppressant toxicity, water-electrolyte imbalance, cerebral apoplexy and intracranial infections after operation, etc. Once seizures are confirmed, sedative and antiepileptic should be given to the patients and various inducements should be treated. The prognosis of the patients is poor.