Seizures after liver transplantation: a clinicopathologic study

We reviewed the clinical and neuropathologic findings in 21 patients who had seizures after orthotopic liver transplants. Tonic-clonic seizures were the most common seizure type. Six patients developed status epilepticus. In 9 patients, seizures occurred within 1 week following transplantation. We found CNS lesions that were probably responsible for the occurrence of seizures in most patients; some had more than 1 finding. Neuropathologic examination revealed ischemic or hemorrhagic strokes in 18 patients, central pontine myelinolysis in 5, and CNS infections in 5. Multiple metabolic abnormalities were a contributing factor to the onset of seizures in some patients.     

Neurosurgical complications of pediatric orthotopic liver transplantation

Liver transplantation is the only definitive treatment of end-stage liver disease. The University of Nebraska began its hepatic transplantation program in July 1985. Since that time, 43 children and 48 adults have undergone orthotopic liver transplantation (OLTx) with survival rates to date of 79.1% and 79.2%, respectively. Eight children developed complications of neurosurgical interest (18.6% incidence). Hemorrhagic complications were the most frequent. Neurosurgical salvage was achieved in five patients, but delayed complications of the transplant caused the death of two of these children. Two survivors are functioning well at home and in kindergarten, one child is doing well but is still hospitalized, and one child is vegetative. Aggressive management of life-threatening CNS problems is thus appropriate in this population. The authors review the pathophysiology of these complications, as well as potential pitfalls in their management.     

原位肝移植前后胆道及血管的磁共振成像评估*

背景：磁共振成像扫描技术的完善,实现了“一站式”磁共振综合检查,即1次检查过程中运用多种序列,同时对肝脏血管、胰胆管系统及上腹部器官进行影像评估,方便、快速、简捷。目的：评价磁共振成像检查在肝移植前后的应用价值。方法：选择中南大学湘雅三医院移植中心收治的肝硬化及肝癌患者38例,男27例,女11例,年龄23~68岁。原位肝移植前后进行磁共振成像检查,同时行双排螺旋CT检查,比较两种方法的优劣,最后以手术、病理检查结果确认。结果与结论：所有终末期肝脏疾病患者原位肝移植前后经磁共振成像检查,能较准确地描述出肝癌病灶的情况,血管及胆道系统的异常解剖形态及其内栓子和结石的情况,其结果明显优于双排螺旋CT检查。说明磁共振成像在肝移植前评估和移植后并发症早期发现中有非常重要的作用。     

原位肝移植后胆管损伤的病理学改变

背景：肝移植术后胆道损伤引起的并发症是临床上诊治的难点，是抑制肝移植发展的瓶颈。 目的：在成功应用胆道内镜治疗肝移植术后胆道并发症的同时，对胆管的损伤进行观察记录并取活检病理，分析不同胆管损伤、组织病理学类型与肝移植术后胆管并发症的关系。 设计、时间及地点：病例分析，于2001-07/2005-10在大连市肝胆外科研究所，友谊医院肝胆外科完成。 对象：将19例肝移植术后患者根据胆管并发症发生情况分为3组：正常组4例，胆管损伤组12例，肝动脉损伤组3例。 方法：利用内镜技术，分别对3组患者进行胆管观察、记录，内镜下取活检进行病理分析。对于无T管者，应用子母胆道镜观察、取活检。 主要观察指标：应用胆道内镜观察T管造影、肝内外胆管黏膜外观及病理学检查结果、供-受体胆管吻合口的愈合情况。胆管损伤组经内镜取石、狭窄扩张治疗后行上述指标的复查。 结果：①正常组患者肝内外胆管解剖正常，无狭窄、瘢痕，胆管黏膜颜色正常，供-受体胆管吻合口愈合佳。病理学检查均可见修复性的黏膜组织，被覆上皮完整。②胆管损伤组患者胆管内有各种类型的单发、多发及铸型结石，胆管均有不同程度损伤，经内镜取净结石、解除梗阻后，胆管黏膜均有不同程度的修复，造影检查胆树恢复正常。③肝动脉损伤组患者胆管壁缺血坏死，丧失胆管的组织结构，明显充血，胆泥和结石完全灌满供体胆树，Ⅲ级胆管间断具有胆管的组织结构；病理学检查发现胆管壁弥漫坏死，结构不清，大量胆汁渗入，可见增生的肉芽组织和化脓灶。 结论：在原位肝移植中胆管均有不同程度的损伤，冷保存/再灌注损伤是导致胆管树损害最重要的始动因素，胆管周围血管丛的损伤和微循环障碍可能是胆管损伤的途径之一。     

肝移植患者术后住院期间的中枢神经系统并发症

目的探讨肝移植术后住院期间中枢神经系统并发症的发病情况、临床和神经影像学特征及可能的危险因素及预后。方法对中山大学附属第一医院1996年1月至2005年6月间共337例患者的358次肝移植手术进行回顾性研究。结果术后住院期间患者出现中枢神经系统并发症共58例，发生率16．2％，病死率41．4％。最常见的表现为肝移植脑病（10．3％），次之为癫痫（4．5％）和脑血管疾病（2．8％）。与无中枢神经系统并发症的肝移植患者相比，术后发生中枢神经系统并发症者的年龄、是否再次肝移植及病死率差异有统计学意义（P〈0．05）。结论肝移植术后住院期间中枢神经系统并发症的发生率及病死率较高，直接影响患者的生活质量及预后。年龄偏大、再次肝移植可能是其危险因素。     

Neurological complications after living-donor liver transplantation in children

AimLiver transplantation (LT) has been used as a definitive management for children with end-stage liver disease or acute liver failure. Living-donor LT (LDLT) has been a common type of LT performed in Asian countries, including Japan, where deceased donors are rarely available. However, the neurological complications (NCs) associated with LDLT remain unknown. The purpose of this study was to clarify the characteristics of NCs in children after LDLT.MethodsThis study is a retrospective observational study carried out at a tertiary children’s hospital in Japan. We studied children who had undergone LDLT between January 2001 and January 2020.ResultsWe examined 602 cases of LT, of which 559 were LDLT cases (92.9%). NCs after LT were present in 21 cases (3.8%). The most common neurological symptoms were seizure (n = 17), whereas disturbance of consciousness without seizure was observed in four cases. The frequency of NCs for each of the indications was 12.2% for fulminant hepatic failure, 6.5% for metabolic liver disease, and 0.7% for cholestatic liver disease.InterpretationWe report the characteristics of NCs after LDLT in children. The frequency of NCs after LT was high in cases of fulminant hepatic failure and metabolic diseases, who might have had neurological symptoms or impaired consciousness before LT.     

肝移植后真菌感染9例次分析

为了探讨肝移植后真菌感染的诊断和治疗,回顾分析解放军总医院第二附属医院器官移植中心2007-09/2008-12收治的52例肝移植中,8例肝移植受体术后发生真菌感染的诊治情况。52例肝移植患者中,8例患者真菌感染9例次(1例患者发生2次感染),感染率15% (8/52)。感染时间发生在肝移植后2~5个月,感染好发的部位依次为肺(67%,6/9),泌尿系统(22%,2/9),肠道(11%,1/9)。病原菌中白色念珠菌感染占6例次,光滑念珠菌感染占2例次,曲霉菌感染占1例次。在8例患者中6例经抗真菌感染治疗顺利康复,2例患者死亡。可见真菌感染是肝移植术后常见并发症之一,病死率较高,早期诊断和治疗是治愈真菌感染的关键。     

Neurological complications after cadaveric and living donor liver transplantation

Problems related to the central nervous system have a major impact on survival and quality of life. The aim of this retrospective study was to evaluate the incidence of neurological complications after liver transplantation (LT), including both cadaveric and living donor liver transplantation. Between April 2001 and March 2004 174 patients (120 cadaveric liver transplantations, 54 living donor transplantations) were admitted to our intensive care after liver transplantation. Of the transplanted patients 24.7% developed neurological complications. These patients’ stay in the intensive care (14.2 ± 17.2 days) was much longer than that of all admitted patients (8.4 ± 10.5 days, p < 0.05). The most common neurological complications were encephalopathy (72.1%) and seizures (11.6 %). The incidence of neurological complications in living donor liver transplanted patients was significantly lower than in cadaveric transplantation patients (20.4% vs 26.7 %). The cold ischemia time in living donor transplanted patients was significantly shorter in comparison with cadaveric transplanted patients (215 ± 119.3 vs. 383.7 ± 214.7). The survival rate after liver transplantation of patients with neurological complications was lower than that of patients without, but not significantly different (79.1 % vs. 82.4%, p > 0.05). The incidence of neurological symptoms was found to be similar between the patients treated with cyclosporine (25%) and tacrolimus (23.8 %) in this study. In conclusion, there was a high incidence of neurological complications after LT, prolonging the patients’ stay in intensive care significantly. The major neurological manifestation in our patients was encephalopathy followed by seizures. Living donor liver transplantation was associated with a significantly lower incidence of neurological complications compared with patients who had received a cadaveric graft. This might be due to the good quality of the organ and the much shorter cold ischemia time of the graft when the donor was alive.     

Cyclosporine A-induced ocular opsoclonus and reversible leukoencephalopathy after orthotopic liver transplantation: brief report

Ocular opsoclonus is a rare neurologic condition that occurs in patients with brain stem encephalitis, neoplasm of the mesencephalon, paraneoplastic syndrome or intoxication. Neurotoxicity is a well-known complication of cyclosporine-A (CSA) therapy. We report a case of a 17-year-old patient, a Caucasian female, who underwent an orthotopic liver transplantation (OLT) for immunologic cirrhosis and chronic cellular rejection respectively. The ocular symptoms occurred 8 days after the OLT. She also developed reversible posterior leukoencephalopathy. The serum level of CSA was 412 ng/mL. The ocular symptoms improved 21 days after the reduction of the CSA level.     

Neurologic complications of liver transplantation

The clinical and neuropathologic findings of 55 adults and 30 children who received liver transplants were reviewed. Encephalopathy was the most common clinical neurologic syndrome and was usually caused by metabolic or anoxic causes. (Alzheimer type astrocytes were present in 73 per cent of patients, and evidence of diffuse hypoxic damage was present in 40 per cent of children and 25 per cent of adults.) Cerebrovascular lesions were a common finding with infarcts or hemorrhages present in 30 per cent of patients. CNS infections were documented in 34 per cent of patients. Seizures were present in a third of patients. Central pontine myelinolysis was present in 12 per cent of patients and was more common in adults than in children. Antemortem diagnosis of neurologic complications was more often based on clinical presentation rather than specific radiologic or laboratory tests.     

Neurologic complications in liver transplantation

A retrospective review is presented of neurologic complications in our first 143 consecutive adult patients (208 liver transplants in 143 adults and 18 children) undergoing liver transplantation. Nineteen (13.2%) of the 143 patients developed neurologic complications in the postoperative period. Immunosuppression was initiated intraoperatively with steroids with the addition of azathioprine on Day 1 and cyclosporine, adjusted by RIA to a level of 400-600 ng/ml, on Day 2 post-transplantation. Azathioprine is discontinued in the third month. Fourteen of the 19 patients (73.6%) presented with CNS complications characterized by: diffuse multifactorial encephalopathy (5 patients); leukoencephalopathy (2 patients) which required temporary (1 case) or permanent (1 case) discontinuation of cyclosporine A; hemorrhage (in 2 cases due to arterial hypertension and coagulopathy and another due to unknown causes); ischemic/anoxic injury secondary to cardiorespiratory arrest (2 patients) or arteriothrombosis (1 patient); and myelopathy (1 patient) due to vertebral compression (T10-T11) secondary to osteoporosis. The diagnostic studies most often employed were computed tomographic (CT) (85.7%) and electroencephalography (EEG) (42.8%). Five of 19 patients (26.3%) suffered peripheral nervous system (PNS) complications: 1 patient with reversible Claude-Bernard-Horner Syndrome caused by central venous catheterization during anesthesia: 2 patients with peroneal nerve palsy due to compression below the knees by operating room table supports; 1 patient with an irreversible lesion of the right recurrent laryngeal nerve secondary to prolonged intubation and central venous catheterization; and 1 patient with a reversible lesion of the left brachial plexus secondary to inadvertant hyperextension of the upper extremity on the O.R. table due to the need for dialysis and catheterization of the axillary vein for veno-venous bypass. Nine of fourteen (9/14, 64.2%) of patients with CNS lesion died. In five of the nine patients (55.5%) who died with CNS lesion, the neurologic lesions (CNS hemorrhage and anoxic-isquemic injury) were directly or indirectly responsable for death. Strict control of patient positioning in the operating room, arterial hypertension and coagulation disturbance in the immediate postoperative period and serum cyclosporine A levels would eliminate the majority of neurologic complications in patients undergoing liver transplantation.     

Neurological complications of liver transplantation

We examined 199 consecutive patients who underwent 220 liver transplantations, to define the type, frequency and aetiology of posttransplant neurological complications and their prognostic value. We found neurological complications in 63 patients (32%), mostly involving the central nervous system. The most frequent complications were mental status changes ranging from delirium to coma and seizures. The aetiology was multifactorial, cyclosporin A neurotoxicity being the main cause. Patients with neurological complications had a higher mortality rate than those without. In our series, neurological complications represented a major medical problem with increased morbidity and mortality.     

Neurological complications in liver transplantation

To define the incidence and type of neurological complications and associated factors, we reviewed 41 consecutive patients who had 45 procedures for liver transplantation. Encephalopathy occurred after 28 procedures (62%) with immediate onset and no significant recovery before death or re-transplantation in 11 (24%), slow recovery in eight (18%) and delayed onset (1-50 days, average 11) in six (13%). Intermittent confusion and agitation with full recovery followed three (6.6%), and focal and generalized seizures followed five (11%) procedures with multifocal myoclonus in two and status epilepticus in one; isolated focal seizures followed two and myoclonus or unclassified seizures, one each. All patients with seizures had encephalopathy. Three patients had neuropathy (2 generalised and 1 focal). Other complications included headache (2), tremors (2), fatigue (2), restlessness, nervousness, transient enuresis, intermittent dizziness, critical illness myopathy and detached retina. Brain imaging showed atrophy in three (6.6%) instances, intracerebral haemorrhage in two, multiple infarctions in one, and intracerebral and subarachnoid haemorrhage with infarction in one. Cerebrospinal fluid analysis showed increased protein in three, hemorrhage in one, and no abnormality in one patient. Of 12 patients (29%) who died before discharge, five in the first and three in the second week post-transplantation, 11 (92%) had encephalopathy post-operatively. Neurological complications after transplantation were associated with increased mortality. Post-operative hypomagnesaemia was associated with the development of nervous system complications. We did not identify any clear pre-operative predictors of development of post-operative neurological complications.     

DA至Lewis大鼠肝移植急性排斥反应模型的建立：技术改良分析*☆

背景：国际上研究肝移植免疫耐受的基础动物模型是大鼠肝移植急性排斥反应模型,国际上公认的肝移植急性排斥反应模型鼠种配对方式为DA至Lewis大鼠、DA至BN大鼠及BN至Lewis大鼠,但由于鼠种缺乏和操作技术有待成熟的原因,国内较少引用以上鼠种配对方式进行该模型的建立。 目的：课题组在大量SD大鼠肝移植模型建立训练的基础上,采用DA大鼠为供体,Lewis大鼠为受体,摸索DA至Lewis大鼠肝移植急排模型建立技巧和经验。 方法：通过改良二袖套法,以雄性DA大鼠为供体,雄性Lewis大鼠为受体,建立原位肝移植动物模型60只,受体大鼠术前1 d和术后1周内饲喂治疗剂量的他克莫司,1周后半量递减并停药,记录移植手术时间,观察受体大鼠的术后生存状况、手术成功率及生存期,分别于术后7,14,21,28 d处死受体大鼠,获取肝组织标本,苏木精-伊红染色,观察肝脏大体和镜下的病理学变化,进行急性排斥反应评分。 结果与结论：供肝冷缺血时间30~60 min,供体手术时间(18.5±4.0) min,供肝修整时间(7±3) min,受体手术时间(35.0± 7.3) min,无肝期为(13.0±3.0) min,手术成功率为98%,1周存活率为91.6%。术后2周随着他克莫司撤药,受体大鼠迅速发生急性排斥反应,于术后14~28 d死亡,平均生存时间为(20.85±0.71) d,中位生存时间为21 d。实验建立DA至Lewis大鼠肝移植急性排斥反应动物模型需要以大量SD大鼠肝移植训练为基础进行,通过对二袖套法技术的改良和围手术期短期应用他克莫司有助于该模型的稳定建立。     

Neuromuscular complications associated with liver transplantation

We studied neuromuscular complications in a cohort of 520 patients with liver transplantation. Perioperative mononeuropathy developed in 9 patients. The peroneal nerve, radial nerve, and cutaneous branch of the femoral nerve were affected in 2 patients each. Two patients had herpes zoster-associated radiculopathy, and 1 patient had Horner's syndrome. Recovery was good in most patients. In 7 patients, severe quadriplegia complicated the perioperative course. In 5 patients, electrophysiologic studies suggested acute necrotic myopathy, and muscle biopsy specimens showed evidence of rhabdomyolysis in 1 patient. Outcome in survivors was good, all recovering completely. We conclude that neuromuscular complications in liver transplantation are uncommon (less than 1%) and do not significantly contribute to morbidity. Mononeuropathies may have iatrogenic perioperative causes, and rhabdomyolysis may be an important cause of generalized muscle weakness after liver transplantation. © John Wiley & Sons, Inc.     

Neurologic complications of pediatric liver transplantation

The neurologic complications of 24 children, ages 5 months to 18 years, following orthotopic liver transplantation at the Indiana University hospitals are reported. Biliary atresia (14 patients) was the most common cause for orthotopic liver transplantation. Three children died. Seventeen children (70%) had no neurologic deficit on follow-up 6 months or longer after transplantation. Eleven children (46%), including 4 of 16 patients (25%) who had received OKT3, had neurologic complications. Seven children (29%) had newonset seizures; 4 of these patients had status epilepticus. Two children had intracranial hemorrhage. Seizures occurred later in children than in adults following orthotopic liver transplantation and were not associated with poor prognosis. Longer term follow-up is indicated to assess subtle, cognitive deficits following liver transplantation in children.     

Neurological complications following liver transplantation.

Neurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerebellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra- and postoperative management may have contributed to the decreased incidence of neurological complications.