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.     

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 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 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.     

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.     

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.     

Cerebrovascular reactivity and vasospasm after subarachnoid hemorrhage: a pilot study

The authors performed serial transcranial Doppler (TCD) and carbon dioxide reactivity (CO2R) testing in 20 aneurysmal subarachnoid hemorrhage patients to determine whether impaired cerebrovascular reactivity was associated with symptomatic vasospasm. Symptomatic vasospasm occurred in 9 of 14 patients with abnormal CO2R and in none of 6 patients with preserved reactivity (p = 0.011). Abnormal CO2R preceded the onset of vasospasm in 7 of 9 patients. Abnormal standard TCD testing was not associated with vasospasm.     

Medical complications after stroke: a multicenter study

BACKGROUND AND PURPOSE: This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. METHODS: We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. RESULTS: Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. CONCLUSIONS: Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.     

Neurologic complications after heart transplantation

OBJECTIVE: Neurologic complications are known as important cause of morbidity and mortality in orthotopic heart transplantation. Our aim was to identify the frequency and outcome of neurologic complications after heart transplantation in a prospective observational study. METHOD: From September 93 to September 99, as part of our routine heart transplantation protocol all patients with end-stage cardiac failure were evaluated by the same neurologist before and at the time of any neurologic event (symptom or complaint) after transplantation. RESULTS: Out of 120 candidates evaluated, 62 were successfully transplanted (53 male; median age 45.5 years, median follow-up 26.8 months). Fifteen patients (24%) had ischemic, 22 (35%) idiopathic, 24 (39%) Chagas' disease and 1 (2%) had congenital cardiomyopathy. Neurologic complications occurred in 19 patients (31%): tremor, severe headache, transient encephalopathy and seizures related to drug toxicity or metabolic changes in 13; peripheral neuropathy in 4; and spinal cord compression in two (metastatic prostate cancer and epidural abscess). No symptomatic postoperative stroke was observed. CONCLUSIONS: Although frequent, neurologic complications were seldom related to persistent neurologic disability or death. Most of the complications resulted from immunosuppression, however, CNS infection was rare. The absence of symptomatic stroke in our series may be related to the lower frequency of ischemic cardiomyopathy.     

Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial.

Severe intraoperative bleeding is one of the main problems during liver transplantation. Acquired hemostatic defects, namely primary or secondary hyperfibrinolysis, are considered significant pathogenetic events. Antithrombin III (ATIII), the main physiological serine protease inhibitor, has a critical role in the regulation of hemostasis. 29 patients with post necrotic cirrhosis undergoing liver transplantation were randomized to receive or not ATIII replacement therapy before the induction of anaesthesia and thereafter throughout surgery. Activation of both coagulation and fibrinolysis (increase of thrombin-antithrombin complexes, fibrin and fibrinogen degradation products) were demonstrated in both groups. Blood loss and transfusion requirements were not affected by ATIII administration.