EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Cardiac transplant is the best available therapy for patients with end-stage heart failure. Neurologic complications occur at a rate of 30% to 70% in patients undergoing cardiac transplant, and they affect mortality and morbidity of these patients. Risk factors for neurologic complications include immunosuppressive medication toxicity, infections, brain lesions, and metabolic disorders. The aim of our study was to determine the incidence of neurologic complications in adult patients undergoing cardiac transplant.

Materials and Methods: We retrospectively evaluated the medical records of 70 patients who underwent cardiac transplant between 2004 and April 2016. We recorded the demographic data, neurologic symptoms, neurologic examination findings, laboratory test results, brain imaging study results, and treatments received of the patients.

Results: Of the 70 patients enrolled, 55 were male and 15 were female patients. The age range was 18 to 63 years, and the mean age was 42.4 years. Twelve patients had encephalopathy, 4 had neuropathic pain, 3 had tremor, 2 had ischemic cerebrovascular accident, 7 had posterior reversible encephalopathy syndrome, and 1 had drop foot. Encephalopathy usually developed secondary to other neurologic disorders. The incidence of neurologic complications in adult patients undergoing cardiac transplant was 30%.

Conclusions: Neurologic complications are common after cardiac transplant. We observed an incidence of 30% for neurologic complications in our clinic, with encephalopathy being the most common complication. Encephalopathy most commonly developed secondary to posterior reversible encephalopathy syndrome.

Key words : Immune suppressant treatment, Encephalopathy, Cardiac transplants

Cardiac transplant is the best available therapy for patients with end-stage heart failure.¹ Neurologic complications are the primary cause of mortality and morbidity in patients undergoing cardiac transplant.² The incidence of neurologic complications ranges between 30% and 70% after cardiac transplant.^3,4 Because adult patients who are candidates for cardiac transplant have an increased prevalence of vascular risk factors, including hypertension, smoking, diabetes, obesity, and hypercholesterolemia, neurologic complications occur more commonly in these procedures compared with other transplant procedures.¹ The most common complication of cardiac transplant in adults is ischemic stroke. Others include hemorrhagic stroke, encephalopathy, neuropathy, and adverse effects associated with prolonged steroid use. The latter may lead to serious toxicity, encephalopathy, posterior reversible encephalopathy syndrome (PRES), infection, and malignancy. Children undergoing cardiac transplant have an increased incidence of seizure compared with other neurologic complications.¹

Materials and Methods

We retrospectively evaluated the medical records of 70 patients who underwent cardiac transplant between 2004 and April 2016 at Baskent University Hospital. We recorded demographic data, immunosuppressive treatment, seizure type, cause, recurrence, and treatment. Patients aged 18 years or older were considered adults. Each patient’s age, sex, seizure history, neurologic study results, immunosuppressive medication use, multidrug use, immunosuppressive agent blood levels, biochemical and complete blood count parameters, and, if available, electroencephalogram and brain imaging results were collected.

Statistical analyses
Statistical analyses were performed with SPSS software (version 16.0 for Windows, SPSS, Inc, Chicago, IL, USA). Data are expressed as number and percent for categorical variables.

This study included 70 adult patients who underwent cardiac transplant at our transplant center. Their ages ranged from 18 to 63 years old, with mean age of 42.4 years. Fifty-five patients were male and 15 were female (Table 1).

Twelve patients developed encephalopathy, 8 had seizures, 4 had neuropathic pain, 3 had tremors, 3 had ischemic cerebrovascular accident, 7 had PRES, and 1 had drop foot. The cause of seizures was PRES in 3 patients, ischemic stroke in 2, metabolic disorder in 2, and hypoxic brain in 1. Seven of the encephalopathy cases were secondary to PRES, 3 were secondary to cerebrovascular accident, and 2 were secondary to metabolic disorders (Table 2). Epileptic seizures were secondary to other complications, of which PRES was most common. Immunosuppressive medications were the most common cause of PRES.

Encephalopathy may occur secondary to many causes; in our patients, it occurred at a rate of 17.1% (n = 12 patients). Posterior reversible encephalopathy syndrome was the most common cause of encephalopathy. The cause of PRES was immunosuppressive medications in most patients (Table 3).

Seizures and encephalopathy developed secondary to other neurologic complications except for 2 patients who developed these conditions due to metabolic disorders. When this occurrence was taken into account, the overall incidence of neurologic complications was 30%.

Cardiac transplant prolongs survival and improves quality of life of patients with end-stage heart failure. Its complications, however, significantly contribute to mortality and morbidity rates in these patients. Neurologic complications markedly increase mortality and morbidity in cardiac transplant recipients.⁴

Studies conducted so far have reported that neurologic complications occur at a rate of 30% to 70%.^1-6 At our center, the corresponding rate was 30%. Encephalopathy was the most common neurologic complication in our study. It was most common in patients with PRES, which is characterized by white and gray matter abnormalities in occipital, parietal, and temporal lobes of the brain. It may occur secondary to immunosuppressive medications, renal failure, and hypertension. Its clinical signs may include seizure, headache, and intracranial hemorrhage. Blood pressure control and tailored immunosuppressive therapy are recommended for its treatment.⁷ In our study, PRES developed secondary to the use of immunosuppressive medications.³

Immunosuppressive medications may lower epileptic threshold and cause PRES, infections, and some malignancies. Despite all of these serious adverse effects, these medications are nevertheless indispensable to prevent organ rejection.¹ Novel immunosuppressive medications prolong survival, but they also increase the risk of neurologic complications. We observed stroke as the second most common complication. Acampa and associates reported that ischemic stroke occurred at a rate of 13% and hemorrhagic stroke at a rate of 2.5% after cardiac transplant. They categorized stroke into perioperative and postoperatively stroke subtypes. They found that 40% of strokes were cryptogenic. We observed no hemorrhagic stroke but observed 2 ischemic strokes in our study. One of them occurred at the perioperative period, and the other occurred long after the procedure.8 Heroux and associates reported that ischemic stroke was the most common early complication.¹ Munoz and associates reported that neurologic complications occurred in 19% of their patients. Ischemic stroke constituted 32% of all neurologic complications.² We observed neuropathic pain in a total of 4 patients. The patients developed neuropathic pain after zona zoster infections. All patients were administered pregabalin at 75 mg/day, and it became necessary to increase the dose to 150 mg/day in 1 patient. The use of immunosuppressive medications resulted in a tendency for zona zoster infection in our patients. Heroux and associates found that histories of hypertension, type 2 diabetes mellitus, hyperlipidemia, obesity, and hypercholesterolemia were risk factors for ischemic stroke and peripheral neuropathy.¹

Munoz and associates reported that neuropathic pain contributed to 11% of all neurologic complications.² Fernandez and associates detected neuropathy occurring at a rate of 6.4% after liver transplant.¹⁰

One patient suffered peripheral nerve injury due to nerve compression, which was treated by anti-inflammatory drugs and vitamin B. Tremor was present in 3 of our patients. In particular, calcineurin inhibitor immunosuppressive medications may be responsible for the development of neuropathy and tremor.⁹ Fernandez and associates observed tremor in 3.2% of their study subjects.¹⁰ In our population, tremor was not too severe to affect daily life activities of our patients, and therefore no treatment was started.

Neurologic complications require clinical attention after cardiac transplant. Encephalopathy was the most common neurologic complication observed in our clinic. Posterior reversible encephalopathy syndrome was the most common cause of encephalopathy. Immunosuppressive medications were responsible for PRES.

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