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ARTICLE
Epilepsy After Heart Transplant: A Single Center Experience

Objectives: Cardiac transplant is the best treatment for patients with end-stage heart failure. Neurologic complications occur at a rate of 30% to 80% in patients undergoing cardiac transplant. Seizures occur at a rate of 2% to 20%. The main causative factors include immunosuppressant drug toxicity, infections, brain lesions, and metabolic disorders. Here, our aim was to determine seizure types and associated conditions in patients undergoing cardiac transplant and to report our treatment experience at our institution.

Materials and Methods: We retrospectively evaluated the medical records of 109 patients who underwent cardiac transplant between 2004 and 2016. We recorded demographic data, immunosuppressive treatment, seizure type, cause, recurrence rate, and treatment.

Results: Of 109 patients, 13 had seizures after cardiac transplant. Our study involved 69 adult and 40 pediatric patients. The pediatric patients had an age range of 1 to 17 years, with a mean age of 9.6 years (22 female and 18 male patients). Five pediatric patients had seizures (4 female and 1 male patient). The seizure causes included 2 postarrest hypoxic encephalopathies and 3 posterior reversible encephalopathies. Adult patients ranged from 18 to 63 years old, with a mean age of 42.3 years (54 male and 15 female patients). Eight patients in the adult patient group had seizures (5 female and 3 male patients). Seizure causes were ischemic cerebrovascular events in 2 patients, metabolic disorders in 2, posterior reversible encephalopathies in 3, and postarrest hypoxic brain in 1.

Conclusions: Seizure is an important complication after cardiac transplant. At our institution, the most common cause of seizure was posterior reversible encephalopathy, with immunosuppressant drugs being responsible.


Key words : Adult patients, Pediatric patients, Seizure, Solid-organ transplantation

Introduction

Cardiac transplant is the best therapy for end-stage heart failure patients.1 Neurologic complications are important causes of morbidity and mortality in patients undergoing cardiac transplant.2 Neurologic complications affect 30% to 70% of patients, and they usually occur during the perioperative period.3,4 Among all neurologic complications, seizure has a rate of 2% to 20%. The main risk factors for seizures include medication toxicity, infections, brain lesions, and metabolic disorders.5 In this study, our aim was to determine types of and conditions associated with seizures, focusing on our center’s treatment experience with seizure in pediatric and adult age groups.

Materials and Methods

We retrospectively evaluated the medical records of 109 patients who underwent cardiac transplant between 2004 and 2016 at Baskent University Hospital. We recorded demographic data, immuno­suppressive treatment, seizure type, cause, recurrence, and treatment. All age groups were included in our study. Patients between 1 and 17 years old were considered to be in childhood, and those above 18 years old were considered as being in adulthood. Age, sex, seizure history, neurologic examination, immunosuppressant and multiple medication use, serum immunosuppressant drug level, biochemical and hematologic parameters, and electroencephalographic and brain imaging studies were recorded and analyzed. Seizure treatment medications and response were also recorded. For heart transplant patients, the immunosuppressive medications initially consisted of steroids, cyclo­sporine, and azathioprine, as well as mycophenolate mofetil.

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

Results

Among 109 patients, 13 patients (11.9%) had seizures after cardiac transplant. Our study involved 69 adult patients (63.3%) and 40 pediatric patients (36.7%). Pediatric patients ranged from 1 to 17 years old, with a mean age of 9.6 years. In the pediatric group, 22 patients (55%) were female and 18 (45%) were male. Adult patients ranged from 18 to 63 years old, with a mean age of 42.3 years. Fifty-four patients were male (78.2%) and 15 were female (21.8%) (Table 1). Five patients in the pediatric age group had seizure episodes (4 females and 1 male). Eight patients in the adult group had seizure episodes (5 female and 3 male) (Table 2).

The seizure episodes in the pediatric group included 2 generalized tonic clonic convulsions, 1 complex partial seizure, and 2 generalized myoclonic seizures. In the adult age group, 4 patients had generalized tonic clonic convulsions, 1 had a complex partial seizure, 2 had generalized myoclonic seizures, and 1 had status epilepticus (Table 3). Generalized tonic-clonic seizures were observed 2 months after transplant, accepted as a late-term complication. Focal motor seizures were seen after 6 months, also accepted as a late-term complication. Generalized myoclonic seizures and status epilepticus were seen as early postoperative complications.

For patients in our study considered as being in childhood, generalized myoclonic convulsions occurred due to postarrest hypoxic encephalopathy. In the other patients, seizure cause was posterior reversible encephalopathy syndrome (PRES). Among patients in the adult group who had generalized tonic clonic convulsion, 1 had ischemic cerebro­vascular accident and 3 had PRES. One adult patient with complex partial seizure had ischemic cerebro­vascular accident, 2 adult patients with generalized myoclonic seizure had metabolic disorders, and 1 adult patient with status epilepticus had postarrest hypoxic brain (Table 4).

In the 2 patients with metabolic disorders, development was due to acute renal failure, which occurred after sepsis. For the other patients, complete blood count, liver and kidney function tests, and electrolytes were within normal levels.

Posterior reversible encephalopathy syndrome was found in 6 patients, with 4 having high levels of immunosuppressive agents. In others, immuno­suppressant drug levels were within normal ranges.

Seizure treatment included carbamazepine for complex partial seizure in 1 pediatric patient and levetiracetam in all other pediatric patients. Leveti­racetam also controlled seizures in 7 adult patients. Status epilepticus in 1 patient was sup­pressed by diphenylhydantoin followed by levetiracetam.

Discussion

Cardiac transplant has prolonged life and improved quality of life in patients with end-stage heart failure. Complications, however, play an important role in morbidity and mortality of patients. Neurologic complications markedly increase mortality and morbidity.4 Preventing complications, such as immunosuppressant drug toxicity, can boost quality of life of patients. Seizure is a common complication after cardiac transplant.1

Studies so far have reported rates of seizure episodes ranging between 2% and 20% after cardiac transplant.2,4,6,7 The corresponding rate at our health center is 13%. No significant difference was observed between adult and pediatric age groups with respect to the rate of seizure episodes.

Many factors may affect the rate of seizure in patients undergoing cardiac transplant. Toxicity of immunosuppressant medications, space occupying brain lesions, metabolic disorders, and posthypoxic encephalopathy may result in seizure episodes.8 A comparison of seizure causes between pediatric and adult age groups revealed that PRES secondary to the use of immunosuppressant medications was more common in pediatric patients, whereas seizure secondary to ischemic stroke was more common among adults. This suggests that seizure is more commonly iatrogenic in the pediatric age group, whereas multiple risk factors (diabetes mellitus, hypertension, atherosclerosis, and so forth) increase the tendency for stroke in adults.

No common treatment algorithm exists for seizure treatment in patients undergoing cardiac transplant. Patient age, seizure characteristics, comorbid conditions, and medications used are important factors when making decisions on seizure treatment. Use of immunosuppressant medications at effective doses is mandatory and vital in patients undergoing cardiac transplant. Medications meta­bolized in the liver may interact with immuno­suppressant medications. On the one hand, reduced immunosuppressant medication levels may lead to organ rejection, with elevated medication dose perhaps resulting in life-threatening neurologic complications such as PRES on the other hand. Lin and associates preferred use of levetiracetam after hepatic transplant due to it having fewer drug interactions. Levetiracetam was found to be effective for seizure suppression, and no need arose for changing immunosuppressant medication doses before and after levetiracetam administration.9 Levetiracetam was also commonly used in conjunction with other antiepileptics and successfully achieved seizure suppression. Diphenylhydantoin (1000 mg/d) was included for status epilepticus in 1 patient, and levetiracetam was added when the former failed to suppress seizure activity. None of the patients died from seizure episodes. Seizure control was achieved in all patients. No seizure recurrence was seen during follow-up with the use of dual antiepileptic medications, and there was no need to increase immunosuppressant levels. Carbamazepine success­fully suppressed focal motor seizure in 1 patient, and there appeared to be no need for changing the immunosuppressive drug dose.

Conclusions

Seizures are an important complication after cardiac transplant. Posterior reversible encephalopathy syndrome was the most common causative factor for seizure episodes at our center. Immunosuppressant medications were found to be responsible for PRES. Seizure suppression was generally achieved by levetiracetam, and no need arose for changing immunosuppressant medication doses in patients receiving antiepileptic treatment.


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DOI : 10.6002/ect.2016.0047


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From the Departments of 1Neurology, 2Pediatric Neurology, and 3Cardiovascular Surgery, Baskent University Hospital, Ankara, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Ruhsen Öcal, Baskent University Neurology Department, Fevzi Çakmak Cad, 10. Sok, no: 45, Bahçelievler, Ankara, Turkey
Phone: +90 505 442 3227
E-mail: ruhsenocal@yahoo.com