Seizure treatment in transplant patients

Abstract

Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neurotoxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and fosphenytoin are the traditional and best evidence-based options, although intravenous levetiracetam, valproate, and lacosamide are emerging options. Availability of several newer AEDs has greatly expanded the therapeutic armamentarium for safe and efficacious treatment of post-transplant seizures, but future prospective clinical trials and pharmacokinetic studies within this specific patient population are needed.

Figure 1

Algorithm for treatment of seizures in transplant patients. Treatment of seizures in transplant patients must take into account the transplanted organ and antirejection comedications so that antiepileptic drugs (AEDs) do not place the transplanted organ at further risk. For single partial-onset or secondary generalized tonic-clonic seizures, investigation for an underlying symptomatic etiology should be promptly undertaken, and treatment may be deferred if a correctable etiology is determined and seizures do not recur. If seizures recur, or when seizure recurrence risk is uncertain or an underlying epileptogenic cause is found, treatment with levetira-cetam or gabapentin should be initiated as appropriate for suspected seizure type. For status epilepticus or acute repetitive seizures, intravenous lorazepam, followed, if necessary, by fosphenytoin should be administered. ABCs airway, breathing, and circulation; BZD benzodiazepine; CSF cerebrospinal fluid; EEG electroencephalography; GBP gabapentin; IV intravenous; LEV levetiracetam.

Figure 2

MRI Findings in posterior reversible encephalopathy syndrome (PRES). A 48-year-old liver transplant patient receiving cyclosporine at toxic levels developed a generalized tonic-clonic seizure. Blood pressure was elevated at 160/90. Cyclo-sporine was held for 2 days, then restarted at a lower dose, and judicious lowering of blood pressure with antihypertensive therapy was administered. Levetiracetam, 500 mg twice daily, was initiated. Shortly following his seizure, brain MRI axial FLAIR images showed hyperintense gyriform signal abnormality in the right more than left posterior temporo-parietal and occipital regions (top row) that nearly completely resolved on repeat imaging 2 months later (bottom row). No further seizures occurred, and levetiracetam was tapered and discontinued.