Abstracts

Rationale: TACROLIMUS (FK506; TAC) is an effective immunosuppressive agent for the prevention of organ transplant rejection. Although neurotoxicity and seizures of TAC has been well documented, the propensity for status epilepticus has only been described in a few isolated case reports. We examined a series of five patients being treated with TAC with therapeutic blood levels, who suffered from focal or diffuse, convulsive or non-convulsive status epilepticus (SE), both acutely and chronically post transplant Methods: Five cases of SE identified by EEG over the past 2 years were noted to occur in the setting of TAC-based immunosuppressive treatment after organ transplants. We reviewed clinical presentation and other data to evaluate for patterns or additional variables that might yield insight into those potentially at risk for SE. Results: Three patients underwent liver transplant, one heart transplant, and another bilateral lung and heart transplant. Blood TAC levels were 6.1-20.9 ng/ml (Reference:3-20 ng/ml). Brain MRI in all patients showed no evidence of TAC-induced leukoencephalopathy. In three cases, focal SE occurred in the acute post transplant period. In one patient, seizures started 10 months prior to the transplant, in the region of a prior right middle cerebral artery watershed infarct. SE occurred after tapering phenytoin, while on TAC and 3 antiseizure agents. In the remaining case, SE occurred 2 years after initiating TAC, and in the setting of pneumonia treated with a fluoroquinolone. Four patients had focal SE, one of which progressed to generalized convulsive SE. Another patient was identified to be in generalized nonconvulsive SE from the start of EEG recording. Four patients were changed to cyclosporine and one to mycophenolate mofetil. Following the transition from TAC, four patients became seizure free (as of 2-13 month follow up). Three patients remained on antiseizure monotherapy, and one self discontinued medication after 10 months. However, the patient with post infarct epilepsy continued to experience partial seizures flare ups every 3-4 months. Conclusions: In addition to isolated seizures, patients treated with TAC can at times present, in both acutely or chronically post transplant, with an aggressive seizure patterns, manifested as status epilepticus, even in the absence of over dosage. Although our series is too small to draw strong conclusions, identification of a focal pattern in 4 or 5 patients raises the possibility that TAC-induced leukoencephalopathy or other focal injury might occur below the resolution of detection with 1.5 T brain MRI. Not unexpectedly, additional risk factors for seizures including use of other medication known to lower the seizure threshold, and pre-existing symptomatic localization-related epilepsy (post infarct epilepsy) may also increase risk for TAC-induced status epilepticus. In this series, all patients appeared to benefit from transition to an alternative immunosuppressant. We propose that status epilepticus should be considered in patients treated with TAC who develop unexplained focal neurological deficits or present with encephalopathy.