New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

Abstract

Purpose: To identify the probable etiologies and characteristics of new-onset seizures after orthotopic liver transplantation (OLT) and to assess their clinical implications and prognosis. Methods: We retrospectively analyzed the clinical, electrophysiologic and laboratory data of 17 patients with new-onset seizures after OLT among 367 adult and pediatric patients who underwent OLT between 1999 and 2001. Results: A suspected etiology of seizures was identified in most patients, including 6 (35.2%) with neurotoxicity due to immunosuppressive therapy, 4 (23.5%) with cerebrovascular disease, 3 (17.6%) with severe metabolic derangement by sepsis or rejection, and 1 each (5.8%) with hyperglycemia and brain edema due to fulminant hepatic failure. Causative factors could not be identified in 2 patients (11.8%). Seizures recurred in 15 patients (88.2%), with 9 occurring on the same day as the original seizure. Attacks caused by neurotoxicity tended to have an earlier onset, within 1 week in 4 of 6 patients, than those caused by cerebrovascular disease and sepsis/rejection, but this was not statistically significant. A total of 21 EEGs were performed in 13 patients. Eleven patients had abnormal EEG findings, of whom 4 (30.7%) showed epileptiform discharges, but the outcome of patients with epileptiform activity did not differ statistically from that of patients without such discharges (p > 0.6). The incidence of poor outcome (death or persistent vegetative state) in the group with seizures was almost 10 times higher than in the group without seizures (52.9 vs. 5.7%, p < 0.001). The prognosis of patients with seizures due to cerebrovascular disease and severe metabolic derangement by sepsis/rejection was poorer than that of patients with seizures caused by the neurotoxicity of immunosuppressive drugs (p < 0.02), suggesting that the underlying cause of seizures is important in determining prognosis. Of 8 patients who survived, 1 was lost to follow-up. The long-term outcome of seizures in surviving patients was excellent, with all survivors available for follow-up being seizure-free for a mean follow-up of 42.5 months (range, 16–58 months). Conclusion: New-onset seizures after OLT may herald fatal outcome, especially in patients with cerebrovascular disease or sepsis. The prognosis of seizures in survivors is excellent, and long-term antiepileptic drugs are not required in most cases.

Seizure as a Neurologic Complication After Liver Transplant

“…6,7 Only 1 study reported a higher frequency of partial seizure. 9 The determination of seizure type is based on clinical observations and electroencephalography findings when available. It is difficult to determine the true incidence of focal and secondary generalized seizures because they can easily be overlooked.…”

“…10 Seizure in LT patients typically occurs in the early postoperative period. 6,9 One study described a bimodal distribution of seizure occurrence: within the first week and between 5 and 16 weeks after transplant. 6 We did not observe a bimodal distribution in the present series, but the majority of our patients experienced seizures within the first 4 weeks after LT.…”

“…Various factors such as immunosuppressive drug toxicity, metabolic factors, infection, and structural lesions may precede seizure in LT patients. 6,9,11 The diagnostic evaluations should consist of extensive examinations including blood tests for metabolic parameters and immunosuppressive drug levels, electro encephalography, and neuroimaging to accurately identify the underlying factor(s). 7 Brain magnetic resonance imaging is the recommended modality to assess for structural abnormalities that cause seizure as in the general population.…”

“…7 Immunosuppressive drug toxicity is the main causative factor in the literature describing seizure in LT patients. 6,7,9,11 Immunosuppressive drug-related seizures may occur independently or in association with posterior reversible leukoencephalopathy syndrome, even in patients on therapeutic drug levels. 12,13 In these patients, reducing the dosage or changing drugs are the recommended treatment approaches.…”

Sirolimus-induced drug fever and ciclosporin-induced leukencephalopathia with seizures in one liver transplant recipient

“…Both patients were on sirolimus and ciclosporin after orthotopic liver transplantation and stabilized after withdrawal of ciclosporin. Choi et al [11] reported that of the 367 patients who received OLT, 48 suffered from neurological complications, 17 …”