Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis

PLOS ONE, Dec 2019

Background Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Patients and Methods Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. Results During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Conclusions Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

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Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis

October Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis Kuang-Lin Lin 0 1 Jainn-Jim Lin 0 1 Shao-Hsuan Hsia 0 1 Min-Liang Chou 0 1 Po- 0 1 Cheng Hung 0 1 Huei-Shyong Wang 0 1 CHEESE Study Group 0 1 0 1 Division of Pediatric Neurology, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, 2 Chang Gung Children's Hospital Study Group for Children with Encephalitis/Encephalopathy Related Status Epilepticus and Epilepsy (CHEESE), Taoyuan, Taiwan, 3 Division of Pediatric Critical Care and Emergency Medicine, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, 4 Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine , Taoyuan , Taiwan 1 Editor: Giuseppe Biagini, University of Modena and Reggio Emilia , ITALY - Funding: The work was supported by grants from Chang Gung Memorial Hospital (grant: CMRPG4C0022), Taiwan(https://www.cgmh.org.tw/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Background Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Patients and Methods Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic Competing Interests: The authors have declared that no competing interests exist. Introduction Encephalitis is a common central nervous system disorder in children. It refers to inflammation and swelling of the brain often caused by either a direct viral infection or an immunemediated process. It is an important cause of acute symptomatic seizures and subsequent epilepsy [1–3]. Previous epidemiologic studies have shown that 2.7–27% of epilepsies are secondary to previous central nervous system infections [4–7]. Encephalitis-related seizures may present as a single seizure or as refractory status epilepticus, or even intractable epilepsy. But few studies have reported on the efficacy and choice of antiepileptic drugs for acute seizures, chronic seizures and epilepsy in children. Acute central nervous system infections are most often evidenced in the first episode of status epilepticus and appear to be markers for morbidity and mortality [8]. Based on the underlying risk factors, optimal treatment should be given to minimize brain damage in the acute phase. If management is not initiated promptly, refractory status epilepticus may develop, with subsequent progression to intractable epilepsy. Postencephalitic epilepsy has been reported to become intractable in 40–50% of children [9,10]. This study, therefore, aimed to report clinical experience on the use of antiepileptic drugs in the management of acute and chronic seizures in children with encephalitis. The outcomes were analyzed after at least one year of follow-up. All case records from the Department of Pediatrics, Chang Gung Children’s Hospital coded with the discharge diagnosis of acute encephalitis from January 2000 to December 2010 were reviewed. Encephalopathy was defined as at least one symptom or sign of parenchymatous brain dysfunction such as altered consciousness, personality or behavioral change, seizure, paresis, or ataxia. Encephalitis was defined as the presence of encephalopathy plus at least two of the following: (1) body temperature >38°C; (2) cerebrospinal fluid examination showing increased protein content >40 mg/dL and/or pleocytosis >5 white blood cells/uL; (3) abnormal electroencephalography (EEG) find (...truncated)


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Kuang-Lin Lin, Jainn-Jim Lin, Shao-Hsuan Hsia, Min-Liang Chou, Po-Cheng Hung, Huei-Shyong Wang, CHEESE Study Group. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis, PLOS ONE, 2015, 10, DOI: 10.1371/journal.pone.0139974