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
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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)