• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.81-88
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• 2020

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, realtime reverse transcriptase-polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.

• Annals of Clinical Neurophysiology
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• v.2 no.2
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• pp.119-124
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• 2000

Background : We studied EEG changes during pilocarpine-induced status epilepticus(SE), a widely used model whose EEG characteristics have not been fully described previously. Methods : Male Sprague-Dawley rats weighing 250-350 grams were used as subjects. SE was induced 5-7 days after placement of chronic epidural electrodes, using 360-380 mg/Kg pilocarpine IP. Rats were observed with continuous EEG recording following pilocarpine injection until end of the SE episode. Results : SE occurred in 10/12 rats studied. SE began with a series of discrete seizures $11.1{\pm}3.93$ minutes after pilocarpine injection. $5.2{\pm}2.71$ seizures occurred over $10.9{\pm}4.62$ minutes, until the EEG converted to a waxing and waning pattern, during which the amplitude and frequency of epileptiform activity increased. After $1.4{\pm}1.82$ minutes, a pattern of continuous high amplitude rapid spiking was established. Continuous spiking continued for $3.4{\pm}0.48$ hours with a very gradual decline in amplitude and frequency, until periodic epileptiform discharges(PEDs) began to occur. The EEG consisted primarily of PEDs for another $7.4{\pm}3.09$ hours, until electrographic generalized seizures began to occur. These continued for $5.8{\pm}4.82$ hours until death. Duration of SE was $17.0{\pm}5.88$ hours. Flat periods were a prominent feature during all EEG patterns in this model. Conclusion : EEG features distinctive in pilocarpine SE(but not unique to it) include flat periods during all patterns and resumption of continuous spiking episodes after the onset of PEDs. The sequence of discrete seizures to waxing and waning to continuous spiking to PEDs was identical to that which has been described in humans and other animal models.

• Clinical and Experimental Pediatrics
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• v.59 no.1
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• pp.35-39
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• 2016

Purpose: This study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS). Methods: The medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained. Results: The records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10-20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50). Conclusion: Intravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV.

• Annals of Clinical Neurophysiology
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• v.5 no.2
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• pp.171-176
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• 2003

Backgrounds and Objectives: Despite of enormous clinical and laboratory researches focused on the useful markers in status epilepticus(SE), clinically applicable methods are not yet available. Although ketogenic diet (KD) is an old method of treating epilepsies, its outstanding antiepileptic effect in some epileptic patients needs re-evaluation of this methods. This study was performed to evaluate the effect of KD on the change of nitric oxide(NO) during the SE. Methods: After the determination of critical EEG stages in the pilocarpine-induced SE model, serum NO levels were measured with Griess reaction. Open cardiac puncture was done immediately after the four different EEG stages of SE in the KD rats and regular diet (RD) rats. Cessation of SE was done with the 10~20 mg/Kg of diazepam i.p. injection in each stages of SE in KD and RD rats. Results: Pilocarpine-induced SE showed reliable EEG and behavioral patterns in all rats. Also, KD did not affect the SE induced by pilocarpine in terms of the SE induction time and SE severity. Serum NO was consistently higher in KD rats than RD rats in all SE stages. Conclusions: KD significantly increases NO during the pilocarpine-induced SE. These finding might contribute the neuroprotective effect of KD in the SE.

• Clinical and Experimental Pediatrics
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• v.62 no.7
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• pp.281-285
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• 2019

Purpose: To evaluate the association between elevated S100B levels with brain tissue damage seen in abnormalities of head magnetic resonance imaging (MRI; diffusion tensor imaging [DTI] sequence) in patients with status epilepticus (SE). Methods: An analytical observational study was conducted in children hospitalized at Dr Soetomo Hospital, Surabaya, from July to December 2016. The patients were divided into 2 groups: SE included all children with a history of SE; control included all children with febrile seizure. Blood samples of patients were drawn within 24 hours after admission. SE patients also underwent cranial MRI with additional DTI sequencing. The Mann-Whitney test and Spearman test were used for statistical analysis. Results: Fifty-three patients were enrolled the study. In the 24 children with SE who met the inclusion criteria, serum S100B and cranial MRI findings were assessed. Twenty-two children admitted with febrile seizures became the control group. Most patients were male (66.7%); the mean age was 35.8 months (standard deviation, 31.09). Mean S100B values of the SE group ($3.430{\pm}0.141{\mu}g/L$) and the control group ($2.998{\pm}0.572{\mu}g/L$) were significantly different (P<0.05). A significant difference was noted among each level of encephalopathy based on the cranial MRI results with serum S100B levels and the correlation was strongly positive with a coefficient value of 0.758 (P<0.001). Conclusion: In SE patients, there is an increase of serum S100B levels within 24 hours after seizure, which has a strong positive correlation with brain damage seen in head MRI and DTI.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.281-289
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• 2019

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

• Journal of Neurocritical Care
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• v.11 no.2
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• pp.137-142
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• 2018

Background: New-onset refractory status epilepticus (NORSE) occurs in people without a history of seizures. In these cases, the seizure causes are unclear, and the seizures are not controlled by standard treatment. Autoimmune encephalitis (AIE) can be a cause of NORSE. Cryptogenic NORSE may be associated with AIE, but antibodies associated with the condition have not yet been identified. Primary immunotherapy may not be effective for AIE. Rituximab has improved the prognosis in some cases. Case Report: We treated a cryptogenic NORSE patient with a combination of antiepileptic drugs and immunotherapy. On the 13th hospital day, the seizures were controlled, but the patient remained in a coma. The patient rapidly recovered after administration of rituximab started on the 26th hospital day. Conclusion: Rituximab may be helpful for cryptogenic NORSE patients in whom primary immunotherapy controls seizures, but fails to improve consciousness.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1342-1347
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• 2005

Purpose : Among perinatal risk factors, neonatal seizures are one of the strongest independent discriminators of adverse outcome, representing high risks of mortality and neurologic morbidity. This study was undertaken to evaluate the neurologic outcome of neonatal status epilepticus according to underlying etiology, seizure pattern, onset time, and duration. Methods : We reviewed retrospectively 36 neonates(19 males, 17 females) with status epilepticus who were admitted to the neonatal intensive care unit, Inha Hospital between July, 1988 and June, 2003. They were evaluated with neurologic examination, laboratory data, EEG findings, and neuroimaging studies etc. Results : The mean gestational period of the patients was $37.0{\pm}3.6$ weeks and birth weight was $2.70{\pm}0.82$ kilogram. Fifty two point eight percent of the neonates were male and 66.7 percent were born at term. The most common cause of neonatal status epilepticus was hypoxic-ischemic encephalopathy. In preterm babies, intracranial hemorrhages showed an especially high frequency(P=0.034). Gestational age and birth weight did not show a correlation with neurologic complications. The incidence of neurological sequelae were significantly related to prolonged seizures lasting more than 1 hour(P=0.002). Neonates with seizures within the first 72 hours tended to be more frequent among those who developed adverse outcomes(P=0.016). Generalized tonic seizures had the worst prognosis, whereas those children who had subtle seizures had better outcomes than any other type(P<0.05). Generalized tonic seizures were primarily represented on EEG by abnormal background, whereas subtle seizure showed a significantly more normal EEG than any other seizures(P<0.05). Conclusion : Our results indicate that neonatal status epilepticus with early onsets, prolonged durations. And generalized tonic types can predict an increased risk for neurologic sequelae. So, those seizures must be perceived as medical emergencies and treated aggressively with antiepileptic drugs.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.3
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• pp.294-299
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• 2017

The aim of this study was to detect the status of epilepticus and seizure based on the initial patterns observed in the first 30 minutes of continuous electroencephalogram (cEEG) monitoring. An cEEG was recorded digitally using electrodes applied according to the International 10~20 System. The EEG data were reviewed from January 2014 to December 2015. The baselines of the EEG patterns were characterized by lateralized periodic discharges, generalized periodic discharges, burst suppression, focal epileptiform, asymmetric background, generalized slowing, and generalized periodic discharges with a triphagic wave. The etiology was classified into five categories. The subjects of this study were 128 patients (age: $56.9{\pm}17.5years$, male:female, 74:54). The mean cEEG monitoring duration was $5.5{\pm}5.1$ (min:max, 1:33) days. The EEG pattern categories included lateralized periodic discharges (N=7), generalized periodic discharges (N=10), burst suppression (N=6), focal epileptiform (N=19), asymmetric background (N=24), generalized slowing (N=51), and generalized periodic discharges with a triphagic wave (N=11). The etiological classifications of the patients with status epilepticus were remote symptomatic (N=4), remote symptomatic with acute precipitant (N=9), acute symptomatic (N=6), progressive encephalopathy (N=2), and febrile seizure (N=1). cEEG monitoring was found to be useful for the diagnosis of non-convulsive epileptic seizures or status epilepticus. The seizure was confirmed by the EEG pattern.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2008.05a
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• pp.78-78
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• 2008