BACKGROUND: EEG shows a sequence of progressive changes in status epilepticus (SE). Timely antiepileptic drug treatment is an important factor for the prognosis of SE. Here we investigated the effect of treatment according to EEG staging in a lithium-pilocarpine SE rat model. METHODS: By analyzing the on-going EEG of SE, we injected propofol (PF) or propofol and valproate (PF+VA) on each defined EEG stage [early period, merging stage; middle period, continuous stage; late period, early periodic epileptiform discharges stage (ePED)]. We measured the duration of each stage after the treatment and the number of principal cells at three hippocampal areas (CA1, CA3, dentate gyrus] after SE. RESULTS: Both PF- and PF+VA-treated groups showed lower mortality rate in the merging stage-treated subgroup than in ePED-treated subgroup. Seizure duration was significantly shortened in the merging stage of both PF- (p<0.005) and PF+VA-treated groups than in untreated group (p<0.002). The durations of the continuous stage and ePED were shortened in the merging stage-treated subgroup, but ePED duration did not decrease in ePED-treated subgroup. The shortening of the continuous stage and ePED was more prominent in the PF+VA-treated group than in PF-treated group. Neuronal loss in both PF- and PF+VA-treated groups was so severe that CA1 and CA3 neuronal loss was decreased more markedly in the ePED-treated group than in the merging stage-treated group (p<0.01). CONCLUSIONS: Early therapy based on the defined EEG staging might be an effective option for shortening duration of SE and decreasing neuronal damage at the hippocampus. Early combination therapy adopting PF+VA requires further investigation for new treatment option.
Animals ; Electroencephalography ; Hippocampus ; Neurons ; Pilocarpine ; Prognosis ; Propofol ; Rats ; Secondary Prevention ; Seizures ; Status Epilepticus ; Valproic Acid

OBJECTIVETo study and compare the prophylatic efficacy of levetiracetam, valproate and phenobarbital on febrile convulsions in rats.

METHODSSixty Wistar rats were randomly administered with levetiracetam (200 mg/kg), valproate (250 mg/kg), phenobarbital (30 mg/kg) or normal saline (8 ml/kg) for 5 days. Five days later, febrile convulsions were induced by hyperthermal bath (45 Celcius degree). The latency, duration and the severity of seizures were observed.

RESULTSIn all the three drug-treated groups, the latency was significantly prolonged, and the duration and the severity of seizures were notably reduced compared with the saline group (P<0.05 or 0.01). The phenobarbital group had the shortest duration of seizures and the least severe seizures among the three drug-treated groups. There were no significant differences between the levetiracetam and valproate groups.

CONCLUSIONSContinuous administration of levetiracetam, valproate or phenobarbital is effective in preventing recurrent febrile convulsions in rats. Phenobarbital appears to be more effective than levetiracetam and valproate. There were no significant differences in the prophylactic efficacy between levetiracetam and valproate.

Animals ; Anticonvulsants ; therapeutic use ; Male ; Phenobarbital ; therapeutic use ; Piracetam ; analogs & derivatives ; therapeutic use ; Rats ; Recurrence ; Seizures, Febrile ; prevention & control ; Valproic Acid ; therapeutic use

BACKGROUND AND PURPOSE: Epilepsy is a chronic neurological disease that represents a tremendous burden on both patients and society in general. Studies have addressed how demographic variables, socioeconomic variables, and psychological comorbidity are related to the quality of life (QOL) of people with epilepsy (PWE). However, there has been less focus on how these factors may differ between patients who exhibit varying degrees of seizure control. This study utilized data from the Managing Epilepsy Well (MEW) Network of the Centers for Disease Control and Prevention with the aim of elucidating differences in demographic variables, depression, and QOL between adult PWE. METHODS: Demographic variables, depression, and QOL were compared between PWE who experience clinically relevant differences in seizure occurrence. RESULTS: Gender, ethnicity, race, education, income, and relationship status did not differ significantly between the seizure-frequency categories (p>0.05). People with worse seizure control were significantly younger (p=0.039), more depressed (as assessed using the Patient Health Questionnaire) (p=0.036), and had lower QOL (as determined using the 10-item Quality of Life in Epilepsy for Adults scale) (p < 0.001). CONCLUSIONS: The present results underscore the importance of early screening, detection, and treatment of depression, since these factors relate to both seizure occurrence and QOL in PWE.
Adult ; Centers for Disease Control and Prevention (U.S.) ; Comorbidity ; Continental Population Groups ; Depression ; Education ; Epilepsy* ; Humans ; Mass Screening ; Quality of Life ; Seizures* ; Self Care

BACKGROUNDThe antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.

METHODSSixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups.

RESULTSThe latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group.

CONCLUSIONSThis study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons. This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.

Animals ; Anterior Thalamic Nuclei ; physiology ; Apoptosis ; Deep Brain Stimulation ; Epilepsy ; pathology ; therapy ; Hippocampus ; pathology ; Kainic Acid ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; prevention & control

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*

BACKGROUNDHistamine H(3) receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H(3) receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.

METHODSChemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.

RESULTSIntracerebroventricular (icv) injections with thioperamide (10 µg, 20 µg) 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide.

CONCLUSIONSThioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

Animals ; Anticonvulsants ; pharmacology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Histamine H3 Antagonists ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Memory Disorders ; prevention & control ; Neuroprotective Agents ; pharmacology ; Pentylenetetrazole ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Seizures ; prevention & control ; Synaptic Transmission

Patients with human immunodeficiency virus (HIV) infection have a higher burden of seizures, but few studies have examined seizures in HIV-infected individuals in Korea. A retrospective study was conducted to determine the epidemiology and clinical characteristics of seizures in patients with HIV infection. Among a total of 1,141 patients, 34 (3%) had seizures or epilepsy; 4 of these individuals had epilepsy before HIV infection, and the others showed new-onset seizures. Most patients exhibited moderate (200 to 500, n = 13) or low (below 200, n = 16) CD4 counts. The most common seizure etiology was progressive multifocal leukoencephalopathy (n = 14), followed by other HIV-associated central nervous system (CNS) complications (n = 6). Imaging studies revealed brain lesions in 21 patients. A total of 9 patients experienced only one seizure during the follow-up period, and 25 patients experienced multiple seizures or status epilepticus (n = 2). Multiple seizures were more common in patients with brain etiologies (P = 0.019) or epileptiform discharges on EEG (P = 0.032). Most seizures were controlled without anticonvulsants (n = 12) or with a single anticonvulsant (n = 12). Among patients with HIV infection, seizures are significantly more prevalent than in the general population. Most seizures, with the exception of status epilepticus, have a benign clinical course and few complications.
Adult ; Aged ; Anticonvulsants/therapeutic use ; Causality ; Comorbidity ; Electroencephalography/*statistics & numerical data ; Female ; HIV Infections/diagnosis/*epidemiology ; Humans ; Incidence ; Longitudinal Studies ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Risk Factors ; Seizures/*diagnosis/*epidemiology/prevention & control ; Treatment Outcome

Potassium plays various important roles in water balance, neuronal maintenance, blood vessel extension, arrhythmia prevention, and blood pressure maintenance. Its deficiency leads to arrhythmia, loss of appetite, convulsions, constipation, fatigue, asthenia, and hypoglycemia etc. Although foods are primary prevention for diseases, there are few literatures on dietary potassium in both Korea and U.S. Also, its acceptable level is not determined yet and is only recommended 2,000-3,000 mg and 1,500-5,000 mg for adult in Korea and US, respectively. The main source of potassium is vegetables such as calabash, fruit, sea tangle, yeast, bean, and banana etc. Therefore, this is to provide information on dietary potassium in order to prevent the risk of cardiovascular disease and guide for patients who suffer from kidney disease etc.
Adult ; Appetite ; Arrhythmias, Cardiac ; Asthenia ; Blood Pressure ; Blood Vessels ; Cardiovascular Diseases ; Constipation ; Fatigue ; Fruit ; Humans ; Hypoglycemia ; Kidney Diseases ; Korea ; Musa ; Neurons ; Potassium ; Potassium, Dietary* ; Primary Prevention ; Seizures ; Vegetables ; Yeasts

OBJECTIVETo evaluate the therapeutic effect and safety of rapamycin in treatment of children with tuberous sclerosis complex (TSC) complicated with epilepsy.

METHODThis was an open-label, prospective, self-controlled study. From Sep. 2011 to Sep. 2013, 52 patients with the diagnosis of tuberous sclerosis complicated with epilepsy receiving rapamycin treatment for at least 24 weeks were enrolled.

RESULTOf the 52 children, 34 were male and 18 female. The median age at onset of epilepsy was 4.8 months (4 days-49 months), the median age for treatment with rapamycin was 27 months (4.5-172.5 months). Ten children had a family history of TSC. In 24 children TSC gene detection was carried out, among whom TSC1 mutation was detected in 4 cases and TSC2 mutation in 20. Before rapamycin therapy, 59.62%, (31/52) patients took more than 3 antiepileptic drugs, of whom 10 cases even took more than 5 kinds of antiepileptic drugs. Fifty-two patients received rapamycin treatment for 24 weeks, seizure free rate was 25.00% (13 cases), the total effective rate was 73.08% (38 cases); 31 cases received treatment for 48 weeks, seizure free 6 cases, total effective 23 cases; 17 cases accepted treatment for 72 weeks, seizure free 5 cases, total effective 13 cases; 12 cases received treatment for 96 weeks, seizure free 3 cases, total effective 9 cases. With the decrease of seizure attacks, use of antiepileptic drug types were reduced simultaneously, they had a negative correlation. Before rapamycin therapy, the average frequency of seizures was 70.27 times/d, the number of antiepileptic drug kinds was 1.30. After 24, 48, 72, 96 weeks' treatment, the average seizure frequency was reduced to 1.94-2.80 times /d and the antiepileptic drugs were reduced to 0.83-0.97 kinds. On every visit during the follow-up, blood and urine routine tests, liver and kidney function test showed no abnormality in the 52 cases. The drug dosage was 1 mg/(m(2)×d), average 0.7 mg/d (0.35-1.20 mg/d). Blood concentrations of rapamycin remained below 10 µg/L (average 6.5 µg/L). The main side effect was oral ulcer which happened in 23.08% (12/52). The oral ulcer would disappeared 2-3 days later. 17.31% (9/52 cases) had upper respiratory infection.

CONCLUSIONRapamycin was effective in children with tuberous sclerosis and epilepsy with few adverse reactions. The daily dose of rapamycin for children patients is 1 mg/m(2), which has a certain effect on seizures and a good safety profile.

Adolescent ; Anticonvulsants ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Epilepsy ; complications ; drug therapy ; Female ; Humans ; Infant ; Male ; Prospective Studies ; Seizures ; prevention & control ; Sirolimus ; adverse effects ; therapeutic use ; Treatment Outcome ; Tuberous Sclerosis ; complications ; genetics

OBJECTIVETo evaluate the therapeutic effect of methylprednisolone for electrical status epilepticus during sleep (ESES) in children.

METHODThe clinical and EEG data of 82 epilepsy patients with ESES, which included benign childhood epilepsy with centro temporal spikes (BECT) variants, epilepsy with continuous spikes and waves during slow sleep (CSWS) , Landau-Kleffner syndrome (LKS) collected from department of pediatrics, Peking University First Hospital were analyzed from July 2007 to September 2012. During ESES period, all patients received methylprednisolone treatment for three courses, which included methylprednisolone intravenous infusion for three days, followed by oral prednisone for four days every time. After three courses, prednisone [1-2 mg/(kg × d)] were taken by all patients for 6 months. The ESES phenomenon and seizures were observed before and after treatment. The efficacy of corticosteroid on ESES suppression, seizure control of three epilepsy syndrome were analyzed.

RESULTThirty-nine cases were male and 43 cases were female. The epilepsy syndromes included 49 patients diagnosed as benign childhood epilepsy with centrotemporal spike (BECT) variants, 27 patients diagnosed as epilepsy with continuous spikes and waves during slow sleep (CSWS), and 6 patients diagnosed as LKS. Age of onset ranged from 1 year and 4 months to 11 years. The age of ESES newly monitored was from 2 years to 10 years and 8 months. The total effective rate of corticosteroid was 83% (68/82) for ESES, BECT variants was 82% (40/49), CSWS was 81% (22/27), LKS was 100% (6/6). There was no statistically significant difference in effective rates between the front two (χ² = 0.09, P > 0.05). The seizures were improved in the first month after methylprednisolone treatment in 3 epilepsy syndromes. The recurrence rate of BECT variants was 47% (23/49) , CSWS was 59% (16/27) , LKS was 50% (3/6) after 1 year follow up. There was no association between disease parameters, including age at seizure onset, duration of ESES and the treatment effect of ESES examined by Kruskal-Wallis method (χ² = 3.585, 0.932, P > 0.05).

CONCLUSIONMethylprednisolone was effective for improving ESES and seizures in 3 epilepsy syndromes combined with ESES. There was no significant correlation between age at seizure onset, duration of ESES and treatment effect of ESES.

Adrenal Cortex Hormones ; therapeutic use ; Child ; Child, Preschool ; Electroencephalography ; Female ; Humans ; Infant ; Landau-Kleffner Syndrome ; drug therapy ; physiopathology ; Male ; Methylprednisolone ; therapeutic use ; Pediatrics ; Seizures ; prevention & control ; Sleep ; physiology ; Status Epilepticus ; drug therapy ; physiopathology ; Treatment Outcome