Cross-talk between the thalamus and cortex has been implicated in attention but its pathogenic role in attention-deficit/hyperactivity disorder (ADHD) remains unknown. Here, I demonstrate that Git1-/- mice, previously proposed as an animal model for ADHD, show abnormal theta oscillation in the thalamus. Multi-electrode recordings revealed that Git1-/- mice have hyper-synchrony of neural activities between the thalamus and cortex. The abnormal thalamic oscillation and thalamocortical synchrony in Git1-/- mice were markedly reduced by amphetamine. In addition, ethosuximide ameliorates abnormal thalamic oscillation and ADHD-like hyperactivity shown in Git1-/- mice. My study suggests critical roles of GIT1 and thalamocortical neural circuitry in ADHD.
Amphetamine ; Animals ; Ethosuximide ; Mice* ; Models, Animal ; Thalamus

PURPOSE: Ethosuximide (ESX) is currently not available due to various reasons in Korea. The aim of this study is to compare the efficacy of valproate (VPA) and lamotrigine (LTG) when ESX monotherapy was replaced by VPA or LTG. METHODS: A retrospective study was done for a total of 34 patients treated with ESX in 5 different hospitals affiliated with Catholic University of Korea from January, 2010 to December, 2012. They all were initially treated with ESX, but later switched to VPA or LTG. The subjects were selected based on clinical symptoms and electroencephalography findings. RESULTS: Among 34 patients, VPA was prescribed to 17 patients (50.0%) and LTG to 17 patients (50.0%). Twenty patients (58.8%) achieved the seizure freedom after 3 months of the treatments, 13 patients (76.5%) by VPA and 7 (41.2%) by LTG respectively. Four patients (23.5%) with VPA and 10 (58.8%) with LTG were replaced by other anticonvulsants due to ineffectiveness and/or side effects of medication. When we compare the efficacy of seizure reduction between VPA and LTG after 3 month period of the treatment, the efficacy of VPA was better than that of LTG (P=0.04). CONCLUSION: The results of this study suggest that the VPA is a better alternative anticonvulsant than LTG for the patients with absence epilepsy who are unable to continue ESX.
Anticonvulsants ; Child ; Electroencephalography ; Epilepsy ; Epilepsy, Absence* ; Ethosuximide ; Freedom ; Humans ; Korea ; Retrospective Studies ; Seizures ; Valproic Acid*

PURPOSE: Typical absence seizures are characterized by the daily presentation of frequent staring and typical 3Hz spike and wave discharges in otherwise healthy children. Typical absence seizures can present in childhood absence epilepsy and related syndromes. Lamotrigine (LTG) has been anecdotally used as a monotherapy for this seizure type; however, the efficacy and tolerability has remained unknown. The aim of this study was to evaluate the efficacy, tolerability, and long-term outcome of LTG in patients with newly diagnosed typical absence seizures. METHODS: Medical records of 36 patients having newly diagnosed typical absence seizures were analyzed. Patients were included based on the history of typical absence seizures and 3 Hz spike and wave discharges in interictal EEG. LTG was administered at a starting dose of 10 mg/day and increased by 10 mg/week until seizure freedom or reaching a dose of 10 mg/kg/day. RESULTS: Thirty-one patients had childhood absence epilepsy (CAE) and five had juvenile absence epilepsy (JAE). Thirty patients (83.3%) experienced more than 50% reduction of seizure frequency after 4 weeks of initial titration. Twenty-three patients (63.9%) achieved seizure freedom for 4 weeks after a mean duration of 8.3 weeks of treatment, and the cumulative numbers of patients with seizure freedom were 6 (16.7%), 18 (50.0%), and 23 (63.9%) within 4, 8, and 12 weeks, respectively. After 12 months of treatment, 12 patients (33.3%) showed normalized EEG findings, and their symptoms also disappeared. Four patients had uncontrolled seizures despite of dose increment and consequently needed additional treatment with valproic acid or ethosuximide. Most adverse effects, including skin rash (n=4), headache (n=1), and dizziness (n=1), were transient and tolerable. CONCLUSION: Lamotrigine, as a first-line monotherapy in newly diagnosed patients with typical absence seizures, could be safely used with good efficacy in seizure control.
Child ; Dizziness ; Electroencephalography ; Epilepsy ; Epilepsy, Absence ; Ethosuximide ; Exanthema ; Freedom ; Headache ; Humans ; Medical Records ; Seizures ; Triazines ; Valproic Acid

BACKGROUND: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. METHODS: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. RESULTS: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. CONCLUSIONS: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.
Animals ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Ethosuximide* ; Injections, Spinal ; Mibefradil* ; Models, Animal* ; Nociceptors ; Pain, Postoperative* ; Plastics ; Rats* ; Spinal Cord

Cortical malformation-associated epileptic seizures are resistant to conventional anticonvulsant drugs. Relatively little research has been conducted on the effects of antiepileptic drugs (AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of ethosuximide (ETX) in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor the amplitude and number of population spikes, and paired pulse inhibition in response to stimulation of the commissural pathway. Pharmaco-resistance was tested by measuring seizure latencies after pilocarpine administration (320 mg/kg, i.p.) with and without pre-treatment with ETX. Pre-treatment with 300 mg of ETX significantly prolonged the latency to the status epilepticus (SE) in both control and MAM-treated groups. Pre-treatment with ETX 100mg and ETX 200 mg had little effect in MAM-exposed rats. However, ETX 200 mg prolonged the latency to the SE in control groups. Spontaneous field potential and secondary after-discharges were higher for MAM-treated rat in comparison with control rats injects with ETX. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard ETX assessed in vivo. These data suggest that ETX do not prolong seizure latencies in MAM-rats exposed to pilocarpine.
Animals ; Anticonvulsants ; Brain ; Epilepsy ; Ethosuximide* ; Methylazoxymethanol Acetate ; Models, Animal* ; Neuronal Migration Disorders* ; Neurons* ; Pilocarpine* ; Rats* ; Seizures* ; Status Epilepticus

BACKGROUND: Juvenile myoclonic epilepsy(JME) is the most common idiopathic generalized epileptic syndrome which occurs mostly in the second decade of life. It is still frequently unrecognized and misdiagnosed. JME responds well to valproate, but is hardly controlled by other commonly used antiepileptic drug such as carbamazepine or phenytoin. We intended to Investigate the clinical symptoms and EEG findings of JME to support the diagnosis and treatment of JME. SUBJECTS AND METHODS: We retrospectively reviewed the medical record of 18 childrens with JME, from March 1991 to February 1997 We have analysed the clinical symptoms, seizure type, EEG findings including photosensitivity, and the effect of antiepileptic drug. RESULTS: 1) Seven patients were boys and eleven patients were girls(M : F=1 : 1.6). The seizure onset between 5 and 7 years of age were noted in 5 cases, that between 8 and 10 years in 5 cases, and in 8 cases seizures began after 11 years of age 2) Generalized convulsive seizures were noted in 16 cases(GTC 13, GC 2, GCTC 1), myoclonic seizures in 18 cases, absence seizures in 5 cases, and photoconvulsive seizures during video game were associated in 3 cases. 3) Epileptiform discharges at the diagnosis of JME were noted 12 cases(66.7%), and no epileptiform discharges were seen in 6 cases(33.3%). The background activities were normal in all cases. In all 12 cases that showed abnormal epileptiform discharge, generalized spike and wave discharges were obtained, and photosensitivies noted in 4 cases. 4) Follow up EEG obtained after treatment, showed normal EEG findings in 16 cases, and abnormal EEG findings were obtained in 2 cases. 5) Sixteen cases responded well to valproate monotherapy, and 2 other cases responded to valproate and ethosuximide combined therapy. In one case who received vigabatrin, the seizure was aggravated. 6) In 5 cases who discontinued antiepicoptic drug medication after 3 year seizure free duration, 3(60%) cases relapsed within 1 year, and 2(40%) cases remained seizure free for over 1 year. CONCLUSION: Juvenile myoclonic epilepsy is an epileptic syndrome with generalized convulsive seizure, myoclonic seizure, and absence seizure, and EEG findings showed generalized spike and wave discharge in 66.7%, and photosensitivity in 22.2%. JME responded well to valproate monotherapy or valproate and ethosuximide combined the rape, but not responded to other antiepileptic drugs.
Anticonvulsants ; Carbamazepine ; Child ; Diagnosis ; Electroencephalography ; Epilepsy, Absence ; Ethosuximide ; Follow-Up Studies ; Humans ; Medical Records ; Myoclonic Epilepsy, Juvenile* ; Phenytoin ; Rape ; Retrospective Studies ; Seizures ; Valproic Acid ; Video Games ; Vigabatrin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2005. The number of participating laboratories were increased to 95, by 6.7% comparing with the previous year. Response rates were 100.0% for both trials just like the two previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.7 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were digoxin, valproic acid, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 65% of participating laboratories, followed by cyclosporine, lithium, vancomycin, tacrolimus, methotrexate, amikacin, gentamycin, tobramycin, salicylate, primidone, acetaminophen, free phenytoin, amitryptyline, and ethosuximide. The most widely used TDM analyzer was Abbott TDx/TDxFLx (41.7%), followed by Abbott AxSym (23.3%), and Roche Cobas Integra (19.2%). The inter-laboratory coefficients of variations were not much improved comparing with previous years. We also determined cyclosporine with reference method using liquid chromatography-tandem mass spectrometry. In conclusion, the TDM external quality assessment of 2005 showed grossly similar pattern comparing with those of previous year with increasing participating laboratories.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Ethosuximide ; Gentamicins ; Korea* ; Lithium ; Mass Spectrometry ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

BACKGROUND AND PURPOSE: Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. METHODS: Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. RESULTS: The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. CONCLUSIONS: This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy.
Academic Medical Centers ; Child ; Electroencephalography ; Epilepsy ; Epilepsy, Absence* ; Ethosuximide ; Follow-Up Studies ; Freedom ; Humans ; Korea ; Prognosis ; Retrospective Studies ; Seizures ; Treatment Failure ; Valproic Acid

We performed two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) in 2009. The number of participating laboratories were 110, which is similar with that of previous 3 years. Average response rates were 97.8% in both trials, similar to those of previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could find the possible systematic errors. The average drug item responded was 6.2 per institution, which was decreased slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, phenytoin, and theophylline which were peformed in more than 63.8% of participating laboratories, followed by phenobarbital, cyclosporine, tacrolimus, vancomycin, lithium, methotrexate, amikacin, gentamicin, acetaminophen, tobramycin, salicylate, free phenytoin, amitryptyline, ethosuximide, and primidone. The widely used TDM analyzers were Abbott AxSym (26.9%), followed by Abbott TDx/TDxFLx (24.8%), Roche Cobas Integra (15.1%), Siemens Diagnostics Viva-E (5.5%), Roche cobas c501 (5.1%), Siemens Diagnostics Dimension (3.4%), and many other analyzers. The inter-laboratory coefficients of variations showed similar tendency comparing with those of the previous years. The number of participating laboratories for drug of abuse (DOA) tests were 19, which was slightly increased compared to that of the previous year. Average DOA items were 3.8~4.2. We found the good performance of participating laboratories for DOA. In conclusion, the TDM and DOA external quality assessment of 2009 showed similar performance comparing with that of the recent 3 years.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring ; Ethosuximide ; Gentamicins ; Korea ; Lithium ; Methotrexate ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Aplastic anemia may develop secondary to environmental exposure to entities such as chemicals, medical drugs, and infectious agents. Fatal complications from antiepileptic medications may occur despite careful and appropriate use. We report the case of a 9-year-old girl with a presenting diagnosis of aplastic anemia following treatment with ethosuximide for absence seizures. Aplastic anemia can now be cured with stem cell transplantation or immunosuppressive therapy. In this case, however, because of the impossibility of bone marrow transplantation and the specific needs of the patient's parents, three courses of methylprednisolone pulse therapy were administered. Following the therapy, there was improvement in pancytopenia and complete remission in the bone marrow. No adverse side effects of therapy were observed. The authors suggest that methylprednisolone pulse therapy may be a treatment for acquired aplastic anemia.
Anemia, Aplastic* ; Anticonvulsants ; Bone Marrow ; Bone Marrow Transplantation ; Child ; Diagnosis ; Environmental Exposure ; Epilepsy, Absence ; Ethosuximide ; Female ; Humans ; Methylprednisolone* ; Pancytopenia ; Parents ; Stem Cell Transplantation