The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

Anticonvulsants/therapeutic use*

OBJECTIVE: To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children. METHODS: English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis. RESULTS: Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE ( CONCLUSIONS LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.
Anticonvulsants/adverse effects* ; Child ; Humans ; Levetiracetam/therapeutic use* ; Pharmaceutical Preparations ; Phenytoin/adverse effects* ; Status Epilepticus/drug therapy*

OBJECTIVES: Due to the narrow therapeutic window of valproic acid (VPA), grievous adverse reactions such as hepatotoxicity, nephrotoxicity may occur in patients with epilepsy for a long time. This study aimed to explore the effect of VPA concentration on biochemical and routine blood test related to liver, renal, and hematology in epileptic outpatients treated with VPA alone or combined with other antiepileptic drugs. METHODS: A total of 3 194 Chinese epileptic outpatients from Xiangya Hospital, were analyzed in a crude analysis after stratifying through dosage regimens. The plasma VPA concentration was detected by gas chromatography method and then standardized through dosage and body weight. Ten biochemical indexes related to liver, renal, and hematology were evaluated. RESULTS: Of all patients, blood urea nitrogen (BUN), serum creatinine (SCr) level, and erythrocyte count (RBC) showed positive correlations with standardized VPA concentration (=0.494, =0.157, =0.596, respectively), while platelet specific volume (PCT) and blood platelet (PLT) showed negative correlations with standardized VPA concentration (=-5.500, =-0.086, respectively). After stratifying through dosage regimens, significantly positive associations between SCr and standardized VPA concentration were found in the juvenile patients from the monotherapy group and combination therapy group (=1.800, =0.352, respectively). In addition, PLT and leukocyte count (WBC) in the juvenile patients from the combination therapy group were negatively correlated with standardized VPA concentration (=-1.463, =-0.079, respectively), while RBC showed a positive association with standardized VPA concentration in the juvenile patients from the monotherapy group (=0.068). CONCLUSIONS SCr level is significantly associated with plasma VPA concentration. Drug combination and age are important factors leading to hematological disorders. The finding provides potential theoretical guidance for the rational and safe clinical use of VPA.
Adolescent ; Anticonvulsants ; therapeutic use ; Combined Modality Therapy ; Drug Therapy, Combination ; Epilepsy ; drug therapy ; Humans ; Outpatients ; Valproic Acid ; therapeutic use

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.
Acidosis, Lactic ; drug therapy ; mortality ; Adolescent ; Anticonvulsants ; therapeutic use ; Carbamazepine ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Lamotrigine ; therapeutic use ; Levetiracetam ; administration & dosage ; therapeutic use ; Male ; Mitochondrial Encephalomyopathies ; drug therapy ; mortality ; Oxcarbazepine ; therapeutic use ; Prospective Studies ; Retrospective Studies ; Stroke ; drug therapy ; mortality ; Topiramate ; therapeutic use ; Valproic Acid ; therapeutic use

OBJECTIVE: To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms. METHODS: A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time. RESULTS: Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05). CONCLUSIONS For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.
Adrenocorticotropic Hormone ; therapeutic use ; Anticonvulsants ; Humans ; Infant ; Proportional Hazards Models ; Spasm ; Spasms, Infantile ; drug therapy

OBJECTIVE: To study the clinical features of electrical status epilepticus during sleep (ESES) in children, as well as the clinical effect of methylprednisolone pulse therapy in children with ESES. METHODS: A retrospective analysis was performed using the clinical data of 78 children with ESES. Among these children, 56 children who had had the failure of antiepileptic drugs were treated with methylprednisolone pulse therapy at a dose of 15-20 mg/(kg·d) for three courses. Each course of treatment was 3 days, followed by oral prednisone [1-2 mg/(kg·d)] for 3 days. The role of methylprednisolone pulse therapy in eliminating ESES, controlling clinical seizures, and improving intelligence and behaviors was analyzed. RESULTS: The mean age of onset of epilepsy in 78 children was 6.8±2.4 years, and the mean age for the first occurrence of ESES was 7.6±2.5 years. Compared with normal children, children with ESES had delayed intelligence development and higher scores of some behavior problems. Methylprednisolone pulse therapy had an overall response rate of 73% (41/56) on clinical seizures, and the overall response rate on electroencephalography (EEG)/spike-wave index was 70% (39/56) after treatment. There were significant improvements in verbal intelligence quotient, performance intelligence quotient and full intelligence quotient, and significant reductions in the scores of learning problems, impulse-hyperactivity and hyperactivity index after treatment (P<0.05). The overall recurrence rate after 1-year follow-up was 29% (11/38). CONCLUSIONS ESES often presents around school age and impairs children's intelligence and behaviors. Methylprednisolone pulse therapy has a marked efficiency in reducing clinical seizures and EEG discharges in children with ESES and can improve intelligence and behavior development, but the recurrence rate remains high.
Anticonvulsants ; Child ; Child, Preschool ; Electroencephalography ; Follow-Up Studies ; Humans ; Methylprednisolone ; therapeutic use ; Retrospective Studies ; Sleep ; Status Epilepticus ; drug therapy

Anticonvulsants ; therapeutic use ; Clonazepam ; therapeutic use ; Female ; Humans ; Levetiracetam ; therapeutic use ; MERRF Syndrome ; drug therapy ; Male ; Myoclonus ; drug therapy

Epilepsy has high incidence and complex etiologies,and its treatment remains challenging.For around 70% of people with epilepsy,seizures can be controlled after proper antiepileptic treatment.The availability of some new antiepileptic drugs in recent years has offered new options for epileptic patients.A solid knowledge on the pharmacokinetics,efficacy,and tolerability profiles of these new antiepileptic drugs will help to provide safe,proper,reasonable,and standardized treatment for patients.
Anticonvulsants ; therapeutic use ; Epilepsy ; drug therapy ; Humans ; Seizures ; drug therapy

In Japan, because the most common site of drowning among patients with epilepsy is the bathtub, showering is generally recommended as an alternative to bathing. We herein report a case involving a female patient with epilepsy who drowned while showering. She had been diagnosed with epilepsy approximately 25 years previously, and her condition had progressed to refractory epilepsy. Carbamazepine, levetiracetam, lamotrigine, clobazam, and perampanel were prescribed daily. One day while showering, the patient was found lying with her face immersed in water that had accumulated on the floor of the bathtub. A forensic autopsy revealed water in the stomach, trachea, and proximal regions of both lung bronchi as well as white and red foam on the pharynx and larynx. A total of 1.9 μg/mL of lamotrigine, 0.14 μg/mL of carbamazepine, and 0.069 μg/mL of perampanel were detected in the patient's blood. The patient's cause of death was determined to be drowning due to an epileptic seizure. Although the patient was prescribed five types of antiepileptic medication, only three were detected in her blood. The current case demonstrates that drowning can occur while showering, suggesting that it is unsafe for patients with medication nonadherence. To prevent unintentional deaths in the bathroom, we recommend that patients with epilepsy maintain high adherence to all prescriptions and are supervised by a family member, even when showering. The current case is the first autopsy report of a patient with epilepsy who drowned while showering.
Adult ; Anticonvulsants ; blood ; therapeutic use ; Autopsy ; Drowning ; etiology ; pathology ; Drug Resistant Epilepsy ; drug therapy ; pathology ; Female ; Humans ; Japan ; Medication Adherence