Angiotensinogen gene polymorphism and ischemic stroke in East Asians A meta-analysis

OBJECTIVE: To investigate the association between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians. DATA RETRIEVAL: A computer-based online search was conducted in PubMed, Google scholar, China National Knowledge lnfrastructure database between January 1990 and April 2012 for relevant studies. The were angiotensinogen or AGT, polymorphism or genetic and ischemic stroke or cerebral infarction. SELECTION CRITERIA: Case-controlled studies addressing the correlation between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians were included. The distribution of genotypes in the included studies was tested for Hardy-Weinberg equilibrium. Quality evaluation of the included studies was conducted by two physicians. Statistical analyses were carried out using Stata 12.0 software for meta-analysis. Heterogeneity tests, sensitivity analysis and publication bias were also conducted. MAIN OUTCOME MEASURES: The association between angiotensinogen gene M235T polymorphism and ischemic stroke risk in East Asians was assessed. RESULTS: Six relevant studies involving 891 patients with ischemic stroke and 727 controls were included in this meta-analysis. Results showed that there was a significant association between angiotensinogen gene M235T polymorphism and the risk of ischemic stroke in East Asians (T vs. M: odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.10-2.16; TT vs. MM: OR = 2.24, 95%CI = 1.37-3.66; TT vs. MT: OR = 1.76, 95%CI = 1.41-2.20; MM + MT vs. TT: OR = 0.57, 95%CI = 0.46-0.70). Sensitivity analysis confirmed that the study results were stable and reliable, with no publication bias. CONCLUSION: The angiotensinogen gene M235T polymorphism is associated with ischemic stroke in East Asians, and the TT genotype and T allele are risk factors for ischemic stroke.     

Relationship between Helicobacterpylori bearing the cytotoxin associated gene-A and cerebral infarction

Objective To explore the relationship between virulent Helicobacter pylori strains infection and cerebral infarction. Method We assessed the prevalence of infection by strains bearing the cytotoxin -associated gene-A(Cag-A),a strong virulence factor ,in 83 patients with cerebral infarction and in 71 age- and sex-matched controls with similar social background. Result Prevalence of Helicobacter pylori infection was significantly higher in patients than in controls(78.3% versus 56.3%,p＜0.05),with an odds ratio of 2.8(95%CI,1.46 to 5.36) adjusted for age, sex, main stroke factors. Patients with cerebral infarction also had a higher prevalence of Cag-A-positive strains(45.8% versus 19.7%, P＜0.01),with an adjusted odds ratio of 3.43(95%CI 1.5 to 7.24).Conclusion It was suggested that chronic Helicobacter pylori infection, especially Cag-A-positive strains infection is an independent risk factor for cerebral infarction.     

A study on levels of neuropeptide Y, neurotensin motilin and calcitonin gene-reliated peptide in plasma in patients with cerebral infarction and dinical isignificance

Objective To explore the relationship between virulent Helicobacter pylori strains infection and cerebral infarction. Method We assessed the prevalence of infection by strains bearing the cytotoxin -associated gene-A(Cag-A),a strong virulence factor ,in 83 patients with cerebral infarction and in 71 age- and sex-matched controls with similar social background. Result Prevalence of Helicobacter pylori infection was significantly higher in patients than in controls(78.3% versus 56.3%,p＜0.05),with an odds ratio of 2.8(95%CI,1.46 to 5.36) adjusted for age, sex, main stroke factors. Patients with cerebral infarction also had a higher prevalence of Cag-A-positive strains(45.8% versus 19.7%, P＜0.01),with an adjusted odds ratio of 3.43(95%CI 1.5 to 7.24).Conclusion It was suggested that chronic Helicobacter pylori infection, especially Cag-A-positive strains infection is an independent risk factor for cerebral infarction.     

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.     

nsulin resistance and occurrence and prognosis of schemic stroke——A non-randomized concurrent control and intra-group comparison

BACKGROUND： Clinical evidence has demonstrated that insulin resistance might be an independent risk factor for ischemic stroke, which has not been recognized. At present, insulin resistance has been proven to be an independent risk factor for coronary arteriosclerotic heart disease. However, the relationship between the onset and prognosis of ischemic stroke remains unclear. OBJECTIVE： This study was designed to analyze the relationship between insulin resistance and ischemic stroke and the correlation between insulin resistance and stroke risk factor, and to investigate the relationship between insulin resistance and ischemic stroke prognosis as well as whether insulin resistance is an independent prognostic factor. DESIGN： A non-randomized concurrent control experiment. SETTING： Department of Geriatric Disease, Second Affiliated Hospital of Kunming Medical College. PARTICIPANTS： A total of 106 inpatients with ischemic stroke of the cervical internal carotid artery, who had suffered from the disease within the previous 72 hours, were admitted to the Department of Neurology, First Affiliated Hospital of Kunming Medical College from March to December in 2005 and, recruited for the present study. All 106 inpatients corresponded to the diagnostic criteria of ischemic stroke, formulated at the Fourth National Cerebrovascular Disease Conference in 1995, and were confirmed as having had an ischemic stroke by CT/MRI examinations. The patient group consisted of 54 males and 52 females. An additional 50 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 26 males and 24 females. Informed consent for laboratory measurements was obtained from all subjects; this study was approved by the Hospital Ethics Committee. METHODS： Following admission, all subjects were inquired of age, gender, previous history, blood pressure, body temperature, admission time, and smoking habits. Meanwhile, they were scored on clinical neurological functi     

Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population

Thromboxane A synthase 1(TBXAS1) catalyses the synthesis of thromboxane A2(TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNa Pshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls(P 0.01 and P = 0.02). Furthermore, compared with the GG + GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke(odds ratio(OR) = 1.80, 95% confidence interval(CI): 1.16–2.79, P 0.01). Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke(OR = 1.94, 95% CI : 1.13–3.33, P = 0.02). The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis(OR = 1.49, 95% CI: 1.10–2.00, P 0.01). These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry(registration number: Chi CTR-COC-17013559).     

Association between PPARG genetic polymorphisms and ischemic stroke risk in a northern Chinese Han population: a case-control study

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860; 95% CI: 0.779–0.940; S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.     

Eosinopenia is a predictive factor for the severity of acute ischemic stroke

Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke.However,the relationship of eosinopenia with infarct volume,infection rate,and poor outcome of acute ischemic stroke is still unknown.The retrospective study included 421 patients(273 males,65%;mean age,68.0± 13.0 years)with first acute ischemic stroke who were hospitalized in the Second Affiliated Hospital of Soochow University,China,from January 2017 to February 2018.Laboratory data,neuroimaging results,and modified Rankin Scale scores were collected.Patients were divided into four groups according to their eosinophil percentage level(0.4%,0.4-1.1%,1 1-2.3%,≥2.3%).Spearman's correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume(rs=-0.514,P0.001).Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia;the area under curve was 0.906 and 0.876,respectively;a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas.Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke(P=0.002).Moreover,eosinophil percentage was significantly associated with large infarct volume,high infection rate(pulmonary and urinary tract infections),and poor outcome(modified Rankin Scale score3)after adjusting for potential confounding factors(P-trend0.001).These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke.This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University,China(approval number:K10)on November 10,2015.     

Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction

Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.     

Xingnao Kaiqiao needling method for acute ischemic stroke: a meta-analysis of safety and efficacy

OBJECTIVE: To evaluate the effectiveness and safety of the Xingnao Kaiqiao needling method for treating acute ischemic stroke.DATA SOURCES: We retrieved relevant randomized controlled trials involving Xingnao Kaiqiao acupuncture for treatment of acute ischemic stroke. The China National Knowledge Infrastructure, Weipu Information Resources System, Wanfang Medical Data System, Chinese Biomedical Literature Database, Cochrane Library, and Pub Med were searched from June 2006 to March 2016.DATA SELECTION: We analyzed randomized and semi-randomized clinical controlled trials that compared Xingnao Kaiqiao acupuncture with various control treatments, such as conventional drugs or other acupuncture therapies, for treatment of acute ischemic stroke. The quality of articles was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions(Version 5.1), and the study was carried out using Cochrane system assessment methods. Rev Man 5.2 was used for the meta-analysis of the included studies.OUTCOME MEASURES: The mortality rate, disability rate, activities of daily living(Barthel Index), and clinical efficacy were observed.RESULTS: Twelve studies met the inclusion criteria for this review. The meta-analysis showed that between Xingnao Kaiqiao acupuncture and the control treatment, Xingnao Kaiqiao acupuncture reduced the disability rate [risk ratio(RR) = 0.51, 95% confidence interval(CI) = 0.27–0.98, z = 2.03, P 0.05], elevated the activities of daily living(weighted mean difference = 12.23, 95% CI: 3.66–20.08, z = 2.80, P 0.005), and had greater clinical efficacy(RR = 1.61, 95% CI: 1.23–2.09, z = 3.53, P 0.0004). However, there was no significant difference in mortality rate(RR = 0.61, 95% CI: 0.15–2.45, z = 0.70, P 0.05). CONCLUSION: The Xingnao Kaiqiao needling method is effective and safe for acute ischemic stroke. However, there was selective bias in this study, and the likelihood of measurement bias is high. Thus, more high-quality randomized controlled trials are needed to provide reliable evidence of the efficacy and safety of Xingnao Kaiqiao acupuncture in the treatment of acute ischemic stroke.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.