Effects of age of onset and medication on cognitive performance and quality of life in patients with epilepsy.

Previous research shows that earlier age of onset of epilepsy and larger antiepileptic drug (AED) load are related to cognitive impairment and lower quality of life in patients with epilepsy. However, there has been a discrepancy in the specific cognitive domains that are affected and whether AED load is a significant contributor to the cognitive impairment. This study aimed to examine (a) the specific cognitive domains that are affected by age of epilepsy onset and (b) the effects of AED treatment and age of onset on cognition and quality of life. Participant data included scores on (1) the Wisconsin Card Sorting Test (WCST), (2) Digit Span subtest of the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV), (3) Test of Everyday Attention (TEA), (4) Brief Visuospatial Memory Test (BVMT), (5) Quality of Life in Epilepsy (QOLIE-31), (6) Beck Depression Inventory (BDI-2), and (7) a medical record review for drug treatment information. Earlier age of epilepsy onset predicted lower auditory attention span and working memory as assessed by digit span forward (DSF) and digit span backward (DSB). Additionally, larger AED load predicted lower visuospatial memory as assessed by BVMT-Delayed Recall (BVMT-DR). No relationship between either age of onset or AED load and quality of life in epilepsy was found. However, depression was highly correlated with quality of life. These results highlight the need to balance epilepsy control and AED effects, especially in early-onset epilepsy, and to gain awareness of the specific cognitive domains affected by epilepsy variables to effectively monitor and treat it.

Bone mineral density and fractures in institutionalised children with epilepsy and intellectual disability.

BACKGROUND: Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). METHODS: A dual-energy X-ray absorptiometry of lumbar spine (L1-L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. RESULTS: Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > - 2.0). Of the 16 children with a low BMD (Z-score ≤ - 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28-2.50 mmol/L) and (supplemented) vitamin D (16-137 nmol/L) were within the normal range. CONCLUSIONS: This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.

Seizures, Antiepileptic Drugs, and CKD.

There are 2 major categories of patients with seizures and chronic kidney disease (CKD): patients who develop acute symptomatic seizures in the setting of CKD and patients with epilepsy who at some point develop CKD. The incidence of uremic seizures with kidney failure is ∼10%. These seizures are often nonconvulsive and may mimic uremic encephalopathy. Recognition and management of such situations may be challenging for treating physicians who are non-neurologists. Furthermore, practitioners caring for patients with seizures with or without an established diagnosis of epilepsy in the setting of CKD frequently encounter challenges in the selection, loading, titration, and maintenance of antiepileptic drugs (AEDs) due to potentially altered pharmacokinetics of the AEDs. We review the pathophysiology of uremia, uremic seizures, and other neurologic complications of kidney failure; management approaches to the treatment of such complications; the relevant mechanisms of action and pharmacokinetics of AEDs with their use in CKD; and in particular, the management of AEDs in patients requiring hemodialysis therapy.

Increased frequency of psychosis after second-generation antiepileptic drug administration in adults with focal epilepsy.

OBJECTIVE: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP. METHODS: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures. RESULTS: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP. CONCLUSION: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated. METHODS: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n = 99) subjects with DRE, aged 5-16 years (n = 85) and 17-45 years (n = 14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n = 33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n = 33), or placebo (high oleic acid sunflower oil, n = 33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment. RESULTS: Fifty-nine subjects (n = 59) completed the study (59.6%). The average number of seizures per month were 9.7 ±â€¯1.2 in the EPA group, 11.7 ±â€¯1.5 in the DHA group, and 16.6 ±â€¯1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CI = 0.42-0.88, p = 0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p = 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p = 0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (p < 0.05). SIGNIFICANCE: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.

Termination of pregnancy in women with epilepsy - A retrospective single center study.

Antiepileptic drugs (AEDs) are commonly prescribed to women of childbearing age. As 0.3%-0.7% of all pregnancies occur in women with epilepsy (WWE), the effect of recurrent seizures and teratogenicity on pregnancy outcome and the fetus have been widely studied. Most of these studies have focused on live births. A significant number of terminated pregnancies in WWE were ignored in past studies, thus reducing the calculated incidence of congenital malformations and possible influence of AED exposure. We scrutinized the medical records at our medical center for termination of pregnancy (TOP) in WWE for the years 2004-2016. Fifty-eight TOPs occurred in WWE during these years. Reasons for TOP included spontaneous abortions necessitating medical intervention (46.6%), patient's request (31.0%), medically recommended (10.3%), and unknown (12.1%).

Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva.

AIM OF THE STUDY: The monitoring of antiepileptic drugs (AEDs) in clinical setting is important for measuring the efficacy of drugs and their safety and in personalizing drug therapy. We investigated the levels of AED, carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association in saliva compared with those in serum during the therapy. MATERIALS AND METHODS: In this study, we performed a prospective study of 116 persons with epilepsy (PWE; mean age 26.90 ± 11.83 years). Serum and saliva samples were collected at trough levels from the patients, who were under the treatment of CBZ, PHT and PHB either alone or in combination of these drugs for at least three months. The drug levels were assessed by high-performance liquid chromatography. RESULTS AND CONCLUSIONS: The number of males (n = 88; 75.86%) was higher than females (n = 28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these AEDs showed a significant correlation (p < 0.05) between serum and saliva. Interestingly, the levels of mono-therapy or bi-therapy showed a significant association (p < 0.05) between serum and saliva, however, there was no significant association in case of poly-therapy. This is the first report in the Indian population on simultaneous estimation of the three commonly used AEDs, such as CBZ, PHT and PHB in serum and saliva implicating their associations, either in mono-therapy or bi-therapy in PWE.

Pharmacodynamic and pharmacokinetic analysis of CNS-active constitutional isomers of valnoctamide and sec-butylpropylacetamide--Amide derivatives of valproic acid.

Valnoctamide (VCD) and sec-butylpropylacetamide (SPD) are CNS-active closely related amide derivatives of valproic acid with unique anticonvulsant activity. This study evaluated how small chemical changes affect the pharmacodynamics (PD; anticonvulsant activity and teratogenicity) and pharmacokinetics (PK) of three constitutional isomers of SPD [sec-butylisopropylacetamide (SID) and tert-butylisopropylacetamide (TID)] and of VCD [tert-butylethylacetamide (TED)]. The anticonvulsant activity of SID, TID, and TED was comparatively evaluated in several rodent anticonvulsant models. The PK-PD relationship of SID, TID, and TED was evaluated in rats, and their teratogenicity was evaluated in a mouse strain highly susceptible to teratogen-induced neural tube defects (NTDs). sec-Butylisopropylacetamide and TID have a similar PK profile to SPD which may contribute to their similar anticonvulsant activity. tert-Butylethylacetamide had a better PK profile than VCD (and SPD); however, this did not lead to a superior anticonvulsant activity. sec-Butylisopropylacetamide and TED did not cause NTDs at doses 4-7 times higher than their anticonvulsant ED50 values. In rats, SID, TID (ip), and TED exhibited a broad spectrum of anticonvulsant activity. However, combined anticonvulsant analysis in mice and rats shows SID as the most potent compound with similar activity to that of SPD, demonstrating that substitution of the isobutyl moiety in the SPD or VCD molecule by tert-butyl as well as a propyl-to-isopropyl replacement in the SPD molecule did not majorly affect the anticonvulsant activity.

Demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage in different types of corpus callosum disorders: a comparative study in children.

BACKGROUND: This study aimed to investigate the demographic and clinical characteristics, types of seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. METHODS: A total of 73 individuals were included in the study and divided into three groups based on the type of corpus callosum abnormality: hypoplasia (H), agenesis (A), and dysgenesis (D). Demographic data, including gender and preterm birth, as well as clinical characteristics such as seizure disorders, attention deficit hyperactivity disorder (ADHD), severe developmental delay/intellectual disability, and other brain malformations, were analyzed. The types of seizure disorders and antiepileptic drugs used were also examined. RESULTS: The H group had the highest number of participants (n = 47), followed by the A group (n = 11) and the D group (n = 15). The A group had the highest percentage of males and preterm births, while the D group had the highest percentage of seizure disorders, other brain malformations, and severe developmental delay/intellectual disability. The A group also had the highest percentage of ADHD. Focal seizures were observed in all three groups, with the highest proportion in the A group. Focal impaired awareness seizures (FIAS) were present in all groups, with the highest proportion in the D group. Generalized tonic-clonic seizures (GTCS) were observed in all groups, with the highest proportion in the H group. Different types of antiepileptic drugs were used among the groups, with variations in usage rates for each drug. CONCLUSION: This study provided insights into the demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. Significant differences were found between the groups, indicating the need for tailored management approaches. However, the study has limitations, including a small sample size and a cross-sectional design. Further research with larger sample sizes and longitudinal designs is warranted to validate these findings and explore the relationship between corpus callosum abnormality severity and clinical outcomes.

In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models.

Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABAA, -8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action.

A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment.

Background and Objective: In traditional Chinese medicine (TCM), natural drugs and their bioactive components have been widely used to treat epilepsy. Epilepsy is a chronic disease caused by abnormal discharge of brain neurons that leads to brain dysfunction and cognitive impairment. Several factors are involved in the mechanisms of epilepsy, and the current treatments do not seem promising. The potential efficacy of natural drugs with lower toxicity and less side effects have attracted increasing attention. Methods: We used the terms, "TCM", "traditional Chinese medicine", "herbal", "epilepsy", "seizure", and the name of each prescription and bioactive components in the review to collect papers about application of TCM in epilepsy treatment from PubMed online database and Chinese database including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Key Content and Findings: We summarized some common TCM prescriptions and related active components used for the treatment of epilepsy. Six prescriptions (Chaihu Shugan decoction, Tianma Gouteng decoction, Kangxian capsules, Taohong Siwu decoction, Liujunzi decoction, Compound Danshen dropping pills) and nine main bioactive compounds (Saikosaponin A, Rhynchophylline, Tetramethylpyrazine, Gastrodin, Baicalin and baicalein, α-Asarone, Ginsenoside, Tanshinone, Paeoniflorin) were reviewed to provide a scientific basis for the development of potential antiepileptic drugs (AEDs). Conclusions: The pharmacological effects and molecular mechanisms of TCM in the treatment of epilepsy are complex, targeting several pathological aspects of epilepsy. However, the limitations of TCM, such as the lack of standardized treatments, have prevented its clinical application in epilepsy treatment. Thus, additional clinical trials are required to further evaluate the effectiveness and safety of TCM prescriptions and their bioactive components in the future.

Comorbid epilepsy and depression-pharmacokinetic and pharmacodynamic drug interactions.

Background: Major depressive disorder may be encountered in 17% of patients with epilepsy and in patients with drug-resistant epilepsy its prevalence may reach 30%. This indicates that patients with epilepsy may require antidepressant treatment. Purpose: Both pharmacodynamic and pharmacokinetic interactions between antiepileptic (antiseizure) and antidepressant drugs have been reviewed. Also, data on the adverse effects of co-administration of antiepileptic with antidepressant drugs have been added. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology. Methods: The review of relevant literature was confined to English-language publications in PUBMED databases. Table data show effects of antidepressants on the seizure susceptibility in experimental animals, results of pharmacodynamic interactions between antiepileptic and antidepressant drugs mainly derived from electroconvulsions in mice, as well as results concerning pharmacokinetic interactions between these drugs in clinical conditions. Conclusion: Antidepressant drugs may exert differentiated effects upon the convulsive threshold which may differ in their acute and chronic administration. Animal data indicate that chronic administration of antidepressants could reduce (mianserin, trazodone) or potentiate the anticonvulsant activity of some antiepileptics (fluoxetine, reboxetine, venlafaxine). There are also examples of neutral interactions (milnacipran).

Sodium Valproate Combined With Topiramate vs. Sodium Valproate Alone for Refractory Epilepsy: A Systematic Review and Meta-Analysis.

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population. Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic-clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies. Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I 2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = -6.02; 95% CI -6.50 to -5.54; I 2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = -4.56, 95% CI -6.02 to -3.10; I 2 = 82.6%) and lower frequency of tonic-clonic seizures (WMD = -3.32; 95% CI -4.75 to -1.89; I 2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups. Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Pharmacological Investigations in Glia Culture Model of Inflammation.

Astrocytes and microglia are the main cell population besides neurons in the central nervous system (CNS). Astrocytes support the neuronal network via maintenance of transmitter and ion homeostasis. They are part of the tripartite synapse, composed of pre- and postsynaptic neurons and perisynaptic astrocytic processes as a functional unit. There is an increasing evidence that astroglia are involved in the pathophysiology of CNS disorders such as epilepsy, autoimmune CNS diseases or neuropsychiatric disorders, especially with regard to glia-mediated inflammation. In addition to astrocytes, investigations on microglial cells, the main immune cells of the CNS, offer a whole network approach leading to better understanding of non-neuronal cells and their pathological role in CNS diseases and treatment. An in vitro astrocyte-microglia co-culture model of inflammation was developed by Faustmann et al. (2003), which allows to study the endogenous inflammatory reaction and the cytokine expression under drugs in a differentiated manner. Commonly used antiepileptic drugs (e.g., levetiracetam, valproic acid, carbamazepine, phenytoin, and gabapentin), immunomodulatory drugs (e.g., dexamethasone and interferon-beta), hormones and psychotropic drugs (e.g., venlafaxine) were already investigated, contributing to better understanding mechanisms of actions of CNS drugs and their pro- or anti-inflammatory properties concerning glial cells. Furthermore, the effects of drugs on glial cell viability, proliferation and astrocytic network were demonstrated. The in vitro astrocyte-microglia co-culture model of inflammation proved to be suitable as unique in vitro model for pharmacological investigations on astrocytes and microglia with future potential (e.g., cancer drugs, antidementia drugs, and toxicologic studies).

Therapeutic levetiracetam monitoring during pregnancy: "mind the gap".

BACKGROUND: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy. METHODS: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy. RESULTS: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed (p = 0.945, p = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range. CONCLUSIONS: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome.

Antiepileptic drug therapy in the elderly: a clinical pharmacological review.

Seizure disorder is the third most common neurological disorder in the elderly after stroke and dementia. With the increasing geriatric population, the situation of clinicians seeing more and more elderly epilepsy patients is very likely. Not only is the diagnosis of epilepsy tedious in the elderly, its management raises many challenging issues for the treating physicians. Altered physiology, age-related decline in organ function, and plasma protein binding and altered pharmacodynamics make the elderly patients with seizure disorder a difficult group to treat. This is further complicated by the presence of comorbidities and polypharmacy which increase the chances of drug interactions. The adverse effects that might be tolerated well in younger populations may be disastrous for the aged. Although the newer antiepileptic drugs are found to have a favorable safety profile, there is relative scarcity of randomized-controlled trials involving older and newer antiepileptics in the geriatric population. This review tries to compile the available literature on management of epilepsy in the elderly population including evidence of safety and efficacy of newer and older antiepileptics with special reference to the 'geriatric giants'. It also deals with the interactions between antiepileptic medications and other commonly prescribed drugs in the elderly such as anti-hypertensives and antiischemic agents. The recommended guidelines of various international bodies are also analyzed from the perspective of elderly with seizure disorder.

Development of a rapid and reliable single-tube multiplex real-time PCR method for HLA-A*24:02 genotyping.

Aim:HLA-A*24:02 is significantly associated with cutaneous adverse drug reactions caused by aromatic antiepileptic drugs. Here, we aimed to establish a fast and reliable detection method for HLA-A*24:02 genotyping. Methods: A single-tube multiplex quantitative real-time polymerase chain reaction (qPCR) assay for HLA-A*24:02 genotyping was established by combining allele-specific primers with TaqMan probes. Results: A 100% concordance was observed between qPCR and SBT result in 106 Han subjects. The detection limit of the new method was 0.05 ng DNA. The positive rate of HLA-A*24:02 in Tibetans (55.6%, n = 81) was significantly higher than those in Han (34%, n = 106), Uighur (27.5%, n = 102), Bouyei (25.9%, n = 116) and Miao populations (26.5%, n = 113). Conclusion: The newly established qPCR assay was reliable for HLA-A*24:02 screening in clinical applications.

Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation.

The aim of this review is to discuss the research presented in a symposium entitled "Current progress in characterizing therapeutic strategies and challenges in experimental CNS injury" which was presented at the 2016 International Behavioral Neuroscience Society annual meeting. Herein we discuss diffuse and focal traumatic brain injury (TBI) and ensuing chronic behavioral deficits as well as potential rehabilitative approaches. We also discuss the effects of stress on executive function after TBI as well as the response of the endocrine system and regulatory feedback mechanisms. The role of the endocannabinoids after CNS injury is also discussed. Finally, we conclude with a discussion of antipsychotic and antiepileptic drugs, which are provided to control TBI-induced agitation and seizures, respectively. The review consists predominantly of published data.

Variability in expression of the human MDR1 drug efflux transporter and genetic variation of the ABCB1 gene: implications for drug-resistant epilepsy.

Among individuals diagnosed with epilepsy, as many as one in three develop resistance to antiepileptic drugs (AEDs) thus rendering their seizures refractory to treatment. Despite current antiepileptic drugs (AEDs) having a variety of modes of action, seizures in drug-resistant individuals often persist even after treatment with two or more drugs. The underlying cause of this broad resistance is currently under debate, but two dominant theories have emerged and have been widely studied. Here we discuss current literature investigating the "transporter theory", the idea that individuals present with drug resistance due to genetic variability in the ABCB1 gene encoding the efflux transporter multidrug resistance protein 1 (MDR1). Results of in vitro and in vivo studies suggest that variability in the expression of the MDR1 transporter may be closely tied to drug resistance. While there is much support for this hypothesis from molecular and mechanistic studies, population-based studies of ABCB1 polymorphisms are divergent in their conclusions, and there is need for additional investigations.

[The decreased level of plasma carnitine in patients with epilepsy]. / Snizhenie kontsentratsii karnitina u patsientov s épilepsiei.

Antiepileptic drugs (AEDs) have long been known to affect carnitine metabolism, dropping the plasma free carnitine. Valproate (VPA) was considered to be the strongest carnitine-reducing agent. VPA-induced hyperammonemic encephalopathy and hepatotoxicity are well known, and pre-existing carnitine deficiency can be a predisposing factor, especially in congenital metabolic disorders. Several studies have shown that carnitine supplementation in patients receiving VPA to result in subjective and objective improvements and to prevent VPA-induced hepatotoxicity and encephalopathy, in parallel with increases in carnitine serum concentrations. Level of free plasma carnitine <20 micromol/l (syn. carnitine deficiency) in patients with epilepsy (in 15-30% of cases) may occur not only with administration of VPA but with administration of other AEDs (phenobarbital, phenytoin, carbamazepine) and low nutritional intake of carnitine. Some findings indicate that the number of AEDs used is a risk factor for carnitine deficiency. It was established that body weight, height and multidrug therapy are significantly associated with low level of free plasma in epileptic patients. Carnitine deficiency can have severe consequences; but most epileptic patients suffering from it are asymptomatic. Although carnitine deficiency is not uncommon among patients receiving AEDs, it seems not necessary to routinely monitor carnitine levels in epileptic ambulatory patients, this is reasonable only in groups of risk. L-carnitine supplementation is clearly indicated in case of VPA-induced hepatotoxicity (i.v. administration) VPA overdose (i.v. administration), primary carnitine-transporter defect and is strongly recommended in specific secondary carnitine deficiency syndromes, symptomatic VPA-associated hyperammonemia, infants and young children receiving VPA, especially those younger than 2 years, patients with a complex neurologic disorder, who are receiving multiple AEDs, patients who have risk factors for hepatotoxicity and carnitine insufficiency. In the absence of double blind trials, clinical practice is based on empiric observation, clinical experience, and theory. Well-designed studies of specific and general uses of L-carnitine replacement therapy in patients with epilepsy are needed.