Drug Treatment Of Epilepsy Research Articles

Sodium Valproate-Induced Hyperammonemia: A Case Series in a Tertiary Care Hospital.

Sodium valproate (VPA) is an extensively used anti-convulsant, which is an effective drug for treatment of epilepsy in adults and children, as well as for conditions like migraine, bipolar disorder, mania, and trigeminal neuralgia. Sedation, vertigo, ataxia, dose-dependent tremors, headaches, and gastrointestinal side effects are the most often reported adverse effects associated with VPA. A potential life-threatening event reported with VPA is hyperammonemia (HA), which is defined as an increase in serum level of ammonia. Only 587 reported cases of HA were found in the VigiAccess database, representing a mere 0.6% of the 95,000 reported adverse events linked to VPA. Hence, this case series was conducted with emphasison monitoring of increased serum ammonia levels with or without hepatic enzymes increase for patients who are on VPA. To assess elevated serum ammonia levels following VPA administration, and to ascertain the percentage of individuals with hepatic enzymes increased who took VPA and subsequently had elevated serum ammonia levels. This study was conducted at the adverse drug reaction (ADR) monitoring centre (AMC) of the Pharmacovigilance Programme of India (PvPI) and Department of Psychiatry, Christian Medical College and Hospital (CMC&H), Ludhiana. The study comprised of 12 patients who were exclusively on VPA and exhibited symptoms related to elevated serum ammonia.An informed consent form (ICF) was provided to the patient prior to taking their personal details. Laboratory investigations were done to establish the diagnosis and liver function tests (LFTs), chiefly ALT (alanine transferase) and AST (aspartate aminotransferase) were also performed.It is a descriptive study which was for a time period of six months. Results: This study includes 12 patients who had HA confirmed by laboratory investigation. Out of these 12 patients, two patients (17%) had a corresponding increase in LFT. The average as of the patients was 53.08 years and average serum ammonia levels were 219.15. None of the patients who presented with HA progressed to hyperammonemic encephalopathy (HAE). This case series on valproate-induced HAshould be of interest to psychiatrists, physicians, internists, family medicine physicians, hospitalists, and surgeons who will have patients on VPA. Delay in recognition of HA can result in the development of potentially life-threatening complications.Rapid diagnosis and management will help in reducing the number of cases which progress to encephalopathy which is highly fatal.

The efficacy and safety of novel antiepileptic drugs in treatment of epilepsy of patients with brain tumors.

This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.

For the love of all that is holy, stop prescribing sodium valproate and carbamazepine together.

Sodium valproate and carbamazepine are two time-tested drugs for treatment of epilepsy. Individually, they are usually excellent choices in treating a broad spectrum of epileptic seizures. They are, however, not friendly with each other. Their co-administration affects the drug levels of each other by influencing the action of hepatic enzymes. This write up attempts to give an overview of the mechanism of this drug interaction, and informs readers why this combination is a bad choice. The author hopes that this will help in raising awareness among the physicians regarding the dangers of this prescription, and in putting a full stop to this practice.

Prophylactic Administration of Cannabidiol Reduces Microglial Inflammatory Response to Kainate-Induced Seizures and Neurogenesis

Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. Newly recognized as an Food and Drug Administration (FDA)-approved drug treatment in epilepsy, it has gained in popularity primarily for pain management. Although CBD is readily available in stores and online retailers, its mechanism of action and specifically its effects on microglia and their functions are yet fully understood. In this study, we examine the effects of commercially available CBD on microglia inflammatory activation and neurogenic response, in the presence and absence of seizures. We use systemic administration of kainate to elicit seizures in mice, which are assessed behaviorally. Artisanal CBD is given in different modes of administration and timing to dissect its effect on seizure intensity, microglial activation and aberrant seizure-related neurogenesis. CBD significantly dampens microglial migration and accumulation to the hippocampus. While long term artisanal CBD use does not prevent or lessen seizure severity, CBD is a promising adjunctive partner for its ability to depress epileptogenic processes. These studies indicate that artisanal CBD is beneficial as it both decreases inflammation in the CNS and reduces the number of ectopic neurons deposited in the hippocampal area post seizure.

Drug Treatment of Epilepsy: From Serendipitous Discovery to Evolutionary Mechanisms.

Epilepsy is a chronic brain disorder caused by the abnormal firing of neurons. Up to now, the use of antiepileptic drugs is the main method of epilepsy treatment. The development of antiepileptic drugs lasted for centuries. In general, most agents entering clinical practice act on the balance mechanisms of brain "excitability-inhibition". More specifically, they target voltage-gated ion channels, GABAergic transmission and glutamatergic transmission. In recent years, some novel drugs representing new mechanisms of action have been discovered. Although there are about 30 available drugs in the market, it is still in urgent need of discovering more effective and safer drugs. The development of new antiepileptic drugs is into a new era: from serendipitous discovery to evolutionary mechanism-based design. This article presents an overview of drug treatment of epilepsy, including a series of traditional and novel drugs.

General Marginal Regression Models for the Joint Modeling of Event Frequency and Correlated Severities with Applications to Clinical Trials

In many clinical trials, information is collected on both the frequency of event occurrence and the severity of each event. For example, in evaluating a new anti-epileptic medication both the total number of seizures a patient has during the study period as well as the severity (e.g., mild, severe) of each seizure could be measured. In order to arrive at a full picture of drug or treatment performance, one needs to jointly model the number of events and their correlated ordinal severity measures. A separate analysis is not recommended as it is inefficient and can lead to what we define as “zero length bias” in estimates of treatment effect on severity. This paper proposes a general, likelihood based, marginal regression model for jointly modeling the number of events and their correlated ordinal severity measures. We describe parameter estimation issues and derive the Fisher information matrix for the joint model in order to obtain the asymptotic covariance matrix of the parameter estimates. A limited simulation study is conducted to examine the asymptotic properties of the maximum likelihood estimators. Using this joint model, we propose tests that incorporate information from both the number of events and their correlated ordinal severity measures. The methodology is illustrated with two examples from clinical trials: the first concerning a new drug treatment for epilepsy; the second evaluating the effect of a cholesterol lowering medication on coronary artery disease.

Pathology-selective antiepileptic effects in the focal freeze-lesion rat model of malformation of cortical development

Malformations of cortical development (MCD) represent a group of rare diseases with severe clinical presentation as epileptic and pharmacoresistant encephalopathies. Morphological studies in tissue from MCD patients have revealed reduced GABAergic efficacy and increased intracellular chloride concentration in neuronal cells as important pathophysiological mechanisms in MCD. Also, in various animal models, alterations of GABAergic inhibition have been postulated as a predominant factor contributing to perilesional hyperexcitability. Along with this line, the NKCC1 inhibitor bumetanide has been postulated as a potential drug for treatment of epilepsy, mediating its antiepileptic effect by reduction of the intracellular chloride and increased inhibitory efficacy of GABAergic transmission.In the present study, we focused on the focal freeze-lesion model of MCD to compare antiepileptic drugs with distinct mechanisms of action, including NKCC1 inhibition by bumetanide. For this purpose, we combined electrophysiological and optical methods in slice preparations and assessed the properties of seizure like events (SLE) induced by 4-aminopyridine. In freeze-lesioned but not control slices, SLE onset was confined to the perilesional area, confirming that this region is hyperexcitable and likely triggers pathological activity. Bumetanide selectively reduced epileptic activity in lesion-containing slices but not in slices from sham-treated control rats. Moreover, bumetanide caused a shift in the SLE onset site away from the perilesional area. In contrast, effects of other antiepileptic drugs including carbamazepine, lacosamide, acezatolamide and zonisamide occurred mostly independently of the lesion and did not result in a shift of the onset region.Our work adds evidence for the functional relevance of chloride homeostasis in the pathophysiology of microgyrus formation as represented in the focal freeze-lesion model. Further studies in different MCD models and human tissue will be required to validate the effects across different MCD subtypes and species and to assess the translational value of our findings.

Fenfluramine for treatment-resistant epilepsy in Dravet syndrome and other genetically mediated epilepsies.

Fenfluramine hydrochloride, initially utilized as a weight loss drug in the 1970s and later removed from the market for adverse cardiopulmonary side effects, has since been repurposed as an antiseizure medicine (ASM). The potential antiseizure effects of fenfluramine were first identified in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. Compared with other ASMs, fenfluramine offers a novel mechanism by acting on serotonin and σ1 receptors, demonstrated in vitro and in vivo in animal models of Dravet syndrome. Results from a large double-blind, placebo-controlled trial demonstrated robust efficacy for seizure reduction in patients with Dravet syndrome, and met its primary endpoint with the 0.7 mg/kg/day fenfluramine treatment group experiencing a 62.3% or greater reduction in mean monthly convulsive seizure frequency (MCSF) compared with placebo. Here we provide a comprehensive review of the preclinical and clinical activity of fenfluramine, a recently approved drug for treatment of epilepsy in patients with Dravet syndrome.

Drug Utilization Pattern and Prescription Auditing of Antiepileptic Drugs and its Adverse Effects in Private Hospital

Background: Epilepsy is a common medical condition characterized by repeated seizures due to a disorder of the brain cells. The data was limited regarding the prescribing pattern and side effects of various antiepileptic drugs in private hospitals. The objective of the present study was to evaluate the prescribing pattern of Antiepileptic drugs in the management of various types of epileptic seizures over a period of twelve months. Methods: A prospective observational study was conducted among epileptic patients on follow up at neurology department of Life line hospital, Azamgarh. During the twelve months study period, epileptic patients who were prescribed with AED’s (antiepileptic drugs) were included in this study. Data were collected through the Patients case files. Results: Our study revealed male predominance over female. In 18-30(35.66%) age group, Patients were more prone to epilepsy. Total 145(48.33%) patients were diagnosed with generalized seizure. Headache (27.55%) was most commonly observed ADRs. Total 959 (94.57%) number of drugs were prescribed with brand name. Valproic acid (15.18%) was most commonly prescribed drugs for treatment of epilepsy for treatment of epilepsy which included 154 encounters. Avg. cost for 6 months of epileptic treatment was 64752.02. Average cost per prescription was Rs. 1553.50. Conclusion: This study highlights the need of drug utilization evaluation as it will help in analysing on-going health care practices, so that lacunae in the system can be identified and Proper strategies can be planned to rectify them. In recent times, there has been done an immense effort to ensure and implement rational drug use.

Epilepsy in Children with Tuberous Sclerosis Complex: A Prospective Observational Study in Bangladesh.

Background and PurposeEpilepsy is an important neurologic feature of patients with tuberous sclerosis complex (TSC). Most common seizure types are focal seizure and epileptic spasm. Seizure control often requires multiple antiepileptic drugs. This study has been done to evaluate the seizure types, electro-encephalography (EEG), neuroimaging features, and drug treatment of epilepsy in TSC.MethodsThis prospective observational study has been conducted on epilepsy patients with TSC at Bangabandhu Sheikh Mujib Medical University from 2011 to 2019.ResultsSeventy patients with a mean±standard deviation age of 5.64±3.96 years were identified and 57.1% were female. Most common type of seizure was focal seizure (46%). Epileptic spasm occurred in 17% of patients and all of them had seizure onset before 1 year. In 47% of patients EEG showed focal epileptic discharge; hypsarrhythmia was found in most of the patients with epileptic spasm. Majority of the patients needed more than one drug to control seizure. Only 34% of patients were seizure free for at least 12 months and 22.8% had drug resistant epilepsy.ConclusionsThis study highlights the pattern of seizure, treatment pattern, response to drug, and short-time outcome of children with TSC with epilepsy in a developing country like Bangladesh.

Chronic treatment with the new anticonvulsant drug lacosamide impairs learning and memory processes in rats: A possible role of BDNF/TrkB ligand receptor system

Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide – 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect.

Indication of antiepileptic drugs to patients with epilepsy: results of the survey of neurologists

To study knowledge and opinions of neurologists about priorities in using antiepileptic drugs (AEP). Eighty-one neurologists from Moscow and surrounding regions were surveyed to identify the factors that influenced the choice of AEP. Valproic acid was the most frequently used drug followed by levetiracetam and carbamazepine, which reflected the overall picture of PEP indication in patients with epilepsy in the Russian population. Levetiracetam occupies a leading position as the starting drug for treatment of epilepsy; most often prescribed to women, patients with generalized seizures and idiopathic epilepsy. It is the drug of choice as adjuvant remedies for Duo therapy.

Epigenetic Histone Deacetylation Inhibition Prevents the Development and Persistence of Temporal Lobe Epilepsy.

Epilepsy is a chronic brain disease characterized by repeated unprovoked seizures. Currently, no drug therapy exists for curing epilepsy or disease modification in people at risk. Despite several emerging mechanisms, there have been few studies of epigenetic signaling in epileptogenesis, the process whereby a normal brain becomes progressively epileptic because of precipitating factors. Here, we report a novel role of histone deacetylation as a critical epigenetic mechanism in epileptogenesis. Experiments were conducted using the histone deacetylase (HDAC) inhibitor sodium butyrate in the hippocampus kindling model of temporal lobe epilepsy (TLE), a classic model heavily used to approve drugs for treatment of epilepsy. Daily treatment with butyrate significantly inhibited HDAC activity and retarded the development of limbic epileptogenesis without affecting after-discharge signal. HDAC inhibition markedly impaired the persistence of seizure expression many weeks after epilepsy development. Moreover, subchronic HDAC inhibition for 2 weeks resulted in a striking retardation of epileptogenesis. HDAC inhibition, unexpectedly, also showed erasure of the epileptogenic state in epileptic animals. Finally, butyrate-treated animals exhibited a powerful reduction in mossy fiber sprouting, a morphologic index of epileptogenesis. Together these results underscore that HDAC inhibition prevents the development of TLE, indicating HDAC's critical signaling role in epileptogenesis. These findings, therefore, envisage a unique novel therapy for preventing or curing epilepsy by targeting the epigenetic HDAC pathway.

To evaluate the anticonvulsant activity of ethanolic extract of Moringa oleifera (drumstick leaves) in albino mice

Background: To evaluate the anti-convulsant activity of ethanolic extract of Moringa oleifera (Drum stick leaves) in seizure induced albino mice and to compare it with standard drug Sodium valproate.Methods: Swiss albino mice of either sex weighing around 25-30g were randomly selected and divided into four groups of six mice each. Group 1: control- treated with gum acacia. Group 2: Standard - Valproic acid 40mg/kg body weight. Group 3: T1- ethanolic extract of Moringa oleifera (150mg/kg). Group 4: T2 - ethanolic extract of Moringa oleifera (300mg/kg). All drugs were administered orally one hour prior to induction of seizure. The anticonvulsant activity was screened using maximal electroshock seizure (MES) model and pentylenetetrazole (PTZ) model.Results: Results were analysed by ANOVA followed by Bonferroni’s post hoc test. Abolition of Tonic hind limb extension was taken as the protective end point against MES induced seizures and prolongation of seizure latency in PTZ model.At both the doses the ethanolic extract of Moringa oleifera significantly (p value <0.05) reduced the duration of hind limb extension in MES test and also significantly (p value <0.05) delayed the onset of clonic seizures in PTZ induced convulsion when compared with control group.Conclusions: On comparing the percentage protection offered by Moringa oleifera leaves against both MES and PTZ model, it possesses significant anticonvulsant activity at both doses, with more efficacy at 300mg/kg BW indicating that the test drug can prove a very promising drug for treatment of epilepsy. Further studies are required for isolation and identification of the active constituent.

Increased expression of (immuno)proteasome subunits during epileptogenesis is attenuated by inhibition of the mammalian target of rapamycin pathway.

Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE). The effect of rapamycin was studied on (immuno)proteasome subunit expression in post-SE rats that were treated for 6 weeks. (Immuno)proteasome expression was validated in the brain tissue of patients who had SE or drug-resistant TLE and the effect of rapamycin was studied in primary human astrocyte cultures. In post-SE rats, increased (immuno)proteasome expression was detected throughout epileptogenesis in neurons and astrocytes within the hippocampus and piriform cortex and was most evident in rats that developed a progressive form of epilepsy. Rapamycin-treated post-SE rats had reduced (immuno)proteasome protein expression and a lower number of spontaneous seizures compared to vehicle-treated rats. (Immuno)proteasome expression was also increased in neurons and astrocytes within the human hippocampus after SE and in patients with drug-resistant TLE. In vitro studies using cultured human astrocytes showed that interleukin (IL)-1β-induced (immuno)proteasome gene expression could be attenuated by rapamycin. Because dysregulation of the (immuno)proteasome system is observed before the occurrence of spontaneous seizures in rats, is associated with progression of epilepsy, and can be modulated via the mTOR pathway, it may represent an interesting novel target for drug treatment in epilepsy.

Effect of intervention on self-esteem level in children with epilepsy based on cross theoretical model

Objective To investigate the effect of (the transtheoretical model of change,TTM) on the level of self-esteem in children with epilepsy (EP). Methods 65 cases of EP were divided into intervention group with 31 cases and control group with 34 cases by random number table. The two groups were treated with anti EP drug treatment and nursing, the use of the change stage and the Self-Esteem Scale (SES) for the baseline assessment, the intervention group according to the assessment results to develop individual TTM intervention measures, the control group received general health education and psychological care, for a period of 6 months. Two groups of patients were followed up for 6 months after hospital discharge, and the distribution of the changes in the changes of the patients and the change of self-esteem scores were analyzed. Results Before the intervention, two groups in the intention stage, preparation stage, operation stage and maintenance stage self-esteem score comparison, the difference was not statistically significant (P>0.05); 6 months after the intervention, the change of phase of self-esteem, the intervention group respectively were (22.61 + 2.88) points, (22.78 + 1.56) points, (24.03 + 1.5) points, (24.39 + 1.60) points, in the control group were (21.15 + 2.44) points, (21.39 + 2.21) points, (22.26 + 2.33) points, (22.01 + 2.31) points, with significant differences between the two groups (t=1.12-3.38, P<0.01). Two groups from the former intention phase to maintain the stage of change in the number of children were increased, the intervention group was better than the control group, the difference was statistically significant (χ2=15.00, P<0.01). Conclusions Using TTM as the guidance can improve the self-esteem of children with EP. Key words: Transtheoretical model; Children with epilepsy; Self-esteem; Intervention study

Evidence for Efficacy of Combination of Antiepileptic Drugs in Treatment of Epilepsy

Epilepsy is the tendency to have recurrent, unprovoked seizures. Although 70% of epileptic seizures can be controlled with monotherapy (treatment by single antiepileptic drug), a combination of two or more anti-epileptic drugs (AEDs) may be required to improve efficacy (seizure control) and tolerability. Polytherapy (treatment with two or more AEDs) can affect efficacies and side effects in additive, supra-additive (synergistic) or infra-additive fashion. The effect is considered supra-additive when the efficacy of the combination is greater than the sum of the individual drug efficacies, while it is considered infra-additive when the efficacy of the combination is less than the sum of the individual drug efficacies. Here, we have reviewed the available studies and evidences for the application of polytherapy in humans and animal models, to understand which combination of AEDs act as a synergistic polytherapy for epilepsy. We have searched the bibliographic databases MEDLINE and PubMed for studies conducted from 1950 to 2013 and have concluded that, although promising results from the experimental point of view support the combinations of topiramate separately with lamotrigine, gabapentin and felbamate, the most reliable evidence supports the use of valproate and lamotrigine, as this combination generates encouraging results in animal models. Though effectiveness of this combination is supported by human data, there is the possibility of increased side effects. The new drugs are all effective as add-on therapy; there is some evidence that at present, in clinical practice, levetiracetam and topiramate may be the most effective add-on therapies in partial and some generalized epilepsies. J Neurol Res. 2015;5(6):267-276 doi: http://dx.doi.org/10.14740/jnr356w

Evidence for Efficacy of Combination of Antiepileptic Drugs in Treatment of Epilepsy

Epilepsy is the tendency to have recurrent, unprovoked seizures. Although 70% of epileptic seizures can be controlled with monotherapy (treatment by single antiepileptic drug), a combination of two or more anti-epileptic drugs (AEDs) may be required to improve efficacy (seizure control) and tolerability. Polytherapy (treatment with two or more AEDs) can affect efficacies and side effects in additive, supra-additive (synergistic) or infra-additive fashion. The effect is considered supra-additive when the efficacy of the combination is greater than the sum of the individual drug efficacies, while it is considered infra-additive when the efficacy of the combination is less than the sum of the individual drug efficacies. Here, we have reviewed the available studies and evidences for the application of polytherapy in humans and animal models, to understand which combination of AEDs act as a synergistic polytherapy for epilepsy. We have searched the bibliographic databases MEDLINE and PubMed for studies conducted from 1950 to 2013 and have concluded that, although promising results from the experimental point of view support the combinations of topiramate separately with lamotrigine, gabapentin and felbamate, the most reliable evidence supports the use of valproate and lamotrigine, as this combination generates encouraging results in animal models. Though effectiveness of this combination is supported by human data, there is the possibility of increased side effects. The new drugs are all effective as add-on therapy; there is some evidence that at present, in clinical practice, levetiracetam and topiramate may be the most effective add-on therapies in partial and some generalized epilepsies. J Neurol Res. 2015;5(6):267-276 doi: http://dx.doi.org/10.14740/jnr356w

Treatment of epilepsy in China: Formal or informal.

Antiepileptic drugs are the preferred treatment approach for epileptic patients. However, informal treatment is important for intractable epilepsy. In this study, 500 epileptic patients were recruited from the General Hospital of Beijing Military Area Command of Chinese PLA during the period of October 2009 to January 2012. These involved patients that had been medically treated for at least 1 year. Information on the initial treatment and changes to treatment regimens for each patient was collected through questionnaires. The survey results showed that 52.3% of the epileptic patients searched for treatment after the first seizure, and the mean numbers of seizures was 12.8; 59.8% of the epileptic patients were diagnosed at the first visit, and the mean onset time was 17 months after the first seizure. After diagnosis, patients were treated for an average of 20 days, and the median time was 1 day. Formal anti-epileptic drugs were selected as the first treatment regimen by 67.8% of patients, and 77.5% of these drugs were monotherapies. The mean and median numbers of seizure were respectively 36.9 and 3.0 times before the first regimen was changed. The regimen was changed within the first 6 months by 46.6% of patients, and after the first and second years of treatment, the proportions increased to 54.0% and 71.8%, respectively. In total, 78.5% of the regimens were changed to informal treatments. The informal treatment of epilepsy in China is common, being initiated by either patients or physicians. Enhancing epileptic treatment services in hospital, improving physicians’ professional quality, and strengthening health propaganda may promote the normalization of drug treatment of epilepsy in China.

Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs

To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. Double-blinded, randomized, parallel, clinical trial. 46 AED-naïve dogs with naturally occurring epilepsy. Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs. Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 μg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], p.o., q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], p.o., q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end. Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.