Medical Treatment Of Epilepsy Research Articles

New approach for barbiturates, phenytoin, methyprylon and glutethimide determination and fragmentation (UHPLC-MS/MS)

Barbiturates which are old pharmaceutical drugs are still widely used in medical treatment of epilepsy and for general anesthesia. To date, more than 2500 different barbituric acid analogs have been synthesized, and 50 of them were introduced into medical use over the last century. Due to their highly addictive properties, pharmaceuticals containing barbiturates are under strict control in many countries. However, by considering the worldwide problem with new psychoactive substances (NPS) the introduction of new designer barbiturate analogs into the dark market might serve a serious public health problem in the near future. For this reason there is an increasing need for application methods for barbiturates monitoring in biological samples. The UHPLC-QqQ-MS/MS method for determination of 15 barbiturates, phenytoin, methyprylon and glutethimide was developed and fully validated. The biological sample volume was reduced to only 50 µL. A simple LLE (pH 3 with ethyl acetate) was successfully applied. The lower LOQ was 10 ng/mL. The method enables differentiation of structural isomers: hexobarbital and cyclobarbital; as well as amobarbital and pentobarbital. Chromatographic separation was achieved with the use of the alkaline mobile phase (pH 9) and Acquity UPLC BEH C18 column. Furthermore, the novel fragmentation mechanism of barbiturates was proposed, which may have a great impact in identification of novel barbiturates analogs introduced to illegal marketplaces. The presented technique has a great potential to be applied in forensic, clinical and veterinary toxicological laboratories, as was evidenced by the positive results of international proficiency tests.

EVALUATION OF ANTICONVULSANT ACTIVITY OF CALLISTEMON CITRINUS (CURTIS) SKEELS (MYRTACEAE) VOLATILE OIL

The use of medicinal plants is on the rise due to the increase of various diseases and shortcomings of orthodox medicine. For many ailments including convulsion, conventional medicine has not been able to find a lasting solution. This study was directed towards assessing the ethnomedicinal use of Callistemon citrinus leaves in the management of convulsion. The volatile oil of the leaves was extracted and an acute toxicity test was carried out following Lorke’s description. Maximal electroshock (MES), strychnine and pentylenetetrazol anticonvulsant methods were used. Separate groups of albino mice were given 200, 400 and 800 mg/kg doses of the volatile oil. Drug solutions; 30 mg/kg phenobarbitone for MES and 2 mg/kg diazepam for strychnine and pentylenetetrazol models were administered as a positive control. The start of tonic leg extension, duration and percentage mortality was recorded. Doses of 200 and 400 mg/kg significantly (P<0.05) inhibited seizure in the mice with scores of 40 % each in the MES model. There was a dose-dependent reduction in the duration of seizures with 68.47, 70.27 and 81.08 % reductions in the pentylenetetrazol model. No significant coverage was given in the strychnine model. C. citrinus oil protected the mice against pentylenetetrazol and maximal electroshock-induced convulsion hence could contribute to the medical treatment of epilepsy.

Changes in epilepsy causes of death: A US population study.

Since 2000, medical treatment for epilepsy and cardiovascular risk-reduction strategies have advanced significantly in the United States (US). However, seizure-free rates remain unchanged, and people with epilepsy are at higher risk than the general population for heart disease and stroke. The purpose of this study is to determine how cardiovascular, epilepsy-related, and other causes of death are changing in epilepsy in comparison with the US population. Changes in the 15 underlying causes of death in epilepsy (ICD-10 G40-G40.9) and the US population were analyzed and compared from 2000 to 2018. The CDC multiple cause-of-death database was utilized as the primary data source. Changes in the relative proportions for each cause-of-death over were evaluated using logistic regression. The proportions of deaths in epilepsy due to heart disease declined 34.4% (p<.001), a rate similar to the general population (39.9%). Epilepsy-related deaths declined 25% as a percentage of all epilepsy deaths (p<.001). The proportions of deaths due to stroke and neoplasms increased significantly in epilepsy versus the US population (p<.001 linear trend). The reduction in ischemic heart disease in epilepsy is a novel and highly significant finding, which reflects widespread implementation of cardiovascular risk-factor reduction and treatment in the United States. Reductions in epilepsy-related deaths are an exciting development which requires further investigation into causality. The increase in deaths due to neoplasms and stroke relative to the US population is concerning, warranting vigilance and increased efforts at recognition, prevention, and treatment.

The medical treatment of epilepsy in the elderly: A systematic review and meta-analysis.

To evaluate the efficacy and tolerability of antiepileptic drugs (AEDs) in elderly individuals with epilepsy. We searched four electronic databases as well as bibliographies and conference abstracts. Published and unpublished, randomized, or quasirandomized trials reporting the use of AEDs in people aged at least 60 years with epilepsy were eligible for inclusion. Two authors independently carried out each stage of the review. Meta-analyses were performed using random-effects models. Three thousand four hundred seventeen titles and abstracts were reviewed. Eighteen studies evaluating 12 AEDs met all eligibility criteria. Ten studies, comprising 1999 subjects, were suitable for meta-analysis. Among the elderly with epilepsy, lamotrigine (LTG) is better tolerated relative to carbamazepine (pooled weighted risk ratio [RR] of experiencing withdrawal due to adverse events=1.83, 95% confidence interval [CI] = 1.23-2.43). There is a higher probability, although with a 95% CI of borderline importance, of seizure freedom when comparing levetiracetam to LTG (RR=0.83, 95% CI = 0.68-0.97). Single studies provide evidence for the efficacy and/or tolerability of other AEDs in the elderly, including brivaracetam, gabapentin, lacosamide, perampanel, and topiramate. The risk of bias of the included studies was frequently low or unclear, although there was on occasion a high risk of bias (especially with regard to selective reporting). There is some evidence for AED use in the elderly with epilepsy. More evidence is required, comparing newer AEDs to prior generations as well as examining the effects of determinants such as frailty, to guide clinicians when treating this rapidly growing patient population.

Analysis of the efficacy of antiepileptic drugs in the treatment of infantile spasms and focal epilepsy associated with tuberous sclerosis complex

Background. Adequate selection of the 1st antiepileptic drug (AED) is an obligatory condition for the successful treatment of epilepsy. It is well known that the first drug in the treatment of infantile spasms (IS) in tuberous sclerosis complex (TSC) is vigabatrin (VGB). With regard to focal seizures (FS) in TSC, there are certain differences: some authors insist on VGB (P. Curatolo, 2012), others as the first choice drugs are mentioning carbamazepine and valproate (A. Saxena, 2015). Data in general on the possible effectiveness of medical treatment of epilepsy in TSC, and the effectiveness of different AEDs are also contradictory.Objective: to make a comparative evaluation of the efficacy of various AEDs in the treatment of epilepsy in patients with TC.Materials and methods. Retrospective analysis of medical records of patients hospitalized with epilepsy and TSC in the Department of Epileptology and Psychoneurology, Research and Clinical Institute for Pediatrics named after Yu.E Vel’tishev of N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, for the last 2 years was completed. Efficacy analysis was conducted in 134 patients (91 (67.9 %) with FS and 43 (32.1 %) with IS). Efficacy was estimated as the remission of epileptic seizures during 6 months. The percentage of patients with remission was also evaluated (seizures were stopped for 1 year or more) and percentage of patients with a decrease in the number of seizures. The results of the first monotherapy and the subsequent administration of two and three AEDs were analyzed.Results. Low efficiency of AEDs in starting monotherapy was noted – the remission of seizures within 6 months on any AED was only 27.5 % (25 from 91) with FS, with IS – 13.9 % (6 from 43). Remission on any 1st AED was observed only in 13.2 % (12 from 91) and 6.9 % (3 from 43), respectively. The effectiveness of individual AED is low, especially in achieving stable remission. So, valproate caused remission of FS in 14 (22.2 %) from 63, but in the future remission was stable only in 11 (17.5 %) from 63. VGB as the first monotherapy proved to be effective in 5 from 6 patients with FS and in 4 from 6 patients with IS. The introduction of the 2nd drug added another 13.3 % and 38.6 % of patients with remission of seizures, the 3rd AED – 7.3 % and 7.7 % in FS and IS, respectively. Most often, an effective drug in additional therapy was VGB. The efficiency of VGB was reduced if it was used not as the first, but as the second and third AED. The percentage of unsuccessful treatment (including combined therapy) is estimated as 51.5 % and 47.8 % of patients with FS and IS, respectively.Conclusion. Epilepsy associated with TSC is less sensitive to AEDs and gives a smaller percentage of remissions. Perhaps in our country this is due to the difficulties of prescription of VGB as a starting therapy for epilepsy in the patients with tuberous sclerosis complex.

Guiding Ketogenic Diet with Breath Acetone Sensors.

Ketogenic diet (KD; high fat, low carb) is a standard treatment for obesity, neurological diseases (e.g., refractory epilepsy) and a promising method for athletes to improve their endurance performance. Therein, the level of ketosis must be regulated tightly to ensure an effective therapy. Here, we introduce a compact and inexpensive breath sensor to monitor ketosis online and non-invasively. The sensor consists of Si-doped WO3 nanoparticles that detect breath acetone selectively with non-linear response characteristics in the relevant range of 1 to 66 ppm, as identified by mass spectrometry. When tested on eleven subjects (five women and six men) undergoing a 36-h KD based on the Johns Hopkins protocol, this sensor clearly recognizes the onset and progression of ketosis. This is in good agreement to capillary blood β-hydroxybutyrate (BOHB) measurements. Despite similar dieting conditions, strong inter-subject differences in ketosis dynamics were observed and correctly identified by the sensor. These even included breath acetone patterns that could be linked to low tolerance to that diet. As a result, this portable breath sensor represents an easily applicable and reliable technology to monitor KD, possibly during medical treatment of epilepsy and weight loss.

Chemotherapy and immunotherapy of brain tumors: What the epileptologist must know

I present an overview of therapy for the most common brain tumors encountered in clinical practice if adult patients. Current therapy paradigms and evolving therapies are reviewed. The introduction of non-enzyme-inducing antiepileptic drugs (NEIADs) has simplified the approach to combined medical treatment of epilepsy and brain tumors, but the major interactions between enzyme-inducing antiepileptic drugs (EIAEDs) are included, to serve as guidance in selecting these medications if they are required.

Medikamentöse Therapie der Epilepsie

Modern medical treatment of epilepsy renders two out of three newly diagnosed epilepsy patients seizure-free. More than 20 drugs are currently available and even for epilepsy specialists it may not be easy to select the drug which is best suited for the individual patient. Current guidelines recommend drugs with proven efficacy and optimal tolerability that address the individual needs of the patient. Non-enzyme-inducing agents are preferred if possible, to protect the patient from loss of efficacy when taking other medications for life-threatening disorders. In one out of three patients, seizure freedom is currently not possible due to drug-resistance, which requires a prompt diagnostic and therapeutic reevaluation of the epilepsy.

The Genetics of Antiepileptic Drug–Induced Skin Reactions

Some antiepileptic drugs (AEDs) may cause allergic cutaneous reactions with significant morbidity and mortality, including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Many epilepsy treatment decisions, including the selection of a treatment agent, and how it is initiated, are influenced by the risk of these rare conditions. Consequently, identification of the genetic factors that predict occurrence of SJS and TEN has altered the medical treatment of epilepsy and increased its safety. Clinical Pharmacology & Therapeutics (2011) 89 6, 908–910. doi:10.1038/clpt.2010.357

Optimizing therapy of seizures in patients with brain tumors

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with structural brain lesions, and a role for multidrug-resistance proteins has been suggested. The medical treatment of epilepsy in brain tumor patients has mainly been studied retrospectively, and the optimal management of seizures with antiepileptic drugs (AEDs) is unclear. Enzyme-inducing anticonvulsants are generally not recommended because they can lead to insufficient serum levels of concomitantly administered chemotherapeutic drugs. Although valproic acid is an enzyme inhibitor and may therefore lead to toxic levels of simultaneously administered chemotherapeutic agents, this does not appear to be a major problem in patients with brain tumors. Preliminary observations of add-on treatment with the AEDs levetiracetam or gabapentin suggest that these non-enzyme-inducing AEDs can be useful for control of seizures in patients with brain tumors. Conversely, prophylactic use of AEDs in brain tumor patients is generally not recommended.

Optimal seizure management in brain tumor patients

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with a structural brain lesion, and a role for multidrug resistance proteins has been suggested. Until now, the medical treatment of epilepsy in brain tumor patients has only been studied retrospectively. Therefore, the optimal seizure management by antiepileptic drugs (AEDs) in this patient category is essentially unsure. Choices depend on the outcome of retrospective studies, a few nonrandomized series, extrapolation from other studies in symptomatic epilepsy, and anticipated interactions, most notably between AEDs and anticancer agents. The newly developed AEDs levetiracetam and gabapentin are recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents. The use of prophylactic AEDs in brain tumor patients is disputable and generally not advised.

Epilepsy among children in Greenland

Introduction. Epilepsy has been considered to be more frequent in Greenland than in Denmark, where the prevalence among children is 0.40 %. Study design. Evaluation of the prevalence, diagnosis and treatment of epilepsy among children in Greenland aged 0–15 years. Methods. During autumn 2000, 13 out of 18 hospitals in Greenland were visited. The population of children in the areas visited was 11,965 of a total of 15,226 in Greenland. All children with the diagnosis of epilepsy were referred for evaluation and the diagnosis was confirmed. When possible, informed consent was obtained to collect data from medical records Results. 43 children (18 boys) had the diagnosis of epilepsy. For 38 (15 boys) further data were obtained. Mean age was 8.5 years (3-14) for boys and 7.9 years (2-14) for girls. The age at diagnosis was 4.9 years (1-11) for boys and 4.2 years (0-10) for girls. The prevalence of epilepsy was 0.34%. In 31 cases an electroencephalograph (EEG) recording was done, comprising sleep recordings in 26 cases. Medication was according to recommendations in Denmark. Conclusion. The prevalence of epilepsy in children and the medical treatment of epilepsy among children in Greenland is the same as in Denmark.

Medical treatment of epilepsy

The licensing of new antiepileptic drugs (AEDs) has led to a marked increase in the pharmaceutical armamentarium available for the treatment of epilepsy since 1990. The new drugs have now secured their place in the pharmacotherapy of epilepsy. The main reason for their success is their good general tolerability (especially with regard to cognitive function), the low rate of drug–drug interaction and the high anticonvulsant potency of some of the compounds. It is fortunate that many of the new AEDs have also proven effective in the treatment of generalised seizures, although they were originally developed for the treatment of focal seizures. However, the wide treatment choice has not solved the problems associated with the medical treatment of epilepsy. In monotherapy, none of the new AEDs have been shown to be superior in their potency to control seizures to older AEDs in comparative studies. Nonetheless, the greater choice of drugs allows treatment to be better tailored to the requirements of individual patients. Now there is a need to study patients whose seizures were not controlled by initial or alternative monotherapy to create an evidence-base for truly rational combination therapy in the future. Additional improvements in the medical treatment of epilepsy may come from AEDs currently in development, many of which use novel or unknown modes of action. So far, however, there is no evidence that any of these compounds will have radically different effects from the drugs currently available, or that they will have antiepileptic rather than purely anticonvulsant potential.

Current status of surgery in the management of epilepsy.

To review systematically the available evidence with regard to the current status of epilepsy surgery in the management of patients with epilepsy. A careful search of published literature, including Medline, published reviews, chapters, and cross-references thereof. With medical treatment of epilepsy being unsuccessful in many cases, the importance of surgical approaches cannot be underscored. Early surgery is the treatment of choice for patients with clear-cut mesial temporal sclerosis and results in significant clinical improvement in up to 80% of cases, provided the EEG, neuropsychological, and neuropsychiatric results are in concordance with this approach. In patients with poorly defined, widespread, or dual pathology, however, invasive recordings may be necessary, and while this is performed in major centres, the outcome is rather more variable in this group. Improved surgical techniques, and the use of stereotactic approaches and image guidance procedures, have resulted in surgical resections becoming more selective. With isolated structural lesions such as dysembryoplastic tumours, low-grade astrocytomas, or focal vascular abnormalities, total macroscopic and radiological evidence of lesional excision is associated with excellent seizure-free outcome. The first randomised controlled trial of epilepsy surgery has demonstrated clearly the efficacy of these techniques, and the risk of complications. Increasing sophistication of noninvasive presurgical evaluation enables surgical candidates to be identified at an earlier stage and presents a realistic alternative to medical treatment in many cases. The introduction of minimally invasive techniques has had a significant impact on surgical practice and its associated morbidity. The future of epilepsy surgery lies with continued basic science research and its application to clinical medicine.

Dipole source localization of ictal epileptiform activity in estimation of epileptogenic zone

Localization analysis of epileptogenic zone was performed by dipole tracing method with scalp–skull–brain head model (SSB-DT) in patients with intractable epilepsy. Eight temporal lobe epilepsy (TLE) and one frontal lobe epilepsy were studied. EEG was recorded by digital electroencephalograph with 21 scalp electrodes. Generator source of the peak of ictal epileptiform activity (IEA) was estimated by SSB-DT. All the patients underwent electrocorticography (ECoG) and resection of epileptogenic zone. Surgical outcome was good in every patient. Locations of generator source of the peak of IEA estimated by SSB-DT were consistent with locations of epileptogenic zone determined by ECoG and neuroimagings, such as magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). In TLE, medial and lateral temporal epileptogenic zone could be discriminated, which could not be determined by visual interpretation of scalp EEG. In medial TLE, as an advance of seizure, generator source of IEA either stayed in the medial temporal lobe, or propagated to the lateral temporal lobe. Locations of epileptogenic zone could be estimated by SSB-DT not invasively. Electrophysiological event in the brain during an advance of seizure attack could also be observed. Application of SSB-DT to IEA was useful in the medical treatment of epilepsy, especially in surgical planning for patients with medically intractable epilepsy.

Knowledge, attitudes and practice of epilepsy: experience at a comprehensive rural health services project

Beliefs regarding cause and preference of the treatment modality are important factors influencing any epilepsy programme. Patients own attitudes towards the on-going treatment are equally important in ensuring success of any such programme. The study involved interviews of 80 patients with epilepsy attending a comprehensive rural health services project, and was conducted according to a structured questionnaire. The majority of the patients were well informed regarding the cause of epilepsy, but more than half had tried alternative treatment methods. Many patients had misconceptions regarding the goal of the treatment and the consequences of missing a prescribed drug dose. Surprisingly few patients avoided taking medicines on days of religious fast. It was also noted that most patients depended on free medical supplies from the clinic dispensary, and a small number of patients would stop the medicines if these were not given free of cost. We stress the need to understand patients' concepts about the cause and the treatment of epilepsy, the need to educate them and their families regarding principles of modern medical treatment of epilepsy and most importantly, the need to maintain a regular, uninterrupted supply of free medicines, to improve the effectiveness of similar epilepsy management programmes in the setting of rural India and other developing countries.

Medical Treatment of Epilepsy

Medical Treatment of Epilepsy

New antiepileptic drugs.

For many years, the medical treatment of epilepsy was based on the use of the same few drugs, which were chosen according to the seizure type in a fairly standardized manner. In the recent past, there have been several changes, and more are expected in the near future. Since 1993, three new antiepileptic drugs have been released in the United States, and two more are expected to be released before the end of 1997. Because the full spectrum of efficacy and side effects of these drugs has not yet been established, the present management of epilepsy requires a larger degree of flexibility, and it is necessary to become acquainted with the new drugs and to follow closely new reports on the experience with new drugs. This is particularly true for the management of epilepsy in children, because controlled studies in children tend to be completed later than those in adults and antiepileptic drug use in children is often "off label." The present review of newer antiepileptic drug consists of a brief summary of background information on each drug, followed by a closer analysis of recently published papers. Information on pediatric use is reviewed, when available. The new antiepileptic drugs selected for discussion are gabapentin, lamotrigine, felbamate, vigabatrin, and topiramate.

The Medical Treatment of Epilepsy; Non-Epileptic Seizures

The Medical Treatment of Epilepsy; Non-Epileptic Seizures

Progress in the medical treatment of epilepsy: an overview of new antiepileptic drugs

Progress in the medical treatment of epilepsy: an overview of new antiepileptic drugs