Symptomatic Epileptic Seizures in Patients with Brain Gliomas

Introduction. Epileptic seizures are an important problem that significantly worsens the quality of patients’ life with both newly diagnosed and recurrent brain gliomas.Review. The analysis of domestic and foreign literature showed that low-grade gliomas, this symptom occurs on average in 76%, with high-grade gliomas – in 21% of patients. Despite the maximum allowable tumor resection, it is likely that epileptic seizures persist in 18-64% of patients, and in 5% of patients they first appear in the postoperative period. From 15 to 50% of epileptic seizures in cerebral gliomas are drug-resistant. In patients undergoing chemotherapy, it is better to use new antiepileptic drugs because their cross-effects are minimal.Conclusion. There is no generally accepted algorithm for prescribing and discontinuing antiepileptic drugs in patients with symptomatic epileptic seizures with cerebral gliomas. Further research is needed to determine the optimal combination and dosage regimen of antiepileptic drugs, especially during chemotherapy.

Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.

Drug treatment of epilepsy: From serendipitous discovery to evolutionary mechanisms

: Epilepsy is a chronic brain disorder caused by abnormal firing of neurons. Up to now, using 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.

Using routinely recorded data in a UK RCT: a comparison to standard prospective data collection methods

Background Routinely recorded data held in electronic health records can be used to inform the conduct of randomised controlled trials (RCTs). However, limitations with access and accuracy have been identified. Objective: Using epilepsy as an exemplar condition, we assessed the attributes and agreement of routinely recorded data compared to data collected using case report forms in a UK RCT assessing antiepileptic drug treatments for individuals newly diagnosed with epilepsy. Methods The case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK multicentre RCT assessing the clinical and cost-effectiveness of antiepileptic drugs as treatments for epilepsy. Ninety-eight of 470 eligible participants provided consent for access to routinely recorded secondary care data that were retrieved from NHS Digital Hospital Episode Statistics (N=71) and primary and secondary care data from The Secure Anonymised Information Linkage Databank (N=27). We assessed data items relevant to the identification of individuals eligible for inclusion in SANAD II, baseline and follow-up visits. The attributes of routinely recorded data were assessed including the degree of missing data. The agreement between routinely recorded data and data collected on case report forms in SANAD II was assessed using calculation of Cohen’s kappa for categorical data and construction of Bland-Altman plots for continuous data. Results There was a significant degree of missing data in the routine record for 15 of the 20 variables assessed, including all clinical variables. Agreement was poor for the majority of comparisons, including the assessments of seizure occurrence and adverse events. For example, only 23/62 (37%) participants had a date of first-ever seizure identified in routine datasets. Agreement was satisfactory for the date of prescription of antiepileptic drugs and episodes of healthcare resource use. Conclusions There are currently significant limitations preventing the use of routinely recorded data for participant identification and assessment of clinical outcomes in epilepsy, and potentially other chronic conditions. Further research is urgently required to assess the attributes, agreement, additional benefits, cost-effectiveness and ‘optimal mix’ of routinely recorded data compared to data collected using standard methods such as case report forms at clinic visits for people with epilepsy. Trial registration Standard and New Antiepileptic Drugs II (SANAD II (EudraCT No: 2012-001884-64, registered 05/09/2012; ISRCTN Number: ISRCTN30294119, registered 03/07/2012))

A newer horizon in non-pharmacological management of intractable epilepsy of childhood: the ketogenic diet

The ketogenic diet (KD) is a high fat, low carbohydrate and adequate protein diet that was formulated in the early 1920s as a treatment of intractable epilepsy, when only bromides and phenobarbitones were available. With the discovery of phenytoin in 1935 and other anticonvulsants in subsequent decades its popularity gradually waned off but recently KD has got a resurgence in the management of intractable epilepsy especially of childhood onset, despite the availability of increasing number of new Antiepileptic drugs and surgical techniques.

Recent advancements to enhance the therapeutic efficacy of antiepileptic drugs

Epilepsy is a multifactorial neurological disorder characterized by recurrent or unprovoked seizures. Over the past two decades, many new antiepileptic drugs (AEDs) were developed and are in use for the treatment of epilepsy. However, drug resistance, drug-drug interaction and adverse events are common problems associated with AEDs. Antiepileptic drugs must be used only if the ratio of efficacy, safety, and tolerability of treatment are favorable and outweigh the disadvantages including treatment costs. The application of novel drug delivery techniques could enhance the efficacy and reduce the toxicity of AEDs. These novel techniques aim to deliver an optimal concentration of the drug more specifically to the seizure focus or foci in the CNS without numerous side-effects. The purpose of this article is to review the recent advancements in antiepileptic treatment and summarize the novel modalities in the route of administration and drug delivery, including gene therapy, for effective treatment of epilepsy.

FEATURES OF MODERN PHARMACOTHERAPY OF EPILEPTIC STATUS

In the presented review of the literature, the most significant problems of modern pharmacotherapy of status epilepticus are indicated. The urgency of treatment of status epilepticus is confirmed by its frequency and ineffectiveness of traditional drugs (benzodiazepines, hydantoins, barbiturates), which have a number of side effects from the cardiovascular and respiratory systems. In Russian intensive care medicine, treatment of status epilepticus is carried out in accordance with international standards and recommendations. For a number of years, the injectable form of valproate has proven its effectiveness, including in pediatric practice. In comparative studies, phenytoin, valproate and levetiracetam are safe and equally effective in treating status epilepticus. A particular difficulty in therapy is caused by benzodiapine-resistant status epilepticus and refractory, which requires consideration of the possibility of using a combination of antiepileptic drugs. The review of foreign and domestic sources presents the results of clinical studies that allow the use of new antiepileptic drugs, which can effectively stop status epilepticus already in the early stages. New antiepileptic drugs are especially relevant in the treatment of patients refractory to drug treatment. However, treatment with antiepileptic drugs does not always show its effectiveness in refractory and super-refractory status epilepticus, which requires new approaches in complex treatment. The tolerance of drugs and the frequency of side effects are important for patients, since most of them require long-term combined use. Correct selection of antiepileptic drugs increases the level of compliance. A special approach requires the treatment of status epilepticus in the context of palliative care and comorbid pathology. In the treatment and prevention of status epilepticus, surgical treatment and the use of a ketogenic diet can be considered.

The role of picornavirus infection in epileptogenesis

Picornaviridae are a family of small positive-strand RNA viruses, and transmitted via the respiratory or fecal-oral route. The neurotropic picornaviruses can induce acute or late recurrent seizures following central nervous system infection, by infecting the peripheral nerve, crossing the blood-brain barrier and migrating in the Trojan-horse method. Theiler’s murine encephalomyelitis virus (TMEV), as a member of Picornaviridae family, can cause encephalitis, leading to chronic spontaneous seizures. TMEV-infected C57BL/6 mice have been used as an animal model for exploring the mechanism of epileptogenesis and assessing new antiepileptic drugs. Astrogliosis, neuronal death and microglial recruitment have been detected in the hippocampus following the picornaviruse-induced encephalitis. The macrophages, monocytes, neutrophils, as well as IL-6 and TNF-α released by them, play an important role in the epileptogenesis. In this review, we summarize the clinical characteristics of picornavirus infection, and the immunopathology involved in the TMEV-induced epilepsy.

The potential antiepileptogenic effect of neuronal Cx36 gap junction channel blockage

Epilepsy is one of the most prevalent neurological disorders and can result in neuronal injury and degeneration. Consequently, research into new antiepileptic drugs capable of providing protection against neuronal injury and degeneration is extremely important. Neuronal Cx36 gap junction channels have been found to play an important role in epilepsy; thus, pharmacological interference using Cx36 gap junction channel blockers may be a promising strategy for disrupting the synchronization of neurons during seizure activity and protecting neurons. Based on these promising findings, several in vivo and in vitro studies are ongoing and the first encouraging results have been published. The results bring hope that neurons can be protected from injury and degeneration in patients with epilepsy, which is currently impossible.