Search

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences"., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest with respect to this manuscript., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Brivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting., Design: Retrospective, observational multicentre study., Setting: We retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist., Participants: Data of 615 epilepsy patients treated with BRV were included in the study., Primary and Secondary Outcome Measures: Efficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X 2 contingency tests and effect sizes were performed., Results: Overall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV., Conclusions: The present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV., Competing Interests: Competing interests: KM has received honoraria as advisory board member from Eisai and UCB. FR has received personal fees from Bayer-Vital, Cerbomed, Eisai, Hexal and Sandoz, personal fees and support for continuing medical education activities from Desitin, Novartis, Shire and UCB Pharma and grants from DFG (German Research Foundation) and the European Union. SS-B reports personal fees from UCB, Eisai, Desitin Pharma, LivaNova, Bial, Novartis and Zogenix outside of the submitted work. FVP reports industry-funded travel with support of Desitin Arzneimittel, UCB Pharma, Eisai Pharma and BIAL, obtained honoraria for speaking engagements from Desitin Arzneimittel, UCB Pharma, Eisai Pharma and BIAL and was part of a speaker’s bureau of Desitin Arzneimittel, UCB Pharma and BIAL. RK reports industry-funded travel with support of Eisai Pharma and Desitin Arzneimittel. MH has received honoraria for lectures from pharmaceutical companies (Eisai, UCB) and research support for participation in clinical trials and registries from Medtronic, Cyberonics and Precisis. TM has received travel expenses for attending a meeting from UCB Pharma. YW received travel grants and honoraries for lectures from UCB Pharma, BIAL, Eisai, Bayer and Novartis, which were not related to the publication. LL has received lecture honoraria from Eisai. MC has received travel expenses for attending meetings from Desitin and Zogenix. AS reports personal fees and/or grants from Desitin Arzneimittel, Eisai, GW Pharma, LivaNova, Medtronic, Sage Therapeutics, UCB Pharma and Zogenix. SK reports honoraria for speaking engagements from Desitin and UCB as well as educational grants from AD Tech, Desitin Arzneimittel, Eisai, GW, Medtronic, Novartis, Siemens and UCB., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The relation between epilepsy and criminal acts has been debated for over a century. The general perception persists that epileptic seizures can be associated with violent behavior. Some studies have provided evidence for such an association; however, it remains uncertain whether it really exists. This review critically evaluates the scientific literature on the possible relation between epileptic seizures and criminal acts., Methods: A PubMed search was undertaken using the search terms "epilepsy and crime", "epilepsy and automatism", "epilepsy and law", and "epilepsy and dyscontrol syndrome" with the aim of identifying studies examining the possible association between epileptic seizure and crime., Results: The combined keywords "epilepsy and crime" yielded 495 articles, the keywords "epilepsy and automatism" 402 results, the keywords "epilepsy and law" 969 articles, and the keywords "epilepsy and dyscontrol syndrome" resulted in 22 search results. After removing publications such as reviews and opinion pieces, we identified and analyzed a total of 24 research articles with relevant original data. These included single case reports. The reviewed literature suggests that there are very rare occasions when criminal acts are committed during the ictal or postictal period, mostly by patients with focal epilepsy., Conclusion: The literature on the relation between epileptic seizures and criminal acts is not conclusive. Behavioral disturbances often seem more closely related to comorbidities of epilepsy than particular seizures characteristics. These comorbidities are often not well-described. There is an urgent need for more systematic and detailed data gathering and reporting, in order to allow a more detailed investigation of the relation between epileptic seizures and criminal acts., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although adjunctive treatment with modern antiepileptic drugs (AEDs) is standard care in refractory epilepsy, it is unclear how much of the effect can be attributed directly to the AEDs and how much to the beneficial changes seen with placebo. Therefore, we performed a systematic review and meta-analysis of the evidence to determine the placebo-corrected net efficacy of adjunctive treatment with modern AEDs on the market for refractory epilepsy. Of 317 potentially eligible articles reviewed in full text, 124 (39%) fulfilled eligibility criteria. After excluding 69 publications, 55 publications of 54 studies in 11,106 adults and children with refractory epilepsy form the basis of evidence. The overall weighted pooled-risk difference in favor of AEDs over placebo for seizure-freedom in the total sample of adults and children was 6% [95% confidence interval (CI) 4-8, z = 6.47, p < 0.001] and 21% (95% CI 19-24, z = 17.13, p < 0.001) for 50% seizure reduction. Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the placebo-corrected efficacy of adjunctive treatment with modern AEDs is disappointingly small and suggest that better strategies of finding drugs are needed for refractory epilepsy, which is a major public health problem.

Purpose and Background: Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies., Methods: Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered., Results: Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation., Conclusion: LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED., ((c) 2008 S. Karger AG, Basel.)

Objectives: We prospectively studied 26 (10 women) patients (age, 37.4 +/- 10.3 years) with different types of refractory focal epilepsy who received topiramate as adjunctive treatment., Methods: Body mass indices (BMI, kg/m2) and serum leptin levels (SLL) were investigated at baseline (n = 26) and 9.5 +/- 2.9 (T1; n = 21) and 25.0 +/- 3.5 (T2; n = 18) weeks after initiation of topiramate., Results: We found significant reductions in BMI (T1, -0.4 +/- 0.7; T2, -1.3 +/- 2.1 kg/m2) but not in SLL, although a tendency for reduced SLL was observed for women. Serum leptin level changes were mostly within the range between fifth and 95th sex-specific BMI-adjusted reference percentiles. Significant inverse correlations were found between baseline values and changes in both BMI (T2; r = -0.76; P < 0.001) and SLL (T2; r = -0.65; P = 0.003). Patients with BMI of 30.0 kg/m2 or greater showed the highest weight loss at T2 (-4.8 +/- 3.2 kg/m2)., Conclusions: Our findings do not provide evidence for a direct causal involvement of leptin in topiramate-related weight loss.

Background: Valproate (VPA) is an antiepileptic drug with a broad spectrum of efficacy. Although usually well-tolerated, it may have side-effects of which encephalopathy is one of the most serious., Objective: To describe the clinical characteristics of valproate encephalopathy (VE) in five older patients with remote symptomatic seizures treated with rapid VPA loading., Design: Case series., Setting: Teaching hospital, Patients: Five patients (71-89 years old) with underlying cerebrovascular disease or dementia and symptomatic seizures., Results: VE was characterised by decline in conscious level and (in some cases) increase in seizure frequency. Three of the five patients had elevated ammonia levels. EEG showed generalised slow activity, in some cases accompanied by additional epileptic discharges. The condition was reversible in four patients after VPA discontinuation. One patient died., Conclusions: Older people may be at particular risk of VE because of co-morbid pathology, age-related metabolic changes and co-medication.

Up to 50-60% of patients with epilepsy may develop psychiatric complications, in particular depression, anxiety, and psychotic disorders. Although this comorbidity has received a great deal of attention in recent years, the anxiety spectrum of psychiatric disturbances in epilepsy patients has not been extensively studied, although this comorbidity has a significant effect on the medical management and quality of life. The etiology is multifactorial, including neurobiological and shared pathophysiological mechanisms as well as psychosocial and iatrogenic factors (e.g., influence of antiepileptic drugs, epilepsy surgery). Despite the high prevalence of comorbid anxiety in epilepsy, very little is known about optimal treatment strategies. This article reviews the complex interrelationships between anxiety disorders and epilepsy from a clinical point of view. The evaluation of anxiety relative to ictal, peri-ictal, and postictal states is described, and medical treatment options for anxiety disorders in patients with epilepsy are discussed, illustrating that their treatment extends far beyond seizure control.

Up to 50 or 60% of patients with chronic epilepsy have various mood disorders including depression and anxiety. Whereas the relationship between epilepsy and depression has received much attention, less is known about anxiety disorders. It is now recognized that anxiety can have a profound influence on the quality of life of patients with epilepsy. The relationship between anxiety disorders and epilepsy is complex. It is necessary to distinguish between different manifestations of anxiety disorder: ictal, postictal, and interictal anxiety. Preexisting vulnerability factors, neurobiological factors, iatrogenic influences (antiepileptic drugs, epilepsy surgery), and psychosocial factors are all likely to play a role, but with considerable individual differences. Despite the high prevalence of anxiety disorders in patients with epilepsy, there are no systematic treatment studies or evidence-based guidelines for best treatment practice. Nevertheless, a practical approach based on the temporal relationship between anxiety and epileptic seizures allows clinicians to consider appropriate treatment strategies to reduce the psychiatric comorbidity in patients with epilepsy.

Patients with epilepsy have a high prevalence of psychiatric comorbid disorders. Many comorbidities have a significant impact on the medical management and quality of life of these patients. The main psychiatric complications in epilepsy include depression, anxiety disorders, and psychosis. Depression in epilepsy is very common, particularly among patients with partial seizures of temporal lobe origin. Despite its high prevalence, depression and other psychiatric complications remain often unrecognized and untreated in patients with epilepsy, and differential diagnosis may be difficult.. Comorbidity of epilepsy may be due to a shared pathophysiological mechanism, however, coincidence or selection bias cannot always be excluded. In addition, genetic, psychosocial and iatrogenic factors may also contribute to the comorbidity. In this review, we discuss the clinical impact of main psychiatric comorbidities and demonstrate that treatment of epilepsy extends far beyond seizure control.

The availability of new antiepileptic drugs (AEDs) has expanded the spectrum of medical treatment options in epilepsy. However, the development of ten new compounds (vigabatrin, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin) has not changed the basic principles of epilepsy treatment. The choice of an AED depends upon seizure type or seizure syndrome, efficacy, safety, tolerability, patient age and gender, concomitant medication, and comorbid conditions. In general, most of the newer AEDs are not necessarily more effective but usually better tolerated than the traditional agents mainly because of their favorable pharmacokinetic profiles and fewer drug interactions. Because treatment options have been widened with the introduction of these new compounds, drug therapy can now be tailored to the requirements of the individual patient. Nevertheless, significant safety and efficacy issues continue to exist and there is a strong need for the development of even better agents. This clinical review focuses on current aspects of drug therapy in epilepsy.

The availability of new antiepileptic drugs has broadened the spectrum of medical treatment options in epilepsy. The new agents, together with established drugs, offer substantial choice for doctors treating patients with focal or generalised epilepsy. The newer antiepileptic drugs are not necessarily more effective but usually better tolerated than the traditional agents, mainly because of favourable pharmacokinetic profiles and fewer interactions. Because treatment options have increased, drug therapy can now be tailored to the requirements of individual patients. Nevertheless, significant safety and efficacy issues continue to exist and there is a need for the development of even better agents. This review describes the clinical use of the new antiepileptic drugs, but focuses in particular on monotherapy, the treatment of generalised seizures, teratogenicity, and the cognitive side effect profile of the newer compounds.

There are many important health issues for women with epilepsy, in particular for women of childbearing age. Recent surveys have shown that only a minority of such patients received information on important issues concerning pregnancy. Pre-pregnancy counselling should include information on interactions of antiepileptic drugs (AEDs) and oral contraceptives, risk of teratogenicity, use of folic acid, the importance of monotherapy with the lowest effective dosage of an AED, and the safety of breast feeding as well as other special aspects of epilepsy and pregnancy. Planned pregnancy and counselling before conception is crucial. With a multidisciplinary approach the majority of pregnancies will have a favourable outcome. The article addresses these issues and describes practical considerations for the counselling of women with epilepsy who are planning pregnancy.

In the human central nervous system, progesterone is rapidly metabolised to 5 alpha-dihydroprogesterone which subsequently is further reduced to allopregnanolone (AP). These conversions are catalysed by 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). Although different isoforms of both enzymes have been identified in the brain, our knowledge of their expression in the human brain remains limited. The aim of the present study was to investigate the mRNA expression of 5 alpha-reductase 1 as well as 3 alpha-HSD 1, 2, 3 and 20 alpha-HSD in brain tissue from patients with pharmacoresistant temporal lobe epilepsy (TLE). Specimens were derived from either the hippocampus or the temporal lobe cortex and from the tumor-free approach corridor tissue of patients with brain tumors. Quantification of different mRNAs was achieved by real time PCR. In addition, we provide data on simultaneous evaluation of serum AP concentrations. We could demonstrate that 3 alpha-HSD 1 was not expressed in the hippocampus and temporal lobe of patients with TLE. In the hippocampus and temporal lobe, the expression levels of 3 alpha-HSD 2 were about 20% of that in liver tissue, those of 3 alpha-HSD 3 about 7% and those of 20 alpha-HSD about 2%, respectively. In patients with TLE, expression of 3 alpha-HSD 2 was significantly higher in the hippocampus than in temporal lobe cortex tissue (P<0.006). AP concentrations did not correlate significantly with the mRNA expression levels of 5 alpha-reductase 1, 3 alpha-HSD 2 and 3 and 20 alpha-HSD in any of the patient groups under investigation. In conclusion, the present study demonstrates mRNA expression of 5 alpha-reductase 1 and 3 alpha-HSD 2 and 3 and 20 alpha-HSD in the hippocampus and temporal lobe of epileptic patients. These findings provide further molecular biological evidence for the formation and metabolism of neuroactive steroids in the human brain.

There is increasing clinical and experimental evidence that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characterized actions of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function via binding to a putative steroid-binding site. Since neuroactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitability of specific brain regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and its metabolites exert anticonvulsant effects. Testosterone and corticosteroids have less consistent effects on seizure susceptibility. Apart from these particular properties, neuroactive steroids may regulate gene expression via progesterone receptors. Based on their molecular properties, these compounds appear to have a promising therapeutical profile for the treatment of different neuropsychiatric diseases including epilepsy. This review focuses on the effects of neuroactive steroids on neuronal excitability and their putative impact on the physiology of epileptic disorders.

The authors report a 5-year-old boy with episodes of epileptic rotational clockwise vertigo without nystagmus. Video-EEG monitoring showed a left frontocentral onset of epileptic discharges accompanied by complaints of vertigo. MRI showed a small low-grade astrocytoma in the left frontal middle gyrus. After lesionectomy, vertiginous seizures ceased. The patient's vertigo seems to be induced by epileptic discharges in a vestibular representation area within the frontal cortex.

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.

The androgen receptor (AR) plays a central role in mediating androgen action. Since the hippocampus is a target of steroid modulation, we studied the expression of AR mRNAs in hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). AR mRNA expression was in the same order of magnitude than in prostate tissue, known for its high expression of AR. AR mRNA concentrations showed no significant difference in AR mRNA expression between men (49.3+/-8.0 arbitrary units (aU); mean+/-SEM) and women (54.3+/-11.2 aU) and no sex-specific hippocampal lateralization pattern was observed. No relationship could be detected between duration of epilepsy, individual seizure frequency, age of the patients and the expression levels of AR. The high expression of AR in the hippocampus suggests that this human brain area is an important target for androgen action.