Search

Background: Glut-1 deficiency Syndrome (GLUT-1 DS) is a rare disease caused by a mutation in the SLC2A1 gene that codes for the glucose transporter protein GLUT-1 DS. Currently, there is no indicated drug therapy for this condition and ketogenic diet (KD) is the most effective remedy to treat it. Objective: The objective of this study was to review the published literature that evaluated the effectiveness of KD in the dietary management of GLUT-1 DS syndrome, describing the state-of-the-art the treatment pathway for patients with GLUT-1 DS syndrome in light of the current European regulatory framework within the National Health Services. Methods: The literature search was carried out on September 10, 2023, and all studies conducted in humans diagnosed with GLUT-1 deficiency syndrome and treated with KD were included. Results: A total of 156 scientific papers have been extracted. Applying the exclusion criteria, 38 articles have been considered eligible. In 29 out of 38 studies, the main outcome for determining the efficacy of KD was the measurement of the number of epileptic seizures, demonstrating that patients treated with KD experienced improvements with a clear reduction in the number of epileptic attacks. Currently, in the European Union, only one country provides full reimbursement by the national health system for KD. Discussion: Although they are crucial for the treatment of GLUT-1 DS, according with current food regulations, KD are not evaluated on the basis of an unambiguous efficacy result, but only on the basis of safety. As a result, it is desirable to carry out clinical studies in the coming years based on the determination of efficacy in target populations, also in view of the marketing of these products on the European market. [ABSTRACT FROM AUTHOR]

Background: Rauvolfia vomitoria (R. vomitoria) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling. Methods: Twenty-five adult Swiss mice (25–30 g) were assigned to five groups (n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed. Results: Compared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms (P > 0.05), but preference for familiar objects, significant (P < 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly (P < 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups. Conclusions: Thus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action. [ABSTRACT FROM AUTHOR]

Background: Alcohol withdrawal is widely recognized as a trigger for acute symptomatic seizures among individuals with chronic alcohol consumption. While most alcohol withdrawal seizures occur shortly after cessation, chronic alcohol consumption can be associated with the development of epilepsy, necessitating anti‐epileptic drug (AED) therapy. This study aimed to investigate the clinical characteristics, seizure recurrence, and epilepsy development in patients with alcohol‐related seizures and to identify prognostic factors for epilepsy. Methods: In a retrospective analysis at Ewha Womans University Mokdong Hospital, 206 patients with alcohol‐related seizures were examined and 15 were excluded due to preexisting epilepsy. Demographic and clinical data, including alcohol withdrawal duration, seizure recurrence, types, and comorbidities, were investigated. Logistic regression models were used to analyze the risk factors for seizure recurrence and epilepsy development. The performance of the final models was evaluated based on the area under the receiver operating characteristic curve (AUC) and validated using calibration plots and leave‐one‐out cross‐validation. Results: Of the 191 patients (146 males; mean age 48.3 ± 12.1 years) with alcohol‐related seizures, 99 patients (51.8%) experienced seizure recurrence and 79 patients (41.4%) developed epilepsy. Factors associated with seizure recurrence included alcohol consumption levels, occurrence of focal impaired awareness seizure, anxiety, and headache. The number of recurrent seizures, semiology, status epilepticus, electroencephalogram findings, and brain imaging findings was associated with epilepsy development. The predictive models showed strong diagnostic performance, with AUCs of 0.833 for seizure recurrence and 0.939 for epilepsy development. Conclusion: High alcohol consumption and specific clinical and diagnostic features are significant predictors of seizure recurrence and the development of epilepsy among patients with alcohol‐related seizures. These findings underscore the importance of early identification and intervention to prevent seizure recurrence and the onset of epilepsy, emphasizing the importance of AED treatment in managing these conditions. [ABSTRACT FROM AUTHOR]

Background/Objectives: The purpose of this study was to determine the influence of H. pylori eradication on the serum level of the orally administered valproic acid (VPA) in children with idiopathic generalized epilepsy; Methods: This prospective cohort observational study included 100 children with idiopathic generalized epilepsy, recruited from a neurology clinic from May 2021 to December 2021. The patients were divided into two groups, each containing 50 children. The first group had a positive H. pylori stool antigen and H. pylori-related symptoms, while the second group had a negative antigen. H. pylori Eradication therapy was given to the positive H. pylori group. The serum level of VPA was obtained at baseline and 4 weeks after eradication therapy. Results: Despite there being no significant difference between the H. pylori-positive and H. pylori-negative groups regarding the baseline VPA serum level (79.9 ± 13.9 and 77.9 ± 13.1 mcg/mL), respectively, the serum VPA level had significantly increased after H. pylori eradication therapy (99.4 ± 11 mcg/mL) (p value = 0.000), as opposed to the H. pylori-negative group (85.3 ± 10.9 mcg/mL) (p value = 0.142). Furthermore, there was a statistically significant association with a negative correlation between the VPA serum level after eradication and the number of epileptic attacks per month (p value = 0.033, R value = −0.301) and the dose of VPA (p value = 0.046, R value = −0.284). Conclusions: The eradication of H. pylori resulted in a highly significant improvement in the serum level of the orally given VPA in children with idiopathic generalized epilepsy, as well as an indirect decrease in the frequency of epileptic events per month, allowing for dose reduction. Eradication therapy may have anticonvulsant properties and might indirectly aid in the management of epileptic activity. H. pylori screening for children with idiopathic generalized epilepsy can optimize serum VPA levels, potentially leading to better seizure control. To our knowledge, this is the first study in the literature to describe the effect of H. pylori eradication on the serum level of the orally administered VPA in children with idiopathic generalized epilepsy. [ABSTRACT FROM AUTHOR]

Migraine and epilepsy belong to the category of chronic paroxysmal neurological disorders and share numerous clinical features, as well as potential treatment options. This narrative review emphasizes the similarities between pediatric migraine and epilepsy, exploring epidemiology, pathophysiology, genetics, clinical presentation, and pharmacology. Although various syndromes exhibit symptoms common to both conditions, further research is needed to clarify the underlying pathophysiological and genetic connections contributing to their coexistence. Prophylactic medications used in the management of both migraines and epilepsy exhibit similar pharmacological characteristics. The review assesses treatment strategies for epilepsy and migraines, emphasizing antiseizure medications alongside nonpharmacological interventions like ketogenic diet, supplements, and vagal nerve stimulation. It aims to highlight how these interventions, originally targeted for epilepsy, may also show promise in preventing migraines. The urgent need for further randomized, controlled clinical trials investigating both pharmacological and nonpharmacological interventions for treating both disorders is emphasized, aiming to pave the way for innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

• Adherence to Ketogenic Diet Therapies (KDT) is challenging for subjects. • The measurement of adherence lacks standardization, despite being essential. • The average adherence rates across age groups range from 63.9 to 71.5%. • Adherence is higher in short-therm KDT treatment. Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half (n = 12) having average quality (2–3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education. A systematic review of 22 articles on ketogenic diet therapy adherence showed high heterogeneity, challenging comparisons with other studies. Mean adherence rates were similar across age groups: 71.5% for children, 66% for adolescents, and 63.9% for adults. Adherence varied over time: 79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively. Adherence was influenced by inefficacy in seizure control, adverse effects, food refusal, meal preparation challenges, diet restrictions, lack of motivation, poor parental compliance, and cost of the diet. Abbreviations: KDT, ketogenic diet therapies; mo, months. [Display omitted] [ABSTRACT FROM AUTHOR]

Background. Epileptic seizure is a transient period of signs and symptoms resulting from the abnormal excessive and synchronous neuronal activity in the brain, resulting in brain damage. To prevent complications, the antiseizure medication is needed. Several agents have a potency of anti-seizure effect, including ibuprofen. Unfortunately, there are few studies regarding the anti-seizure effect of ibuprofen. Aim. To determine the anti-seizure effect of ibuprofen to reduce the symptoms of epileptic seizures. Materials and Methods. A systematic review using the databases ScienceDirect, SpringerLink, Nature, and Pubmed. The article was obtained using the keywords “ibuprofen” and (“epilepsy” or “anticonvulsant” or “antiseizure” or “epileptic” or “neuroinflammation”) in the period 2012 to 2022 and screened with inclusion and exclusion criteria. Out of the 1376 articles screened, there are three studies included in this review. The SYRCLE Risk of Bias Tool was used to assess the risk of bias, and the data was synthesised using SWiM guidelines. Results. Ibuprofen affects seizures by reducing the number, grade, and duration of seizure intensity in the PTZ-induced rats. Despite the risk of bias assessment revealing some potential bias in the studies, our study shows that ibuprofen has potency as an additional agent for epileptic seizures among febrile convulsive patients. Conclusion. In animal models of seizures, ibuprofen has an antiseizure effect by reducing the number, grade, and duration of seizures [ABSTRACT FROM AUTHOR]

Background: Epilepsy secondary to acquired immunodeficiency syndrome (AIDS) can be challenging to manage. The potential interactions between antiretroviral drugs and antiepileptic drugs may result in the failure of both treatments. Therefore, it is crucial to develop more effective strategies to enhance the clinical outcomes of patients. Case presentation: We report a case of epilepsy secondary to AIDS. After administration of Bacteroides Fragilis 839 (BF839), the secondary generalized tonic-clonic seizures disappeared, the frequency of complex partial seizures decreased by 70%, and the duration of each episode was shortened. Additionally, long-term diarrhea associated with antiretroviral therapy for AIDS resolved, and the syphilis serofast reaction turned negative. No serious adverse reactions were observed during the three-year follow up. Conclusions: This case report suggests that the specific gut microbiota preparation could possibly improve refractory epilepsy in HIV patients while also potentially alleviating adverse reactions to antiretroviral drugs and concurrent syphilis infection. Our case may provide a new perspective for the treatment of HIV infection/AIDS. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to adapt the Health Literacy Questionnaire (HLQ) in English and Norwegian for use with parents. Methods: The research group evaluated all HLQ items and, where relevant, modified them to refocus the attribution of care to that of a child by a parent. Five cognitive interviews with parents were undertaken to gain a detailed depiction of the meanings and processes they used to respond to the HLQ items. Assessment of the psychometric properties of the revised HLQ was undertaken using data from a cross-sectional survey of 254 parents of children with epilepsy. Analysis included internal consistency (Cronbach's alpha) and confirmatory factor analysis (CFA). Results: Some 22 out of 44 items and the names of three domains were modified (e.g. attribution changed from 'me' to 'my child'). Cognitive interviews indicated that parents interpreted the HLQ-Parent items in the way intended. All but three factor loadings were high to acceptable. All nine HLQ scales showed satisfactory to good internal consistency (Cronbach's alpha 0.70 to 0.87). When fitting one-factor CFA models, correlated residuals were required for four scales to generate an acceptable fit. One scale, '8. Ability to find good health information', required inclusion of two correlated residuals to generate an acceptable CFA model fit, indicating that further work on this scale is warranted. Conclusions: The results from both the adaptation process and the CFA analysis supported the relevance, understanding and theoretical structure of the instrument in a parental context. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is the most common neurological condition globally. Integrating health and social care is fundamental in epilepsy management, but the scope of progress in this area is unclear. This scoping review aimed to capture the range and type of integrated care components and models in epilepsy management. Methods: Four databases were searched for articles published since 2010 that reported on integrated care in epilepsy. Data were extracted and synthesised into components of integrated care that had been implemented or recommended only. Models of integrated care were identified, and their components tabulated. Results: Fifteen common and interrelated components of integrated care emerged that were aligned with four broad areas: healthcare staff and pathways (e.g., epilepsy nurses); tasks and services (e.g., care coordination); education and engagement (e.g., shared decision making); and technology for diagnosis and communication (e.g., telehealth). Twelve models of integrated care were identified; seven were implemented and five were recommended. Discussion: There is a growing evidence-base supporting integrated, person-centred epilepsy care, but implementation is challenged by entrenched silos, underdeveloped pathways for care, and deficits in epilepsy education. Conclusion: Integrating epilepsy care relies on changes to workforce development and policy frameworks to support whole-of-system vision for improving care. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ankara University Faculty of Medicine / Ankara Üniversitesi Tip Fakültesi Mecmuasi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prevention of epilepsy and its progression remains the most urgent need for epilepsy research and therapy development. Novel conceptual advances are required to meaningfully address this fundamental challenge. Maladaptive epigenetic changes, which include methylation of DNA and acetylation of histones - among other mechanisms, are now well recognized to play a functional role in the development of epilepsy and its progression. The methylation hypothesis of epileptogenesis suggests that changes in DNA methylation are implicated in the progression of the disease. In this context, global DNA hypermethylation is particularly associated with chronic epilepsy. Likewise, acetylation changes of histones have been linked to epilepsy development. Clinical as well as experimental evidence demonstrate that epilepsy and its progression can be prevented by metabolic and biochemical manipulations that target previously unrecognized epigenetic functions contributing to epilepsy development and maintenance of the epileptic state. This review will discuss epigenetic mechanisms implicated in epilepsy development as well as metabolic and biochemical interactions thought to drive epileptogenesis. Therefore, metabolic and biochemical mechanisms are identified as novel targets for epilepsy prevention. We will specifically discuss adenosine biochemistry as a novel therapeutic strategy to reconstruct the DNA methylome as antiepileptogenic strategy as well as metabolic mediators, such as beta-hydroxybutyrate, which affect histone acetylation. Finally, metabolic dietary interventions (such as the ketogenic diet) which have the unique potential to prevent epileptogenesis through recently identified epigenetic mechanisms will be reviewed. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.

Post - stroke epilepsy (PSE) patients generally respond well to low - dose antiepileptic seizure medicine (ASM), but some patients still develop drug - resistant epilepsy (DRE). Thus, the development of effective drugs that can prevent or reverse epilepsy and disease modifying therapy (DMT) drugs are urgently needed. It was proved that new ASM such as levetiracetam (LVT), lamotrigine (LTG) and zonisamide, natural compounds such as cannabidiol and polyphenolic compounds, mitochondrial antioxidants and non - steroidal anti - inflammatory drug (NSAID) can not only control seizure but also intervene the occurrence of PSE, playing anti-epileptogenic and DMT role. This article intends to further summarize DMT drugs for PSE, providing new research ideas for PSE modifying therapy. [ABSTRACT FROM AUTHOR]

Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes. Yet only a small number of patients with autoimmune encephalitis develop epilepsy in the proper sense where the brain transforms into a state where it will acquire the enduring propensity to produce seizures if it is not hindered by interventions. Hence, the term autoimmune epilepsy is often wrongfully used in the context of autoimmune encephalitis since most of the seizures are acute encephalitis-associated and will abate as soon as the encephalitis is in remission. Given the overlapping clinical presentation of immune-mediated seizures originating from different aetiologies, a clear distinction among the aetiological entities is crucial when it comes to discussing pathophysiological mechanisms, therapeutic options, and long-term prognosis of patients. Moreover, a rapid and accurate identification of patients with immune-mediated epilepsy syndromes is required to ensure an early targeted treatment and, thereby, improve clinical outcome. In this article, we review our current understanding of pathogenesis and critically discuss current and potential novel treatment options for seizures and epilepsy syndromes of underlying or suspected immune-mediated origin. We further outline the challenges in proper terminology. [ABSTRACT FROM AUTHOR]

Epilepsy is a common clinical neurological disease, the pathogenesis of which has not yet been elucidated. As the main treatment, antiepileptic seizure medicine (ASM) fights against seizures rather than improve epilepsy. According to the chronological order of "past", "present" and "future", this article reviews the development history of ASM from the aspects of pharmacokinetics, pharmacological mechanism, indications, efficacy and adverse reactions, and looks forward to the future development direction. It can provide a theoretical basis for the prevention and treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders. [ABSTRACT FROM AUTHOR]

Dingxian Pill (DXP), a famous traditional Chinese medicine prescription, and has been widely proven to have positive therapeutic effects on "Xianzheng" (the name of epilepsy in ancient China). However, the anti-epileptic molecular mechanisms of DXP are not yet fully understood and remain to be further investigated. To elucidate the molecular mechanism of DXP's improvement in epileptic neuronal loss, damage and apoptosis by regulating TNF-α/TNFR1 signaling pathway. Sixty Kunming mice were randomly divided in 6 groups: control group (equal volume of normal saline), model group (180 mg kg−1 pilocarpine hydrochloride – used to establish the epilepsy animal model), carbamazepine group (30 mg kg−1), and low, medium, and high-dose Dingxian Pill groups (4.08, 8.16, and 16.32 g kg−1, respectively – oral administration once daily for 2 weeks). Successful establishment of the epileptic mouse model was monitored with electroencephalography. Pathological changes in hippocampal tissue were analyzed with hematoxylin-eosin staining. Hippocampal neuronal apoptosis was analyzed with TUNEL staining. TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein expression levels in hippocampal tissue were analyzed with real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blot, respectively. Cleaved caspase-8 protein levels in hippocampal tissue were measured with immunohistochemistry and Western blot. Compared to control, the model group showed an increase in continuous epileptic discharge waves on EEG, a damaged hippocampal neuron morphological structure, increased hippocampal neuronal apoptosis, and significantly increased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels, and increased caspase-8 cleavage (P < 0.05). Compared to the model group, the carbamazepine group as well as the low-, medium-, and high-dose Dingxian Pill groups showed decreased epileptic discharges on EEG, an obvious hippocampal neuron morphological structure restoration, varying degrees of attenuated hippocampal neuronal apoptosis, and significantly decreased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels as well as decreased caspase-8 cleavage (P < 0.05). Dingxian Pill exerts an anti-epileptic effect through inhibition of TNF-α/TNFR1 signaling pathway-mediated apoptosis in hippocampal neurons. [Display omitted] • Epilepsy pathogenesis was first investigated via TNF-α/TNFR1 apoptosis pathway. • Pharmacodynamics and dose-effect of Dingxian Pill in epilepsy was first studied. • Dingxian Pill inhibits seizures via TNF-α/TNFR1 apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that patients with epilepsy (PWE) perceived significant disruption in the quality and provision of care due to the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to investigate the effect of this pandemic on seizure control status and changes in seizure frequency in PWE. Methods: A consecutive sample of adult PWE registered in the database of Shiraz Epilepsy Center (Shiraz, Iran) was included in the study. In July 2021, phone interviews were conducted with all selected patients. Information such as age, sex, last seizure, seizure type, and frequency during the 12 months before the study, and history of COVID-19 contraction was extracted. The seizure control status of the patients in 2019 (pre-pandemic) was compared with that during the COVID-19 pandemic. Data were analyzed using SPSS software with the Fisher's exact test and Pearson's Chi squared test. P<0.05 was considered statistically significant. Results: A total of 158 patients were included in the study, out of which 62 (39.2%) patients had a stable seizure control status, 47 (29.7%) had fewer seizures, and 50 (31.6%) had more seizures. Breakthrough seizures were reported by 32 (34.4%) patients. Seizure frequency increased in 18 (27.7%) and decreased in 46 (70.7%) patients. Conclusion: Overall, the COVID-19 pandemic has not been a major precipitating factor nor has it affected the seizure control status of PWE. In treated epilepsy, a fluctuating course with periods of seizure freedom followed by relapses is part of its natural history. [ABSTRACT FROM AUTHOR]

Genetics is rapidly evolving and is actively playing a role in how we diagnose and manage epilepsy. The definition of an epilepsy syndrome has changed throughout the years. The International League Against Epilepsy (ILAE) has developed a classification of the epilepsies and has recently described specific epilepsy syndromes taking into account emerging genetic information which is rapidly evolving as well as etiology-specific syndromes. Understanding genetics can help clarify the syndrome and its treatment. This review provides a history of the definition of a syndrome, and the evolving contribution of genetic information that is part of the syndromic classification. We provide few examples of several phenotypes/genotypes of epilepsy syndromes in infancy and childhood and treatment issues that may arise from the available genetic information. Epilepsy syndromes and their genetics have been rapidly changing as new gene technologies are being developed. Understanding genetics can help clarify the syndrome, its treatment, and will help change the field of epilepsy to improve patients qualify of life by creating new means of preventing, controlling, and curing epilepsy. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common and preventable causes of death for people with learning disabilities and/or autism. [ABSTRACT FROM AUTHOR]

The research and treatment of epilepsy is entering a new era. In order to meet the arrival of this era, organizations such as International League Against Epilepsy (ILAE) have proposed a series of reform measures, which will bring new concepts to the prevention and treatment of epilepsy, establish a new knowledge framework, and promote scientific progress in this field. This article introduces the significance of the transition from anti-epileptic to anti-seizure, the new classification of epilepsy syndromes of the ILAE, the new international standard of EEG, and discusses the international treatment methods for status epilepticus (SE). [ABSTRACT FROM AUTHOR]

Recent developments in metabolomics, transcriptomic and epigenetics open up new horizons regarding the pharmacological understanding of phytocannabinoids as neuromodulators in treating anxiety, depression, epilepsy, Alzheimer's, Parkinson's disease and autism. The present review is an extensive search in public databases, such as Google Scholar, Scopus, the Web of Science, and PubMed, to collect all the literature about the neurobiological roles of cannabis extract, cannabidiol, 9-tetrahydrocannabinol specially focused on metabolomics, transcriptomic, epigenetic, mechanism of action, in different cell lines, induced animal models and clinical trials. We used bioinformatics, network pharmacology and enrichment analysis to understand the effect of phytocannabinoids in neuromodulation. Cannabidomics studies show wide variability of metabolites across different strains and varieties, which determine their medicinal and abusive usage, which is very important for its quality control and regulation. CB receptors interact with other compounds besides cannabidiol and Δ9-tetrahydrocannabinol, like cannabinol and Δ8-tetrahydrocannabinol. Phytocannabinoids interact with cannabinoid and non-cannabinoid receptors (GPCR, ion channels, and PPAR) to improve various neurodegenerative diseases. However, its abuse because of THC is also a problem found across different epigenetic and transcriptomic studies. Network enrichment analysis shows CNR1 expression in the brain and its interacting genes involve different pathways such as Rap1 signalling, dopaminergic synapse, and relaxin signalling. CBD protects against diseases like epilepsy, depression, and Parkinson's by modifying DNA and mitochondrial DNA in the hippocampus. Network pharmacology analysis of 8 phytocannabinoids revealed an interaction with 10 (out of 60) targets related to neurodegenerative diseases, with enrichment of ErbB and PI3K-Akt signalling pathways which helps in ameliorating neuro-inflammation in various neurodegenerative diseases. The effects of phytocannabinoids vary across sex, disease state, and age which suggests the importance of a personalized medicine approach for better success. Phytocannabinoids present a range of promising neuromodulatory effects. It holds promise if utilized in a strategic way towards personalized neuropsychiatric treatment. However, just like any drug irrational usage may lead to unforeseen negative effects. Exploring neuro-epigenetics and systems pharmacology of major and minor phytocannabinoid combinations can lead to success. [Display omitted] • Cannabidomics studies reveal wide variability of metabolites across different cannabis strains and varieties. • Phytocannabinoids interact with both cannabinoid and non-cannabinoid receptors to improve various neurodegenerative diseases. • Despite the benefits, the abuse of THC raises concerns; epigenetic and transcriptomic studies emphasize responsible usage. • The effects of phytocannabinoids vary based on sex, disease state, and age. • This underscores the importance of adopting a personalized medicine approach for successful neuropsychiatric treatment. [ABSTRACT FROM AUTHOR]

Background: Glycogen storage disease type XII is a rare metabolic disease resulting from Aldolase A deficiency that causes muscle glycogen accumulation, with crisis of rhabdomyolysis and hemolytic anemia. In the very few cases described, rhabdomyolysis crises are caused by fever and/or exercise and can accompany acute hemolytic anemia. Although currently there is no therapy available for this disease, the guidelines for the management of other forms of glycogen storage diseases recommend a nutritional therapy in order to avoid hypoglycemia or prevent exercise-induced rhabdomyolysis. Case presentation: In this case report we describe a new phenotype of the disease in a 14-year-old boy, characterized by seizures and rhabdomyolysis. Beside an antiepileptic treatment, we propose a new therapeutic approach based on ketogenic diet in order to supply an energetic substrate for skeletal muscle and neurons. Conclusions: The anti-epileptic therapy and the dietetic approach were well tolerated by the patient who showed good compliance. This led to a deceleration of the disease with no other acute episodes of seizures and rhabdomyolysis, without any side effects observed. [ABSTRACT FROM AUTHOR]

Introduction: The present study was conducted to evaluate the effect of Chlorogenic Acid (CA) and Diazepam (DZP) on epileptic complication that induced by repetitive intra-peritoneal injections of Pentylenetetrazle (PTZ) in aged rats. Methods: Twenty-four month-old male Wistar rats (age > 12 months, 300-350 g) were divided in 4 experimental groups. Animal in control group (PTZ + Vehicle) received only PTZ. Animal in treated groups (PTZ + DZP, PTZ + CA10 and PTZ + 25) received diazepam 2 mg/kg, CA 10 mg/kg, or CA 25 mg/kg. All drugs injection were performed 30 min prior to each PTZ injection. Epilepsy was induced by injection of subconvulsive dose of PTZ every other day until the rats were completely kindled or epileptic. After each PTZ injection, animal was monitored for 40 min and epileptic behaviors were scored. At the end of the study, rats were sacrificed and the brains removed for evaluation of histological changes and Brain Derived Neurothrophic Factor (BDNF) gene expression. Results: CA at dose of 25 mg/kg reduced percent of Generalized Tonic-Clonic Seizure (GTCS) in aged rats (24%) in compared to control group (50%) (p < 0.05). The latencies to the start of GTCS were decreased in both dose of CA (p < 0.05). Also, the percent of survived neurons in rats treated with CA (154%) were significantly higher relative to that of control animals (100%) (p < 0.05). The mRNA levels of BDNF significantly increased in CA treated rats (p < 0.05). Conclusion: Hence, these findings revealed that CA have antiepileptic, neuroprotective and trophic effects in aged rats. CA can protect aged brain from deteriorative processes and save neurons during epilepsy in rats. [ABSTRACT FROM AUTHOR]

Psychogenic nonepileptic events (PNEE) are paroxysmal changes in behavior resembling epileptic seizures but with no electrographic correlate and are instead caused by psychological factors. In this qualitative study, semistructured interviews were conducted with 10 school nurses to identify how they perceive the experience of caring for a student with PNEE as well as supportive factors and barriers to optimal management of PNEE in schools. Several themes were identified: lack of diagnosis awareness by school staff leading to impressions that the student was "faking" the events, inadequate information provided by a health-care provider regarding the diagnosis in general and specifically about the individual student leading to a reliance on information from the student's family, feelings of doubt and insecurity about the diagnosis and management of the events, and reliance on the school nurse to develop a response plan and to manage the events which can be very time-consuming. [ABSTRACT FROM AUTHOR]

New-onset refractory status epilepticus (NORSE) is defined as a refractory status epilepticus (SE) in a patient, without a clear acute or active structural, toxic, or metabolic cause, previous active epilepsy, or preexisting relevant neurological disorder. Cryptogenic NORSE cases, often immunotherapy is considered empirically as a favorable response, have been documented in anecdotal case reports. More than half of children with the anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis develop seizures and SE may also occur during the clinical course. But NORSE as a presenting feature of anti-NMDAR encephalitis is extremely rare, as most children present with subacute onset neuropsychiatric and extrapyramidal features. We are describing one such case in an adolescent girl with anti-NMDAR encephalitis, in whom even intravenous anesthetic infusion and first-line immunotherapy including corticosteroid and IVIG were insufficient to achieve seizure control. Super refractory left focal SE in this child resolved after 96 h of injection rituximab, following which intravenous anesthetics could be tapered and child survived with only mild functional limitation on follow-up at 6 months. In children with cryptogenic NORSE, the clinicians need to rule out the cerebrospinal fluid anti-NMDAR antibody. Rituximab is one of the most promising second-line immunotherapy options in children with anti-NMDAR encephalitis for achieving seizure control and inducing long-term remission. [ABSTRACT FROM AUTHOR]

Objectives: Vagal nerve stimulation (VNS) is an appropriate treatment option for refractory patients who are not eligible for resective epilepsy surgery. In this study, the clinical and demographic characteristics of VNS patients were documented and it was aimed to determine the effect of VNS on seizure control. Methods: A retrospective survey was performed for patients who were diagnosed as drug resistant epilepsy and underwent VNS implantation, with at least 1 year of follow-up. Nine patients (eight males and one female) with an average age of 30.11 (18-42), were included. Reduction in seizure frequency prior and in the 3rd, 6th, and 12th months after VNS implantation was compared. Patients were considered responders when a reduction of seizures of more than 50% was reported. Results: The mean time from the onset of the disease to VNS implantation was 17.33±9.75 years and the mean age when VNS was implanted was 24.53 (9-39). Decrease in frequency of seizures from VNS implantation to 3 months and 6 months was statistically significant (p=0.003 and p=0.012, respectively). No statistical significance was found between the frequency of seizures before treatment and at the 12th month (p=0.153). Conclusion: In our study, we observed a decrease in seizure frequency in patients with drug resistant epilepsy with a variety of etiologies, which was similar with the literature data. Although a cumulative effect was reported, we have observed a minimal decrease in frequency after the 3rd month. [ABSTRACT FROM AUTHOR]

Objective: In this paper, we aim to provide a comprehensive description of the multicomponent self-management intervention for adults with epilepsy, ZMILE. Rationale or theory: Acquiring self-management skills has been shown to play a vital role in enabling patients with epilepsy overcoming (health-related) struggles in daily life and coping with limitations their condition poses on them. ZMILE is a course consisting of education (to increase concordance to treatment), goal-setting (proactive coping), and self-monitoring. Resources needed: The course is guided by two nurse practitioners and each patient is allowed to bring one family member or friend. Self-monitoring plays an important role and can be done through e-Health tools or written diaries. Processes involved: During and after the course, patients are required to work toward a personally defined goal using a five-step approach by means of pro-active coping. Moreover, patients are expected to use self-monitoring tools to reflect on their own behavior and identify ways to optimize medication intake when required. Quantification: ZMILE is provided in an outpatient setting over five weekly group sessions and one booster session. From the start, patients are encouraged to set individual goals. Each group session will have a different theme but part of every session is reflecting on personal goals and to learn from eachother. Conclusions: The ZMILE-intervention has been evaluated and may be a promising intervention in terms of effectiveness and feasibility for adults with epilepsy, relatives, and professionals. We present the adapted version which can be implemented in clinical practice. [ABSTRACT FROM AUTHOR]

Over the last decade, advances in genetics, neuroimaging and EEG have enabled the aetiology of epilepsy to be identified earlier in the disease course than ever before. At the same time, progress in the study of experimental models of epilepsy has provided a better understanding of the mechanisms underlying the condition and has enabled the identification of therapies that target specific aetiologies. We are now witnessing the impact of these advances in our daily clinical practice. Thus, now is the time for a paradigm shift in epilepsy treatment from a reactive attitude, treating patients after the onset of epilepsy and the initiation of seizures, to a proactive attitude that is more broadly integrated into a 'P4 medicine' approach. This P4 approach, which is personalized, predictive, preventive and participatory, puts patients at the centre of their own care and, ultimately, aims to prevent the onset of epilepsy. This aim will be achieved by adapting epilepsy treatments not only to a given syndrome but also to a given patient and moving from the usual anti-seizure treatments to personalized treatments designed to target specific aetiologies. In this Review, we present the current state of this ongoing revolution, emphasizing the impact on clinical practice. [ABSTRACT FROM AUTHOR]

Epilepsy is a neurological disorder characterized by a long-lasting predisposition to generate epileptic seizures that affects millions of people around the world. The International League Against Epilepsy (ILAE) has presented an operational classification of the types of seizures depending on the etiology of the disease. A common denominator of the different types of epilepsy is the existence of imbalance of excitation and inhibition as the main mechanism of the transition from normal brain function to seizure. An imbalance between the glutamate and gamma-aminobutyric acid neurotransmitter systems can cause hyperexcitability, excitotoxicity, proliferation of reactive oxygen species and reactive nitrogen species, oxidative stress, mitochondrial damage and subsequently cell death. Oxidative stress plays a fundamental role in the mechanisms of action in the disease, since neuronal hyperexcitability plays a fundamental role in the initiation and progression of epilepsy. To avoid the damage generated by oxidative stress, cells are equipped with a variety of antioxidants that serve to counteract the effect of oxidants in which enzymatic and non-enzymatic components are involved. Enzyme compounds are regulated by Nrf2, which under oxidative stress conditions bind to antioxidant response elements and thus increases the induction of cytoprotective enzymes mediated by this factor in astrocytes and neurons. For the study of the role that oxidative stress plays in epilepsy, animal models are used that reproduce these disease conditions. This review summarizes the evidence on the role that Nrf2 plays in epilepsy by mediating the activation of antioxidant systems as cellular protectors against oxidative stress. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To enhance your understanding of the central nervous system, its embryological development, anatomical features and pathophysiology • To strengthen your knowledge of the aspects of neurological assessment in infants and children • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers) This article is the fourth in a series on the biological basis of child health. It explains the embryological development of the nervous system and describes some of the anatomical and physiological features of the central nervous system, which is comprised of the brain and spinal cord. It also outlines the principles of neurological assessment in infants and children, before detailing the presentation and management of three conditions that can affect the central nervous system in this patient population – seizures, meningitis and raised intracranial pressure. [ABSTRACT FROM AUTHOR]

Aim: The present study aims to investigate the effects of seizure or epilepsy formation on mortality and morbidity in epileptic patients after craniectomy. Material and Methods: The patients were divided into the following groups: Group 1, those who had no seizures, but were routinely treated with 3x100 mg of epanutin daily (n=6), Group 2, those who had at least one or multiple seizures and were initiated a second antiepileptic drug in addition to 3x100 mg of epanutin daily (n=13), and Group 3, those who had multiple seizures and who were sedated or narcotized in addition to being treated with 3x100 mg of epanutin daily (n=7). All patients underwent decompressive craniectomy within a maximum period of 48 hours and their characteristics such as age, gender, localization of infarct, hemiplegia, monoplegia, operation time, Glasgow coma and outcome scales were recorded. Results: According to the Glasgow Outcome Scale, 1 patient in Group 1, 8 patients in Group 2 and 6 patients in Group 3 died and there was a significant increase in patient losses in Group 2 and Group 3 compared to Group 1 (p<0.05). 10 patients continued to live their lives with the support of home-care services and 2 patients with other forms of help. Conclusion: It was seen that there is a high incidence of seizure and epilepsy in MMCA infarcts after decompressive craniectomy and this significantly increased mortality or dysfunctional recovery if epilepsy could not be brought under control. [ABSTRACT FROM AUTHOR]

Objective: SCN8A encephalopathy is a developmental and epileptic encephalopathy (DEE) caused by de novo gain-of-function mutations of sodium channel Nav 1.6 that result in neuronal hyperactivity. Affected individuals exhibit early onset drug-resistant seizures, developmental delay, and cognitive impairment. This study was carried out to determine whether reducing the abundance of the Scn8a transcript with an antisense oligonucleotide (ASO) would delay seizure onset and prolong survival in a mouse model of SCN8A encephalopathy.Methods: ASO treatment was tested in a conditional mouse model with Cre-dependent expression of the pathogenic patient SCN8A mutation p.Arg1872Trp (R1872W). This model exhibits early onset of seizures, rapid progression, and 100% penetrance. An Scn1a +/- haploinsufficient mouse model of Dravet syndrome was also treated. ASO was administered by intracerebroventricular injection at postnatal day 2, followed in some cases by stereotactic injection at postnatal day 30.Results: We observed a dose-dependent increase in length of survival from 15 to 65 days in the Scn8a-R1872W/+ mice treated with ASO. Electroencephalographic recordings were normal prior to seizure onset. Weight gain and activity in an open field were unaffected, but treated mice were less active in a wheel running assay. A single treatment with Scn8a ASO extended survival of Dravet syndrome mice from 3 weeks to >5 months.Interpretation: Reduction of Scn8a transcript by 25 to 50% delayed seizure onset and lethality in mouse models of SCN8A encephalopathy and Dravet syndrome. Reduction of SCN8A transcript is a promising approach to treatment of intractable childhood epilepsies. Ann Neurol 2020;87:339-346. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between MRI types and epilepsy control following tumor removal of dysembryoplastic neuroepithelial tumor (DNT). Methods The clinical and follow-up data of DNT cases were retrospectively collected from January 2012 to July 2019, and the data were further analyzed with respect to prognostic factors. Results Epilepsy occurred in all cases. According to MRI-based classification, 8 patients belonged to type I, 4 patients were type II, and the other 2 patients were type III. Tumor total removal was performed in all cases. Postoperative pathological HE staining confirmed each tumor simple contained specific neuronal components in all cases, and in 13 cases, synaptin (Syn), oligodendrocyte transcription factor 2 (Olig-2) and neuronal nuclear antigen (NeuN) were positive in routine immunohistochemical staining. In the postoperative follow-up period from 6-84 months, Engel I outcome was achieved in all type I cases and 2 type II cases, Engel III was in 2 type II cases, Engel II was in 2 type III cases. Conclusions Postoperative seizure control in PNT may be closely associated with the MRI types, and type I may have a better prognosis in seizure control following tumor removal than type II and type III. [ABSTRACT FROM AUTHOR]

Background: Epilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known. Methods: Here, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-distance Swedish cross-country ski race Vasaloppet (n = 197,685) and compared it to the incidence of non-participating-matched controls included in the Swedish population register (n = 197,684). Individuals diagnosed with diseases such as stroke and epilepsy before entering the race were excluded from both groups. Experimentally, we also determined how physical activity could affect the development of epilepsy in epilepsy-prone synapsin II knockout mice (SynIIKO), with and without free access to a running wheel. Results: We identified up to 40–50% lower incidence of epilepsy in the Vasaloppet participants of all ages before retirement. A lower incidence of epilepsy in Vasaloppet participants was seen regardless of gender, education and occupation level compared to controls. The participants included both elite and recreational skiers, and in a previous survey, they have reported a higher exercise rate than the general Swedish population. Sub-analyses revealed a significantly lower incidence of epilepsy in participants with a faster compared to slower finishing time. Dividing participants according to specified epilepsy diagnoses revealed 40–50% decrease in focal and unspecified epilepsy, respectively, but no differences in generalized epilepsy. Voluntary exercise in seizure-prone SynIIKO mice for 1 month before predicted epilepsy development decreased seizure manifestation from > 70 to 40%. Brain tissue analyses following 1 month of exercise showed increased hippocampal neurogenesis (DCX-positive cells), while microglial (Iba1) and astrocytic activation (GFAP), neuronal Map2, brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B intensity were unaltered. Continued exercise for additionally 2 months after predicted seizure onset in SynIIKO mice resulted in a 5-fold reduction in seizure manifestation (from 90 to 20%), while 2 months of exercise initiated at the time of predicted seizure development gave no seizure relief, suggesting exercise-induced anti-epileptogenic rather than anti-convulsive effect. Conclusion: The clinical study and the experimental findings in mice indicate that physical activity may prevent or delay the development of epilepsy. [ABSTRACT FROM AUTHOR]

Background: Lamotrigine is not recommended in the prevention of migraine in general but some reports suggest that it might be effective for treating specifically migraine with aura (MA). This review aims to summarize the related data from the literature and to better understand this discrepancy. Methods: All reports from the literature related to the use of lamotrigine in migraine with or without aura published prior to February 2019 found using PUBMED and the 2 keywords "migraine" AND "lamotrigine" were reviewed. Original studies, published in full, systematic reviews, and all case reports were synthetized. We also examined the risk profile, pharmacokinetics, and mode of action of lamotrigine in view of the presumed mechanism of MA. Results: Lamotrigine was tested in different populations of migraineurs, but previous studies had small sample sizes (n < 35) and might not have been powered enough for detecting a potential benefit of lamotrigine in MA. Accumulating data suggest that the drug can reduce both the frequency and severity of aura symptoms in multiple conditions and is well tolerated. Conclusion: Lamotrigine appears promising for treating attacks of MA and related clinical manifestations because of its high potential of efficacy, low‐risk profile, and cost. Additional studies are needed for testing lamotrigine in patients with MA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate potential harm and benefits of antiepileptic drugs (AED) given prophylactically to prevent de novo brain tumour-related epilepsy after craniotomy.Methods: Randomised controlled trials (RCT) and retrospective studies published before 27 November 2018 were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied. Eligible patients were diagnosed with a brain tumour, were seizure naïve and underwent craniotomy. The random effects model was used for quantitative synthesis. The analysis was adjusted for the confounding effect of including patients with a history of seizure prior to study inclusion.Results: A total of 454 patients received prophylactic AED whereas 333 were allocated to placebo or no treatment. Two RCTs and four retrospective studies were identified. The OR was 1.09 (95% CI 0.7 to 1.8, p=0.7, I2=5.6%, χ2 p=0.5), indicating study consistency and no significant differences. An additional two RCTs and one retrospective study combined craniotomy and diagnostic biopsy, and were subgroup analysed-which supported no difference in odds for epilepsy.Conclusions: A prophylactic effect of AED could not be demonstrated (nor rejected statistically). Levetiracetam was associated with less adverse effects than phenytoin. The potential harm of AED was not balanced by the potential prophylactic benefit. This study suggests that prophylactic AED should not be administered to prevent brain tumour-related epilepsy after craniotomy. [ABSTRACT FROM AUTHOR]

Abstract Aims The first-line anti-epileptic agent carbamazepine has narrow therapeutic index and can potentially interact with piperine, the major component from black pepper. The present study aimed to delineate the mechanism of such interaction for safe usage of carbamazepine during epilepsy control. Materials and methods The effect of piperine on carbamazepine hepatic metabolism was examined using rat or human liver microsomes. Mechanistic static model was applied to predict the extent of interaction. In addition, liver microsomal activities, mRNAs and protein expressions of genes regulating carbamazepine metabolism were evaluated after two weeks oral administrations of 3.5 and 35 mg/kg piperine in rats. Moreover, the effect of piperine on the xenobiotic receptor constitutive androstane receptor (CAR) was further accessed. Key findings Time-dependent inhibitory effect of piperine on carbamazepine metabolism was observed, with k inact and K I of 0.0153 min−1 and 18.34 μM for rat, and 0.0093 min−1 and 9.45 μM for human. Based on such in-vitro metabolic parameters, further estimation using mechanistic static model indicated that piperine could increase the AUC of CBZ by 7% and 11% in rat and human, respectively. Significant inhibition on rat liver microsomal activity, Cyp3a2 mRNA and protein expression, CAR mRNA were demonstrated with piperine at 35 mg/kg. Yet, no direct effect on the activity of CAR for piperine was found. Significance We have demonstrated the time-dependent inhibition by piperine on carbamazepine metabolism as the interaction mechanism. Prolonged use of piperine at high dose could increase carbamazepine concentrations through inhibiting metabolic enzyme activities and their related genes expressions. [ABSTRACT FROM AUTHOR]

Objectives: To gain insight into the main advantages and disadvantages that might result from valproate being unavailable for women who intend to become pregnant. Materials and Methods: Analysis of data from the Australian Pregnancy Register concerning pregnancies exposed to valproate (N = 501) and pregnancies where previous valproate intake had been ceased before pregnancy (N = 101). Results: The risk of foetal malformation associated with valproate exposure during pregnancy was dose‐related, and there was a tendency for the more major malformations, including those often managed by therapeutic abortion, for example spina bifida, to occur at higher valproate doses. Had there been no exposure to valproate during pregnancy, some 80% of the foetal malformations that occurred might have been avoided. Cessation of previous valproate therapy before pregnancy was associated with an increased hazard of seizure‐affected pregnancy. This was particularly the case for women with generalized epilepsies, in whom the incidence of seizure‐affected pregnancy was increased by 50% to nearly 100%. Conclusions: Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate‐treated epilepsy who are considering pregnancy. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) and cannabidivarin (CBDV) are natural cannabinoids which are consumed in increasing amounts worldwide in cannabis extracts, as they prevent epilepsy, anxiety, and seizures. It was claimed that they may be useful in cancer therapy and have anti-inflammatory properties. Adverse long-term effects of these drugs (induction of cancer and infertility) which are related to damage of the genetic material have not been investigated. Therefore, we studied their DNA-damaging properties in human-derived cell lines under conditions which reflect the exposure of consumers. Both compounds induced DNA damage in single cell gel electrophoresis (SCGE) experiments in a human liver cell line (HepG2) and in buccal-derived cells (TR146) at low levels (≥ 0.2 µM). Results of micronucleus (MN) cytome assays showed that the damage leads to formation of MNi which reflect chromosomal aberrations and leads to nuclear buds and bridges which are a consequence of gene amplifications and dicentric chromosomes. Additional experiments indicate that these effects are caused by oxidative base damage and that liver enzymes (S9) increase the genotoxic activity of both compounds. Our findings show that low concentrations of CBD and CBDV cause damage of the genetic material in human-derived cells. Furthermore, earlier studies showed that they cause chromosomal aberrations and MN in bone marrow of mice. Fixation of damage of the DNA in the form of chromosomal damage is generally considered to be essential in the multistep process of malignancy, therefore the currently available data are indicative for potential carcinogenic properties of the cannabinoids. [ABSTRACT FROM AUTHOR]

Epilepsy appears in 1% of global population and despite a progress in medicine still around 30% of patients have drug-resistant epilepsy. In recent years increasing attention is paid to possibility of epilepsy prevention. Candidate groups for such treatment are eagerly looked for. One of them is tuberous sclerosis complex (TSC). [ABSTRACT FROM AUTHOR]

Background: Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.Objective: The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.Methods: Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).Results: Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55-8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87-16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.Conclusions: Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo. [ABSTRACT FROM AUTHOR]

Five percent of all epilepsy cases are attributed to traumatic brain injury (TBI), which are known as post-traumatic epilepsy (PTE). Finding preventive strategies for PTE is valuable. Remarkable feature of TBI is activation of microglia and subsequent neuroinflammation, which provokes epileptogenesis. The toll-like receptor agonists monophosphoryl lipid A (MPL) and tri-palmitoyl-S-glyceryl-cysteine (Pam3Cys) are safe, well-tolerated and effective adjuvants existing in prophylactic human vaccines. We examined the impact of early injection of MPL and Pam3Cys to rats, on the rate of kindled seizures acquisition following TBI. Rats received a single dose (1 µg/rat) of MPL or Pam3Cys through intracerebroventricular injection. 5 days later, trauma was exerted to temporo-parietal cortex of rats by controlled cortical impact device. After 24 h, traumatic rats underwent amygdala kindling. Brain level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also measured in traumatic rats by immunoblotting. Compared to non-traumatic (sham-operated) rats, traumatic rats showed three times lower seizure threshold (133 ± 5 µA vs. 416.3 ± 16 µA, p < 0.001); about three times less number of stimuli to become kindled (5 ± 1 vs. 14 ± 2, p < 0.01); longer duration of kindled seizure parameters including entire seizure behavior, generalized seizures, and afterdischarges (p < 0.001); and a two times increase in the TNF-α level. MPL and Pam3Cys did not change kindling rate and the seizure parameters in sham-operated rats. The MPL- and Pam3Cys-pretreated traumatic rats displayed seizure threshold, speed of kindling, and duration of kindled seizure parameters, similar to the non-traumatic rats. Pretreatment by MPL and Pam3Cys prevented the increase in TNF-α level by trauma. Given that MPL and Pam3Cys currently have clinical use as well-tolerated vaccines with reliable safety, they have the potential to be used in prevention of PTE. [ABSTRACT FROM AUTHOR]

Epileptic seizures are a common cause for presentation to acute medical services. Whether presenting with an isolated, unprovoked seizure or with status epilepticus, a good understanding of seizures and their mimics ensures appropriate investigation and treatment. This article describes the practical aspects of the management of patients presenting with seizures to the emergency department or the acute medical unit. [ABSTRACT FROM AUTHOR]

Aim: Epilepsy is increasingly developed worldwide, considered as one of the most important healthcare problems in the second half of 12th century. Methodology: This study is a quantitative-qualitative/cross sectional-practical method research. The conceptual model was derived from comparative studies of the United States, Australia, United Kingdom, Canada and the relevant experts' perspectives. The study population consisted of all professionals related to the healthcare management of epilepsy in all geographical regions of Iran. The obtained data were analyzed using software SPSS 16 and AMOS. Exploratory and confirmatory factor analysis were also performed, and the final model was obtained and its fitness was confirmed. Results: Nine factors were entirely identified for the final model of healthcare management of epileptic patients: Organizational structure of the leading policy, makers, methods of governmental interventions in financing resources, types of services necessary to provide patients, instances of epilepsy, monitoring, and controlling epilepsy healthcare services among which methods of governmental interventions in financing resources and monitoring and controlling epilepsy healthcare services had the minimum and maximum factor load value, respectively. Conclusion: As it can be observed from the study data, training and raising the public awareness toward epilepsy in the country is an essential tool to prevent these types of diseases, as identifying the initial main risks aiming at prohibition of epidemic diseases and also proper healthcare services in case of development are the most important initiations to be taken. [ABSTRACT FROM AUTHOR]

Highlights • Lithium, a mood stabilizer, prevents apoptosis-dependent cellular death and is used to treat various neurological disorders. • At a low dose (10 mg/kg), lithium attenuates susceptibility to and the severity of pilocarpine-induced seizures. • At a higher dose (40 mg/kg), lithium exhibits the opposite effect; this may be related to suppression of gamma oscillation. • The low-dose effect is likely due to increased theta and gamma oscillation and reduced ripple activity. Abstract Lithium, a classic mood stabilizer, prevents apoptosis-dependent cellular death and has garnered considerable interest as a neuroprotective agent that is efficacious in the treatment of many neurological diseases. However, the effects of lithium in epilepsy remain controversial. We found that different doses of lithium affect epileptic seizure activity and bidirectionally modulate the susceptibility to and severity of seizures induced by pilocarpine in rats. Recently, it has been demonstrated that systematically administered lithium affects the powers of hippocampal gamma and theta oscillations in baseline electroencephalograms. Low-dose lithium (10 mg/kg) administered to pilocarpine-treated rats markedly increased the powers of basal gamma (30–80 Hz) and theta (4–12 Hz) oscillations, decreased the proportion of Racine stage 4–5 seizures, extended latency until seizure onset, and significantly reduced the frequency of lower-class seizures (p < 0.05). Conversely, when the dose was increased to 40 mg/kg, lithium reduced the frequency of lower-class seizures compared to control treatment (p < 0.05). Further, at this high dose, lithium reduced the power of basal gamma oscillations and markedly increased the susceptibility to and severity of pilocarpine-induced seizures and enhanced ripple rhythms (80–200 Hz) postictally. Our results provide a framework for further investigations of the underlying electrophysiological mechanisms of lithium-induced imbalances in excitatory and inhibitory neural circuits that regulate seizure activity in rats. In conclusion, the observed in vivo changes in the powers of basal gamma and theta oscillations in response to different doses of lithium may reflect hippocampal neural network responsiveness. [ABSTRACT FROM AUTHOR]

The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Clinical trials have shown that mTOR inhibitors such as everolimus reduce seizures in tuberous sclerosis complex patients with intractable epilepsy. Furthermore, accumulating preclinical data suggest that mTOR inhibitors may have anti-seizure or anti-epileptogenic actions in other types of epilepsy. However, the chronic use of rapalogs such as everolimus is limited by poor tolerability, particularly by immunosuppression, poor brain penetration and induction of feedback loops which might contribute to their limited therapeutic efficacy. Here we describe two novel, brain-permeable and well tolerated small molecule 1,3,5-triazine derivatives, the catalytic mTORC1/C2 inhibitor PQR620 and the dual pan-PI3K/mTOR inhibitor PQR530. These derivatives were compared with the mTORC1 inhibitors rapamycin and everolimus as well as the anti-seizure drugs phenobarbital and levetiracetam. The anti-seizure potential of these compounds was determined by evaluating the electroconvulsive seizure threshold in normal and epileptic mice. Rapamycin and everolimus only poorly penetrated into the brain (brain:plasma ratio 0.0057 for rapamycin and 0.016 for everolimus). In contrast, the novel compounds rapidly entered the brain, reaching brain:plasma ratios of ∼1.6. Furthermore, they significantly decreased phosphorylation of S6 ribosomal protein in the hippocampus of normal and epileptic mice, demonstrating effective mTOR inhibition. PQR620 and PQR530 significantly increased seizure threshold at tolerable doses. The effect of PQR620 was more marked in epileptic vs. nonepileptic mice, matching the efficacy of levetiracetam. Overall, the novel compounds described here have the potential to overcome the disadvantages of rapalogs for treatment of epilepsy and mTORopathies directly connected to mutations in the mTOR signaling cascade. [ABSTRACT FROM AUTHOR]

Objective: Rose oil (from Rosa damascene) has several effects which are analgesic, antispasmodic, antioxidant and neuroprotective role. Its antiepileptic effect has not been yet studied enough. In the present study, it was aimed to investigate acute effects of rose oil on the epileptiform activity in penicillin-induced epilepsy model in rats. Methods: Forty-two male Wistar rats weighing 230 to 260 g were divided into six groups with seven rats in each group. Control (+Penicillin), RO alone, Diazepam, and different doses of Rose oil including 100, 500 and 1000 mg/kg. Rats were pretreated with different doses of RO 30 min prior to penicillin treatment. Electrocorticogram recordings were taken from each animal for 2 hours after penicillin treatment. Results: Only the dose of 100 mg/kg of rose oil reduced significantly epileptic spike- wave frequency of epileptiform activity. However, comparing in terms of latency and spike-wave amplitude of epileptiform activity, there were no significant difference between the groups. Conclusions: In conclusion, acute administration of rose oil reduces spike-wave frequency of penicillin-induced epileptiform activity in rats. Therefore, these findings indicate that rose oil has antiepileptic effects. [ABSTRACT FROM AUTHOR]