Refractory Epileptic Seizures Research Articles

BRAIN TUMOR AND EPILEPSY IN CHILDREN: CLINICAL COMPLICATIONS AND SURGICAL TREATMENT

Introduction: Brain tumors in children often present a complex intersection with epilepsy, creating significant challenges for diagnosis and treatment. The presence of brain tumors can lead to the development of epilepsy, which may manifest in various forms depending on the tumor's location and type. Clinical complications include refractory epileptic seizures, neuropsychomotor development impairment, and deterioration in quality of life. Surgical treatment can be crucial for both tumor removal and seizure control, offering the possibility of seizure remission and improving overall prognosis. Objective: The systematic literature review aimed to evaluate the relationship between brain tumors and epilepsy in children, focusing on clinical complications and surgical treatment strategies. Methodology: The methodology followed the PRISMA checklist to ensure a comprehensive and rigorous review. Databases such as PubMed, Scielo, and Web of Science were consulted using descriptors like "pediatric brain tumor," "epilepsy in children," "clinical complications," "surgical treatment," and "pediatric neurosurgery." Inclusion criteria were studies on brain tumors in children, research addressing epilepsy as a symptom or complication, and articles describing surgical treatment. Articles not available in full text, studies outside the pediatric scope, and publications prior to 2014 were excluded. Results: The review revealed that brain tumors can cause epilepsy due to cortical irritation and neural dysfunction. Surgical treatment is often effective in reducing or eliminating epileptic seizures but can be challenging due to the tumor's location and characteristics. Additionally, the results showed that complete tumor resection is associated with better clinical outcomes in terms of seizure control. The literature also highlighted the importance of postoperative monitoring to detect and manage complications. Conclusion: Brain tumors in children frequently lead to epilepsy, and surgical treatment is essential for seizure control and improving quality of life. Complete tumor removal is crucial for positive outcomes, and ongoing monitoring is necessary to manage potential complications. The review highlighted the importance of a multidisciplinary approach to optimize clinical outcomes and patient quality of life.

SMC1A epilepsy syndrome: clinical data from a large international cohort.

SMC1A epilepsy syndrome or developmental and epileptic encephalopathy-85 with or without midline brain defects (DEE85, OMIM #301044) is an X-linked neurologic disorder associated with mutations of the SMC1A gene, which is also responsible for about 5% of patients affected by Cornelia de Lange syndrome spectrum (CdLS). Only described in female patients, SMC1A epilepsy syndrome is characterized by the onset of severe refractory epileptic seizures in the first year of life, global developmental delay, a variable degree of intellectual disability, and dysmorphic facial features not typical of CdLS. This was a descriptive observational study for the largest international cohort with this specific disorder. The main goal of this study was to improve the knowledge of the natural history of this phenotype with particular attention to the psychomotor development and the epilepsy data. The analyzed cohort shows normal prenatal growth with the subsequent development of postnatal microcephaly. The incidence of neonatal problems (seizures and respiratory compromise) is considerable (51.4%). There is a significant prevalence of central nervous system (20%) and cardiovascular malformations (20%). Motor skills are generally delayed. The presence of drug-resistant epilepsy is confirmed; the therapeutic role of a ketogenic diet is still uncertain. The significant regression of previously acquired skills following the onset of seizures has been observed. Facial dysmorphisms are variable and no patient shows a classic CdLS phenotype. To sum up, SMC1A variants caused drug-resistant epilepsy in these patients, more than two-thirds of whom were shown to progress to developmental and epileptic encephalopathy. The SMC1A gene variants are all different from each other (apart from a couple of monozygotic twins), demonstrating the absence of a mutational hotspot in the SMC1A gene. Owing to the absence of phenotypic specificity, whole-exome sequencing is currently the diagnostic gold standard.

Voluntary Running Improves Behavioral and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. CDD is characterized by a broad spectrum of clinical manifestations, including early-onset refractory epileptic seizures, intellectual disability, hypotonia, visual disturbances, and autism-like features. The Cdkl5 knockout (KO) mouse recapitulates several features of CDD, including autistic-like behavior, impaired learning and memory, and motor stereotypies. These behavioral alterations are accompanied by diminished neuronal maturation and survival, reduced dendritic branching and spine maturation, and marked microglia activation. There is currently no cure or effective treatment to ameliorate the symptoms of the disease. Aerobic exercise is known to exert multiple beneficial effects in the brain, not only by increasing neurogenesis, but also by improving motor and cognitive tasks. To date, no studies have analyzed the effect of physical exercise on the phenotype of a CDD mouse model. In view of the positive effects of voluntary running on the brain of mouse models of various human neurodevelopmental disorders, we sought to determine whether voluntary daily running, sustained over a month, could improve brain development and behavioral defects in Cdkl5 KO mice. Our study showed that long-term voluntary running improved the hyperlocomotion and impulsivity behaviors and memory performance of Cdkl5 KO mice. This is correlated with increased hippocampal neurogenesis, neuronal survival, spine maturation, and inhibition of microglia activation. These behavioral and structural improvements were associated with increased BDNF levels. Given the positive effects of BDNF on brain development and function, the present findings support the positive benefits of exercise as an adjuvant therapy for CDD.

One Patient, Three Providers: A Multidisciplinary Approach to Managing Common Neuropsychiatric Cases.

Neuropsychiatric cases require a multidisciplinary approach for effective management. This paper presented case-based discussions on migraine, dementia, epilepsy, mood disorders, neuralgia, and psychosis from the perspectives of a family physician, neurologist, and psychiatrist. The goal was to highlight the importance of collaboration between healthcare providers in managing these complex cases. The paper was based on the proceedings of the Mediterranean Neuropsychiatry Symposium, where experts from family medicine, neurology, and psychiatry came together for comprehensive case-based discussions. The CARE framework (Case Report, Appraisal, Research, and Education) was developed to guide reporting and evaluation of case reports in clinical practice. Six cases were presented and discussed, highlighting the importance of a multidisciplinary approach in managing neuropsychiatric cases. The cases included chronic migraine with medication overuse, memory dysfunction with language and behavioral problems, refractory epileptic seizures with subjective sensory symptoms, bipolar affective disorder with normal pressure hydrocephalus, postherpetic neuralgia in a case with bipolar affective disorder, and psychosis with recurrent attacks with the abuse of several substances. A biopsychosocial multidisciplinary approach is essential for managing neuropsychiatric cases effectively on behalf of the patients and public health of the country. The CARE framework can guide the reporting and evaluation of case reports in clinical practice, ensuring that patients receive comprehensive and effective care. Healthcare providers should collaborate to provide the best possible care for patients with complex and multifaceted needs.

Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives.

Animal models of epilepsy are of great importance in epileptology. They are used to study the mechanisms of epileptogenesis, and search for new genes and regulatory pathways involved in the development of epilepsy as well as screening new antiepileptic drugs. Today, many methods of modeling epilepsy in animals are used, including electroconvulsive, pharmacological in intact animals, and genetic, with the predisposition for spontaneous or refractory epileptic seizures. Due to the simplicity of manipulation and universality, genetic models of audiogenic epilepsy in rodents stand out among this diversity. We tried to combine data on the genetics of audiogenic epilepsy in rodents, the relevance of various models of audiogenic epilepsy to certain epileptic syndromes in humans, and the advantages of using of rodent strains predisposed to audiogenic epilepsy in current epileptology.

Diagnostics and age-related evolution of Lennox–Gastaut syndrome. Management in diverse patient age periods

Lennox–Gastaut syndrome is an epileptic encephalopathy with onset in childhood. The classical triad of diagnostic criteria is well known: 1) presence of various types of refractory epileptic seizures (tonic, atypical absences, myoclonic, tonic/atonic drop attacks, generalized tonic-clonic, focal); 2) cognitive disorders with frequent behavioral disorders (not always evident by the beginning of epileptic seizures); 3) generalized, slow (≤2.5 Hz) spike-wave activity of wakefulness and generalized paroxysmal fast activity on sleep electroencephalogram. Despite the seizure onset usually occurring before the age of 8 (peak at 3–5) years old, the Lennox–Gastaut syndrome is often featured with a lifelong course. Many patients with this syndrome suffer from refractory epilepsy in adulthood, however, not always being provided a proper syndromological diagnosis. Expanding the criteria to diagnose the Lennox–Gastaut syndrome discussed here would allow to choose a proper treatment algorithm. Rufinamide is the drug of the second choice in the adjunctive therapy of epileptic seizures associated with Lennox–Gastaut syndrome. However, a pediatric-to-adult clinic transition of patients with Lennox–Gastaut syndrome may pose some obstacles. Herein, an effective patient management requires not only seizure control, but also improvement of patient's quality of life by influencing cognitive and behavioral issues, sleep disorders, disability (both physical and social), educational problems and employment.

Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs.

The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.

Uncommon variants of speech disorder in children: congenital bilateral perisylvian syndrome

This paper describes two cases of congenital bilateral perisylvian syndrome (CBPS), a rare disorder of late neuronal migration, which is characterized by language delay, intellectual disorders, epilepsy and bilateral perisylvian polymicrogyria. Pseudobulbar paralysis and orofacial muscles dyspraxia causing drooling and feeding difficulties are common for patients with CBPS. Communicational problems lead to low self-esteem and social maladaptation. Literature data regarding correlation between polymicrogyria topography and speech disorders and articulation impairment severity are presented. The results demonstrate the association of diffuse spreading of bilateral polymicrogyria and more severe speech disorders comparing to mild speech disorders in patients with more local polymicrogyria. Known etiology factors of this syndrome are bilateral cerebral hypoperfusion, brain damage while neuronal migration period, postmigrational vascular insults and gene mutations. Syndrome can be inherited in autosome dominant and X-linked manner. Speech apraxia with normal impressive speech, refractory epileptic seizures and status dysraphicus must be red flags for a physician regarding this syndrome. Overnight video-EEG monitoring and brain MRI confirm a thesis that this syndrome is underdiagnosed in everyday clinical practice.

Benefits of ketogenic diet in a pediatric patient with Ehlers-Danlos syndrome and STXBP1-related epileptic encephalopathy

Purpose/Aim Ehlers-Danlos syndrome (EDS) is a hereditary connective tissue disease. Epilepsy is not a common neurological finding in EDS. Here we report a pediatric patient with EDS comorbid with STXBP1 related epileptic encephalopathy as ‘electrical status epilepticus during slow-wave sleep (ESES)’ and whose refractory epileptic seizures were controlled with ketogenic diet. Case report A 6-year-old girl who had EDS presented with refractory seizures and worsening cognitive functions. Her sleep electroencephalography (EEG) revealed electrical status epilepticus during slow-wave sleep (ESES). The epileptic encephalopathy panel revealed a de novo c.560C > T (p.pro187Leu) heterozygous mutation in the STXPB1 gene. Ketogenic diet treatment was started for her refractory seizures and seizures stopped in the third month of the 3:1 classical ketogenic diet. Conclusion Our case is remarkable due to the coexistence of EDS and epileptic encephalopathy as well as ESES findings in STXBP1-associated epileptic encephalopathy and is therefore presented. Ketogenic diet would be beneficial on the management of refractory seizures in STXBP1-related epileptic encephalopathy and ESES.

Utilização da dieta cetogênica como estratégia para o manejo de pacientes com epilepsia refratária: uma revisão da literatura

Introdução: A epilepsia é uma doença que afeta milhões de pessoas em todas as partes do mundo. Crises epilépticas se apresentam nos pacientes de forma parcial ou generalizada, dependendo do grau de atividade da doença. Atualmente, há muitos fármacos disponíveis no mercado, os quais possuem diversos mecanismos de ação e que podem ser utilizados de forma isolada ou concomitante. No entanto, em alguns pacientes, principalmente, em crianças e adolescentes, esses fármacos se mostram ineficazes e incapazes de promover o controle tanto da frequência quanto da intensidade das crises epilépticas, a quais são denominadas de epilepsia refratária. Assim, a busca por tratamentos alternativos capazes de controlar as frequência e intensidade das crises epilépticas refratárias é incessante e intensa e, dentre as estratégias usadas, atualmente, destaca-se a dieta cetogênica (DC), que consiste numa elevada ingestão de lipídios e baixa ingestão de carboidratos e proteínas e que tem fornecido uma melhora na qualidade de vida de pacientes, principalmente, em crianças e adolescentes com epilepsia refratária. Objetivo: Realizar uma revisão da literatura sobre os benefícios causados pela utilização da DC, como tratamento adjuvante e/ou alternativo, no tratamento da epilepsia refratária, principalmente, em crianças e adolescentes. Metodologia: O estudo foi realizado por meio de uma revisão bibliográfica e integrativa da literatura, através da compilação de artigos científicos e livros sobre o tema proposto. As informações foram pesquisadas na base de dados Google acadêmico, Scielo e PubMed. As palavras-chave utilizadas para a busca dos artigos científicos foram: Epilepsia, Epilepsia refratária, Dieta cetogênica. Para a elaboração deste estudo foram pesquisadas publicações a partir de 2008 a 2018, levando em consideração o fator atualidade e relevância do tema, cujo título estabelecia a relação com o estudo. Das publicações encontradas, 22 foram utilizadas. Conclusão: Conclui-se que a DC se apresenta como uma importante opção terapêutica muito segura, barata e eficaz e que, por isso, pode ser utilizada no manejo de pacientes com epilepsia refratária, principalmente, em crianças e adolescentes.

The Conceptual Design of a Novel Workstation for Seizure Prediction Using Machine Learning With Potential eHealth Applications.

Recent attempts to predict refractory epileptic seizures using machine learning algorithms to process electroencephalograms (EEGs) have shown great promise. However, research in this area requires a specialized workstation. Commercial solutions are unsustainably expensive, can be unavailable in most countries, and are not designed specifically for seizure prediction research. On the other hand, building the optimal workstation is a complex task, and system instability can arise from the least obvious sources imaginable. Therefore, the absence of a template for a dedicated seizure prediction workstation in today’s literature is a formidable obstacle to seizure prediction research. To increase the number of researchers working on this problem, a template for a dedicated seizure prediction workstation needs to become available. This paper proposes a novel dedicated system capable of machine learning-based seizure prediction and training for under U.S. $1000, which is significantly less expensive (U.S. $700 or more) than comparable commercial solutions. This powerful workstation will be capable of training sophisticated machine learning algorithms that can be deployed to lightweight wearable devices, which enables the creation of wearable EEG-based seizure early warning systems.

Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

ABSTRACT The purpose of this work was to evaluate the influence of the clinical profile on lamotrigine (LTG) plasma concentrations from patients with refractory epileptic seizures. In this cross-sectional study, therapeutic monitoring of LTG, and questionnaires with 75 patients with refractory epileptic seizures of a Hospital in Ribeirao Preto-SP-Brazil were performed. The multiple linear regression model was used to verify association between the LTG plasma concentrations and the independent variables. Covariance analysis was used to compare the mean LTG plasma concentration among the co-medication groups. The LTG plasma concentration was associated both with the LTG dosage (mg/kg/day) (p=0.0096) and with the use of first generation antiepileptic drugs (AED) (p<0.01), being carbamazepine (CBZ) and phenytoin (PHT), the AEDs showing the most prominent influence in reducing LTG plasma concentrations. Adverse events, adherence to the pharmacological treatment, and epileptic seizures frequency, did not show significant correlation with LTG plasma concentration values. The conclusion is that LTG plasma concentration is significantly influenced by the LTG dosage and by the concomitant use of a first generation AED.

Functional neuroimaging in Rasmussen syndrome

PurposeFor a diagnosis of Rasmussen syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. MethodsTwenty-three patients diagnosed with RS according to Bien’s (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. ResultsHypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. ConclusionIn RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.

Mozart's music in children with drug-refractory epileptic encephalopathies: Comparison of two protocols

In this prospective, randomized, open label study, we compared the effect on seizure recurrence and quality-of-life parameters, of two different protocols of music therapy in children and adolescents with refractory epileptic encephalopathies. Nine out of 19 patients (13 males and 6 females, aged between 1 and 24years) were randomized to listen to Mozart's sonata in D major for two pianos K448 for 2h/day for 2weeks; other 10 children were randomized on a set of Mozart's compositions.In group 1 (K448), 2/9 children (22.2%) had a ≥75% seizure decrease; two patients had less than 50% seizure reduction, and the other five were unchanged.In group 2 (set Mozart), 7/10 patients (70%) had a significant seizure reduction (specifically, ≥50% in 1/10; ≥75% in 4/10; 100% in 2/10).An overall more significant behavioral improvement including less irritability and tearfulness, reduced self-/heteroaggression, a better daytime vigilance, and nighttime sleep quality, was also reported in children from group 2.In conclusion, the present study seems to confirm that music therapy may be an additional, nonpharmacological, effective treatment for patients with refractory epileptic seizures in childhood. The Mozart's set of different compositions can be better accepted and effective than the K448.

Distinct magnetic resonance imaging features in a patient with novel RARS2 mutations: A case report and review of the literature

Pontocerebellar hypoplasia type 6 (PCH6) is a rare autosomal recessive disease that occurs due to mutations in the mitochondrial arginyl-tRNA synthetase 2 (RARS2) gene. To the best of our knowledge, 23 cases with relatively complete clinical data have been reported thus far. In the present study, a case with PCH6 caused by novel RARS2 mutations is described, in which distinct magnetic resonance imaging (MRI) features were identified. In addition, 23 PCH6 cases found in the literature were reviewed. Early onset hypotonia (43.48%), epileptic seizures (34.78%), encephalopathy (26.08%) and feeding difficulties (17.39%) were common initial symptoms of PCH6. During disease progression, the patients presented refractory epileptic seizures (94.12%), feeding problems (60.87%), severe developmental delay (100%), microcephaly (88.89%) and hyperlactacidemia (76.47%). The clinical features of the present patient were suggestive of PCH6, with early onset epilepsy, feeding difficulties, severe developmental delay, microcephaly, hearing loss and hyperlactacidemia. According to available MRI data from 20 reported cases with PCH6, the characteristic finding in MRI was pontocerebellar dysplasia or progressive cerebral/pontocerebellar atrophy in 16 cases, while 4 cases did not present pontocerebellar hypoplasia, and no basal ganglia involvement was observed in any of the cases. Distinctive MRI features were also identified in the present case, including pontocerebellar preservation after 1 year of age, as well as a high diffusion-weighted imaging signal suggesting intracellular edema in the cerebellar hemispheres, basal ganglia, thalamus and corpus callosum. Progressive loss of cerebral white matter and cortical volume were common features shared by all patients. In conclusion, in the present study, two novel heterozygous mutations were identified in RARS2, namely c.1718C>T(p.Thr573Ile) and c.991A>G (p.Ile331Val). Thus, the present case enriched the phenotypic and genotypic spectrum of the RARS2 mutations.

Paraganglioma exhibiting symptoms of epileptic seizures: Case report

Background: Catecholamines produced by paragangliomas were rarely associated with the occurrence of refractory epileptic seizures.

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery.

In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed.

EP 123. Impaired conflict processing in patients with hippocampal sclerosis

Introduction Hippocampal sclerosis (HS) frequently underlies temporal lobe epilepsy. Patients often suffer from refractory epileptic seizures, but episodic memory deficits, depressive syndromes or impaired special navigation are also common symptoms. Much less is known about the role of the hippocampus for conflict processing. Patients with impaired conflict processing show specific behavioral deficits. They lack goal-directed behavior, are more distractible or have personality characteristics such as unsteadiness, emotional instability, with frequent and rapid mood changes. Early evidence for a hippocampal role in conflict processing comes from Gray’s 1982 model of anxiety, which suggests that the hippocampus supports avoidance behavior during approach-avoidance-conflicts. In addition, the hippocampus is thought to be important for inhibitory learning, a fundamental process that might modulate higher cognitive functions like memory or even conflict processing ( Chan et al., 2001 ). A recent fMRI-EEG study confirmed a role of the human hippocampus for conflict processing by showing hippocampal activity during cognitive conflicts in an auditory stroop task ( Oehrn et al., 2015 ). Here we investigate how hippocampal damage relates to deficits in conflict processing. Methods Patients with temporal lobe epilepsy and HS, patients with TLE and a temporolateral lesion and 27 healthy controls perform the auditory stroop task. Subjects listen to the words “high”, “low” and “good” (semantic aspect) in a low or high pitch (phonetic aspect). Semantic and phonetic aspects either matched (congruent condition) or contradicted (incongruent condition). Results So far, we collected data from two patients with HS and 27 healthy controls. Patients show higher conflict-related slowing of response time (166 ms ± 94) than healthy controls (68 ms ± 53). Patients also show less correct responses during conflict (61% ± 51) compared to non-conflict condition (86% ± 19). However, healthy controls responded correctly in most trials during incongruent (99% ± 1) and congruent condition (95% ± 8). Conclusions The preliminary descriptive data indicate conflict-related slowing of information processing in patients with hippocampal damage. The findings can further our understanding of the role of the hippocampus for conflict processing. It may also help to explain psychiatric comorbidities in patients with temporal lobe epilepsy.

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

States and the federal government are under growing pressure to legalize the use of cannabis products for medical purposes in the United States. Sixteen states have legalized (or decriminalized possession of) products high in cannabidiol (CBD) and with restricted ∆(9) -tetrahydrocannabinol (∆(9) -THC) content. In most of these states, the intent is for use in refractory epileptic seizures in children, but in a few states, the indications are broader. This review provides an overview of the pharmacology and toxicology of CBD; summarizes some of the regulatory, safety, and cultural issues relevant to the further exploitation of its antiepileptic or other pharmacologic activities; and assesses the current status and prospects for clinical development of CBD and CBD-rich preparations for medical use in the United States. Unlike Δ(9) -THC, CBD elicits its pharmacologic effects without exerting any significant intrinsic activity on the cannabinoid receptors, whose activation results in the psychotropic effects characteristic of Δ(9) -THC, and CBD possesses several pharmacologic activities that give it a high potential for therapeutic use. CBD exhibits neuroprotective, antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties. In combination with Δ(9) -THC, CBD has received regulatory approvals in several European countries and is currently under study in trials registered by the U.S. Food and Drug Administration in the United States. A number of states have passed legislation to allow for the use of CBD-rich, limited Δ(9) -THC-content preparations of cannabis for certain pathologic conditions. CBD is currently being studied in several clinical trials and is at different stages of clinical development for various medical indications. Judging from clinical findings reported so far, CBD and CBD-enriched preparations have great potential utility, but uncertainties regarding sourcing, long-term safety, abuse potential, and regulatory dilemmas remain.

Clinical analysis of three children patients with MELAS

This study aims to investigate the clinical manifestations, laboratory and imaging features, pathological and genetic testing, diagnosis and treatment in 3 children patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Focal refractory epileptic seizures were the main clinical manifestations of 3 children, at the same time with stroke-like episodes, exercise intolerance, short stature, paroxysmal headache, vomiting, cognitive impairment, visual impairment, increased blood lactic acid (LA) level and metabolic acidosis. Head MRI showed the lesions were located in temporo-parieto-occipital lobes, and EEG showed slow-wave background, bilateral asymmetry and interictal epileptiform discharges of occiput. Mitochondrial DNA (mtDNA) A3243G mutation was found in the peripheral blood samples of 2 cases. The mutation was not detected in the other case, however, the muscle biopsy revealed pathological changes of mitochondrial myopathy. All 3 cases were treated by antiepileptic drugs (AEDs) including topiramate, levetiracetam and oxcarbazepine, and cocktail therapy. One case died of status epilepticus (SE) after 46 months of follow-up, one case had stroke-like episodes for 2-3 times per year during the follow-up of 40 months, and one case was lost. The clinical manifestations, laboratory and imaging characteristics, pathological and genetic testing in children of MELAS have certain features, which will be helpful for early identification and definite diagnosis, and thus may reduce misdiagnosis and mistreatment. DOI: 10.3969/j.issn.1672-6731.2016.05.009