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1.
Braz J Med Biol Res ; 54(9): e11097, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133540

RESUMO

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5'-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.


Assuntos
Epilepsia , Ácido Valproico , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Polimorfismo de Nucleotídeo Único , Convulsões/tratamento farmacológico , Convulsões/genética , Ácido Valproico/uso terapêutico
2.
Zhonghua Er Ke Za Zhi ; 59(6): 506-510, 2021 Jun 02.
Artigo em Chinês | MEDLINE | ID: mdl-34102826

RESUMO

Objective: To summarize the genotype and phenotype of epilepsy in patients with interferon regulatory factor 2 binding protein-like (IRF2BPL) gene variants. Methods: Data of 6 epilepsy patients with IRF2BPL gene variants seen from May 2017 to September 2020 in the Department of Pediatrics of Peking University First Hospital were retrospectively collected. The clinical characteristics and genetic test results were analyzed. Results: A total of 6 patients with IRF2BPL gene variants (1 boy and 5 girls) were identified. The age of seizure onset was from 3.5 to 7.0 months. Epileptic spasms were observed in 6 patients, tonic seizures and tonic-spasms were observed in 1 patient and focal seizure was observed in 1 patient. All 6 patients presented with developmental delay, 5 patients presented with hypotonia, and 2 patients presented with dysphagia. Microcephaly,nystagmus,chorea and athetosis were observed in 1 patient. The electroencephalography (EEG) showed slow background activity in 2 patients. Hypsarrhythmia was observed in all 6 patients. Focal epileptic discharges were observed in 2 patients. Epileptic spasms were monitored in all 6 patients. Focal seizure and tonic-spasm were monitored in 2 patients respectively. The brain magnetic resonance imaging (MRI) showed cerebral atrophy and dysplasia of the corpus callosum in 1 patient, delayed myelination in 2 patients and normal in 3 patients. Two patients had missense variants c.1280C>T/p.L474F and c.1420C>T/p.S427L, 3 patients had frameshift variants c.232delG/p.V78Sfs*73, c.244del/p.A82Pfs*70 and c.283-308del/p.Ala95Thrfs*29, 1 patient had non-frameshift deletion variant c.1453-c.1455delTTC/p.F485del, and all of the 6 cases had de novo variants. All patients were diagnosed with infantile spasms. The last follow-up age ranged from 1 year to 3.8 years. Four patients achieved seizure-free and 2 patients still had frequent seizures after the treatment with antiepileptic drugs (adrenocorticotropic hormone, topiramate, and vigabatrin). Conclusions: IRF2BPL gene variants are mainly de novo. The age of seizure onset is mainly in infancy, and epilepsy and developmental delay are the main clinical manifestations. Infantile spasm is the main phenotype, some patients have hypotonia and dysphagia. Cerebral atrophy can be observed in a few patients.


Assuntos
Epilepsia , Espasmos Infantis , Proteínas de Transporte , Criança , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/genética , Feminino , Humanos , Lactente , Masculino , Proteínas Nucleares , Estudos Retrospectivos , Convulsões , Espasmos Infantis/genética
3.
London; NICE; May 12, 2021. 97 p.
Monografia em Inglês | BIGG - guias GRADE | ID: biblio-1247830

RESUMO

The guideline covers diagnosing, treating and managing epilepsy and seizures in children, young people and adults in primary and secondary care. It offers best practice advice on managing epilepsy to improve health outcomes so that people with epilepsy can fully participate in daily life. MHRA advice on antiepileptic drugs in pregnancy: In May 2021, we reviewed and amended recommendations on carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate and zonisamide in line with the MHRA updated safety advice on antiepileptic drugs in pregnancy. MHRA advice on valproate: We have amended recommendations in line with the MHRA guidance on valproate use by women and girls. Valproate must not be used in women and girls of childbearing potential (including young girls who are likely to need treatment into their childbearing years), unless other options are unsuitable and the pregnancy prevention programme is in place. The MHRA has published temporary advice on the valproate pregnancy prevention programme during the COVID-19 pandemic.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Epilepsia/diagnóstico por imagem , Eletroencefalografia , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Testes Neuropsicológicos
4.
Xenobiotica ; 51(7): 859-864, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000957

RESUMO

We explored the potential effects of genetic variations on the concentration to dose ratio (CDR) of valproic acid (VPA) in paediatric epilepsy patients.Two hundred and twenty-nine epileptic children on VPA monotherapy were included, and the VPA trough concentrations at steady-state of all subjects were determined.Nineteen single nucleotide polymorphisms (SNPs) of seven selected genes related to the metabolising enzymes and transporters of VPA were identified, and their influences on CDRVPA (a logarithmic transformation was performed if abnormally distributed) were evaluated.UGT2B7 rs7668258 (C>T) TT genotype was associated with a decrease in lnCDRVPA among epileptic children receiving VPA monotherapy (ß=-0.191, p = 0.036). Significantly lower lnCDRVPA was also observed in paediatric patients with UGT1A6 rs2070959 (A>G) GG genotype compared to those AA genotype (ß=-0.270, p = 0.021).This research indicated that UGT2B7 rs7668258 (C>T) and UGT1A6 rs2070959 (A>G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children. The associations could be abolished after Bonferroni's correction and our findings need to be validated in further and larger investigations.


Assuntos
Epilepsia , Ácido Valproico , Anticonvulsivantes , Criança , China , Epilepsia/tratamento farmacológico , Epilepsia/genética , Glucuronosiltransferase/genética , Humanos , Polimorfismo de Nucleotídeo Único
5.
Medicine (Baltimore) ; 100(20): e25831, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011048

RESUMO

BACKGROUND: : The gene mutation of coding sodium channel is one of the most important mechanisms in the pathogenesis of epilepsy. There exists a large inter-individual variation in the efficacy of valproic acid (VPA) against epilepsy. What are the genetic polymorphism influences of sodium channels on VPA response is still under discussion. In this study, a meta-analysis was used to further explore the effects of SCN1A and SCN2A gene polymorphism on VPA response in children with epilepsy. METHODS: : The PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc, and Wan Fang Database were searched up to April 2021 for appropriate studies regarding the association between SCN1A and SCN2A gene polymorphism on VPA response in children suffering from epilepsy. The meta-analysis was conducted by Review Manager 5.3 software. RESULTS: : The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: : This meta-analysis will summarize the effects of SCN1A and SCN2A gene polymorphisms on VPA response in children with epilepsy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/N2786.


Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Ácido Valproico/farmacologia , Anticonvulsivantes/uso terapêutico , Criança , Resistência a Medicamentos/genética , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/genética , Humanos , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Ácido Valproico/uso terapêutico
6.
Paediatr Drugs ; 23(3): 253-286, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33956338

RESUMO

Impairments in cognition are common in epilepsy and may be caused or exacerbated by antiseizure medications (ASMs). Positive effects on cognition may also be seen with some ASMs. Cognitive outcomes are of particular concern in children who may be at an increased risk of cognitive adverse effects of treatment. A comprehensive literature search was conducted in PubMed in order to evaluate the evidence for cognitive changes associated with treatment with ASMs in paediatric epilepsy patients. The ASMs considered were those in the current edition of the British National Formulary (BNF). For most ASMs, remarkably few studies providing robust data on cognitive effects in paediatric patients were identified. The available evidence suggests cognitive impairments may be associated with treatment with phenobarbital. Topiramate and phenytoin are also associated with negative effects on cognition, in particular word-finding difficulties and other language deficits with topiramate, but there are few data available specifically on children. Lamotrigine, levetiracetam and fenfluramine are associated with improvements in some cognitive domains, although it is unclear whether these effects are directly attributable to the medications or are a result of improvements in seizures. Neutral effects on cognition (no substantial evidence of worsening) were suggested for carbamazepine, everolimus, lacosamide, oxcarbazepine, perampanel and valproate. There is limited data for cannabidiol, clobazam, eslicarbazepine acetate, ethosuximide, rufinamide, vigabatrin and zonisamide, although the available evidence suggests these drugs are not associated with severe cognitive impairment. There was too little information to reach conclusions about the effects of brivaracetam, felbamate, gabapentin, pregabalin, retigabine, stiripentol or tiagabine.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/complicações , Transtornos Neurocognitivos/induzido quimicamente , Adolescente , Criança , Epilepsia/tratamento farmacológico , Humanos
7.
Georgian Med News ; (312): 88-92, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33964834

RESUMO

Epilepsy is one of the most common neurological disorder affecting up to 1% of the world population. It is a heterogeneous disorder and includes genetic, structural, metabolic causes, sometimes reason is unknown. In recent 20 years inflammation has been considered as a possible etiologic factor in angiogenesis and epileptogenesis in experimental models but there is still lack of evidence if inflammation could be seen in clinical cases of children with different forms of epilepsy. Epileptic encephalopathies are the group of epilepsies when seizure itself can cause severe cognitive and behavioral abnormalities. Besides seizures occurring in epileptic encephalopathies prone to be highly resistant to medication. Thus any etiological factor contributing to epileptogenesis could have high clinical relevance in modern epileptology. The aim of our research was to study the pro-inflammatory cytokines in different forms of epilepsy in children. We have assessed 56 children from 0-16 years of age. 20 were included in control group (Group 1), 20 children with resolved seizures were involved in study group (Group 2a) and 16 children with resistant seizures were identified as group 2b. The concentration of the following pro-inflammatory cytokines was assessed in blood serum: VCAM-1, CCL2, CCL3, CCL11 as well as a correlation between concentration and seizure repetition rate was also studied. All pro-inflammatory markers were within normal range in controls as well as in both study groups except CCL11. The concentration of CCL11 was elevated in group 2b. Thus we could hypothesize that inflammation could contribute to etiology of resistant epilepsies including epileptic encephalopathies. This evidence could serve as very significant information for pharmaceutical industry for future development of anti-inflammatory medicines as add on therapy with antiepileptic drugs for treatment of drug resistant epilepsies.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Síndromes Epilépticas , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Síndromes Epilépticas/tratamento farmacológico , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico
8.
Cochrane Database Syst Rev ; 5: CD011922, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973646

RESUMO

BACKGROUND: Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018. OBJECTIVES: To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease). SEARCH METHODS: For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data. MAIN RESULTS: We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low. AUTHORS' CONCLUSIONS: This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.


Assuntos
Doença de Alzheimer/complicações , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Fenobarbital/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Cognição/efeitos dos fármacos , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Levetiracetam/administração & dosagem , Masculino , Fenobarbital/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária
9.
Medicine (Baltimore) ; 100(18): e25577, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950934

RESUMO

INTRODUCTION: Brugada syndrome may be unmasked by non-antiarrhythmic pharmaceuticals or drugs. Lacosamide is an antiepileptic agent with a novel mechanism of sodium channel inhibition and has the potential to cause cardiac sodium channel blockade. PATIENT CONCERNS: In this report, we describe the case of patient with a history of a seizure disorder who presented with Brugada I electrocardiogram morphology in the setting of septicemia. DIAGNOSIS: Brugada I electrocardiogram morphology was unmasked by lacosamide antiepileptic monotherapy. INTERVENTIONS: Lacosamide therapy was discontinued. OUTCOMES: Normalization of the electrocardiogram and resolution of Brugada morphology occurred on hospital day 1. CONCLUSION: Caution should be exercised in the use of lacosamide in those at risk for conduction delay, or in combination therapy with medications that impair renal clearance, metabolism of lacosamide, or that display inherent sodium channel blocking properties.


Assuntos
Anticonvulsivantes/efeitos adversos , Síndrome de Brugada/induzido quimicamente , Epilepsia/tratamento farmacológico , Lacosamida/efeitos adversos , Sepse/complicações , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversos , Idoso de 80 Anos ou mais , Anticonvulsivantes/farmacocinética , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Humanos , Lacosamida/farmacocinética , Masculino , Eliminação Renal/fisiologia , Sepse/fisiopatologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacocinética
10.
Artigo em Russo | MEDLINE | ID: mdl-33834715

RESUMO

OBJECTIVE: To evaluate the efficacy and tolerability of extended release carbamazepine (finlepsin-retard and tegretol CR) in adult patients with new-onset focal epilepsy (FE) with the assessment of epileptiform activity index (EAI). MATERIAL AND METHODS: The study included 62 patients (38 (61.3%) men and 24 (38.7%) women) with new-onset FE aged ≥18 years (mean age 42.9±18.4 years). All patients underwent video-ECG-monitoring with EAI assessment at each visit. Treatment efficacy was assessed using the criteria of seizure absence (medically induced remission), seizure rate decrease by >50% (responders), seizure rate decrease by <50% - insufficient efficacy, retention on treatment and seizure rate increase compared to baseline and/or development of new type of seizures (aggravation). Overall study period was 12 months. RESULTS: By the end of the 12-month follow-up period, there was a 4.3-fold decrease of the total EAI compared to baseline (p<0.001). Retention on carbamazepine treatment during 12 months was achieved in 61.3% (n=38) patients; medically induced remission - in 40.3% (n=25); seizure rate decrease by >50% - in 21.0% (n=13). In 29.1% (n=18) of patients, treatment change was performed; double-drug therapy, including carbamazepine, was prescribed in 9.6% (n=6) of patients. Incidence of adverse events was 29.1% (n=18). CONCLUSIONS: Carbamazepine is an effective and promising drug for initial monotherapy of FE. Its use in the treatment of FE results in a 4.3-fold decrease of EAI (p<0.001), which reflects the efficacy of treatment. EAI is an additional objective measure of treatment efficacy.


Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Epilepsia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Artigo em Russo | MEDLINE | ID: mdl-33834730

RESUMO

OBJECTIVE: To study the possibility of using the polypeptide drug cortexin for the treatment of cognitive, emotional and behavioral disorders in children and adolescents with epilepsy and to assess the efficacy and safety of the drug in this group of patients. MATERIALS AND METHODS: Eighty-six patients (41 girls and 45 boys) were examined at the age of 3 to 17 y.o. Cortexin was used along with antiepileptic drugs. Clinical and pathopsychological methods were administered. RESULTS: Children and teenagers with epilepsy have average IQ (91-110) in 72% of cases, 24% had mental deficiency of various intensity, these were children with pharmacoresistant epilepsy, including 2% with IQ 154 and 2% with IQ 71-80. CONCLUSION: Clinical, neurophysiological and psychological study of children and adolescents with epilepsy reveal the improvement of electrophysiological parameters, there are no aggravation of seizures in 95% cases. The improvement of cognitive functions is observed in 65% of patients.


Assuntos
Epilepsia , Peptídeos e Proteínas de Sinalização Intercelular , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Cognição , Epilepsia/tratamento farmacológico , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino
12.
Molecules ; 26(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920713

RESUMO

Rosa webbiana L. (Rosaceae) is one of the least reported and most understudied members of this family. It is native to the Himalayan regions of Pakistan and Nepal. The anti-convulsant effect of n-hexane extract of fruit of Rosa webbiana was investigated in a pentylenetetrazole (PTZ)-induced animal model of epilepsy. Male Sprague-Dawley rats were divided into six groups (n = 7) including control, PTZ (40 mg/kg), diazepam (4 mg/kg) and n-hexane extract (at 50, 150 and 300 mg/kg). Convulsive behavior was observed and resultant seizures were scored, animals sacrificed and their brains preserved. Chitosan nanoparticles were prepared using the ionic gelation method and characterized by UV-analysis, zeta potential and Fourier transform infrared spectroscopy (FTIR). The effects of all the treatments on the expression of phosphorylated cytokine tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) expression in the cortex and hippocampus of the brains of treated rats were studied through enzyme linked immunosorbent assay (ELISA) and morphological differences and surviving neuronal number were recorded through hematoxylene and eosin (H&E) staining. Significant changes in seizures score and survival rate of rats were observed. Downregulation of neuro-inflammation, p-TNF-α and p-NF-κB was evident. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of this fraction showed multiple constituents of interest, including esters, alkanes and amines.


Assuntos
Apoptose/efeitos dos fármacos , Frutas/química , Rosa/química , Fator de Necrose Tumoral alfa/genética , Quitosana/química , Quitosana/farmacologia , Epilepsia/tratamento farmacológico , Epilepsia/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/genética , Fármacos Neuroprotetores/farmacologia
13.
ACS Chem Neurosci ; 12(8): 1281-1292, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33813829

RESUMO

Epilepsy is a result of unprovoked, uncontrollable, and repetitive outburst of abnormal and excessive electrical discharges, known as seizures, in the neurons. Epilepsy is a devastating neurological condition that affects 70 million people globally. Unfortunately, only two-thirds of epilepsy patients respond to antiepileptic drugs while others become drug resistant and may be more prone to epilepsy comorbidities such as SUDEP. Oxidative stress, mitochondrial dysfunction, imbalance in the excitatory and inhibitory neurotransmitters, and neuroinflammation are some of the common pathologies of neurological disorders and epilepsy. Studies suggests that melatonin, a pineal hormone that governs sleep-wake cycles, may be neuroprotective against neurological disorders and thus may be translated as an antiepileptic as well. Melatonin has been shown to be an antioxidant, antiexcitotoxic, and anti-inflammatory hormone/molecule in neurodegenerative diseases, which may contribute to its antiepileptic and neuroprotective properties in epilepsy as well. In addition, melatonin has evidently been shown to play a regulatory role in the cardiorespiratory system and sleep-wake cycles, which may have positive implications toward epilepsy associated comorbidities, such as SUDEP. However, studies investigating the changes in melatonin release due to epilepsy and melatonin's antiepileptic role have been inconclusive and scarce, respectively. Thus, this comprehensive review aims to summarize and elucidate the potential role of melatonin in the pathogenesis of epilepsy and its comorbidities, in hopes to develop new diagnostic and therapeutic approaches that will improve the lives of epileptic patients, particularly those who are drug resistant.


Assuntos
Epilepsia , Melatonina , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Melatonina/uso terapêutico , Convulsões
14.
ACS Chem Neurosci ; 12(10): 1791-1801, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33926190

RESUMO

The resin of the tree Boswellia sacra Flueck. (synonym: B. carterii; Burseraceae), also known as "frankincense", is a traditional remedy used for central nervous system disorders in East Africa. Here we report the evaluation of its antiseizure activity in zebrafish and mouse epilepsy models to identify novel antiseizure compounds. The resin was extracted by solvents of increasing polarity. The hexane extract demonstrated the strongest antiseizure activity and was therefore subjected to bioactivity-guided isolation, which leaded to the isolation of eight terpene derivatives. A new prenylbicyclogermacrene derivative (2) was isolated along with seven other compounds (1, 3-8). Among them, the triterpene ß-boswellic acid (5) showed the strongest activity and reduced 90% of pentylenetetrazole (PTZ)-induced seizures at 100 µg/mL. In parallel to B. sacra, a commercial extract of Boswellia serrata was also evaluated and showed moderate bioactivity (45% reduction at 30 µg/mL). The extract of B. serrata was subjected to targeted isolation of other boswellic acid derivatives (9-13), which were evaluated for antiseizure activity in comparison with 5. In the whole series, ß-boswellic acid (5) was the most active (60% reduction at 200 µM), and its potency was also confirmed with its purchased standard (S5). Pure nanoparticles of S5 and a commercially formulated extract of B. serrata were tested in a PTZ-kindling mouse seizure model. This notably revealed that the S5 administration reduced seizures by 50% in this mouse model, which was consistent with its detection and quantification in plasma and brain samples. This study and the preclinical evaluation performed indicate that ß-boswellic acid, common to various species of Boswellia, has some potential as an antiseizure agent.


Assuntos
Boswellia , Epilepsia , Triterpenos , Animais , Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Camundongos , Extratos Vegetais/farmacologia , Resinas Vegetais , Triterpenos/farmacologia , Peixe-Zebra
15.
Expert Rev Clin Pharmacol ; 14(6): 749-760, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33792454

RESUMO

OBJECTIVE: Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC. METHODS: We evaluated the pattern of routine ASD use and everolimus prescriptions based on a 2019 multicenter survey of 268 individuals with TSC-associated epilepsy. We contextualized the results with a structured review of real-world and clinical study evidence. RESULTS: TSC-associated epilepsy treatment comprises a wide variety of ASDs. In this German sample, the majority of patients were treated with polytherapy, and lamotrigine (34.7%), valproate (32.8%), oxcarbazepine (28.7%), vigabatrin (19.0%), and levetiracetam (17.9%) were identified as the most-commonly used ASDs. In addition, everolimus was used by 32.5% of patients. In adherence to current TSC guidelines, the disease-modifying ASD vigabatrin was widely used in children (58% below the age of 5 years), whereas treatment in adults did not necessarily reflect guideline preference for (partial) GABAergic ASDs. CONCLUSIONS: The selection of ASDs for patients with TSC-associated epilepsy follows well-evaluated recommendations, including the guidelines regarding vigabatrin use in children. Several characteristics, such as the comparatively high frequency of valproate use and polytherapy, reflect the severity of TSC-associated epilepsy.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Epilepsia/etiologia , Everolimo/administração & dosagem , Alemanha , Humanos , Lactente , Recém-Nascido , Padrões de Prática Médica , Esclerose Tuberosa/complicações , Adulto Jovem
16.
Cochrane Database Syst Rev ; 4: CD010682, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860531

RESUMO

BACKGROUND: Depressive disorders are the most common psychiatric comorbidity in people with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that people may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best, and the perceived risk of exacerbating seizures. This review aimed to address these issues, and inform clinical practice and future research. This is an updated version of the original Cochrane Review published in Issue 12, 2014. OBJECTIVES: To evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence, in people with epilepsy and depression. SEARCH METHODS: For this update, we searched CRS Web, MEDLINE, SCOPUS, PsycINFO, and ClinicalTrials.gov (February 2021). We searched the World Health Organization Clinical Trials Registry in October 2019, but were unable to update it because it was inaccessible. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective non-randomised studies of interventions (NRSIs), investigating children or adults with epilepsy, who were treated with an antidepressant and compared to placebo, comparative antidepressant, psychotherapy, or no treatment for depressive symptoms.  DATA COLLECTION AND ANALYSIS: The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement, mean difference, and proportion who achieved complete remission) and change in seizure frequency (mean difference, proportion with a seizure recurrence, or episode of status epilepticus). Secondary outcomes included the number of participants who withdrew from the study and reasons for withdrawal, quality of life, cognitive functioning, and adverse events. Two review authors independently extracted data for each included study. We then cross-checked the data extraction. We assessed risk of bias using the Cochrane tool for RCTs, and the ROBINS-I for NRSIs. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs for specific adverse events. We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs.  MAIN RESULTS: We included 10 studies in the review (four RCTs and six NRSIs), with 626 participants with epilepsy and depression, examining the effects of antidepressants. One RCT was a multi-centre study comparing an antidepressant with cognitive behavioural therapy (CBT). The other three RCTs were single-centre studies comparing an antidepressant with an active control, placebo, or no treatment. The NRSIs reported on outcomes mainly in participants with focal epilepsy before and after treatment for depression with a selective serotonin reuptake inhibitor (SSRI); one NRSI compared SSRIs to CBT.  We rated one RCT at low risk of bias, three RCTs at unclear risk of bias, and all six NRSIs at serious risk of bias. We were unable to conduct any meta-analysis of RCT data due to heterogeneity of treatment comparisons. We judged the certainty of evidence to be moderate to very low across comparisons, because single studies contributed limited outcome data, and because of risk of bias, particularly for NRSIs, which did not adjust for confounding variables. More than 50% improvement in depressive symptoms ranged from 43% to 82% in RCTs, and from 24% to 97% in NRSIs, depending on the antidepressant given. Venlafaxine improved depressive symptoms by more than 50% compared to no treatment (mean difference (MD) -7.59 (95% confidence interval (CI) -11.52 to -3.66; 1 study, 64 participants; low-certainty evidence); the results between other comparisons were inconclusive. Two studies comparing SSRIs to CBT reported inconclusive results for the proportion of participants who achieved complete remission of depressive symptoms.  Seizure frequency data did not suggest an increased risk of seizures with antidepressants compared to control treatments or baseline. Two studies measured quality of life; antidepressants did not appear to improve quality of life over control. No studies reported on cognitive functioning. Two RCTs and one NRSI reported comparative data on adverse events; antidepressants did not appear to increase the severity or number of adverse events compared to controls. The NSRIs reported higher rates of withdrawals due to adverse events than lack of efficacy. Reported adverse events for antidepressants included nausea, dizziness, sedation, headache, gastrointestinal disturbance, insomnia, and sexual dysfunction.  AUTHORS' CONCLUSIONS: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited. Rates of response to antidepressants were highly variable. There is low certainty evidence from one small RCT (64 participants) that venlafaxine may improve depressive symptoms more than no treatment; this evidence is limited to treatment between 8 and 16 weeks, and does not inform longer-term effects. Moderate to low evidence suggests neither an increase nor exacerbation of seizures with SSRIs.  There are no available comparative data to inform the choice of antidepressant drug or classes of drug for efficacy or safety for treating people with epilepsy and depression. RCTs of antidepressants utilising interventions from other treatment classes besides SSRIs, in large samples of patients with epilepsy and depression, are needed to better inform treatment policy. Future studies should assess interventions across a longer treatment duration to account for delayed onset of action, sustainability of treatment responses, and to provide a better understanding of the impact on seizure control.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Antidepressivos/efeitos adversos , Viés , Criança , Terapia Cognitivo-Comportamental , Depressão/etiologia , Epilepsia/induzido quimicamente , Epilepsia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
17.
Epilepsy Res ; 173: 106625, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33819756

RESUMO

OBJECTIVE: No data exist regarding the impact of the lockdown due to the COVID-19 pandemic on the risk factors of sudden unexpected death in epilepsy (SUDEP). This study aimed to stratify risk factors of SUDEP in relation to COVID-19 lockdown, among patients with epilepsy (PWE) in Cairo University epilepsy unit (CUEU). Therefore, we can detect risk factors and mitigate such factors in the second wave of the virus. METHODS: an observational, cross-sectional study carried on 340 Egyptian patients with active epilepsy. Individual risk identification and stratification was done by using The SUDEP and seizure Safety Checklist, after which sharing risk knowledge to PWE and their caregivers was undertaken. RESULTS: The mean age of patients was 29.72 ± 12.12. The median of the static factors was 4 (IQR 3-5) whereas, the median of the modifiable factors was 2 (IQR 1-3). Epilepsy emergencies (serial seizures or status epilepticus) were reported in 24.1 % of patients, for which non-compliance was the commonest cause, followed by deferral of epilepsy surgery for patients with drug resistant epilepsy (DRE). Stepwise logistic regression analysis showed that use of anxiolytic medications, non-compliance, keeping patients with DRE on dual anti-seizure medications (ASMs), or adding third medication increased the odds of increased seizure frequency by 2.7, 3.5, 16.6 and 6.1 times, respectively. CONCLUSION: Some COVID-19 related issues had influenced the risk of seizure worsening including postponing epilepsy surgery for patients with DRE, non-compliance, and psychiatric comorbidities. Special attention should be paid to these issues to mitigate the risk of SUDEP.


Assuntos
COVID-19/epidemiologia , Pandemias , Morte Súbita Inesperada na Epilepsia/epidemiologia , Adolescente , Adulto , Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Agendamento de Consultas , COVID-19/psicologia , Lista de Checagem , Estudos Transversais , Egito/epidemiologia , Procedimentos Cirúrgicos Eletivos , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Epilepsia/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Medição de Risco , Fatores de Risco , Morte Súbita Inesperada na Epilepsia/prevenção & controle , Centros de Atenção Terciária/estatística & dados numéricos , Tempo para o Tratamento , Adulto Jovem
18.
Epilepsy Behav ; 118: 107946, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33848848

RESUMO

OBJECTIVE: This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. METHODS: A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. RESULTS: Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. CONCLUSIONS: The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy.


Assuntos
Epilepsia , Bloqueadores dos Canais de Sódio/uso terapêutico , Espasmos Infantis , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Síndromes Epilépticas , Humanos , Lactente , Proteínas Serina-Treonina Quinases/genética , Estudos Retrospectivos , Espasmos Infantis/complicações , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-33920188

RESUMO

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.


Assuntos
Canabidiol , Cannabis , Epilepsia , Adolescente , Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Convulsões
20.
Epilepsy Behav ; 118: 107927, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33812233

RESUMO

OBJECTIVES: Combination regimens of antiepileptic drugs (AEDs) with various mechanisms of action (MOA) are commonly used in patients with refractory epilepsy. However, outcomes related to combination AEDs with novel MOA, such as perampanel (PER), are not well described. This study compared healthcare resource utilization (HRU) among recipients of PER-based combinations versus recipients of other non-PER-based combinations. METHODS: This retrospective study used claims data from the Symphony Health's IDV® (Integrated Dataverse) database (August 2012 to July 2018). Patients were aged ≥12 years with epilepsy or non-febrile convulsions, were treated with AED combinations, and had ≥12 and ≥6 months pre- and post-index date, respectively (date of initiation of the second AED in the combination). AEDs were categorized based on MOA: selective non-competitive antagonist of AMPA receptors (i.e., PER), sodium channel blocker (SC), synaptic vesicle protein 2A binding (SV2), and gamma-aminobutyric acid analog (G). Patients were then classified into MOA-based cohorts: PER + SC, PER + SV2, PER + G, SC + SC, SC + SV2, SC + G, SV2 + G, and G + G. HRU outcomes were evaluated during follow-up and compared between PER-based cohorts and non-PER-based cohorts. RESULTS: On average, patients in the PER + SC (N = 3,592), PER + SV2 (N = 2,200), and PER + G (N = 1,313) cohorts were younger and had a lower Quan-Charlson comorbidity index than those in non-PER-based cohorts. PER + SC and PER + SV2 users had significantly fewer all-cause hospitalizations than non-PER-based users (adjusted RR range: 0.66-0.89, all P < 0.05), while PER + G recipients had fewer all-cause hospitalizations than recipients of SV2 + G and G + G (adjusted RR range: 0.92-0.94). Similar trends were observed for epilepsy-related hospitalizations. Across all comparisons, PER-based combinations were associated with significantly lower rates of all-cause clinic/office/outpatient visits relative to non-PER-based combinations (adjusted RR range: 0.69-0.86, all P < 0.05). SIGNIFICANCE: Results showed that patients treated with PER-based combinations had fewer all-cause and epilepsy-related hospitalizations, and fewer all-cause clinic/office/outpatient visits compared with patients treated with most other non-PER-based combinations.


Assuntos
Anticonvulsivantes , Epilepsia , Idoso , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Piridonas/uso terapêutico , Estudos Retrospectivos , Estados Unidos
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