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1.
Toxicol Lett ; 325: 67-76, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017982

RESUMO

Racemic 3-quinuclidinyl-α-methoxydiphenylacetate (MB266) was synthesised. Its activity at muscarinic acetylcholine receptors (mAChRs), and muscle and neuronal nicotinic acetylcholine receptors (nAChRs), was compared to that of atropine and racemic 3-quinucidinyl benzilate (QNB) using a functional assay based on agonist-induced elevation of intracellular calcium ion concentration in CN21, Chinese Hamster Ovary (CHO) and SHSY5Y human cell lines. MB266 acted as an antagonist at acetylcholine receptors, displaying 18-fold selectivity for mAChR versus nAChR (compared to the 15,200-fold selectivity observed for QNB). Thus O-methylation of QNB reduced the affinity for mAChR antagonism and increased the relative potency at both muscle and neuronal nAChRs. Despite MB266 having a pharmacological profile potentially useful for the treatment of anticholinesterase poisoning, its administration did not improve the neuromuscular function in a soman-poisoned guinea-pig diaphragm preparation pretreated with the organophosphorus nerve agent soman. Consideration should be given to exploring the potential of MB266 for possible anticonvulsant action in vitro as part of a multi-targeted ligand approach.


Assuntos
Antídotos/farmacologia , Antídotos/uso terapêutico , Inibidores da Colinesterase/envenenamento , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Agentes Neurotóxicos/envenenamento , Antagonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/uso terapêutico , Animais , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Antídotos/síntese química , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , Diafragma/efeitos dos fármacos , Cobaias , Humanos , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/síntese química , Músculo Esquelético/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Antagonistas Nicotínicos/síntese química , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Soman/envenenamento
2.
J Matern Fetal Neonatal Med ; 33(2): 258-266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29898629

RESUMO

Introduction: There is little information on the effect of maternal characteristics and on-admission laboratory parameters to the therapeutic serum magnesium sulfate (MgSO4) levels in women with preeclampsia (PE). We sought to identify factors that may predict timely attainment of therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis.Materials and methods: On-admission factors of 360 women with PE who received intravenous MgSO4 (4-g loading and 2-g/h maintenance) for seizure prophylaxis were retrospectively reviewed. Parameters of those who attained therapeutic serum concentrations (4.8-8.4 mg/dL) within 2 h (Group A) and those who did not (Group B) were compared.Results: There was no seizure or magnesium toxicity in this cohort. Median (min-max) level of serum magnesium was 4.3 (2.5-8.4) mg/dL. Women in Group A (n = 105) had lower gestational age, body mass index (BMI), and platelets count, higher blood urea nitrogen (BUN), serum creatinine, uric acid, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin, and partial thromboplastin times than those in Group B (n = 255) (p < .05). Women with mild PE were less likely to attain therapeutic serum magnesium levels compared with those with severe phenotypes (adjusted OR 23.57, 95% CI 8.20-67.76 versus adjusted OR 14.72, 95% CI 3.56-60.89, respectively; p < .05), which may be explained by their significantly lower serum BUN and uric acid (p < .05).Conclusions: On-admission factors, especially BMI and renal clearance indices, of women with PE may affect timely attainment of therapeutic serum magnesium levels. Validation of its clinical impact requires further study focusing on women with severe PE.


Assuntos
Sulfato de Magnésio/sangue , Pré-Eclâmpsia/sangue , Convulsões/prevenção & controle , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Infusões Intravenosas/métodos , Sulfato de Magnésio/administração & dosagem , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
3.
Med. intensiva (Madr., Ed. impr.) ; 43(8): 489-496, nov. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-185886

RESUMO

Los pacientes con patología neuroquirúrgica requieren frecuentemente el ingreso en unidades de cuidados intensivos tanto para su manejo en el postoperatorio inmediato como para el control de las complicaciones que puedan presentar. La patología neuroquirúrgica es amplia y requiere profilaxis, tratamiento y monitorización específica. El tratamiento del paciente neuroquirúrgico se basa en asegurar una correcta perfusión tisular cerebral, es decir, mantener un flujo sanguíneo suficiente para aportar energía al parénquima cerebral. Con el objetivo de optimizar el tratamiento y el manejo de estos pacientes, en los últimos años se han desarrollado y perfeccionado diferentes sistemas para monitorizar variables como la presión intracraneal, la actividad eléctrica cerebral (electroencefalografía), el flujo cerebral, la oxigenación del parénquima (presión tisular de oxígeno) o el metabolismo locorregional (microdiálisis). Esta revisión sintetiza el manejo general del paciente neuroquirúrgico así como el de las principales complicaciones que puede desarrollar durante el postoperatorio. Asimismo, se propone un algoritmo de actuación para facilitar la decisión de los profesionales responsables que incluye la neuromonitorización multimodal


Neurosurgical patients frequently require admission to intensive care units, either for postoperative management or for treating complications. Most neurosurgical diseases require specific monitoring and prophylaxis. The basic principle of neurosurgical patient management is to ensure correct brain tissue perfusion, i.e., maintaining a sufficient blood flow to supply energy and oxygen to the brain parenchyma. In the last few years, several systems have been developed and improved for monitoring variables such as intracranial pressure, cerebral electrical activity (electroencephalography), cerebral blood flow, parenchymal oxygenation (tissue oxygen pressure) or locoregional metabolism (microdialysis). The present study provides an overview of the general management of neurosurgical patients and the main complications that may occur during the postoperative period. An interventional algorithm is also proposed to facilitate physician decisions, with the inclusion of multimodal neuromonitoring


Assuntos
Humanos , Cuidados Críticos/normas , Neurocirurgia , Neurologia , Cuidados Pós-Operatórios , Unidades de Terapia Intensiva , Pressão Intracraniana , Eletroencefalografia , Complicações Pós-Operatórias , Respiração Artificial , Hidratação , Antibioticoprofilaxia , Convulsões/prevenção & controle
4.
Psychiatr Danub ; 31(Suppl 3): 467-474, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488774

RESUMO

Music is a very important factor in everyday life, involving mood, emotions and memories. The effect of music on the brain is very debated. Certainly, music activates a complex network of neurones in auditory areas, mesolimbic areas, cerebellum and multisensory areas. In particular, music exerts its effects on the brain of patients with epilepsy, having a dichotomous influence: it can either be seizure-promoting in musicogenic epilepsy or antiepileptic. Several studies have shown that seizure-prone neural networks may be stimulated by certain periodicities while other frequencies may prevent seizure activity. There are a lot of data in the literature about the so-called "Mozart effect" (Rauscher et al. 1993). In previous studies we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of the cases. In this study we are conducting a survey on the observation of what happens to the brain of patients suffering from drug-resistant epilepsy through electroencephalographic investigations, brain MRI and behavioural analysis before and after six months of listening to Mozart music (Sonata K.448). The first step is to present the data of the first patient under investigation.


Assuntos
Epilepsia/fisiopatologia , Epilepsia/reabilitação , Musicoterapia , Música/psicologia , Convulsões/prevenção & controle , Convulsões/fisiopatologia , Estimulação Acústica , Mapeamento Encefálico , Eletroencefalografia , Epilepsia/complicações , Humanos , Convulsões/complicações
5.
Rev. neurol. (Ed. impr.) ; 69(5): 181-189, 1 sept., 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-184455

RESUMO

Objetivo. Evaluar la adecuación y el efecto del tratamiento antiepiléptico preventivo en pacientes adultos con una primera crisis epiléptica en cuanto a resultados adversos a los 30 días del alta del servicio de urgencias hospitalario (SUH). Pacientes y métodos. ACESUR fue un registro observacional de cohortes multipropósito, prospectivo y multicéntrico con un muestreo sistemático. Se realizó seguimiento telefónico a los 30 días. Se recogieron variables clínicas en la visita índice y de resultado en seguimiento. La variable principal fue "tratamiento preventivo adecuado según indicaciones", y la de resultado, "algún resultado adverso" (recurrencia de crisis epiléptica, revisita a SUH, hospitalización o muerte) a los 30 días del alta de urgencias. Se realizó un modelo de regresión logística para aislar el efecto del tratamiento preventivo adecuado. Resultados. Se incluyó a 151 (22,7%) pacientes con una media de 55 años con primera crisis epiléptica, dados de alta de 18 SUH con datos de seguimiento. El tratamiento preventivo se consideró adecuado en 128 (84,8%) pacientes. Cuarenta y un (27,2%) pacientes presentaron algún resultado adverso a los 30 días del alta. Tras la regresión logística, el tratamiento preventivo adecuado al alta del SUH ejerce un efecto protector sobre la variable "algún resultado adverso a 30 días". Conclusiones. En el registro ACESUR, el tratamiento preventivo fue adecuado en la mayoría de los pacientes y su efecto resultó, de forma independiente, protector a los 30 días. Por tanto, el tratamiento preventivo adecuado podría mejorar los resultados a corto plazo de pacientes adultos dados de alta con una primera crisis epiléptica del SUH


Aim. To evaluate the adequacy and effect of preventive antiepileptic treatment in adult patients with the first epileptic seizure in adverse outcomes at 30 days after discharge from the hospital emergency department (HED). Patients and methods. ACESUR was an observational registry of multipurpose, prospective and multicentric cohorts with a systematic sampling. Phone follow-up was done at 30 days. Clinical variables were collected in the index visit and the follow-up result. The main variable was "adequate preventive treatment according to indications" and the result of "some adverse outcome" (recurrence of epileptic seizure, revisits to HED, hospitalization or death) 30 days after discharge from HED. A logistic regression model was used to isolate the effect of adequate preventive treatment. Results. 151 (22.7%) patients with a mean age of 55 years old were included with first epileptic seizure discharged from 18 HED with follow-up data. Preventive treatment was considered adequate in 128 (84.8%) patients. 41 (27.2%) patients presented some adverse outcome 30 days after discharge. After the logistic regression, the appropriate preventive treatment to the discharge of the HED exerts a protective effect on the variable "some adverse outcome to 30 days". Conclusions. In the ACESUR registry, preventive treatment was adequate for most patients and its effect was independent protective at 30 days. Therefore, adequate preventive treatment could improve the short-term results of adult patients discharged with the first epileptic seizure of the HED


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Anticonvulsivantes/administração & dosagem , Serviço Hospitalar de Emergência , Anticonvulsivantes/efeitos adversos , Convulsões/prevenção & controle , Epilepsia/tratamento farmacológico , Estudos Prospectivos , Seguimentos
6.
Cochrane Database Syst Rev ; 7: CD001911, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318037

RESUMO

BACKGROUND: This is an update of a Cochrane Review first published in 2002 and last updated in 2017. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly-used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first-line treatment for focal onset seizures in the USA and Europe. Phenytoin is no longer considered a first-line treatment, due to concerns over adverse events associated with its use, but the drug is still commonly used in low- to middle-income countries because of its low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials; however, the confidence intervals generated by these trials are wide, and therefore, synthesising the data of the individual trials may show differences in efficacy. OBJECTIVES: To review the time to treatment failure, remission and first seizure with carbamazepine compared with phenytoin when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: For the latest update, we searched the following databases on 13 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy's Specialised Register and CENTRAL; MEDLINE; the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov); and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing monotherapy with either carbamazepine or phenytoin in children or adults with focal onset seizures or generalised onset (tonic-clonic) seizures. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 595 participants out of 1102 eligible individuals, from four out of 11 trials (i.e. 54% of the potential data). For remission outcomes, a HR greater than 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, a HR greater than 1 indicates an advantage for carbamazepine. Most participants included in analysis (78%) were classified as experiencing focal onset seizures at baseline and only 22% were classified as experiencing generalised onset seizures; the results of this review are therefore mainly applicable to individuals with focal onset seizures.Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 546 participants: 0.94, 95% CI 0.70 to 1.26, moderate-certainty evidence); time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 546 participants: 0.99, 95% CI 0.69 to 1.41, moderate-certainty evidence); both showing no clear difference between the drugs and time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 546 participants: 1.27, 95% CI 0.87 to 1.86, moderate-certainty evidence), showing that treatment failure due to adverse events may occur earlier on carbamazepine than phenytoin, but we cannot rule out a slight advantage to carbamazepine or no difference between the drugs.For our secondary outcomes (pooled HRs adjusted for seizure type), we did not find any clear differences between carbamazepine and phenytoin: time to first seizure post-randomisation (582 participants): 1.15, 95% CI 0.94 to 1.40, moderate-certainty evidence); time to 12-month remission (551 participants): 1.00, 95% CI 0.79 to 1.26, moderate-certainty evidence); and time to six-month remission (551 participants): 0.90, 95% CI 0.73 to 1.12, moderate-certainty evidence).For all outcomes, results for individuals with focal onset seizures were similar to overall results (moderate-certainty evidence), and results for the small subgroup of individuals with generalised onset seizures were imprecise, so we cannot rule out an advantage to either drug, or no difference between drugs (low-certainty evidence). There was also evidence that misclassification of seizure type may have confounded the results of this review, particularly for the outcome 'time to treatment failure'. Heterogeneity was present in analysis of 'time to first seizure' for individuals with generalised onset seizures, which could not be explained by subgroup analysis or sensitivity analyses.Limited information was available about adverse events in the trials and we could not compare the rates of adverse events between carbamazepine and phenytoin. Some adverse events reported on both drugs were abdominal pain, nausea, and vomiting, drowsiness, motor and cognitive disturbances, dysmorphic side effects (such as rash). AUTHORS' CONCLUSIONS: Moderate-certainty evidence provided by this systematic review does not show any differences between carbamazepine and phenytoin in terms of effectiveness (retention) or efficacy (seizure recurrence and seizure remission) for individuals with focal onset or generalised onset seizures.However, some of the trials contributing to the analyses had methodological inadequacies and inconsistencies, which may have had an impact on the results of this review. We therefore do not suggest that results of this review alone should form the basis of a treatment choice for a person with newly-onset seizures. We did not find any evidence to support or refute current treatment policies. We implore that future trials be designed to the highest quality possible, with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Fenitoína/uso terapêutico , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Humanos , Fenitoína/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Convulsões/prevenção & controle , Falha de Tratamento , Resultado do Tratamento
7.
BMJ Case Rep ; 12(7)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352381

RESUMO

Temporal lobe epilepsy (TLE), a common form of localisation-related epilepsy, is characterised by focal seizures and accompanied by variety of neuropsychiatric symptoms. This form of epilepsy proves difficult to manage as many anticonvulsant and psychotropic medications have little to no effect on controlling the seizure and neuropsychiatric symptoms respectively. The authors, report a patient with TLE and recurrent seizures that were refractory to multiple classes of antiepileptic therapy. Additionally, she exhibited psychosis, depression and irritability that required antipsychotic medication. After several years of poorly controlled seizure disorder, the patient underwent anterior temporal lobectomy and amygdalohippocampectomy, which proved beneficial for seizure control, as well as her neuropsychiatric symptoms. While it is common to treat refractory temporal lobe epilepsy with surgical interventions, there is little literature about it also treating the neuropsychiatric symptoms. This case underscores both the neurological and psychiatric benefits following surgical intervention for patients with TLE.


Assuntos
Lobectomia Temporal Anterior , Anticonvulsivantes/uso terapêutico , Epilepsia do Lobo Temporal/terapia , Transtornos Psicóticos/terapia , Convulsões/prevenção & controle , Adulto , Tonsila do Cerebelo/cirurgia , Emigrantes e Imigrantes , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/psicologia , Feminino , Acesso aos Serviços de Saúde , Hipocampo/cirurgia , Humanos , Transtornos Psicóticos/fisiopatologia , Convulsões/fisiopatologia , Resultado do Tratamento
8.
Seizure ; 70: 30-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31247400

RESUMO

As our surgical, radiation, chemotherapeutic and supportive therapies for brain malignancies improve, and overall survival is prolonged, appropriate symptom management in this patient population becomes increasingly important. This review summarizes the published literature and current practice patterns regarding prophylactic and perioperative anti-epileptic drug use. As a wide range of anti-epileptic drugs is now available to providers, evidence guiding appropriate anticonvulsant choice is reviewed. A particular focus of this article is radiation therapy for brain malignancies. Toxicities and seizure risk associated with cranial irradiation will be discussed. Epilepsy management in patients undergoing radiation for gliomas, glioblastoma multiforme, and brain metastases will be addressed. An emerging but inconsistent body of evidence, reviewed here, indicates that anti-epileptic medications may increase radiosensitivity, and therefore improve clinical outcomes, specifically in glioblastoma multiforme patients.


Assuntos
Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Convulsões/prevenção & controle , Neoplasias Encefálicas/cirurgia , Irradiação Craniana/efeitos adversos , Gerenciamento Clínico , Epilepsia/etiologia , Epilepsia/terapia , Glioma/complicações , Glioma/radioterapia , Glioma/cirurgia , Humanos , Convulsões/etiologia
9.
Pediatr Dermatol ; 36(4): 524-527, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31134637

RESUMO

Sturge-Weber syndrome (SWS) is characterized by facial capillary malformation, leptomeningeal capillary malformations, and choroidal and episcleral vascular malformations. These malformations produce neurologic and ophthalmological symptoms including seizures and glaucoma. A premature male newborn without prenatal diagnosis presented with severe bilateral SWS and was started on systemic sirolimus and aspirin. The patient has remained seizure-free for 23 months and demonstrated an excellent response to pulsed dye laser treatment.


Assuntos
Aspirina/uso terapêutico , Recém-Nascido Prematuro , Convulsões/prevenção & controle , Sirolimo/uso terapêutico , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/tratamento farmacológico , Administração Oral , Quimioterapia Combinada , Eletroencefalografia/métodos , Humanos , Recém-Nascido , Lasers de Corante/uso terapêutico , Imagem por Ressonância Magnética/métodos , Masculino , Mancha Vinho do Porto/diagnóstico , Mancha Vinho do Porto/cirurgia , Prevenção Primária/métodos , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Síndrome de Sturge-Weber/diagnóstico por imagem , Resultado do Tratamento
10.
Seizure ; 69: 140-146, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31048270

RESUMO

PURPOSE: The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. METHOD: The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included "Anticonvulsants", "Intracerebral Hemorrhage", and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg's and Egger's tests. RESULTS: A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I2 = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. CONCLUSIONS: The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b).


Assuntos
Anticonvulsivantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Convulsões/prevenção & controle , Hemorragia Cerebral/complicações , Humanos , Convulsões/etiologia , Fatores de Tempo , Resultado do Tratamento
11.
Acta Neurobiol Exp (Wars) ; 79(1): 86-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038487

RESUMO

Epilepsy is a life­threatening disorder that is marked by recurrent seizures. Febrile seizure is a common neurological disorder observed in neonates. In many cases, reducing body temperature can prevent febrile seizure. Transient receptor potential cation channel subfamily M member 8 (TRPM8) is a cation channel that is involved in body thermoregulation. It was reported that M8­B, a TRPM8 antagonist, can reduce body temperature. Thus, we aimed to investigate the effect of M8­B on different experimental seizure models. Eight­day­old male Wistar rat pups were used for induction of febrile seizure. M8­B and diazepam were injected intraperitoneally. The rat pups were then transferred to a heated plexiglas chamber and the latency to the first febrile seizure was measured. In addition, different groups of mice were pretreated with M8­B and received a convulsant dose of pentylenetetrazol (PTZ). Latencies to stages 2 and 4 and duration of stage 5 seizure episodes were measured. Furthermore, the effect of M8­B on electroshock­induced seizures was also investigated and hindlimb extension time was measured. The results showed that M8­B decreased the body temperature of rat pups and increased the latency to the first febrile seizure, implying a significant protective effect. It also induced a significant anticonvulsant effect in PTZ ­ but not electroshock­induced convulsions. M8­B showed anticonvulsant effects in both febrile­ and PTZ­induced seizures. M8­B had a hypothermic effect with significant protective effects on febrile­ and PTZ­induced seizures; however, it did not produce similarly protective effects on seizures induced by electroshock.


Assuntos
Anticonvulsivantes/uso terapêutico , Convulsivantes/toxicidade , Pentilenotetrazol/toxicidade , Convulsões Febris/tratamento farmacológico , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Tiofenos/uso terapêutico , Animais , Animais Recém-Nascidos , Temperatura Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/metabolismo , Fatores de Tempo
12.
J Neurooncol ; 143(3): 437-445, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054098

RESUMO

PURPOSE: Dysembryoplastic neuroepithelial tumors (DNETs) are a common cause of chronic drug-resistant epilepsy and are known for their favorable surgical outcomes. Nevertheless, the seizure recurrence-free rate is not as favorable if tumorous nodules are present near the main mass. We call these small tumorous nodules in the vicinity of the main mass satellite lesions (SLs). We analyzed tumor and seizure control in the presence and following the subsequent removal of SLs. METHODS: We retrospectively reviewed the medical records, radiological data, and surgical procedures to obtain the outcomes of children who underwent resection surgery for DNET. The analyses were designed to address the associations among the demographic, tumor and seizure-related variables. A Cox proportional hazard model was used for the univariate and multivariate analyses. RESULTS: In total, 39 consecutive patients were included (26 males and 13 females). SLs were found in 22 patients (56%). The year-to-year analysis of patients with Engel class I was approximately 80% during the follow-up period. However, the actual seizure recurrence-free survival (RFS) rate was 82, 73 and 70% at the first, second and fifth year, respectively. The patients who initially presented with SLs had 46% seizure recurrence rates, while those without SL had 18% seizure recurrence rates. CONCLUSIONS: As the seizure-RFS rate significantly declines over time, a more accurate seizure-free rate analysis using survival curves could be important for determining the outcome of DNET surgery. A thorough review identifying satellite lesions preoperatively and using intraoperative neuronavigation, electrocorticography (ECoG) or intraoperative ultrasonography is warranted to accomplish the wide resection of tumors with accompanying satellite lesions.


Assuntos
Neoplasias Neuroepiteliomatosas/prevenção & controle , Procedimentos Neurocirúrgicos/mortalidade , Procedimentos Neurocirúrgicos/métodos , Convulsões/prevenção & controle , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/patologia , Neuronavegação/métodos , Prognóstico , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/patologia , Taxa de Sobrevida
13.
Neurol Res ; 41(7): 652-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31025607

RESUMO

Introduction: We have been exploring the effects of dihydroprogesterone in female amygdala-kindled rats. For intraperitoneal (i.p.) time-response studies, we used a vehicle containing the common solvent, benzyl alcohol (BnOH). The vehicle containing BnOH was also tested alone as a control. Method and Results: Unexpectedly, it was found that the vehicle containing BnOH had clear-cut anti-seizure effects in the kindling model, with an ED50 of 100 mg/kg. In a follow-up study, dose- and time-response studies of i.p. BnOH were done in male mice in the maximal pentylenetetrazol (PTZ) model. BnOH suppressed PTZ seizures in a dose-dependent manner, with an ED50 of 300 mg/kg against hindlimb tonic extension. Effects were fully established at 5-min post injection and lasted for an hour. Conclusion: BnOH is not an inert solvent. It has clear-cut anti-seizure effects against both focal and generalized seizures.


Assuntos
Álcool Benzílico/farmacologia , Convulsões/prevenção & controle , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estimulação Elétrica , Eletrodos Implantados , Feminino , Excitação Neurológica/efeitos dos fármacos , Masculino , Camundongos , Pentilenotetrazol , Ratos
14.
Transfusion ; 59(S2): 1529-1538, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980755

RESUMO

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.


Assuntos
Transfusão de Componentes Sanguíneos , Lesões Encefálicas Traumáticas , Cuidados Críticos/métodos , Hospitalização , Adulto , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/terapia , Feminino , Humanos , Hipotensão/etiologia , Hipotensão/mortalidade , Hipotensão/fisiopatologia , Hipotensão/prevenção & controle , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/mortalidade , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/prevenção & controle , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/mortalidade , Hipertensão Intracraniana/fisiopatologia , Hipertensão Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Convulsões/etiologia , Convulsões/mortalidade , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/fisiopatologia , Tromboembolia Venosa/prevenção & controle
15.
Stroke ; 50(5): 1095-1099, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30935318

RESUMO

Background and Purpose- We sought to evaluate the available literature to determine whether primary seizure prevention with antiepileptic drugs reduces the risk of poor outcomes and clinically relevant seizures among adult patients with spontaneous intracerebral hemorrhage. Methods- Meta-analysis of observational studies and randomized controlled trials evaluating the use of any antiepileptic drug for primary seizure prevention among adult (≥18 years) patients with spontaneous intracerebral hemorrhage. The primary end point was poor clinical outcome at the longest recorded follow-up, defined as either a high (>3) modified Rankin Scale score or all-cause mortality during follow-up if the modified Rankin Scale score was not recorded. Early and late seizures were secondary outcomes. A random mixed effects model was used to estimate the pooled odds ratio of outcomes and associated 95% CI. Results- We identified 7 studies with a total of 3241 patients for analysis of the primary outcome and 4 studies with a total of 1861 patients for analysis of the secondary outcomes. Overall, the use of antiepileptic drugs was not associated with a high Rankin Scale or all-cause mortality (odds ratio: 0.99; 95% CI, 0.66-1.49) or incident seizures (odds ratio: 0.89; 95% CI, 0.52-1.51) at the longest recorded follow-up time. Conclusions- The use of antiepileptic drugs as primary prevention among adult patients with spontaneous intracerebral hemorrhage is not associated with improved neurological function during long-term follow-up. Future studies should focus on the preventive use of distinct antiepileptic agents among patients at high risk of both seizures and poor outcomes.


Assuntos
Anticonvulsivantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , Convulsões/epidemiologia , Convulsões/prevenção & controle , Hemorragia Cerebral/diagnóstico , Humanos , Estudos Observacionais como Assunto/métodos , Prevenção Primária/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Convulsões/diagnóstico
16.
Toxicol Ind Health ; 35(5): 387-397, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30991910

RESUMO

Cytochrome P450 2E1 (CYP2E1) can be induced by diabetes mellitus, nonalcoholic liver disease, and obesity. This study assessed the protective effects of three sulfur compounds, namely phenethyl isothiocyanate (PEITC), dimethyl trisulfide (DMTS), and sodium thiosulfate (STS), on acrylonitrile (ACN)-induced acute toxicity in rats enriched with CYP2E1. PEITC and DMTS were administered intragastrically (i.g.), whereas STS was injected intraperitoneally (i.p.) at an identical dose of 0.5 mmol/kg for 3 days in acetone-pretreated rats before ACN (90 mg/kg) injection (i.p.). Acetone-treated rats that expressed high levels of CYP2E1 were more susceptible to ACN-induced acute toxicity. The sulfur compounds reduced the rate of convulsions and loss of the righting reflex in acute ACN-exposed CYP2E1-induced rats; PEITC and DMTS also increased the survival rates. PEITC inhibited hepatic CYP2E1 activity and protected hepatic and cerebral cytochrome c oxidase (CcOx) activities in acute ACN-exposed CYP2E1-enriched rats; DMTS protected hepatic CcOx activity. DMTS attenuated ACN-induced oxidative injury by reducing malondialdehyde (MDA) levels and increasing glutathione content in the brain. STS only reduced cerebral MDA levels, whereas PEITC did not exhibit any antioxidant effects. Collectively, PEITC provided superior protective effects against ACN-induced acute toxicity in rats with increased CYP2E1 activity, followed by DMTS; STS provided limited effects. PEITC and DMTS might be considered as promising chemopreventive agents against ACN-induced acute toxicity in vulnerable subpopulations with increased CYP2E1 activity.


Assuntos
Acrilonitrila/toxicidade , Isotiocianatos/farmacologia , Reflexo de Endireitamento/efeitos dos fármacos , Convulsões/prevenção & controle , Sulfetos/farmacologia , Tiossulfatos/farmacologia , Animais , Citocromo P-450 CYP2E1/administração & dosagem , Sistema Enzimático do Citocromo P-450/análise , Estimativa de Kaplan-Meier , Masculino , Mortalidade , Distribuição Aleatória , Ratos , Convulsões/induzido quimicamente , Compostos de Enxofre/farmacologia
17.
Nat Commun ; 10(1): 1917, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015467

RESUMO

STXBP1 and SCN2A gene mutations are observed in patients with epilepsies, although the circuit basis remains elusive. Here, we show that mice with haplodeficiency for these genes exhibit absence seizures with spike-and-wave discharges (SWDs) initiated by reduced cortical excitatory transmission into the striatum. Mice deficient for Stxbp1 or Scn2a in cortico-striatal but not cortico-thalamic neurons reproduce SWDs. In Stxbp1 haplodeficient mice, there is a reduction in excitatory transmission from the neocortex to striatal fast-spiking interneurons (FSIs). FSI activity transiently decreases at SWD onset, and pharmacological potentiation of AMPA receptors in the striatum but not in the thalamus suppresses SWDs. Furthermore, in wild-type mice, pharmacological inhibition of cortico-striatal FSI excitatory transmission triggers absence and convulsive seizures in a dose-dependent manner. These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice.


Assuntos
Corpo Estriado/metabolismo , Proteínas Munc18/genética , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Neocórtex/metabolismo , Convulsões/genética , Transmissão Sináptica , Potenciais de Ação/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dioxóis/farmacologia , Eletroencefalografia , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/metabolismo , Epilepsia Tipo Ausência/fisiopatologia , Etossuximida/farmacologia , Regulação da Expressão Gênica , Haploinsuficiência , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Interneurônios/patologia , Camundongos , Camundongos Knockout , Proteínas Munc18/deficiência , Canal de Sódio Disparado por Voltagem NAV1.2/deficiência , Neocórtex/efeitos dos fármacos , Neocórtex/patologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Piperidinas/farmacologia , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Convulsões/metabolismo , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Transdução de Sinais , Tálamo/efeitos dos fármacos , Tálamo/metabolismo
18.
Neuroscience ; 406: 176-185, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30872164

RESUMO

Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented this impairment. Then, we investigated the involvement of α-adrenergic receptors in this effect of LFS. EA was induced by increasing the extracellular K+ concentration to 12 mM and EPSPs were recorded from CA1 neurons in whole cell configuration. EA increased EPSP amplitude from 6.9 ±â€¯0.7 mV to 9.6 ±â€¯0.6 mV. For LTP induction, the Schaffer collaterals were stimulated by high frequency stimulation (HFS; two trains of 100 pulses, 100 Hz at the interval of 20 s). The application of HFS resulted in 40.9 ±â€¯2.3% increase in the amplitude of EPSPs. However, following EA, HFS could not produce any significant changes in EPSP amplitude. Administration of LFS (1 Hz, 900 pulses) to Schaffer collaterals at the beginning of EA restored LTP induction to the hippocampal slices and HFS increased the EPSPs amplitude up to 41.7 ±â€¯3.1% of baseline. When slices were perfused by prazosin (α1-adrenergic receptor antagonist; 10 µM) before and during LFS application, LFS improvement on LTP induction was reduced significantly. Perfusion of slices by yohimbine (α2-adrenergic receptor antagonist; 5 µM) had no effect on LFS action. Therefore, it may be concluded that following epileptiform activity, LFS can improve the impairment of LTP generation through α1, but not α2, adrenergic receptor activity.


Assuntos
Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Receptores Adrenérgicos alfa 1/fisiologia , Receptores Adrenérgicos alfa 2/fisiologia , Convulsões/fisiopatologia , Sinapses/fisiologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Estimulação Elétrica , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Convulsões/prevenção & controle , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
19.
NASN Sch Nurse ; 34(5): 257-261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30920895

RESUMO

The Specialized Health Needs Interagency Collaboration (SHNIC) program at the Kennedy Krieger Institute is a community-based program that provides on-site training and technical assistance to safely manage the integration of children with special health needs into educational and community settings. SHNIC frequently receives seizure education requests throughout the school year, specifically regarding vagus nerve stimulation. Vagus nerve stimulation involves an implanted medical device used to deliver electrical pulses to the vagus nerve for additional seizure management. The school nurse needs to understand the purpose and function of the hidden medical device, including the parameters for use of the device and magnet, safety considerations, and side effects. SHNIC has developed educational materials specific to vagus nerve stimulation to aid the school nurse in providing staff training, developing care plans, and creating a safe school experience for students with special health needs.


Assuntos
Convulsões/prevenção & controle , Estimulação do Nervo Vago/instrumentação , Humanos , Serviços de Enfermagem Escolar , Estimulação do Nervo Vago/enfermagem
20.
Int J Hematol ; 109(6): 694-699, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915718

RESUMO

Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug-drug interactions.


Assuntos
Anticonvulsivantes/administração & dosagem , Bussulfano/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Levetiracetam/administração & dosagem , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Ácido Valproico/administração & dosagem , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ácido Valproico/efeitos adversos , Adulto Jovem
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