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2.
Iran J Med Sci ; 48(1): 70-76, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36688194

RESUMO

Background: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. Methods: A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. Results: CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Conclusion: Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.


Assuntos
Anticonvulsivantes , Síndrome de Stevens-Johnson , Humanos , Anticonvulsivantes/efeitos adversos , Lamotrigina/efeitos adversos , Irã (Geográfico) , Síndrome de Stevens-Johnson/genética , Alelos , Estudos de Casos e Controles , Antígenos HLA-B/genética , Carbamazepina/efeitos adversos , Benzodiazepinas
3.
No Shinkei Geka ; 51(1): 59-67, 2023 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-36682749

RESUMO

It has been reported that the incidence of epilepsy in individuals over the age of 75 years is similar to or higher than one year, suggesting that epilepsy is an important clinical condition in older people. The aging rate in Japan, which reached 27.3% in 2017, makes this an issue of increasing concern. Diagnosis begins with the collection of medical history and knowledge of seizure semiology. In the elderly, most seizures are of extratemporal origin with various seizure semiologies. Difficulties in diagnosis lie in the influence of the autonomic nervous system and nonconvulsive status epilepticus(NCSE). It is necessary to suspect "epilepsy" for any sudden-onset episodes of atypical symptoms and unusual behaviors. NCSE can be diagnosed by recording EEG for more than 6 hours. The narrow therapeutic window and pharmacokinetics complicated by aging make treatment much more difficult with anti-seizure medication(ASM). Comorbidities and drug interactions should also be considered. Stroke is the most common etiology of geriatric epilepsy. Despite several clinical reports on the risk factors of post-stroke epilepsy(PSE)on the preventive administration of enzyme-inducing ASM, a treatment protocol has not yet been established. Prophylactic administration is not recommended; however, ASM is often administered in the acute phase. Therefore, some guidelines for non-enzyme-inducing ASM are required for efficient control of PSE.


Assuntos
Epilepsia , Estado Epiléptico , Acidente Vascular Cerebral , Humanos , Idoso , Epilepsia/etiologia , Epilepsia/diagnóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Estado Epiléptico/diagnóstico , Japão , Eletroencefalografia/efeitos adversos , Anticonvulsivantes/uso terapêutico
4.
No Shinkei Geka ; 51(1): 95-104, 2023 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-36682754

RESUMO

One to three antiseizure medications(ASM) achieve good seizure control in 60-70% of patients with epilepsy. However, a large number of patients experience adverse effects and have to change the ASM. Prolonged newer ASMs elicit fewer adverse effects and fewer drug interactions than traditional ASMs. Their teratogenicity has also been reported to be low. The antiseizure effects of the new ASMs are not greater than those of traditional AEMs; however, these ASM characteristics improve adherence and allow combination therapy for drug-resistant epilepsy. Newly developed ASMs have fewer drug interactions than conventional drugs do. Therefore, even for symptomatic epilepsy caused by cerebral lesions such as cerebrovascular disorders or brain tumors, it is easier to use antiepileptic drugs in combination with other drugs for the treatment of these diseases. Furthermore, prescriptions for epilepsy in the elderly, which will increase in the aging society, should be made without increasing the risk of stroke or bone fractures caused by antiepileptic drugs, while simultaneously minimizing the effects of antiepileptic drugs on cognitive function and psychiatric disorders. This review outlines the pharmacotherapy for patients with epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Idoso , Humanos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Convulsões , Envelhecimento
5.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674911

RESUMO

Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.


Assuntos
Anticonvulsivantes , Ácido Valproico , Animais , Camundongos , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/farmacocinética , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Eletrochoque , Interações Medicamentosas , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Fenobarbital/farmacologia , Fenobarbital/uso terapêutico , Encéfalo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga
6.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677661

RESUMO

Indoles and hydantoins are important heterocycles scaffolds which present in numerous bioactive compounds which possess various biological activities. Moreover, they are essential building blocks in organic synthesis, particularly for the preparation of important hybrid molecules. The series of hybrid compounds containing indoles and imidazolidin-2-one moiety with direct C-C bond were synthesized using an amidoalkylation one-pot reaction. All compounds were investigated as a growth regulator for germination, growth and development of wheat seeds (Triticum aestivum L). Their effect on drought resistance at very low concentrations (4 × 10-5 M) was evaluated. The study highlighted identified the leading compounds, 3a and 3e, with higher growth-regulating activity than the indole-auxin analogues.


Assuntos
Hidantoínas , Indóis , Indóis/farmacologia , Indóis/química , Anticonvulsivantes , Hidantoínas/farmacologia , Ácidos Indolacéticos
7.
Acta Pharm ; 73(1): 59-74, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692466

RESUMO

Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is controversial, attributing it to anticonvulsant but also proconvulsant properties. Clarification of this dual effect of NO might lead to the development of new antiepileptic drugs. Previous results in our laboratory indicated that this contradictory role of NO in seizures could depend on the nitric oxide synthase (NOS) isoform involved, which could play opposite roles in epileptogenesis, one of them being proconvulsant but the other anticonvulsant. The effect of convulsant drugs on neuronal NO (nNO) and endothelial NO (eNO) levels was investigated. Considering the distribution of neuronal and endothelial NOS in neurons and astrocytes, resp., primary cultures of neurons and astrocytes were used as a study model. The effects of convulsant drugs pentylenetetrazole, thiosemicarbazide, 4-aminopyridine and bicuculline on NO levels were studied, using a spectrophotometric method. Their effects on NO levels in neurons and astrocytes depend on the concentration and time of treatment. These convulsant drugs caused an increase in nNO, but a decrease in eNO was proportional to the duration of treatment in both cases. Apparently, nNO possesses convulsant properties mediated by its effect on the glutamatergic and GABAergic systems, probably through GABAA receptors. Anticonvulsant properties of eNO may be the consequence of its effect on endothelial vasodilation and its capability to induce angiogenesis. Described effects last as seizures do. Considering the limitations of these kinds of studies and the unexplored influence of inducible NO, further investigations are required.


Assuntos
Convulsivantes , Óxido Nítrico , Humanos , Convulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Óxido Nítrico Sintase Tipo III , Inibidores Enzimáticos/farmacologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Pentilenotetrazol/farmacologia , Neurônios
8.
Anal Chim Acta ; 1240: 340775, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36641145

RESUMO

Development of high-throughput and rapid screening analytical method is in high demand for anti-doping and clinical point-of-care (POC) analysis. Solid-phase microextraction and mass spectrometry direct coupling (SPME-MS) has been proved as a rapid and effective way for target analysis in complex sample matrixes. An online direct coupling of in-tube SPME (IT-SPME) with MS using polymer coated open-tubular column has been developed in this work. A sharp stainless-steel needle was attached at the end of the SPME column, which enables the direct ionization of the analytes after elution from the IT-SPME column. Itaconic acid-benzene co-polymer was in-situ grown on the inner surface of the fused silica capillary and used as extraction phase. This column has low backpressure and provides both hydrophobic and weak cationic exchange interaction with the target analytes due to the chemical properties. The developed online IT-SPME-MS method showed good extraction performance towards various target analytes and good reusability at least for 60 times. As a proof-of-concept application, the above method was applied for the analysis of antiepileptic drugs (AEDs) in both plasma and urine samples with linear range (1 ng/mL-200 ng/mL), good linearity (R2 ≥ 0.99), and good reproducibility (intra-day RSDs less than 4.36%, inter-day RSDs less than 6.55%). The method exhibited high enrichment factors between 187 and 204 for the two AEDs and high sensitivity for the analysis of human plasma samples and urine samples.


Assuntos
Anticonvulsivantes , Polímeros , Humanos , Polímeros/química , Microextração em Fase Sólida/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas/métodos
9.
Sci Rep ; 13(1): 758, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641484

RESUMO

Twelve healthy eight-week-old male Wistar rats weighing 200 g were used. Rats were chosen randomly, and their tails were identified and separated into cages/groups. The first group received an oral dose of 11.5 mg of levetiracetam in 5 mL of water, and the second group was given date syrup (250 g mixed with 250 mL water) for seven days, then 11.5 mg LEV in 5 mL water on day 7. One week of preadministered date molasses significantly decreased levetiracetam pharmacokinetic parameters in rats, such as Cmax (72 vs. 14 ng/mL, p = 0.01), Tmax (1.78 vs. 0.44 h, p < 0.001), and AUC (880 vs. 258 ng.h/mL, p < 0.001). This decrease in plasma levetiracetam levels caused by date molasses could be attributed to decreased levetiracetam absorption. On the other hand, the current study discovered that rats given date molasses for a week had a reduced rate and extent of absorption. As a result, date molasses might increase the risk of epileptic seizures in oral LEV-treated ones.


Assuntos
Anticonvulsivantes , Piracetam , Ratos , Masculino , Animais , Levetiracetam , Melaço , Ratos Wistar
10.
Cochrane Database Syst Rev ; 1: CD013847, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688481

RESUMO

BACKGROUND: Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure. OBJECTIVES: 1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis). 2. To evaluate the mortality rate following a first unprovoked epileptic seizure. SEARCH METHODS: We searched the following databases on 19 September 2019 and again on 30 March 2021, with no language restrictions. The Cochrane Register of Studies (CRS Web), MEDLINE Ovid (1946 to March 29, 2021), SCOPUS (1823 onwards), ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). 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 Epilepsy. In MEDLINE (Ovid) the coverage end date always lags a few days behind the search date. SELECTION CRITERIA: We included studies, both retrospective and prospective, of all age groups (except those in the neonatal period (< 1 month of age)), of people with a single unprovoked seizure, followed up for a minimum of six months, with no upper limit of follow-up, with the study end point being seizure recurrence, death, or loss to follow-up. To be included, studies must have included at least 30 participants. We excluded studies that involved people with seizures that occur as a result of an acute precipitant or provoking factor, or in close temporal proximity to an acute neurological insult, since these are not considered epileptic in aetiology (acute symptomatic seizures). We also excluded people with situational seizures, such as febrile convulsions. DATA COLLECTION AND ANALYSIS: Two review authors conducted the initial screening of titles and abstracts identified through the electronic searches, and removed non-relevant articles. We obtained the full-text articles of all remaining potentially relevant studies, or those whose relevance could not be determined from the abstract alone and two authors independently assessed for eligibility. All disagreements were resolved through discussion with no need to defer to a third review author. We extracted data from included studies using a data extraction form based on the checklist for critical appraisal and data extraction for systematicreviews of prediction modelling studies (CHARMS). Two review authors then appraised the included studies, using a standardised approach based on the quality in prognostic studies (QUIPS) tool, which was adapted for overall prognosis (seizure recurrence). We conducted a meta-analysis using Review Manager 2014, with a random-effects generic inverse variance meta-analysis model, which accounted for any between-study heterogeneity in the prognostic effect. We then summarised the meta-analysis by the pooled estimate (the average prognostic factor effect), its 95% confidence interval (CI), the estimates of I² and Tau² (heterogeneity), and a 95% prediction interval for the prognostic effect in a single population at three various time points, 6 months, 12 months and 24 months. Subgroup analysis was performed according to the ages of the cohorts included; studies involving all ages, studies that recruited adult only and those that were purely paediatric. MAIN RESULTS: Fifty-eight studies (involving 54 cohorts), with a total of 12,160 participants (median 147, range 31 to 1443), met the inclusion criteria for the review. Of the 58 studies, 26 studies were paediatric studies, 16 were adult and the remaining 16 studies were a combination of paediatric and adult populations. Most included studies had a cohort study design with two case-control studies and one nested case-control study. Thirty-two studies (29 cohorts) reported a prospective longitudinal design whilst 15 studies had a retrospective design whilst the remaining studies were randomised controlled trials. Nine of the studies included presented mortality data following a first unprovoked seizure. For a mortality study to be included, a proportional mortality ratio (PMR) or a standardised mortality ratio (SMR) had to be given at a specific time point following a first unprovoked seizure. To be included in the meta-analysis a study had to present clear seizure recurrence data at 6 months, 12 months or 24 months. Forty-six studies were included in the meta-analysis, of which 23 were paediatric, 13 were adult, and 10 were a combination of paediatric and adult populations. A meta-analysis was performed at three time points; six months, one year and two years for all ages combined, paediatric and adult studies, respectively. We found an estimated overall seizure recurrence of all included studies at six months of 27% (95% CI 24% to 31%), 36% (95% CI 33% to 40%) at one year and 43% (95% CI 37% to 44%) at two years, with slightly lower estimates for adult subgroup analysis and slightly higher estimates for paediatric subgroup analysis. It was not possible to provide a summary estimate of the risk of seizure recurrence beyond these time points as most of the included studies were of short follow-up and too few studies presented recurrence rates at a single time point beyond two years. The evidence presented was found to be of moderate certainty. AUTHORS' CONCLUSIONS: Despite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.


Assuntos
Epilepsias Parciais , Epilepsia , Adulto , Criança , Humanos , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/etiologia , Convulsões/tratamento farmacológico
13.
BMJ Case Rep ; 16(1)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720516

RESUMO

We describe a man in his 30s with haemophagocytic lymphohistiocytosis (HLH), secondary to an upper respiratory tract infection, with subsequent febrile infection-related epilepsy syndrome. He had a prolonged hospital admission, during which he was treated with chemotherapy for HLH and antiepileptic medications for refractory seizures. He was discharged fully dependent to a care facility and died from aspiration pneumonia 11 months later. This case report highlights his management and discusses these conditions' pathophysiology and future management.


Assuntos
Epilepsia , Linfo-Histiocitose Hemofagocítica , Masculino , Humanos , Adulto , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Convulsões/etiologia , Convulsões/complicações , Anticonvulsivantes/uso terapêutico
14.
Neurosciences (Riyadh) ; 28(1): 66-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36617459

RESUMO

OBJECTIVE: To evaluate drug resistance epilepsy (DRE) patients with persistent seizures after using of standard antiepileptic drugs. This single center study aimed to investigate the utility of Epilepsy Monitoring Unit (EMU) resulted in a definitive diagnosis. METHODS: This was an observational retrospective study in 323 children who were admitted to the EMU for evaluation between 2012 and 2020. RESULTS: Of the 323 patients, 168 (52.01%) were males. The most common referral for EMU were better characterization 91 (28.17%) and pre-surgical evaluation 56 (17.3%). Of the participants, 273 (84.5%) had seizures one to 2 times per day. At discharge, 75.5% of admissions received a definitive diagnosis. CONCLUSION: The EMU admission for pediatric epilepsy patients is very important for early accurate diagnosis and management with surgery for those consider DRE patients.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Masculino , Humanos , Criança , Feminino , Estudos Retrospectivos , Eletroencefalografia , Epilepsia/tratamento farmacológico , Convulsões/diagnóstico , Anticonvulsivantes/uso terapêutico , Monitorização Fisiológica/métodos , Epilepsia Resistente a Medicamentos/diagnóstico
15.
Medicine (Baltimore) ; 102(2): e32681, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637934

RESUMO

RATIONALE: Hypertrophic subolivine degeneration (HOD) was destroyed by Guillain-Mollaret triangle (GMT) due to various injuries, resulting in anterograde cavity-like degeneration of the lower olive nucleus. In addition, the brain stem is related to the muscle coordination of the upper respiratory tract. Obstructive sleep apnea hypopnea syndrome may affect the respiratory center due to the injury of the brain stem. Brain stem hemorrhage damage GMT, resulting in transsynaptic neuronal degeneration. Clinical manifestations can be complex, and enhanced magnetic resonance imaging can be helpful in distinguishing them. PATIENT CONCERNS: HOD is a self-limiting disease with no effective treatment and a long course of disease. Most patients can improve their symptoms after symptomatic treatment, and some patients can relieve their symptoms by themselves after 3 to 4 years. DIAGNOSIS INTERVENTIONS: The limbs wobble involuntarily. His clinical symptoms and signs are consistent with HOD. Imaging with a clear primary lesion confirmed HOD. After treatment with antiepileptic drugs, the patient's symptoms were relieved. Moreover, the patient had snoring and apnea, and respiratory sleep monitoring showed moderate obstructive sleep apnea hypopnea syndrome, which was treated with noninvasive ventilator. OUTCOMES: After treatment with antiepileptic drugs and noninvasive ventilator, the patient's symptoms were significantly relieved. LESSONS: HOD is a rare clinical disorder. Therefore, for similar patients, more attention should be paid to early diagnosis and treatment to avoid missed diagnosis, misdiagnosis and unnecessary intervention measures. The diagnosis can be confirmed by primary disease, clinical symptoms, and imaging based on GMT.


Assuntos
Anticonvulsivantes , Apneia Obstrutiva do Sono , Humanos , Estudos Retrospectivos , Núcleo Olivar/patologia , Hipertrofia/patologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia
16.
PLoS One ; 18(1): e0280842, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36701411

RESUMO

A purified preparation of cannabidiol (CBD), a cannabis constituent, has been approved for the treatment of intractable childhood epilepsies such as Dravet syndrome. Extensive pharmacological characterization of CBD shows activity at numerous molecular targets but its anticonvulsant mechanism(s) of action is yet to be delineated. Many suggest that the anticonvulsant action of CBD is the result of G protein-coupled receptor 55 (GPR55) inhibition. Here we assessed whether Gpr55 contributes to the strain-dependent seizure phenotypes of the Scn1a+/- mouse model of Dravet syndrome. The Scn1a+/- mice on a 129S6/SvEvTac (129) genetic background have no overt phenotype, while those on a [129 x C57BL/6J] F1 background exhibit a severe phenotype that includes hyperthermia-induced seizures, spontaneous seizures and reduced survival. We observed greater Gpr55 transcript expression in the cortex and hippocampus of mice on the seizure-susceptible F1 background compared to those on the seizure-resistant 129 genetic background, suggesting that Gpr55 might be a genetic modifier of Scn1a+/- mice. We examined the effect of heterozygous genetic deletion of Gpr55 and pharmacological inhibition of GPR55 on the seizure phenotypes of F1.Scn1a+/- mice. Heterozygous Gpr55 deletion and inhibition of GPR55 with CID2921524 did not affect the temperature threshold of a thermally-induced seizure in F1.Scn1a+/- mice. Neither was there an effect of heterozygous Gpr55 deletion observed on spontaneous seizure frequency or survival of F1.Scn1a+/- mice. Our results suggest that GPR55 antagonism may not be a suitable anticonvulsant target for Dravet syndrome drug development programs, although future research is needed to provide more definitive conclusions.


Assuntos
Canabidiol , Epilepsias Mioclônicas , Hipertermia Induzida , Convulsões Febris , Camundongos , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Camundongos Endogâmicos C57BL , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/metabolismo , Convulsões/tratamento farmacológico , Convulsões/genética , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Convulsões Febris/tratamento farmacológico , Convulsões Febris/genética , Receptores de Canabinoides/metabolismo
17.
Medicine (Baltimore) ; 102(3): e32657, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36701733

RESUMO

RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction characterized by fever, lymphadenopathy, hematologic abnormalities, single or multiple organ involvement, and viral reactivation.[1] The most frequently reported offending drugs are aromatic antiepileptic agents, antibiotics, and allopurinol.[2] Though a relatively rare syndrome, DRESS can lead to severe multi-organ system dysfunction, and in some cases even death. DRESS is one of the severe drug eruptions in dermatological diseases, but it is difficult to diagnose for internist. In this paper, a typical drug hypersensitivity syndrome with abnormal liver function and fever as the first manifestations was reported. The objective of this study was to improve the understanding of rare drug hypersensitivity syndrome in digestion and other fields, and to avoid missed diagnosis and misdiagnosis. PATIENT CONCERNS: A 33-year-old Chinese female was initially diagnosed with acute hepatic insufficiency. Combined with the suspicious drug history, she developed DRESS with fever, target erythema, left lymph node enlargement, hematological abnormalities, and abnormal liver function. DIAGNOSES: Combined with the above characteristics, liver toxicity is the main manifestation, accompanied by fever, mainly moderate to high fever (above 38 °C) , sporadic rash, other organs (kidney, immune system) damage, and a marked increase in eosinophil granulocytic. Therefore the patient was diagnosed with definite case of DRESS syndrome based on clinical and laboratory findings. INTERVENTIONS: Hormones (methylprednisolone 60 mg/day for 12 days and 80 mg/day for 12 days) and immunoglobulins (intravenous immunoglobulin 10 g/day for 5 days and 20 g/day for 7 days) were given. OUTCOMES: The patient was discharged from the hospital after recovery. One month after discharge, she was re-admitted to the hospital because of elevated blood sugar and was diagnosed as diabetes. LESSONS: DRESS syndrome is a rare but life-threatening hypersensitivity reaction. The mortality will be very high if it's not diagnosed and treated timely. This paper presents a successful case of methylprednisolone plus intravenous immunoglobulin therapy, which provides a stronger evidence for the future diagnosis and treatment of the disease.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Hepatopatias , Feminino , Humanos , Adulto , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Eosinofilia/induzido quimicamente , Eosinofilia/diagnóstico , Eosinofilia/complicações , Febre/induzido quimicamente , Febre/complicações , Metilprednisolona/uso terapêutico , Hepatopatias/complicações
18.
Rev Neurol ; 76(3): 83-89, 2023 02 01.
Artigo em Espanhol | MEDLINE | ID: mdl-36703501

RESUMO

INTRODUCTION: Pharmacological treatment of epilepsy is not healing; it tries to avoid seizures, as far as possible, in children who probably would still have them. PATIENTS AND METHODS: Our purpose is to analyse our experience with epileptic children and those who have a first non-symptomatic seizure without pharmacological treatment. Patients seen in a paediatric neurology consultation, from 2017 to 2021, who had suffered one or more acute non-symptomatic crises and who had not been treated pharmacologically, were analysed. RESULTS: Sixty-five patients meet the selection criteria. Twenty-four patients had had a single crisis with a mean duration of 12 minutes (1-60). In 66.7% it was nocturnal. 41.7% presented pathological electroencephalogram, and 21% pathological findings in neuroimaging. The mean control time was 2.7 years (0.003-13.6 years). Forty-one presented more than one crisis, with a mean duration of nine minutes (1-60). Five patients presented more than 20 seizures, the rest between two and 17. Twenty-four (58.5%) presented only nocturnal seizures. An electroencephalogram was performed in all: epileptiform graphoelements in 63.4%; and neuroimaging in all: pathological in 4.9%. Mean control time was 3.8 years (0.01-9.1 years). CONCLUSIONS: Seizure frequency, underlying pathology or test results should not be the only variables to take into consideration when starting antiepileptic drug treatment. The repercussion on their quality of life and neurodevelopment should prevail, agreeing on this decision with the parents.


TITLE: Wait and see en epilepsia pediátrica. Nuestra experiencia.El tratamiento farmacológico de la epilepsia no es curativo; pretende, en lo posible, evitar crisis en niños que probablemente van a seguir teniéndolas. Pacientes y métodos. El objeto es analizar nuestra experiencia en niños con epilepsia y con primera crisis no sintomática aguda no tratados con antiepilépticos. Se analizó a pacientes atendidos en una consulta de neuropediatría, desde 2017 hasta 2021, que habían sufrido una o más crisis no sintomáticas agudas y a los que no se les había tratado farmacológicamente. Resultados. Sesenta y cinco pacientes cumplieron los criterios de selección. Veinticuatro habían tenido una única crisis, con un tiempo medio de duración de 12 minutos (1-60). En un 66,7% fue nocturna. Un 41,7% presentó electroencefalograma patológico, y un 21%, hallazgos patológicos en la neuroimagen. El tiempo medio de control fue de 2,7 años (0,003-13,6 años). Cuarenta y uno presentaron más de una crisis, con una duración media de nueve minutos (1-60). Cinco pacientes presentaron más de 20 crisis, y el resto, entre dos y 17. Veinticuatro (58,5%) presentaron únicamente crisis nocturnas. Se realizó un electroencefalograma en todos: grafoelementos epileptiformes en el 63,4%; y neuroimagen en todos: patológica en el 4,9%. El tiempo medio de control fue de 3,8 años (0,01-9,1 años). Conclusiones. La frecuencia de las crisis, la patología de base o los resultados de las pruebas complementarias no deberían ser las únicas variables que habría que considerar para iniciar el tratamiento farmacológico antiepiléptico en los niños. Debería prevalecer, por encima de aquéllos, el potencial perjuicio sobre la calidad de vida y el neurodesarrollo, las funciones atencionales y el comportamiento del niño, y siempre consensuar esta decisión con los padres.


Assuntos
Epilepsia Reflexa , Qualidade de Vida , Humanos , Criança , Convulsões/tratamento farmacológico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neuroimagem
20.
PLoS One ; 18(1): e0281040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36706124

RESUMO

This study sought to identify differences in cannabis use and perceptions about cannabis in mitigating seizure-related symptoms in patients with epilepsy, and to evaluate differences in these patterns between drug-resistant versus pharmacoresponsive epilepsy. A collection of self-report surveys completed by patients with epilepsy (n = 76) were used to retrospectively compare differences in those with drug-resistant versus pharmacoresponsive epilepsy regarding 1) proportion who used cannabis, 2) frequency of use, 3) method of use, and 4) reason for use. A Cochran-Armitage test for trend indicated that of patients who used cannabis, a higher proportion of patients in the drug-resistant group used more frequently than in the pharmacoresponsive group. Almost half (48%) of those in the drug-resistant group reported daily use compared to approximately a third (36%) of those in the pharmacoresponsive group. Additionally, no patient in either group reported that cannabis was harmful in relation to seizure-related symptoms. Results from this study highlight the need for epilepsy providers to formally assess patients' perceptions and use of non-prescribed cannabis to inform clinical care decisions, particularly in the drug-resistant epilepsy population.


Assuntos
Cannabis , Epilepsia Resistente a Medicamentos , Epilepsia , Alucinógenos , Humanos , Anticonvulsivantes/uso terapêutico , Estudos Retrospectivos , Centros de Atenção Terciária , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Convulsões/tratamento farmacológico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/epidemiologia , Alucinógenos/uso terapêutico , Agonistas de Receptores de Canabinoides/uso terapêutico
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