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1.
Pediatr Dermatol ; 36(4): e99-e101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31132165

RESUMO

Lymphadenopathy is a common sign for drug reaction and eosinophilia with systemic symptoms (DRESS) syndrome, but hilar and mediastinal lymphadenopathy may be underreported. We describe a 7-year-old boy who started taking ethosuximide for absence seizures and presented with diffuse rash, fever, elevated transaminases, facial swelling, and hilar and mediastinal lymphadenopathy. His mediastinal lymphadenopathy was concerning for lymphoma, which led to more invasive testing to rule out malignancy. This report highlights an unusual and likely underreported presenting sign of DRESS syndrome in children.


Assuntos
Corticosteroides/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/efeitos adversos , Linfadenopatia/induzido quimicamente , Biópsia por Agulha , Criança , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Eosinofilia/induzido quimicamente , Eosinofilia/fisiopatologia , Epilepsia Tipo Ausência/diagnóstico , Etossuximida/uso terapêutico , Seguimentos , Humanos , Imuno-Histoquímica , Linfadenopatia/patologia , Linfadenopatia/fisiopatologia , Masculino , Mediastino/patologia , Recidiva , Medição de Risco
2.
Cochrane Database Syst Rev ; 2: CD003032, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734919

RESUMO

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2017.Absence seizures (AS) are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with AS. OBJECTIVES: To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures (AS), when compared with placebo or each other. SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web, 29 May 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 29 May 2018), ClinicalTrials.gov (29 May 2018) and the WHO International Clinical Trials Registry Platform (ICTRP, 29 May 2018). Previously we searched Embase (1988 to March 2005) and SCOPUS (1823 to 31 March 2014), but this is no longer necessary because randomised controlled trials (RCTs) and quasi-RCTs in Embase and SCOPUS are now included in CENTRAL. No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively. SELECTION CRITERIA: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with AS: ethosuximide, sodium valproate, lamotrigine, or placebo. DATA COLLECTION AND ANALYSIS: Outcome measures were: (1) proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test; and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). We used GRADE quality assessment criteria to evaluate the certainty of evidence derived from all included studies. MAIN RESULTS: On the basis of our selection criteria, we included no new studies in the present review. Eight small trials (total number of participants: 691) were included from the earlier review. Six of them were of poor methodological quality (unclear or high risk of bias) and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from RCTs to support a specific effect on AS for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control (P < 0.001) and intolerable adverse events (P < 0.037) was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the valproic acid group. Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. The risk of bias for this study was low. We rated the overall certainty of the evidence available from the included studies to be moderate or high. AUTHORS' CONCLUSIONS: Since the last version of this review was published, we have found no new studies. Hence, the conclusions remain the same as the previous update. With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with AS. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Lamotrigina/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Etossuximida/efeitos adversos , Humanos , Lamotrigina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Valproico/efeitos adversos
4.
Ned Tijdschr Tandheelkd ; 125(7-8): 397-402, 2018 Jul.
Artigo em Holandês | MEDLINE | ID: mdl-30015815

RESUMO

Adverse effects of medications and self care products on the gingiva can be divided into inflammation, intrinsic discolouration, irritation, trauma, cytotoxicity, lichenoid reaction, and proliferation. This article deals with the last-mentioned type of adverse effects; the other 6 have been discussed in a previous article. Proliferation of the gingiva as an adverse effect of medications has been reported for anticonvulsants, calcineurin inhibitors, calcium channel blockers and isotretinoin. With regard to the anticonvulsants that have been registered in the Netherlands, proliferation of the gingiva is predominantly induced by phenytoin, but also by carbamazepine, ethosuximide, phenobarbital, gabapentin, levetiracetam, primidone and valproic acid. All calcineurin inhibitors registered in the Netherlands may induce the adverse effect. This is also the case for nearly all calcium channel blockers, but particularly for dihydropyridines. Presumably, proliferation of the gingiva may be prevented or reduced in a number of ways. The most important one is good oral hygiene. Furthermore, proteins and cells that play an important role [in the process of gingival proliferation] have been discovered and there are medications that have the potential to eliminate these proteins and cells.


Assuntos
Anticonvulsivantes/efeitos adversos , Proliferação de Células , Gengiva/efeitos dos fármacos , Gengiva/patologia , Higiene Bucal , Carbamazepina/efeitos adversos , Etossuximida/efeitos adversos , Humanos , Países Baixos , Fenobarbital/efeitos adversos , Fenitoína/efeitos adversos , Primidona/efeitos adversos , Ácido Valproico/efeitos adversos
5.
J Dermatol ; 45(5): 592-595, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29430697

RESUMO

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens-Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/efeitos adversos , Glucocorticoides/uso terapêutico , Síndrome de Stevens-Johnson/etiologia , Administração Intravenosa , Biópsia , Pré-Escolar , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Epiderme/efeitos dos fármacos , Epiderme/patologia , Exantema/sangue , Exantema/diagnóstico , Exantema/virologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pulsoterapia , Testes Sorológicos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/patologia , Fatores de Tempo , Resultado do Tratamento
6.
BMJ Case Rep ; 20172017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29222216

RESUMO

A 50-year-old man with known multidrug resistant coexistent focal and generalised epilepsy was commenced on ethosuximide, with normalisation of his electroencephalogram and cessation of absence seizures. Within 3 weeks, he developed a rapidly worsening paranoid psychosis with visual and olfactory hallucinations. A month after the cessation of ethosuximide and concurrent treatment with olanzapine, his psychosis resolved and permitted reinitiation of ethosuximide at a lower dose without recurrence of psychotic symptoms.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Etossuximida/uso terapêutico , Alucinações/diagnóstico , Transtornos Psicóticos/diagnóstico , Anticonvulsivantes/efeitos adversos , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Diagnóstico Diferencial , Eletroencefalografia , Epilepsia/fisiopatologia , Etossuximida/efeitos adversos , Alucinações/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Transtornos Psicóticos/etiologia
7.
Cochrane Database Syst Rev ; 2: CD003032, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28195639

RESUMO

BACKGROUND: This is an updated version of the original Cochrane review originally published in 2003, Issue 3, and updated in 2005, Issue 4.Absence seizures are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with typical absence seizures. OBJECTIVES: To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialized Register (1 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 1 September 2016), MEDLINE (Ovid, 1946 to 1 September 2016), ClinicalTrials.gov (1 September 2016) and the WHO International Clinical Trials Registry Platform ICTRP (1 September 2016). Previously we searched Embase (1988 to March 2005) and SCOPUS (1823 to 31 March 2014). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively. SELECTION CRITERIA: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: ethosuximide; sodium valproate; lamotrigine; or placebo. DATA COLLECTION AND ANALYSIS: Outcome measures were: (1) proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test; and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). MAIN RESULTS: Eight small trials were found (three of them not included in the previous version of the review). Six of them were of poor methodological quality and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from randomised controlled trials to support a specific effect on absence seizures for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for ethosuximide and valproic acid (VPA) were similar and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control (P < 0.001) and intolerable adverse events (P < 0.037) was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the VPA group. Overall, this large study demonstrates the superior effectiveness of ethosuximide and VPA compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. AUTHORS' CONCLUSIONS: With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Etossuximida/efeitos adversos , Humanos , Lamotrigina , Ensaios Clínicos Controlados Aleatórios como Assunto , Triazinas/efeitos adversos , Ácido Valproico/efeitos adversos
9.
J Pediatr Endocrinol Metab ; 27(5-6): 549-54, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24468605

RESUMO

BACKGROUND: Antiepileptics may affect cortisol metabolism through CYP3A4. There is little known about ethosuximide. CLINICAL CASE: Our patient is a 12-year-old girl with salt-wasting congenital adrenal hyperplasia (CAH) owing to 21 hydroxylase deficiency. A standard treatment regimen was initiated with satisfactory results until the age of 6 years, when she developed absence seizures treated with ethosuximide. She received such therapy until the age of 12 years, at which point ethosuximide was discontinued. During ethosuximide administration, she experienced worsening control of CAH disease activity that responded to progressive increases in hydrocortisone dose up to 28 mg/m2 per day. Despite high doses of hydrocortisone, she suffered no cushingoid symptoms. Her requirements for high glucocorticoid replacement doses resolved shortly after ethosuximide was discontinued. We provide data over 6 years demonstrating a correlation between adrenal hormone secretion, cortisol requirements and ethosuximide dose. CONCLUSION: This is the first case demonstrating an interaction between ethosuximide and hydrocortisone clearance in the treatment of salt-wasting CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/efeitos adversos , Etossuximida/efeitos adversos , Hidrocortisona/metabolismo , Hidrocortisona/uso terapêutico , Criança , Interações Medicamentosas , Epilepsia Tipo Ausência/complicações , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tônico-Clônica/complicações , Epilepsia Tônico-Clônica/tratamento farmacológico , Feminino , Humanos
11.
PLoS One ; 8(12): e82543, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24340038

RESUMO

The anticonvulsant ethosuximide has been previously shown to increase life span and promote healthspan in the nematode Caenorhabditis elegans at millimolar concentrations. Here we report that following exposure to ultraviolet irradiation at 254 nm, ethosuximide is converted into a compound that displays toxicity toward C. elegans. This effect is specific for ethosuximide, as the structurally related compounds trimethadione and succinimide do not show similar toxicities following UV exposure. Killing by UV-irradiated ethosuximide is not attenuated in chemosensory mutants that are resistant to toxicity associated with high doses of non-irradiated ethosuximide. Non-irradiated ethosuximide extends life span at 15°C or 20°C, but not at 25°C, while irradiated ethosuximide shows similar toxicity at all three temperatures. Dietary restriction by bacterial deprivation does not protect against toxicity from irradiated ethosuximide, while non-irradiated ethosuximide further extends the long life spans of restricted animals. These data support the model that ethosuximide extends life span by a mechanism that is, at least partially, distinct from dietary restriction by bacterial deprivation and demonstrates an unexpected photochemical conversion of ethosuximide into a toxic compound by UV light.


Assuntos
Anticonvulsivantes/efeitos adversos , Caenorhabditis elegans/metabolismo , Etossuximida/efeitos adversos , Longevidade/efeitos dos fármacos , Longevidade/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Anticonvulsivantes/farmacologia , Etossuximida/farmacologia , Privação de Alimentos
12.
Biomed Res Int ; 2013: 726478, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24324971

RESUMO

The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ), ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM), levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf)) to termination of hatching (72 hpf) which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI) of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.


Assuntos
Anticonvulsivantes/efeitos adversos , Teratogênese/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento , Acetamidas/efeitos adversos , Acetamidas/uso terapêutico , Animais , Anticonvulsivantes/classificação , Anticonvulsivantes/uso terapêutico , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Modelos Animais de Doenças , Etossuximida/efeitos adversos , Etossuximida/uso terapêutico , Feminino , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Lacosamida , Lamotrigina , Levetiracetam , Piracetam/efeitos adversos , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Gravidez , Topiramato , Triazinas/efeitos adversos , Triazinas/uso terapêutico , Estados Unidos , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico
14.
Epilepsia ; 54(1): 141-55, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23167925

RESUMO

PURPOSE: Determine the optimal initial monotherapy for children with newly diagnosed childhood absence epilepsy (CAE) based on 12 months of double-blind therapy. METHODS: A double-blind, randomized controlled clinical trial compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed CAE. Study medications were titrated to clinical response, and subjects remained in the trial unless they reached a treatment failure criterion. Maximal target doses were ethosuximide 60 mg/kg/day or 2,000 mg/day, valproic acid 60 mg/kg/day or 3,000 mg/day, and lamotrigine 12 mg/kg/day or 600 mg/day. Original primary outcome was at 16-20 weeks and included a video-electroencephalography (EEG) assessment. For this report, the main effectiveness outcome was the freedom from failure rate 12 months after randomization and included a video-EEG assessment; differential drug effects were determined by pairwise comparisons. The main cognitive outcome was the percentage of subjects experiencing attentional dysfunction at the month 12 visit. KEY FINDINGS: A total of 453 children were enrolled and randomized; 7 were deemed ineligible and 446 subjects comprised the overall efficacy cohort. There were no demographic differences between the three cohorts. By 12 months after starting therapy, only 37% of all enrolled subjects were free from treatment failure on their first medication. At the month 12 visit, the freedom-from-failure rates for ethosuximide and valproic acid were similar (45% and 44%, respectively; odds ratio [OR]with valproic acid vs. ethosuximide 0.94; 95% confidence interval [CI] 0.58-1.52; p = 0.82) and were higher than the rate for lamotrigine (21%; OR with ethosuximide vs. lamotrigine 3.08; 95% CI 1.81-5.33; OR with valproic acid vs. lamotrigine 2.88; 95% CI 1.68-5.02; p < 0.001 for both comparisons). The frequency of treatment failures due to lack of seizure control (p < 0.001) and intolerable adverse events (p < 0.037) was significantly different among the treatment groups. Almost two thirds of the 125 subjects with treatment failure due to lack of seizure control were in the lamotrigine cohort. The largest subgroup (42%) of the 115 subjects discontinuing due to adverse events was in the valproic acid group. The previously reported higher rate of attentional dysfunction seen at 16-20 weeks in the valproic acid group compared with the ethosuximide or lamotrigine groups persisted at 12 months (p < 0.01). SIGNIFICANCE: As initial monotherapy, the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine in controlling seizures without intolerable adverse events noted at 16-20 weeks persisted at 12 months. The valproic acid cohort experienced a higher rate of adverse events leading to drug discontinuation as well as significant negative effects on attentional measures that were not seen in the ethosuximide cohort. These 12-month outcome data coupled with the study's prespecified decision-making algorithm indicate that ethosuximide is the optimal initial empirical monotherapy for CAE. This is the first randomized controlled trial meeting International League Against Epilepsy (ILAE) criteria for class I evidence for CAE (or for any type of generalized seizure in adults or children). (NCT00088452.).


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Fatores Etários , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Etossuximida/administração & dosagem , Etossuximida/efeitos adversos , Feminino , Humanos , Lamotrigina , Masculino , Resultado do Tratamento , Triazinas/administração & dosagem , Triazinas/efeitos adversos , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
15.
J Child Neurol ; 28(1): 111-4, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22467741

RESUMO

Coexistence of 2 idiopathic epilepsy syndromes (ie, childhood absence and Rolandic epilepsy), as evidenced by electroencephalographic (EEG) findings with or without clinical features of the 2 conditions, is uncommon and remains controversial. Few case reports support this coexistence either as a continuum or drug-induced conversion, whereas a large sample case review did not find such co-occurrence. The authors report a case of conversion of typical absence to Rolandic spikes after treatment with ethosuximide. An 11-year-old girl was diagnosed with typical childhood absence epilepsy at the age of 6 years with classic clinical and EEG features. She became seizure-free on ethosuximide but her follow-up EEGs consistently recorded right centrotemporal and centroparietal spikes without associated clinical seizures. This case may suggest simultaneous presence of these 2 common childhood idiopathic epilepsies either as a continuum or a drug-induced conversion.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Rolândica/induzido quimicamente , Etossuximida/efeitos adversos , Criança , Eletroencefalografia , Epilepsia Rolândica/diagnóstico , Feminino , Lobo Frontal/patologia , Humanos , Imagem por Ressonância Magnética
16.
Ann Agric Environ Med ; 19(3): 487-90, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23020044

RESUMO

Depression is becoming a growing problem in rural areas. This psychiatric disorder often accompanies epilepsy. The aim of this study was to assess the influence of fluoxetine (FXT), a commonly used antidepressant, on the protective action of two conventional antiepileptic drugs: ethosuximide (ETX) and valproate (VPA), against pentylenetetrazole (PTZ)-induced convulsions in mice. Motor coordination and long-term memory deficits induced by FXT, antiepileptic drugs alone and in combinations with FXT were assessed in the chimney test and passive-avoidance task, respectively. Brain concentrations of ETX and VPA were measured by immunofluorescence. Obtained results indicate that FXT at the dose of 15 mg/kg (i.p., 30 min before the test) significantly increased the threshold for clonic convulsions. The antidepressant drug at lower doses remained ineffective in this respect. Moreover, FXT at the highest subprotective dose (10 mg/kg, i.p.) markedly enhanced the anticonvulsant effects of VPA, but not of ETX, against PTZ-induced seizures. The interaction between FXT and VPA seems to be pharmacodynamic because the antidepressant drug did not alter the brain concentration of VPA. With regard to adverse effects, FXT, VPA, ETX, and the combinations of FXT with antiepileptic drugs, did not impair motor coordination and long-term memory in mice. In conclusion, the combination of FXT with VPA may be advantageous in the treatment of myoclonic epilepsy, and therefore it should be recommended for further study in clinical conditions.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsias Mioclônicas/tratamento farmacológico , Etossuximida/administração & dosagem , Fluoxetina/administração & dosagem , Convulsões/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Ácido Valproico/administração & dosagem , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacocinética , Aprendizagem da Esquiva , Convulsivantes/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Epilepsias Mioclônicas/induzido quimicamente , Etossuximida/efeitos adversos , Etossuximida/farmacocinética , Imunofluorescência , Fluoxetina/efeitos adversos , Fluoxetina/farmacocinética , Masculino , Memória de Longo Prazo , Camundongos , Atividade Motora , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/farmacocinética , Ácido Valproico/efeitos adversos , Ácido Valproico/farmacocinética
17.
Brain Dev ; 34(5): 344-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21893390

RESUMO

PURPOSE: We performed this study to evaluate the long-term efficacy and tolerability of ethosuximide (ESX), valproic acid (VPA), and lamotrigine (LTG) as initial monotherapies for patients with newly diagnosed childhood absence epilepsy. METHODS: We retrospectively reviewed the medical records of 128 patients (45 boys and 83 girls) diagnosed with childhood absence epilepsy at the Seoul National University Hospital. The diagnosis was based on the criteria proposed by Panayiotopoulos in 2005. We measured the seizure-free rate and the retention rate observed during 2 years of treatment. Follow-up electroencephalography (EEG), any reported adverse events, and reasons for antiepileptic drug (AED) discontinuation were reviewed. RESULTS: The seizure-free rate of ESX (84%) was significantly higher than that of VPA (62%) and LTG (53%) at 3 months. The seizure-free rate of ESX (90%) was significantly higher than that of LTG (63%) at 6 months. After 9 months, there was no significant difference in seizure-free rate among the three groups. There were no significant differences among the three groups in terms of normalization of EEG at 12 months (ESX, 77%; VPA, 83%; and LTG, 64%), retention rate throughout the whole treatment period, and adverse-event rates (ESX, 25%; VPA, 29%; and LTG, 14%). CONCLUSION: This study suggests that ESX, VPA, and LTG are equally effective in the long-term treatment of newly diagnosed CAE patients. However, the onset of efficacy was faster for ESX compared with VPA or LTG. Efficacy, tolerability, and adverse event profiles should be carefully considered when selecting AEDs to treat individual patients with CAE.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Eletroencefalografia , Etossuximida/efeitos adversos , Feminino , Seguimentos , Humanos , Lamotrigina , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Triazinas/efeitos adversos , Ácido Valproico/efeitos adversos , Adulto Jovem
18.
Epilepsy Behav ; 21(4): 483-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21689989

RESUMO

Psychosis and suicidal ideation have been reported as side effects of ethosuximide treatment, but previous reports seldom place these symptoms in the context of mania. Given the recent renewed interest in ethosuximide as first-line therapy in children and adolescents, it is important for clinicians to be aware of the potential psychiatric complication of mania with this medication. Described here is the case of a 10-year-old boy who developed acute mania, as well as psychotic symptoms and suicidal ideation, on ethosuximide.


Assuntos
Transtorno Bipolar/induzido quimicamente , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/efeitos adversos , Psicoses Induzidas por Substâncias/diagnóstico , Transtorno Bipolar/diagnóstico , Criança , Etossuximida/uso terapêutico , Humanos , Masculino , Ideação Suicida
19.
Artigo em Russo | MEDLINE | ID: mdl-21675229

RESUMO

Antiabsence drug ethosuximide (300 mg/kg/day in drinking water for 17 days) produced an antidepressant effect (a decrease in immobility time in forced swimming test) only in WAG/Rij rats genetically predisposed to absence epilepsy only at age of 5 months when spike-wave discharges well pronounced. On rats without spike-wave discharges (21-day-old WAG/Rij and Wistar rats at the age of both at 21 day and 5 months), ethosuximide didn't produce the antidepressant effect but tended to increases the immobility time and significantly decreases the number of divings (active behavior oriented to escape from stressful situation). Ethosuximide didn't substantially change the anxiety level in WAG/Rij rats but significantly enhanced anxiety in 21-day-old Wistar rats. The results suggest that ethosuximide is not possessed of antidepressant potential unrelated to its suppressive effect on spike-wave discharges.


Assuntos
Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Animais , Depressão/etiologia , Epilepsia Tipo Ausência/complicações , Etossuximida/efeitos adversos , Masculino , Ratos , Ratos Endogâmicos , Ratos Wistar
20.
J Assist Reprod Genet ; 28(1): 23-30, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20859763

RESUMO

PURPOSE: To assess the involvement of L-type and T-type Ca²(+) channel blockers in inducing male infertility. METHODS: Prepubertal male mice were fed Ca²(+) channel blockers nifedipine and ethosuximide for 20 days at dosages below maximum tolerated dose (MTD) and assayed for gross morphological changes in the testis such as body weight, testis size and weight. Sperm and Leydig cell counting were conducted concomitantly with serum testosterone level measurement by radioimmunoassay (RIA) and StAR protein mRNA measurement by reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: A chronic exposure to nifedipine or ethosuximide caused a significant reduction in body weight, testis size/weight and sperm production in a dose-dependent fashion associated with a spermatogenic arrest largely at the elongating spermatid stage. The number of Leydig cells, the serum testosterone level but not the luteinizing hormone level, and the content of StAR protein mRNA were also drastically reduced relative to the controls. CONCLUSIONS: Both T- and L-type Ca²(+) channel blockers play an adverse role in normal spermatogenesis and steroidogenesis partly by blocking postmeiotic germ cell maturation and/or by abrogating StAR protein expression, contributing to male sterility. Therefore, any therapeutic application of Ca²(+) channel blockers must be used with caution due to its potential adverse side effects on male infertility.


Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Etossuximida/efeitos adversos , Nifedipino/efeitos adversos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Peso Corporal , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Infertilidade Masculina/induzido quimicamente , Células Intersticiais do Testículo/citologia , Hormônio Luteinizante/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho do Órgão , Fosfoproteínas/metabolismo , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testículo/patologia , Testosterona/sangue
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