Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 389
Filtrar
1.
Doc Ophthalmol ; 138(3): 195-203, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30826910

RESUMO

PURPOSE: The anti-epileptic drug vigabatrin is associated with reduction in light-adapted 30-Hz flicker electroretinogram (ERG) amplitude. Ophthalmological assessments, including ERGs, monitor retinal health during vigabatrin treatment. RETeval™ is a hand-held ERG device adapted for dilation-free ERG assessment. To evaluate the usefulness of RETeval™ for vigabatrin ERG assessment, we evaluated intra-visit reliability and clinical feasibility of RETeval™ ERG assessment in children under 3 years of age undergoing vigabatrin treatment. METHODS: In this prospective study, children underwent 30-Hz flicker ERG assessment with RETeval™ before routine vigabatrin monitoring including sedated-ERG using the Espion E2 Colour Dome. Intraclass correlation coefficient (ICC) statistics identified the degree of intra-visit reliability from two repeated measurements of the same participant within one testing session. The omega squared (ω2) statistic identified the level of association between RETeval™ and Espion light-adapted 30-Hz flicker responses. RESULTS: Nine children completed RETeval™ ERG testing. The intra-visit ICCs for the RETeval™ 30-Hz flicker amplitude (µV) were high: 0.81 (right eye) and 0.86 (left eye), while the implicit times (ms) were 0.79 (right eye) and 0.42 (left eye). The RETeval™ 30-Hz flicker amplitude was positively associated with the Espion 30-Hz flicker response (ω2 = 0.71). The Bland-Altman plot showed no bias in the mean difference of amplitudes between the two systems. CONCLUSION: This is the first study to assess the utility of RETeval™ device in children under 3 years of age undergoing vigabatrin treatment. RETeval™ demonstrated high intra-visit reliability with responses consistent with the standard Espion ERG. RETeval™ may be beneficial for assessment of retinal toxicity in young children treated with vigabatrin.


Assuntos
Anticonvulsivantes/uso terapêutico , Eletrorretinografia/efeitos dos fármacos , Eletrorretinografia/instrumentação , Retina/fisiologia , Vigabatrina/uso terapêutico , Pré-Escolar , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Estimulação Luminosa , Estudos Prospectivos , Reprodutibilidade dos Testes , Retina/efeitos dos fármacos , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/fisiopatologia
2.
Epilepsy Res ; 150: 38-45, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30639958

RESUMO

Vigabatrin is indicated as adjunctive therapy for refractory focal seizures. For children, European recommendations indicate maintenance doses varying from 30 to 100 mg/kg/day for this indication. Since cumulated dose was associated with retinal toxicity, it is essential to administrate the lowest effective dose to patients. This work was conducted with the purpose to determine the pediatric doses of vigabatrin that allow a similar exposure than effective doses in adults (2-3 g/day) through a pharmacokinetic (PK) study, using both pediatric and adult data. For this study, we focused on the active S(+) enantiomer of vigabatrin. First, the adult effective exposition range of vigabatrin-S was determined from an adult PK model. Then, this same model was scaled to the pediatric population using allometry and maturation principles to account for growth and development. The ability of the model to predict pediatric data was assessed by comparing population predictions with observed pediatric data. Finally, the extrapolated pediatric model was used to simulate pediatric expositions which were compared to the adult exposition range (36.5-77.9 mg.h/L). From those simulations, we determined that, for children aged between 3 months and 18 years, doses between 40 and 50 mg/kg/day allow vigabatrin-S expositions similar to those found in adults at the recommended posology. We proposed those doses as optimal maintenance doses that may be increased, if necessary, by slow titration.


Assuntos
Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Vigabatrina/farmacocinética , Vigabatrina/uso terapêutico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Método de Monte Carlo
3.
Brasília; CONITEC; abr. 2018. graf, ilus, tab.
Não convencional em Português | LILACS, BRISA/RedTESA | ID: biblio-905573

RESUMO

CONTEXTO: A epilepsia é uma doença cerebral crônica caracterizada pela recorrência de crises epilépticas não provocadas. De acordo com o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) do Ministério da Saúde (MS) aproximadamente 30% dos pacientes, tratados adequadamente, continuam a ter crises, sem remissão. O tratamento disponível no SUS inclui os agentes antiepilépticos fenobarbital, fenitoína, primidona, topiramato, lamotrigina, carbamazepina e valproato de sódio. Recentemente foi avaliado e incorporado o levetiracetam. TECNOLOGIA: Lacosamida (Vimpat®). INDICAÇÃO: Terapia aditiva para o tratamento da epilepsia focal em pacientes refratários aos tratamentos prévios já disponíveis pelo Sistema Único de Saúde (SUS). PERGUNTAS: 1) A lacosamida oral como terapia adjuvante é tão segura e eficaz quanto a lamotrigina, topiramato, vigabatrina e gabapentina no tratamento da epilepsia focal em pacientes já submetidos a duas linhas de monoterapia? 2) Qual a efetividade da lacosamida como tratamento adjuvante na epilepsia focal não controlada, em pacientes adultos, em comparação ao uso de esquemas terapêuticos convencionais, quanto à redução da frequência de crises epilépticas, eventos adversos e custos? EVIDÊNCIAS CIENTÍFICAS: Não existem estudos de comparação direta entre a lacosamida e outro antiepiléptico. As evidências apresentaram comparações indiretas que apontam similaridade de eficácia e segurança entre a lacosamida e os medicamentos antiepilépticos disponíveis no SUS para o tratamento aditivo de pacientes com epilepsia focal, refratários a monoterapia. AVALIAÇÃO ECONÔMICA: Foi apresentada análise de custo-minimização para o tratamento aditivo da epilepsia focal refratária com lacosamida, porém o custo do tratamento com lacosamida, por paciente, só foi inferior ao custo do tratamento utilizando a vigabatrina. Os demais medicamentos já disponíveis para esta condição apresentam menor custo ao sistema. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A incorporação da lacosamida proporcionaria economia ao sistema de saúde apenas se comparado ao tratamento com vigabatrina. EXPERIÊNCIA INTERNACIONAL: Em outros países a lacosamida é fornecida para o tratamento da epilepsia focal refratária, em similaridade de condições à carbamazepina, clobazam, gabapentina, lamotrigina, levetiracetam, oxcarbazepina, valproato de sódio ou topiramato, se ocorrer refratariedade ou intolerância ao tratamento em primeira linha. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Há medicamentos em fase de desenvolvimento clínico para o tratamento da epilepsia focal, com diferentes mecanismos de ação, em estágios avançados de pesquisa clínica. RECOMENDAÇÃO PRELIMINAR: De acordo com o exposto, a CONITEC em sua 62ª reunião, no dia 7 de dezembro de 2017, recomendou a não incorporação da lacosamida no SUS como terapia aditiva em pacientes com epilepsia focal, refratários aos tratamentos prévios com os fármacos antiepilépticos disponíveis. A matéria será disponibilizada em consulta pública. CONSULTA PÚBLICA: Foram recebidas 13 contribuições técnico-científicas e 23 contribuições de experiência ou opinião, sendo quase a totalidade discordante da recomendação preliminar da CONITEC. As contribuições técnico-científicas embasaram-se no fato das comparações indiretas se tratarem da melhor qualidade de evidência disponível, sobre a efetividade da lacosamida em resposta à pergunta de pesquisa realizada. As contribuições de experiência e opinião expressaram o desejo dos participantes em agregar mais um medicamento ao tratamento disponibilizado pelo SUS como uma alternativa a mais para os pacientes refratários. A CONITEC entendeu que não houve evidência adicional e/ou argumentação suficientes para alterar sua recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da CONITEC em 07/03/2018 deliberaram por não recomendar a lacosamida como terapia aditiva em pacientes com epilepsia focal, refratários aos tratamentos prévios com os fármacos antiepilépticos disponíveis no SUS. Foi assinado o Registro de Deliberação nº 335/2018. DECISÃO FINAL: O Secretário de Ciência, Tecnologia e Insumos Estratégicos do Ministério da Saúde, por meio da Portaria SCTIE/MS nº 20, de 27 de abril de 2018, publicada no DOU nº 82 de 30 de abril de 2018, Seção I, tornou pública a decisão de não incorporar a lacosamida como terapia aditiva em pacientes com epilepsia focal refratários aos tratamentos prévios com os fármacos antiepilépticos disponíveis no SUS no âmbito do Sistema Único de Saúde - SUS.(AU)


Assuntos
Humanos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Vigabatrina/uso terapêutico , Brasil , Resistência a Medicamentos , Avaliação em Saúde , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde
4.
Clin Drug Investig ; 38(2): 113-124, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29086890

RESUMO

West syndrome (WS), also known as infantile spasms, occurs in infancy with a peak between 4 and 7 months. Spasms, neurodevelopmental regression and hypsarrhythmia on electroencephalogram (EEG) basically define WS. The International League Against Epilepsy commission classifies the aetiologies of WS into genetic, structural, metabolic and unknown. Early diagnosis and a shorter lag time to treatment are essential for the overall outcome of WS patients. These goals are feasible with the addition of brain magnetic resonance imaging (MRI) and genetic and metabolic testing. The present work analysed the medical literature on WS and reports the principal therapeutic protocols of its management. Adrenocorticotropic hormone (ACTH), vigabatrin (VGB) and corticosteroids are the first-line treatments for WS. There is no unique therapeutic protocol for ACTH, but most of the evidence suggests that low doses are as effective as high doses for short-term treatment, which is generally 2 weeks followed by dose tapering. VGB is generally administered at doses from 50 to 150 mg/kg/day, but its related retinal toxicity, which occurs in 21-34% of infants, is most frequently observed when treatment periods last longer than 6 months. Among corticosteroids, a treatment of 14 days of oral prednisolone (40-60 mg/day) has been considered effective and well tolerated. Considering that an early diagnosis and a shorter lag time to treatment are essential for successful outcomes in these patients, further studies on efficacy of the different therapeutic approaches with evaluation of final outcome after cessation of therapy are needed.


Assuntos
Pediatras/normas , Guias de Prática Clínica como Assunto/normas , Espasmos Infantis/diagnóstico por imagem , Espasmos Infantis/tratamento farmacológico , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Hormônio Adrenocorticotrópico/farmacologia , Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Espasmos Infantis/fisiopatologia , Resultado do Tratamento , Vigabatrina/farmacologia , Vigabatrina/uso terapêutico
5.
J Pediatr ; 190: 215-221.e1, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29144248

RESUMO

OBJECTIVES: To characterize and quantify diagnostic and treatment delay among children with infantile spasms, and to estimate the developmental impact of this delay. STUDY DESIGN: In this cohort study, we surveyed the parents of 100 patients with infantile spasms about their experiences with diagnosis and treatment, and ascertained medical and sociodemographic factors potentially related to care of these infants. We specifically determined the latency to first visit an "effective provider," defined as a provider who identified infantile spasms, and prescribed an appropriate first-line treatment, namely adrenocorticotropic hormone, corticosteroids, or vigabatrin. Time to the first visit to an effective provider was evaluated using Cox proportional hazards regression. RESULTS: The median time from the onset of infantile spasms to first visit with an effective provider was 24.5 days. Only 29% of patients were evaluated by an effective provider within 1 week of infantile spasms onset. The time to first effective provider visit was associated with parental language preference, but with no other sociodemographic characteristics. Parents' suspicions that "something is wrong" were often discounted by healthcare providers, and survey respondents frequently reported that pediatricians and neurologists were unfamiliar with infantile spasms. CONCLUSION: This study demonstrates that substantial delay (ie, >1 week) in appropriate care is common, and suggests that the poor awareness of infantile spasms among healthcare providers is at least partly responsible for preventable and potentially significant delays in treatment.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Espasmos Infantis/diagnóstico , Corticosteroides/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Competência Clínica , Eletroencefalografia , Feminino , Seguimentos , Humanos , Lactente , Los Angeles , Masculino , Neurologia , Pais , Pediatria , Relações Profissional-Família , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espasmos Infantis/tratamento farmacológico , Centros de Atenção Terciária , Vigabatrina/uso terapêutico
6.
Epilepsia ; 58(12): 2098-2103, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29105055

RESUMO

OBJECTIVE: The multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia. METHODS: Patients aged 2 months to 2 years were enrolled prospectively with new-onset infantile spasms. Treatment choice and categorization of hypsarrhythmia were determined clinically at each site. Response to therapy was defined as resolution of clinical spasms (and hypsarrhythmia if present) without relapse 3 months after initiation. RESULTS: Eighty-two percent of patients had hypsarrhythmia, but this was not associated with gender, mean age, preexisting developmental delay or epilepsy, etiology, or response to first-line therapy. Infants with hypsarrhythmia were more likely to receive standard treatment (adrenocorticotropic hormone, prednisolone, or vigabatrin [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-4.7] and preexisting epilepsy reduced the likelihood of standard treatment (OR 3.2, 95% CI 1.9-5.4). Hypsarrhythmia was not a determinant of response to treatment. A logistic regression model demonstrated that later age of onset (OR 1.09 per month, 95% CI 1.03-1.15) and absence of preexisting epilepsy (OR 1.7, 95% CI 1.06-2.81) had a small impact on the likelihood of responding to the first-line treatment. However, receiving standard first-line treatment increased the likelihood of responding dramatically: vigabatrin (OR 5.2 ,95% CI 2-13.7), prednisolone (OR 8, 95% CI 3.1-20.6), and adrenocorticotropic hormone (ACTH; OR 10.2, 95% CI 4.1-25.8) . SIGNIFICANCE: First-line treatment with standard therapy was by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.


Assuntos
Espasmos Infantis/terapia , Hormônio Adrenocorticotrópico/uso terapêutico , Idade de Início , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Prednisolona/uso terapêutico , Cobertura de Condição Pré-Existente , Estudos Prospectivos , Fatores Sexuais , Espasmos Infantis/fisiopatologia , Resultado do Tratamento , Vigabatrina/uso terapêutico
7.
Epilepsia ; 58(10): 1734-1741, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28857179

RESUMO

OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. METHODS: Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. RESULTS: Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. SIGNIFICANCE: Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipocampo/patologia , Adolescente , Adulto , Idoso , Aminas/uso terapêutico , Ataxia/induzido quimicamente , Benzodiazepinas/uso terapêutico , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Clobazam , Ácidos Cicloexanocarboxílicos/uso terapêutico , Bases de Dados Factuais , Diplopia/induzido quimicamente , Tontura/induzido quimicamente , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Gabapentina , Humanos , Lamotrigina , Letargia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Oxcarbazepina , Pregabalina/uso terapêutico , Estudos Retrospectivos , Esclerose , Topiramato , Resultado do Tratamento , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Vertigem/induzido quimicamente , Vigabatrina/uso terapêutico , Transtornos da Visão/induzido quimicamente , Adulto Jovem , Ácido gama-Aminobutírico/uso terapêutico
8.
Epilepsia ; 58(9): 1575-1585, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28691157

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of vigabatrin in pediatric epilepsy. METHODS: We retrospectively reviewed patients with epilepsy treated with vigabatrin over a 2-year period at a pediatric tertiary center. We assessed the relationship between seizure frequency, etiology, vigabatrin dose, adverse events, medication discontinuation reasons, and electroencephalography (EEG) characteristics. RESULTS: One hundred three patients followed at Boston Children's Hospital were treated with vigabatrin and had complete medical records. Within the follow-up interval, 69 (67%) of 103 patients had discontinued vigabatrin therapy. Two patients (1.9%) died during therapy for unknown reasons. Median age at vigabatrin initiation was 8 months (interquartile range [IQR] 5-15). Median starting dose was 48.1 mg/kg per day (IQR 29.8-52.3) with a median target of 100 mg/kg (IQR 81.9-107.9). Median treatment duration was 12.1 months (n = 89, IQR 5.0-22.9) overall, and 13.3 months (IQR 5.2-23.2) for patients who discontinued vigabatrin. The most common reasons for discontinuation were controlled seizures in 31 (43.7%) of 71 and unsatisfactory therapeutic effect in 23 (32.4%) of 71. Median percent seizure reduction from baseline to first follow-up was 83.3% (IQR 27.4-99.8) and 96.7% (IQR 43.3-100) to last follow-up. Twenty-four (38.7%) of 62 patients with a follow-up posttreatment remained seizure-free. Four patients who had initially achieved seizure freedom relapsed. Patients with structural/metabolic etiology had greater median percent seizure reduction at first follow-up than patients with genetic etiology (98.7% vs. 61.4%, respectively, p = 0.001). Hypsarrhythmia resolved after therapy in 18 of 20 (90%, 95% confidence interval [CI] 70-97) patients with pretreatment hypsarrhythmia, and 2 patients presented with hypsarrhythmia posttreatment. Risk of having hypsarrhythmia was reduced by 32% (95% CI 14.9-49.1) posttreatment. SIGNIFICANCE: Vigabatrin is efficacious in all seizure types and resolved hypsarrhythmia in most patients. In this series with a median treatment duration of 12.1 months, vigabatrin had a good safety profile with a low rate of discontinuation due to nonophthalmologic and ophthalmologic adverse effects.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Vigabatrina/uso terapêutico , Anticonvulsivantes/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Vigabatrina/efeitos adversos
9.
Pediatr Neurol ; 72: 76-80, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28506505

RESUMO

BACKGROUND: Seizures are a common early presentation in infants with tuberous sclerosis complex (TSC) and can be preceded by electrographic changes on electroencephalography (EEG) before clinical seizure onset. A limited number of studies have addressed the initial EEG findings in TSC and the outcome of early treatment with antiepileptic medication prior to clinical seizure onset. METHODS: We describe two infants with tuberous sclerosis complex whose surveillance EEG showed focal seizures that were not previously recognized by caregivers. We review previously reported patients with TSC with early EEG findings. Our patients were started on vigabatrin after the onset of focal seizures with the aim of preventing seizure recurrence, halting the possible progression to infantile spasms or focal seizures, and preventing neurodevelopmental decline. RESULTS: Both patients remain seizure free and have reached appropriate developmental milestones. CONCLUSIONS: We recommend early serial EEG monitoring once a diagnosis of TSC is suspected or confirmed in infants. Additional prospective studies are needed to assess the long-term outcome of early antiepileptic drug initiation as soon as electrographic seizure activity is detected.


Assuntos
Anticonvulsivantes/uso terapêutico , Encéfalo/fisiopatologia , Convulsões/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Vigabatrina/uso terapêutico , Eletroencefalografia , Feminino , Humanos , Lactente , Estudos Prospectivos , Resultado do Tratamento , Esclerose Tuberosa/fisiopatologia
10.
Epilepsia ; 58(5): 872-881, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28401986

RESUMO

OBJECTIVES: To investigate acoustic auditory processing in patients with recent infantile spasms (IS). METHODS: Patients (n = 22; 12 female; median age 8 months; range 5-11 months) had normal preceding development, brain magnetic resonance imaging (MRI), and neurometabolic testing (West syndrome of unknown cause, uWS). Controls were healthy babies (n = 22; 11 female; median age 6 months; range 3-12 months). Event-related potentials (ERPs) and psychometry (Bayley Scales of Infant Development, Second Edition, BSID-II) took place at a month following IS remission. RESULTS: Following a repeated pure tone, uWS patients showed less suppression of the N100 at the mid-temporal electrodes (p = 0.006), and a prolonged response latency (p = 0.019). Their novelty P300 amplitude over the mid-temporal electrodes was halved (p = 0.001). The peak of the novelty P300 to environmental broadband sounds emerged later over the left temporal lobe in patients (p = 0.015), the lag correlating with duration of spasms (r = 0.547, p = 0.015). BSID-II scores were lower in patients (p < 0.001), with no correlation to ERP. SIGNIFICANCE: Complex acoustic information is processed poorly following IS. This would impair language. Treatment did not reverse this phenomenon, but may have limited its severity. The data are most consistent with altered connectivity of the cortical acoustic processing areas induced by IS.


Assuntos
Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Espasmos Infantis/diagnóstico , Espasmos Infantis/fisiopatologia , Estimulação Acústica , Vias Auditivas/efeitos dos fármacos , Vias Auditivas/fisiopatologia , Percepção Auditiva/efeitos dos fármacos , Estudos de Casos e Controles , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Estudos Transversais , Eletroencefalografia , Potencial Evocado P300/efeitos dos fármacos , Potencial Evocado P300/fisiologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , Lactente , Masculino , Prednisolona/uso terapêutico , Prognóstico , Estudos Prospectivos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Processamento de Sinais Assistido por Computador , Espasmos Infantis/tratamento farmacológico , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/fisiologia , Gravação em Vídeo , Vigabatrina/uso terapêutico
11.
Clin Neurol Neurosurg ; 157: 70-75, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28412542

RESUMO

OBJECTIVE: Vigabatrin (VGB) is currently served as an effective adjunctive therapy for patients with partial epilepsy worldwide. In this study, meta-analysis was conducted to comprehensively evaluate the changes in peripapillary retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography (OCT) in epilepsy patients who were treated by VGB. MATERIAL AND METHODS: Publications on PubMed, Wiley Online Library and the Elsevier Science databases were searched by September 2016. The statistical analysis was performed by RevMan 5.3 software. RESULTS: Four studies were identified, and 202 eyes in VGB-exposed patients (VGB group) as well as 162 eyes in patients who never received VGB treatment (NON-VGB group) were included. The studies demonstrated that the total RNFL thickness is attenuated in VGB treated patients (weighted mean differences in µm, WMD=-15.96, 95% CI: -23.69 to -8.23, P<0.0001). RNFL thickness in 3 quadrants were significantly reduced in VGB group: superior (WMD=-18.15, 95% CI: -23.31 to -12.98, P<0.00001), inferior (WMD=-23.19, 95% CI: -32.23 to -14.15, P<0.00001) and nasal (WMD=-19.29, 95% CI: -35.57 to -3.02, P=0.02). However, the temporal RNFL thickness in these two groups showed no significant difference: temporal (WMD=-2.41, 95% CI: -6.67 to 1.85, P=0.27). CONCLUSION: Based on the meta-analysis, RNFL thickness appears to reduce in epilepsy patients who received VGB treatment, and OCT could be a useful tool to help clinicians assessing its retinal toxicity and guiding its dosage.


Assuntos
Epilepsia/tratamento farmacológico , Fibras Nervosas/efeitos dos fármacos , Retina/efeitos dos fármacos , Vigabatrina/farmacologia , Epilepsia/patologia , Feminino , Humanos , Masculino , Fibras Nervosas/patologia , Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Vigabatrina/uso terapêutico , Campos Visuais/efeitos dos fármacos
12.
Rev Neurol ; 64(4): 169-174, 2017 Feb 16.
Artigo em Espanhol | MEDLINE | ID: mdl-28169412

RESUMO

INTRODUCTION: Vigabatrin (VGB) is a first-line drug for the treatment of infantile spasms. Recently, several reports claim the existence of abnormalities in magnetic resonance imaging (MRI) (particularly affecting basal ganglia, and visible in T2 and diffusion sequences) in infants with spasms that were receiving high doses of VGB (> 100 mg/kg/day), which appear to be reversible after withdrawal of treatment. CASE REPORTS: We present two cases with an epileptic encephalopathy in the first year of life and seizures consisting of infantile spasms. Both were treated with several antiepileptic drugs, including VGB up to a maximum dosage of 200 mg/kg/day. At the age of 11 and 28 months, respectively, MRI images showed marked signal hyperintensities on T2-sequences on bilateral globus pallidus, thalamus, posterior portion of the brainstem and dentate nuclei, also visible on diffusion sequences. Both had previous unaltered MRI studies. After excluding an underlying metabolic disease, VGB withdrawal is decided, appreciating the reversibility of those lesions in a prospective MRI study, three months later. CONCLUSIONS: We must consider and carefully evaluate findings on brain MRI in infants receiving VGB at high doses for treatment of spasms. The apparent cytotoxic effect on basal ganglia could simulate metabolic/mitochondrial diseases. By knowing this effect of VGB and its typical MRI features, unnecessary testing can be avoided in young infants with epileptic encephalopathies, including complex procedures like muscle biopsy or a new metabolic screening.


Assuntos
Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Neuroimagem , Espasmos Infantis/diagnóstico por imagem , Vigabatrina/uso terapêutico , Encéfalo/patologia , Resistência a Medicamentos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/patologia , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/patologia
13.
Epilepsy Behav ; 69: 153-160, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28188045

RESUMO

This is the third of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper focuses on treatment issues that arise during the course of childhood epilepsy and make the process of transition to adult care more complicated. Some AEDs used during childhood, such as stiripentol, vigabatrin, and cannabidiol, are unfamiliar to adult epilepsy specialists. In addition, new drugs are being developed for treatment of specific childhood onset epilepsy syndromes and have no indication yet for adults. The ketogenic diet may be effective during childhood but is difficult to continue in adult care. Regional adult epilepsy diet clinics could be helpful. Polytherapy is common for patients transitioning to adult care. Although these complex AED regimes are difficult, they are often possible to simplify. AEDs used in childhood may need to be reconsidered in adulthood. Rescue medications to stop prolonged seizures and clusters of seizures are in wide home use in children and can be continued in adulthood. Adherence/compliance is notoriously difficult for adolescents, but there are simple clinical approaches that should be helpful. Mental health issues including depression and anxiety are not always diagnosed and treated in children and young adults even though effective treatments are available. Attention deficit hyperactivity disorder and aggressive behavior disorders may interfere with transition and successful adulthood but these can be treated. For the majority, the adult social outcome of children with epilepsy is unsatisfactory with few proven interventions. The interface between pediatric and adult care for children with epilepsy is becoming increasingly complicated with a need for more comprehensive transition programs and adult epileptologists who are knowledgeable about special treatments that benefit this group of patients.


Assuntos
Congressos como Assunto , Dieta Cetogênica/tendências , Epilepsia/terapia , Transição para Assistência do Adulto/tendências , Adolescente , Adulto , Fatores Etários , Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Criança , Dieta Cetogênica/métodos , Dioxolanos/uso terapêutico , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/psicologia , Humanos , Resultado do Tratamento , Vigabatrina/uso terapêutico , Adulto Jovem
14.
Rev. neurol. (Ed. impr.) ; 64(4): 169-174, 16 feb., 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-160508

RESUMO

Introducción. La vigabatrina (VGB) es un fármaco de primera línea para el tratamiento de espasmos infantiles. Diversos estudios han hallado anomalías en la resonancia magnética (RM) cerebral, que afectaban particularmente a los ganglios de la base, y especialmente en secuencias de difusión, en lactantes con espasmos que recibían VGB en altas dosis (> 100 mg/kg/día), y se ha observado la desaparición de las lesiones tras la retirada de dicho tratamiento. Casos clínicos. Se presentan dos casos clínicos con inicio de una encefalopatía epiléptica en el primer año de vida y crisis en forma de espasmos infantiles. Ambos recibieron tratamiento con distintos fármacos, entre ellos VGB hasta dosis de 200 mg/kg/día. Con 11 y 28 meses de vida, respectivamente, aparecían imágenes en la RM cerebral con una marcada hiperintensidad de señal en secuencias ponderadas en T2 en ambos pálidos, tálamos, porción posterior del tronco encefálico y núcleos dentados, que asociaban restricción en secuencias de difusión. Ambos disponían de estudios previos de RM, sin alteraciones. Tras excluir una metabolopatía subyacente, se decidió la retirada de la VGB y tres meses después, en una RM de control, se apreció la total reversibilidad de dichas lesiones. Conclusiones. Deben evaluarse con cautela los hallazgos de la RM cerebral en lactantes que reciban VGB en altas dosis para el tratamiento de espasmos. Su aparente efecto citotóxico sobre los ganglios de la base podría simular metabolopatías/ enfermedades mitocondriales. Conocer este efecto de la VGB y sus características típicas en la RM puede evitar pruebas innecesarias, como una biopsia muscular o un nuevo cribado metabólico (AU)


Introduction. Vigabatrin (VGB) is a first-line drug for the treatment of infantile spasms. Recently, several reports claim the existence of abnormalities in magnetic resonance imaging (MRI) (particularly affecting basal ganglia, and visible in T2 and diffusion sequences) in infants with spasms that were receiving high doses of VGB (> 100 mg/kg/day), which appear to be reversible after withdrawal of treatment. Case reports. We present two cases with an epileptic encephalopathy in the first year of life and seizures consisting of infantile spasms. Both were treated with several antiepileptic drugs, including VGB up to a maximum dosage of 200 mg/ kg/day. At the age of 11 and 28 months, respectively, MRI images showed marked signal hyperintensities on T2-sequences on bilateral globus pallidus, thalamus, posterior portion of the brainstem and dentate nuclei, also visible on diffusion sequences. Both had previous unaltered MRI studies. After excluding an underlying metabolic disease, VGB withdrawal is decided, appreciating the reversibility of those lesions in a prospective MRI study, three months later. Conclusions. We must consider and carefully evaluate findings on brain MRI in infants receiving VGB at high doses for treatment of spasms. The apparent cytotoxic effect on basal ganglia could simulate metabolic/mitochondrial diseases. By knowing this effect of VGB and its typical MRI features, unnecessary testing can be avoided in young infants with epileptic encephalopathies, including complex procedures like muscle biopsy or a new metabolic screening (AU)


Assuntos
Humanos , Masculino , Lactente , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia , Convulsões/complicações , Convulsões , Espasmos Infantis/complicações , Espasmos Infantis/prevenção & controle , Espasmos Infantis , Vigabatrina/uso terapêutico , Cosintropina/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Biópsia , Ácido Valproico/uso terapêutico , Epilepsia/fisiopatologia
15.
Lancet Neurol ; 16(1): 33-42, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27838190

RESUMO

BACKGROUND: Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone. METHODS: In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27. FINDINGS: Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1-24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment. INTERPRETATION: Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up. FUNDING: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich.


Assuntos
Anticonvulsivantes/uso terapêutico , Hormônios/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Resultado do Tratamento , Vigabatrina/uso terapêutico , Cosintropina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Eletroencefalografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prednisolona/uso terapêutico
16.
Rev. neurol. (Ed. impr.) ; 64(supl.3): s71-s75, 2017.
Artigo em Espanhol | IBECS | ID: ibc-163060

RESUMO

Introducción. La refractariedad es una característica común del tratamiento de los síndromes de Ohtahara, Aicardi, West, Dravet y epilepsia maligna del lactante con crisis migrantes. Objetivo. Actualizar el manejo terapéutico y analizar si la etiología determina de alguna manera el tratamiento. Desarrollo. Las crisis convulsivas en el primer año de vida pueden deberse a una etiología potencialmente tratable, por lo que es imperativo una completa evaluación para instaurar de manera precoz el tratamiento adecuado y el sintomático no específico para el control de las crisis, que evite o minimice el efecto deletéreo de éstas. Es obligado hasta descartar metabolopatía y ensayar pauta de vitaminas y cofactores, además de antiepilépticos. En los síndromes de Ohtahara y Aicardi, la primera línea es fenobarbital y fenitoína, y en segunda línea, los más habituales son midazolam, levetiracetam, lidocaína y valproato. En el síndrome de West, la primera línea la constituye la hormona adrenocorticotropa y la vigabatrina para el caso de esclerosis tuberosa; si no hay respuesta, considerar otros fármacos, dieta cetogénica y cirugía. Para el síndrome de Dravet, los principales son valproato con clobazam y estiripentol, y de segunda línea, considerar otros fármacos y dieta cetogénica. En la epilepsia con crisis migrantes, los más eficaces son bromuros, estiripentol, clonacepam y levetiracetam. Conclusiones. Actualmente existe poco consenso en el abordaje terapéutico para establecer indicaciones taxativas. La etiología influye en el tratamiento, tanto en el caso de disponer de tratamiento curativo (metabolopatías) como en el abordaje sintomático con antiepilépticos u otros tratamientos (dieta cetogénica o cirugía) (AU)


Introduction. Resistance to treatments is a common feature of Ohtahara, Aicardi, West and Dravet syndromes, as well as malignant migrating epilepsy in infancy. Aims. To update the therapeutic management and to analyse whether the aetiology somehow determines the treatment. Development. Convulsive seizures in the first year of life may be due to a potentially treatable aetiology, which makes it essential to carry out a complete evaluation so as to be able to begin, as early as possible, the most suitable and the non-specific symptomatic treatments to control the seizures, which prevents or minimises their deleterious effects. Metabolic disease must be ruled out and it is also essential to try a therapeutic regimen of vitamins and cofactors, as well as antiepileptic drugs. In Ohtahara and Aicardi syndromes, the first-order treatment is phenobarbital and phenytoin, and the most commonly used second-order drugs are midazolam, levetiracetam, lidocaine and valproate. In West’s syndrome, the first-order treatment consists of adrenocorticotropic hormone and vigabatrine for the case of tuberous sclerosis; if there is no response, other pharmaceuticals, a ketogenic diet and surgery must be considered. For Dravet’s syndrome, the main treatment consists in valproate with clobazam and stiripentol, and as the second order, other drugs and a ketogenic diet should be considered. In epilepsy with migrating seizures, the most effective treatment is with bromides, stiripentol, clonazepam and levetiracetam. Conclusions. Today there is little consensus on the therapeutic approach to be able to establish specific indications. The aetiology has an influence on the treatment, both in cases in which a curative treatment exists (metabolic diseases) and in the symptomatic management with antiepileptic drugs or other treatments (ketogenic diet or surgery) (AU)


Assuntos
Humanos , Lactente , Epilepsia/etiologia , Epilepsia/terapia , Encefalopatias/etiologia , Encefalopatias/terapia , Dieta Cetogênica , Espasmos Infantis/etiologia , Síndrome de Aicardi/etiologia , Síndrome de Aicardi/terapia , Vigabatrina/uso terapêutico , Hormônio Liberador da Corticotropina/análise , Ácido Valproico/uso terapêutico
17.
J Nippon Med Sch ; 83(4): 167-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27680485

RESUMO

In a patient with cardiofaciocutaneous syndrome complicated by intractable infantile spasms (West syndrome), cardiac hypertrophy developed during adrenocorticotropic hormone treatment. Various types of antiepileptic drugs, intravenous immunoglobulin, thyrotropin releasing hormone, and a ketogenic diet were ineffective in this case. However, vigabatrin both decreased clinical seizures and improved electroencephalogram findings. Although vigabatrin has not been approved for use in Japan, the results in the present case suggest that this drug should be considered as an alternative therapy for cases of infantile spasms associated with syndromes involving cardiomyopathy or its potential risk factors, such as cardiofaciocutaneous syndrome.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Cardiomegalia/complicações , Displasia Ectodérmica/complicações , Insuficiência de Crescimento/complicações , Cardiopatias Congênitas/complicações , Espasmos Infantis/complicações , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico , Pré-Escolar , Displasia Ectodérmica/diagnóstico por imagem , Eletrocardiografia , Facies , Insuficiência de Crescimento/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Espasmos Infantis/diagnóstico por imagem
18.
Epilepsia ; 57(11): 1834-1842, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27615012

RESUMO

OBJECTIVE: Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. RESULTS: One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). SIGNIFICANCE: Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Falha de Tratamento , Vigabatrina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino
20.
Paediatr Drugs ; 18(5): 357-66, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27541933

RESUMO

Infantile spasms, and specifically within the context of West syndrome , is one of the most common epileptic encephalopathies to occur in early infancy. Early recognition and treatment can improve neurodevelopmental outcome in some cases, although the underlying aetiology is probably the most important prognostic factor in both spasm suppression and developmental outcome. Corticosteroids, either adrenocorticotrophic hormone (ACTH) or prednisolone, and vigabatrin are currently the preferred first-line treatment options. Vigabatrin is the treatment of choice when the underlying cause is tuberous sclerosis complex (TSC). Emerging evidence suggests that a combination of steroid and vigabatrin may be more effective in the suppression of spasms and resolution of hypsarrhythmia, the electro-encephalographic signal of spasms. Several other anti-epileptic drugs (AEDs) (levetiracetam, nitrazepam, sodium valproate, topiramate, zonisamide) are usually used as add-on or adjunctive treatment in refractory cases. Pyridoxine (or pyridoxal phosphate) and the ketogenic diet are established treatment options in refractory cases. There is some evidence that neuro-active steroids, including ganaxolone, may be effective; however, clinical trials undertaken intermittently for over a decade have yet to prove their efficacy, not only for the suppression of infantile spasms but also for the resolution of hypsarrhythmia, which may be as important as seizure control in developmental outcome in these children. Insights into developing novel treatment options have emerged from rodent models of infantile spasms, and research is continuing into the efficacy of rapamycin in improving outcomes in infantile spasms. This review provides a brief overview of the existing scientific literature around treatment options and outlines emerging newer treatment options in infantile spasms.


Assuntos
Corticosteroides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Hormônio Adrenocorticotrópico/uso terapêutico , Humanos , Lactente , Piridoxina/uso terapêutico , Convulsões/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Vigabatrina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA