Effect of levetiracetam on DNA oxidation and glutathione content in a temporal lobe epilepsy model.

Levetiracetam (LEV) is a drug commonly used as an anticonvulsant. However, recent evidence points to a possible role as an antioxidant. We previously demonstrated the antioxidant properties of LEV by significantly increasing catalase and superoxide dismutase activities and decreasing the hydrogen peroxide (H2O2) levels in the hippocampus of rats with temporal lobe epilepsy (TLE) showing scavenging properties against the hydroxyl radical. The aim of the present work was to evaluate, the effect of LEV on DNA oxidation, by determining 8­hydroxy­2­deoxyguanosine (8­OHdG) levels, and glutathione content, through reduced (GSH) and oxidized (GSSG) glutathione levels, in the hippocampus of rats with TLE. Male Wistar rats were assigned to the control (CTRL), CTRL+LEV, epileptic (EPI) and EPI+LEV groups. TLE was induced using the lithium­pilocarpine model. Thirteen weeks after TLE induction, LEV was administered for one week through osmotic pumps implanted subcutaneously. The determination of 8­OHdG, GSH and GSSG levels were measured using spectrophotometric methods. We showed that LEV alone significantly increased 8­OHdG and GSSG levels in the hippocampus of control rats compared to those in epileptic condition. No significant differences in GSH levels were observed. LEV could induce changes in the hippocampus increasing DNA oxidation and GSSG levels under nonepileptic condition but not protecting against the mitochondrial dysfunction observed in TLE probably by mechanisms related to changes in chromatin structure, neuroinflammation and alterations in redox components.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Experience of Subcutaneous Levetiracetam in Palliative Care.

BACKGROUND: Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care. OBJECTIVE: The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia. METHODS: We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019-2021. Data were extracted from medical records, and participants were followed up as outpatients. RESULTS: Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days. CONCLUSION: Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.

Piracetam-induced neuroprotection in lipopolysaccharides-challenged EOC-20 cells and mouse brain via attenuating oxidative stress

Abstract Therapeutically, piracetam has been used for decades as a cognitive enhancer for memory- related neuronal disorders. The present study aimed to investigate the neuroprotective potential of piracetam on lipopolysaccharides (LPS)-induced neuronal deficit using both in-vitro and in-vivo experimental models. For the in-vitro analysis, EOC-20 murine microglial cells were induced with a neuronal toxicity of 100 µg/ml of LPS, and the formation of intracellular reactive oxygen species (ROS) and nitric oxide (NO) productions were determined. For in-vivo neuroprotective analysis, groups of mice were treated orally with two doses of piracetam (200 and 400 mg/kg) for 30 days. Neuronal toxicity was induced by four intraperitoneal injections of LPS (250 µg/kg/day). The malondialdehyde (MDA) level was measured for oxidative stress, and catalase reduced glutathione (GSH), glutathione reductase (GRD), and superoxide dismutase (SOD) levels were determined as the antioxidant parameters. The result of the cell viability study was that pre-treatment with piracetam significantly protected the LPS-induced cell loss, and attenuated the ROS generation and NO production in LPS-induced EOC-20 cells. Moreover, the treatment of piracetam significantly reduced the MDA levels and improved catalase, GSH, GRD, and SOD activities in LPS-induced mice brains. The overall results from this study supported the neuroprotective effects of piracetam against LPS-induced neuronal toxicity.

Behavioral alterations associated with levetiracetam in pediatric epilepsy.

Levetiracetam (LEV) has an improved pharmacological profile and is one of the most commonly used antiepileptic drugs (AEDs). However, associations between this pharmacological profile and behavioral side effects have been extensively reported in pediatric populations. We assessed behavioral changes after initiation of LEV, prescribed by the treating neurologist, in Chilean patients with epilepsy aged 4-15 years. A behavioral questionnaire was applied at baseline and at two, four, and twelve weeks of treatment. Thirty patients were enrolled: 16 males, 14 females, average age 8 years (range: 4-14). By week four, 23.3% of patients showed significant behavioral alterations that persisted throughout the observation period. No significant alterations emerged after four weeks in the remaining patients. Family history of psychiatric disease and prior behavioral difficulties were predisposing factors for adverse behavioral effects. Although previous studies associated adverse behavioral effects with LEV in pediatric patients with epilepsy, we believe that this is the first study to use a prospective methodology and standardized tools to quantify the symptomatology. Adverse behavioral effects may significantly affect quality of life for patients and families, diminishing the tolerability of treatment. To ensure successful therapy and improve medical decision-making, it is essential to consider predisposing factors for drug-related adverse effects and to regularly assess for behavioral alterations during treatment.

Psychostimulant Use for Neuroenhancement (Smart Drugs) among College Students in Brazil.

Background: College students are susceptible to using cognitive enhancement drugs, also known as smart drugs. Objectives: estimate the prevalence of smart drug use and investigate the factors related to access and use among undergraduate students. Methods: cross-sectional study performed among all students who entered the university in 2017 using an anonymous, self-administered questionnaire. Smart drug usage was defined as taking methylphenidate, modafinil or piracetam at any point in life and in the preceding 12 months. We characterized the means of obtaining smart drugs, reasons for using and students' residential situation. We asked students who did not use any medication if they were interested in taking it and the reasons for not using. Results: Out of 1865 respondents, 4.2% had used smart drugs in the last 12 months, and the prevalence among law students reached 14.3%. The most commonly used smart drug was methylphenidate. Among the students who did not present ADD diagnosis, the drug was obtained mostly through a friend. More than 300 students reported a desire to use some smart drug, but they did not, mainly due to the fear of side effects. Conclusions: The current study has found a variety of frequency of smart drug use among college students and has also showed that many students are willing to take some kind of cognitive enhancement drug. Therefore, it is important to discuss this issue from a public health perspective.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients.

OBJECTIVE: The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. METHODS: Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. RESULTS: In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. CONCLUSION: Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

Blood mononuclear cells as speculum of emotional stress analyzed by synchrotron infrared spectroscopy and a nootropic drug.

Chronic psychological stress is an important public health issue which generates behavioral changes, anxiety, immunosuppression and oxidative damage. Piracetam is a cognitive enhancer, at cellular level it protects from oxidative stress. The aim of this study was to evaluate the effect of psychological stress and of piracetam on circulating mononuclear cells by analyzing the biochemical spectrome using Synchrotron Radiation Fourier Transform Infrared Microspectroscopy (SR-µFTIR). Rats were exposed for five days to a stressor (cat odor) under oral administration of piracetam (600 mg/kg). SR-µFTIR analysis showed a decrease in bands associated to the lipids region (2852 cm-1, 2923 cm-1 and 2962 cm-1) and an increase absorption of the amide I band (1654 cm-1) under stress conditions. The principal component analysis showed increase oxidation of lipids (decrease of 3010 cm-1, 2923 cm-1 and 2852 cm-1 bands) as well as proteins denaturation (increase of 1610 cm-1 and 1690 cm-1 bands) under stress. Piracetam provided protection to polyunsaturated lipids (p ≤ 0.001) and lipids/proteins ratio (p ≤ 0.001). Behaviorally, this drug diminished fear and anxiety in stressed animals by the plus maze test (p ≤ 0.002). However, this drug induced oxidative stress in mononuclear cells from unstressed animals and altered their behavior.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Benign rolandic epilepsy and generalized paroxysms: A study of 13 patients.

PURPOSE: To present a retrospective study of 13 children with benign epilepsy with centrotemporal spikes (BECTS), also known as benign rolandic epilepsy (BRE), associated with generalized spikes and waves as the only EEG manifestation at onset. METHOD: Charts of children with typical clinical criteria of BRE electroclinically followed-up between February 2000 and February 2015 were reviewed. RESULTS: Among 309 patients who met the electroclinical criteria of BRE, we identified 13 children who presented with the typical clinical manifestations but who, on the EEG, only had generalized paroxysms at onset that continued along the course of the syndrome. Generalized spike-and-wave discharges were observed in all patients when awake and during sleep (100%). During the evolution no particular electroclinical pattern was observed. The patients responded well to antiepileptic drugs, such as valproic acid and levetiracetam. Outcome was good in all patients. CONCLUSIONS: We found evidence that patients with BRE may have generalized EEG discharges at onset as the sole manifestation lasting throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of BRE. Response to valproic acid and levetiracetam was found to be particularly good.

Antinociceptive and pronociceptive effect of levetiracetam in tonic pain model.

BACKGROUND: Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model. METHODS: Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50µL of 1% formalin in the paw; sham-group rats were administered 50µL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300mg/kg), and 40min later 50µL of 1% formalin was injected in the paw. RESULTS: LEV exhibited antinociceptive effect in the 300mg/kg LEV group (p<0.05) and a pronociceptive effect in the 100mg/kg LEV group (p<0.05) and in the 50mg/kg LEV group (p<0.001). CONCLUSIONS: The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent.

Levetiracetam para o tratamento da epilepsia / Levetiracetam for the treatment of epilepsy

CONTEXTO: A epilepsia é uma desordem crônica neurológica prevalente, caracterizada por sinais e sintomas característicos (crises convulsivas) associados a descargas elétricas cerebrais anormais. O tratamento da epilepsia geralmente inclui o uso contínuo em longo prazo de medicamentos com efeito anticonvulsivante. No eixo topográfico, as epilepsias são separadas em generalizadas e focais. Este relatório foi elaborado como parte da conduta de revisão do PCDT de epilepsia e tem por objetivo avaliar as evidências de eficácia e segurança do levetiracetam no tratamento de epilepsia focal e generalizada, a fim de embasar a avaliação da CONITEC a respeito de sua incorporação na versão atualizada do PCDT. TECNOLOGIA: levetiracetam (Keppra®). INDICAÇÃO: Tratamento da epilepsia focal e generalizada. PERGUNTA: O uso do levetiracetam em monoterapia ou e em terapia de adição no tratamento de crianças ou adultos com epilepsia, crises focais (parciais) ou generalizadas, é eficaz, seguro e custo-efetivo, comparativamente ao tratamento ativo (antiepilépticos de primeira ou segunda linha previstos no PCDT de epilepsia) ou placebo? EVIDÊNCIAS CIENTÍFICAS: há evidências de superioridade do levetiracetam em comparação ao placebo, em terapia de adição, para o tratamento de crises focais e primariamente generalizada em crianças e adultos que não responderam à monoterapia, com magnitude de efeito pequena a moderada, com taxas de resposta maiores entre crianças. Não foram estudados efeitos adversos em longo prazo. Não foi possível estabelecer a relação de eficácia comparativa em relação a outros agentes potencialmente úteis após falha de agentes de segunda linha no tratamento de adição da epilepsia refratária. Mais estudos são necessários para estabelecer sua eficácia em monoterapia. O nível de evidência é muito baixo, pois se trata de ensaios clínicos abertos, com pequeno número de pacientes. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário da incorporação do levetiracetam será superior à R$ 29 milhões de reais no primeiro ano, considerando um cenário base onde a assumiu-se que a dose média por paciente seria de 2000mg por dia. CONSIDERAÇÕES FINAIS: Há evidências de eficácia e segurança para a utilização do levetiracetam em terapia de adição para tratamento de pacientes com epilepsia focal e epilepsia primariamente generalizada em adultos e crianças com mais de 6 anos (12 anos para crises tônico-clônico generalizadas) que não responderam à monoterapia com anticonvulsivante de primeira linha conforme previsto no PCDT de epilepsia. RECOMENDAÇÃO FINAL: Os membros da CONITEC presentes na 57ª reunião ordinária do plenário realizada nos dias 05 e 06 de julho de 2017, recomendaram por unanimidade a ampliação de uso do levetiracetam para o tratamento da epilepsia conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 272/2017. DECISÃO: Incorporado levetiracetam para o tratamento da epilepsia segundo Portaria SCTIE/MS nº 56, DE 1º DE DEZEMBRO DE 2017.(AU)

Levetiracetam para o tratamento de convulsões em pacientes com microcefalia / Levetiracetam for the treatment of seizures in patients with microcephaly

CONTEXTO: A infecção decorrente do Zika vírus vem apresentando possíveis complicações nos pacientes acometidos pela doença desde sua chegada ao Brasil. O Zika possui sintomas semelhantes aos outros flavivírus prevalentes no país, sendo transmitido pelo mesmo mosquito (Aedes aegypti). A doença tem sido associada ao desenvolvimento de microcefalia e alterações neurológicas em filhos de mulheres que tiveram contato com o vírus durante a gravidez, destacando-se relatos de episódios convulsivos. O SUS fornece medicamentos anticonvulsivantes para outras doenças com sintomas de convulsão, como a epilepsia. TECNOLOGIA: LEVETIRACETAM (KEPPRA®). INDICAÇÃO: CONVULSÕES EM PACIENTES PEDIÁTRICOS. PERGUNTA 1: O levetiracetam, em comparação aos tratamentos anticonvulsivantes disponíveis no SUS, é eficaz, efetivo e seguro no controle de convulsões em pacientes com microcefalia? PERGUNTA 2: O Levetiracetam, em comparação aos tratamentos anticonvulsivantes disponibilizados pelo SUS, é eficaz, efetivo e seguro no tratamento de convulsões em pacientes pediátricos com epilepsia? EVIDÊNCIAS CIENTÍFICAS: Foi elaborado um Parecer Técnico-Científico seguindo as Diretrizes do Ministério da Saúde. Após duas buscas contemplando os desfechos em questão, foram incluídos três estudos, sendo que dois deles comparavam o levetiracetam com carbamazepina e o último com o ácido valpróico. A análise do risco de viés evidenciou estudos com qualidade moderada. A avaliação conjunta dos estudos não demonstrou eficácia ou efetividade superior do levetiracetam em comparação aos anticonvulsivantes já padronizados pelo SUS. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O custo incremental total estimado para o tratamento com levetiracetam na população pediátrica, com peso médio de 10 kg, foi de R$1.682.535,63 em cinco anos. EXPERIÊNCIA INTERNACIONAL: O levetiracetam foi incorporado como terapia adjuvante pela agência Inglesa e Escocesa. Pela agência do Canadá, existe o uso em primeira linha em algumas províncias ou em situações especiais. CONSIDERAÇÕES FINAIS: Foram realizadas duas buscas para atender ao demandante, a Secretaria Estadual de Saúde de Pernambuco. Na primeira, não foi recuperado nenhum estudo e na segunda busca foram recuperados três estudos. Em nenhuma das publicações analisadas foram encontradas evidências da superioridade do Levetiracetam em comparação com a carbamazepina ou o ácido valpróico. DELIBERAÇÃO FINAL: Os membros da CONITEC, presentes na 57ª reunião ordinária, realizada nos dias 5 e 6 de julho de 2017, deliberaram por unanimidade recomendar a ampliação de uso do medicamento levetiracetam para o tratamento de convulsões em pacientes com microcefalia decorrente de infecção pelo vírus zika. Foi assinado o Registro de Deliberação nº nº 271/2017. DECISÃO: Incorporado levetiracetam para o tratamento de convulsões em pacientes com microcefalia segundo Portaria SCTIE/MS nº 38, DE 31 DE AGOSTO DE 2017.(AU)

Levetiracetam como terapia adjuvante em pacientes com epilepsia mioclônica juvenil resistentes à monoterapia / Levetiracetam as adjuvant therapy in patients with juvenile myoclonic epilepsy resistant to monotherapy

CONTEXTO: A epilepsia é uma doença cerebral crônica caracterizada pela recorrência de crises epilépticas não provocadas. Conforme Protocolo Clínico e Diretrizes Terapêuticas (PCDT) vigente do Ministério da Saúde (MS), o tratamento disponível no Sistema Único de Saúde (SUS) inclui os agentes antiepilépticos fenobarbital, fenitoína, primidona, topiramato, lamotrigina, carbamazepina e valproato de sódio. As epilepsias idiopáticas generalizadas são classificadas como síndromes epilépticas. A EMJ é a mais comum dentre as síndromes da adolescência e uma das mais frequentemente diagnosticadas. A maioria dos pacientes com EMJ apresentam bom controle do quadro clínico com a utilização do valproato de sódio em monoterapia, mas na falha ou impossibilidade de seu uso, fármacos como a lamotrigina e o levetiracetam podem ser utilizados. TECNOLOGIA: levetiracetam (Keppra®). INDICAÇÃO: Terapia adjuvante, ou seja em associação com o valproato de sódio, em pacientes com epilepsia mioclônica juvenil (EMJ) resistentes à monoterapia. PERGUNTA: O uso do levetiracetam em regime de terapia adjuvante, é eficaz, seguro e custoefetivo em relação à continuação da monoterapia em pacientes com epilepsia mioclônica juvenil, resistentes a outros agentess antiepilépticos na perspectiva do SUS? EVIDÊNCIAS CIENTÍFICAS: A evidência da utilização do levetiracetam associado à tratamento prévio com um agente antiepiléptico para o tratamento da EMJ é baseada em um ensaio clínico duplo-cego que apresentou redução significante de 50% no número de dias por semana com crises convulsivas s (OR = 4,77; IC 95% 2,12 ­ 10,77; p<0,0001 e um maior número de pacientes, que receberam levetiracetam, apresentaram ausência total de crises durante o tratamento (16,7% dos pacientes, p = 0,03, vs 3,3 % do grupo que recebeu placebo). AVALIAÇÃO ECONÔMICA: Foi apresentado um modelo de custo-efetividade comparando a monoterapia com ácido valpróico ao tratamento adjuvante do levetiracetam (associado) ao ácido valpróico. Foi elaborado um modelo baseado primeiramente em uma árvore de decisão, seguido por um modelo de Markov. No caso-base a razão de custo-utilidade incremental (RCUI) foi de R$ 58.294 por ano de vida ajustada pela qualidade, que na análise de sensibilidade univariada variou entre R$ 22.119 e R$ 80.359. Avaliação de Impacto Orçamentário: Conforme as estimativas feitas pelo demandante o impacto orçamentário será de aproximadamente R$ 1,58 milhão no primeiro ano e de R$ 43,6 milhões nos primeiros 5 anos após a incorporação. Na análise de sensibilidade realizada o impacto orçamentário para os próximos 5 anos variou entre R$ 14,5 e R$ 87,3 milhões. EXPERIÊNCIA INTERNACIONAL: o levetiracetam é utilizado em terapia adjuvante para o tratamento de crises mioclônicas em agências como o National Institute for Health and Clinical Excellence (NICE) e Canadian Agency for Drugs and Technologies in Health (CADTH), de acordo com condições estabelecidas Discussão: A evidência do tratamento com levetiracetam em pacientes resistentes à monoterapia padrão, associado ao medicamento já utilizado, ocasionou em redução significante de pelo menos 50% no número de dias por semana com crises convulsivas e um maior número de pacientes apresentaram ausência total de crises convulsivas durante seu período de seguimento. Porém trata-se de evidência indireta e de baixa qualidade. Os estudos para essa indicação da tecnologia são escassos e há baixa probabilidade de novos estudos serem realizados. A avaliação econômica foi custo-efetiva na adição do levetiracetam ao medicamento previamente utilizado em monoterapia, em pacientes resistentes, com um impacto orçamentário de até R$ 87,3 milhões em 5 anos, de acordo com a análise de sensibilidade. A secretaria executiva da CONITEC estimou o número de pacientes, que considera mais adequada para o cálculo, que foi 7,8% maior que a população considerada na análise do demandante, o que levaria a um impacto orçamentário ainda maior. RECOMENDAÇÃO DA CONITEC: A CONITEC em sua 54ª reunião no dia 06 de abril de 2017, recomendou preliminarmente a incorporação no SUS do levetiracetam como terapia adjuvante em pacientes com epilepsia mioclônica juvenil resistentes à monoterapia, condicionada à redução de preço e consonância com a atualização do PCDT de Epilepsia. Consulta pública: Foi realizada a Consulta Pública nº 22/2017, entre os dias 25/04/2017 e 16/05/2017 e recebeu 105 contribuições, sendo 88 sobre experiência ou opinião e 17 técnicocientíficas. Todas as contribuições foram avaliadas quantitativamente e qualitativamente. Seu conteúdo não trouxe novas evidências e informações que pudessem modificar a recomendação inicial da CONITEC. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 56ª reunião ordinária do plenário do dia 07/06/2017 deliberaram, por unanimidade, por recomendar a incorporação do levetiracetam para pacientes com epilepsia mioclônica juvenil (EMJ) resistentes à monoterapia, associando-o ao medicamento já utilizado, condicionado à negociação de preço e conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 264/2017.(AU)

Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients.

Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.

[Astrocytoma and epilepsy. Clinical case]. / Astrocitoma y epilepsia. Caso clínico.

BACKGROUND: Pilocytic astrocytoma is a rare tumour, usually occurring in paediatric ages, and mainly located in the posterior fossa. It can cause hydrocephalus and intracranial hypertension and, less frequently, seizures, or a focal neurological deficit. The main imaging study by magnetic resonance imaging, which shows a tumour with solid and cystic components without peri-lesional swelling. The election treatment is surgical, and the patient is considered cured if a total resection is accomplished. CLINICAL CASE: The case is presented of 22-year-old female patient with a supratentorial pilocytic astrocytoma and epilepsy. Histopathology reported a low grade glial proliferation, with an extensive fibrillar matrix, small cells without atypia, extensive calcifications and piloid areas consisting of bipolar fusiform cells, and some Rosenthal fibres. There were also spongiotic areas consisting of multipolar cells and associated microcysts. The final report was a pilocytic astrocytoma. CONCLUSIONS: Pilocytic astrocytoma is more frequent in paediatric patients and in the posterior fossa. The case presented is of a young female adult with supratentorial location, making it a special case. The surgery achieved a total resection. The long-term prognosis is good, but it is necessary to perform a follow-up, particularly in adult patients because of a higher risk of recurrence.

Levetiracetam as an antiepileptic, neuroprotective, and hyperalgesic drug.

The main purpose of this review was to expound upon the mechanism of action of Levetiracetam (LEV) as an antiepileptic, neuroprotective, and hyperalgesic drug. LEV is a second-generation anti-epileptic drug (AED) that is approved for clinical use as monotherapy and may also be used for adjunctive treatment of patients with seizures. Several researchers have recommended LEV as a treatment option in different diseases causing neuronal damage, and recently, LEV has been used as an antihyperalgesic drug. LEV exhibits favorable characteristics, including a low potential for interaction, a short elimination half-life, and has neither active metabolites nor major negative effects on cognition. This has generated many new research avenues for the utilization of this drug. However, the precise mechanism of action of LEV has not been fully elucidated. In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation index for studies evaluating the effects of LEV as an antiepileptic, neuroprotective, and hyperalgesic drug. A total of 32 studies related to the use of LEV suggested different mechanisms of action, such as binding to the synaptic vesicle glycoprotein 2A (SV2A) protein, inhibition of Ca2+ N-type channels, and its presence as a neuromodulator. These studies concluded that the pharmacodynamics of LEV should be viewed as a single pathway, and should not be based on specific molecular targets that depend on the physiological or pathological conditions prevalent at that time.

Effect of low-frequency repetitive transcranial magnetic stimulation on sleep pattern and quality of life in patients with focal epilepsy.

OBJECTIVE: In this study we analyzed the effects of transcranial magnetic stimulation (TMS) on sleep and on the self-perceived quality of life in epileptic patients. METHODS: A total of 24 male patients diagnosed with focal epilepsy were included in the study. Pharmacological treatment with levetiracetam was standardized at 2 g daily. Before TMS onset, all-night polysomnographic recording (PSG) was performed, and the Quality of Life in Epilepsy Inventory (QOLIE-31) was administered. Thereafter, patients underwent low-frequency repetitive TMS (1000 pulses/1 Hz) daily for 10 days. After the end of the treatment, a second polysomnographic study was performed, and the QOLIE-31 questionnaire was administered again. RESULTS: TMS induced a significant increase in sleep efficiency and in total sleep time, along with a decrease in sleep latency and the number of awakenings. In addition, the number of interictal discharges during sleep decreased significantly. Concerning the QOLIE-31 scale values, the patients showed great improvement in the self-perceived quality of life. CONCLUSION: The present results indicate that TMS may mediate therapeutic effects in the treatment of patients with focal epilepsy, and that TMS treatment is accompanied by improvement of sleep patterns as well as improvement in self-perceived quality of life. However, a study that includes a control group undergoing sham stimulation is needed to confirm these findings.