Registro de epilepsias na gravidez, complicações obstétricas e fetais e o uso de drogas antiepilépticas em Alagoas-BR / Registry of epilepsy during pregnancy, obstetric and fetal complications and the use of antiepileptic drugs in Alagoas-BR

Objetivos: artigo 1: Descrever a prevalência das nas mulheres gestantes com epilepsia (MGCE), perfil sociodemográfico e desfechos obstétricos e analisar associação dessas variáveis com a doença. Artigo 2: Descrever o perfil de MAC (medicação anticrise) e tipos de crises e analisar a associação desses perfis com a incidência de complicações maternas e fetais nas MGCE. Artigo 3: Descrever a prevalência, perfil sociodemográfico e clínico, perfil de MAC, tipos de crises e analisar a associação da incidência de complicações maternas e fetais com essas variáveis nas MGCE. Métodos: Artigos 1 e 2: coortes retrospectivas com 234 MGCE e 492 MGSE. Artigo 3 coorte prospectiva coletou dados de 95 MGCE e 380 sem epilepsia (MGSE). Ambas as coortes com idade 40 anos em prontuários e entrevistas em 4 maternidades de alto risco em Alagoas no período de 2008 a 2021 na coorte retrospectiva e 2021 e 2022 na prospectiva. Resultados: A prevalência de MGCE nas coortes retrospectiva e prospectiva foi de 0,49% (n = 224/44917) e 0,53% (n = 105/19.624) com médias de idade (24,94 ± 6,25 e 23,98 ± 6,89); (24,42 ± 5,64 e 24,42 ± 5,62) anos. MGCE procederam da zona rural (58,2%; 64,2%), eram de cor parda (88,6%;98%), (7%; 3,2%) analfabetas e com ensino fundamental (40%; 52,1%), solteiras (47,3%; 49,5%) e (76,9%; 78,9%) donas de casa, respectivamente. Em relação a partos, a maioria (60,3%; 54,8%) eram multíparas, (74,6%; 70,8%) tiveram parto cesáreo, respectivamente. Na coorte prospectiva 15,8% sem renda, 54,7% com menos de 1 salário mínimo, 44,2% eram de religião católica e 87.4% não planejou a gravidez. A análise dos desfechos obstétricos e neonatais mostrou um risco maior nas MGCE para hipertensão relacionada à gravidez (HRG) (OR =6.29; 95% CI =3.50-11.30), pré-eclâmpsia (OR=8.04; 95% CI=2.22-29.10) na coorte retrospectiva, e em ambas coortes um risco de sangramento vaginal (OR=2.54; 95% CI=1.15-5.59);(OR=4.13; 95% CI=1.45-9.11), aborto espontâneo (OR=1.75; 95% CI=1.16-2.63); (OR=1.50; 95% CI=1.00-2.22) e natimorto (OR=11,16; 95% CI=2.22-29.10); (OR=5.27; 95% CI=2.29-10.30). Nas coortes retrospectiva e prospectiva (14%; 14,7%) não usaram MAC, (50,2%; 85,3%) monoterapia (35,8%; 12,6%) politerapia, respectivamente. O fenobarbital foi o MAC mais prescrito seguido pela carbamazepina em ambas coortes. Na prospectiva MGCE que usaram MAC e em politerapia tiveram maior risco de hemorragia vaginal, admissão em UTI materna e natimorto. Analisando os tipos de epilepsia a maioria 40% tinha o tipo generalizada. A respeito do tipo de crise, a maioria 53,3% apresentou crise focal na coorte retrospectiva, enquanto na prospectiva a maioria delas 48,4% teve CTCG e 19% estado de mal epiléptico associados a desfechos obstétricos e neonatais adversos. Conclusão: Ambos os estudos relatam um perfil sociodemográfico da MGCE de alta vulnerabilidade social e alto risco de desfechos obstétricos e neonatais adversos, provavelmente devido à procedência de uma região pobre do Brasil. Foi constatado algumas limitações na distribuição de MACs apropriados para essa população.

Objectives: article 1: To describe the prevalence of epilepsy in pregnant women, sociodemographic profile and obstetric outcomes and analyze the association of these variables with a disease. Article 2: Describe the profile of ASM (anti-crisis medication) and types of seizures and analyze the association of these profiles with the incidence of maternal and fetal complications in pregnat women with epilepsy (PWWE). Article 3: Describe the prevalence, sociodemographic and clinical profile, types of ASM used and seizures and analyze the association of the incidence of maternal and fetal complications with these variables in PWWE. Methods: Articles 1 and 2: retrospective cohorts with 234 PWWE and 492 pregnant women without epilepsy (PWNE). Article 3 prospective cohort collected data from 95 PWWE and 380 PWNE. Both cohorts aged 40 years in medical records and interviews from four high-risk maternity hospitals in Alagoas. The period from 2008 to 2021 in the cohort retrospective and 2021 and 2022 in the prospective. Results of the articles: The prevalence of PWWE in the retrospective and prospective cohorts were 0.49% (n = 224/44917) and 0.53% (n = 105/19,624) with mean ages (24.94 ± 6.25 and 23 .98 ± 6.89); (24.42 ± 5.64 and 24.42 ± 5.62) years, respectively. PWWE came from the countryside (58.2%; 64.2%), had brown skin (88.6%; 98%), illiterate (7%; 3.2%) and had primary education (40%; 52 .1%), single (47.3%; 49.5%) and (76.9%; 78.9%) homemakers, respectively. Regarding deliveries, the most of them (60.3%; 54.8%) were multiparous, (74.6%; 70.8%) had cesarean delivery, respectively. In the prospective cohort, 15.8% had no income, 54.7% earned less than 1 minimum wage, 44.2% were Catholic religious and 87.4% had not planned the pregnancy. Analysis of obstetric and neonatal outcomes showed a higher risk in PWWE for pregnancy-related hypertension (PrH) (OR=6.29; 95% CI=3.50-11.30), preeclampsia OR=8.04; 95% CI=2.22-29.10) in the retrospective cohort, and in the retrospective and prospective cohorts a risk of vaginal bleeding (OR=2.54; 95% CI=1.15-5.59);(OR=4.13; 95% CI=1.45-9.11), miscarriage (OR=1.75; 95% CI=1.16-2.63); (OR=1.50; 95% CI=1.00-2.22) and stillbirth (OR=11.16; 95% CI=2.22-29.10); (OR=5.27; 95% CI=2.29-10.30), respectively. In both cohorts (14%; 14.7%) they did not use MAC, (50.2%; 85.3%) monotherapy (35.8%; 12.6%) polytherapy, respectively. Phenobarbital was the most prescribed ASM followed by carbamazepine in both cohorts. In prospective PWWE who used ASM and polytherapy had a higher risk of vaginal bleeding, maternal ICU admission and stillbirth. Analyzing the types of epilepsy, most of them 40% had the generalized type. Regarding the type of seizure, most 53.3% had focal seizures in the retrospective cohort, while in the prospective cohort, most of them 48.4% had GTCS (tonic-clonic generalized) and 19% had status epilepticus, associated with adverse obstetric and neonatal outcomes. Conclusion: Both studies report a sociodemographic profile of PWWE with high social vulnerability and higher risk of adverse obstetric and neonatal outcomes, probably due to the origin of a poor region of Brazil. Some limitations were found in the distribution of appropriate ASM for this population

Esclerosis tuberosa / Tuberous sclerosis

Se presenta el caso de paciente masculino de 15 años de edad que es llevado a sala de urgencia s del Hospital Roosevelt por convulsiones tónico clónico generalizadas de 2 minutos de duración, con período postictal, con antecedentes familiares de convulsiones mostradas en el árbol genealógico (grafico 2 ). Además presenta antecedente de síndrome convulsivo desarrollado a los tres años de edad, tratado con múltiples anticonvulsivantes sin llegar a un dia gnóstico. Paciente al examen físico se presenta normocéfalo, cabello adecuada implantación, alerta, orientado en tiempo, espacio y persona, escleras y mucosas normales, con lesiones angiofibromatosas de distribución en alas de mariposa en región de puente nasal, alas nasales, mejillas y frente , frecuencia respiratoria de 14 por minuto, con ruidos respiratorios conservados, frecuencia cardíaca 70 por minuto, presión arteria l 100/60 mmHg, ritmo cardíaco normal, sincrónico con el pulso, abdomen sin alteraciones, extremidades y evaluación de sistema nervioso central sin presentar alteraciones...(AU)

We present the case of a 15-year-old male patient who is taken to the emergency room s Roosevelt Hospital for generalized 2-minute clonic tonic convulsions, with a period postictal, with family history of seizures shown in the pedigree (chart 2). It also presents a history of convulsive syndrome developed at three years of age, treated with multiple anticonvulsants without reaching a Gnostic day. Patient to the physical examination presents normocephalus, adequate hair implantation, alert, oriented in time, space and person, normal scleras and mucous membranes, with angiofibromatosis lesions of distribution in butterfly wings in nasal bridge region, nasal wings, cheeks and forehead, frequency respiratory rate of 14 per minute, with preserved respiratory sounds, heart rate 70 per minute, artery pressure l 100/60 mmHg, normal heart rate, synchronous with the pulse, abdomen without alterations, extremities and evaluation of the central nervous system without presenting alterations. . (AU)

Phenytoin induced severe disabling osteomalacia in a young male with seizure disorder.

While the use of anti epileptic drugs (AEDs) for a long period is a known risk factor for bone loss and pathological fractures, yet the physicians are not yet sensitized to this possibility. It is now believed that the patients who have fractures due to long-term treatment with anticonvulsants have osteomalacia as the predominant lesion. This has been attributed to the alterations in the levels of circulating calcium and calcitropic hormones. Here we report a case of a young male who had been on anticonvulsants for 11 years and was admitted with us with severe bone pains, multiple pathological pseudo fractures and a severe degree of disability secondary to phenytoin induced osteomalacia.

Patients' preferences towards antiepileptic drug therapy following first attack of seizure.

BACKGROUND: Antiepileptic drug (AED) therapy following first unprovoked seizure is controversial. AIM: To study the patients' preferences towards AED therapy following first unprovoked generalized tonic clonic seizure (GTCS). DESIGN: Prospective cohorts with one year follow-up study. SETTING: Government teaching hospital, a tertiary care center. MATERIALS AND METHODS: Patient cohort included patients with first attack of unprovoked GTCS within 30 days of onset, aged between 18-60 years and with normal brain CT scan. Counseling was done for all the patients and the relatives regarding seizure recurrence, duration and adverse effects of AED therapy if preferred. Patients were encouraged to make their own decision in preferring or deferring AED with reasons. They were followed up for one year. RESULTS: Of the 73 enrolled (54 males and 19 females) 39 (53%) preferred to go on AED therapy. The reasons for preferring AED therapy were; (a) fear of seizure recurrence, 21 (54%); (b) risky occupation, 14 (36%); and (c) fear of injury, 4 (10%). The reasons for deferring were: (a) fear of adverse effects of long-term AED therapy, 19 (56%) and (b) preferring to wait for the second attack, 15 (44%). All the patients were happy about being involved in the decision-making. CONCLUSION: Following first attack of unprovoked GTCS the decision regarding AED therapy may be taken by the patients and their family members after adequate counseling and such decisions have more relevance from their perspective.

Topiramate for the treatment of juvenile myoclonic epilepsy

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of topiramate (TPM) in juvenile myoclonic epilepsy (JME). METHOD: We assessed seizure control and adverse effects of TPM in 22 patients (18 females) aged 13 to 53 years. Target TPM dosage was up to 200 mg/day. The patients were subdivided into 3 groups: those treated with seizure control plus side effects (n=4); treated with non-controlled seizures (n=15) and with JME newly diagnosed (n=3). RESULTS: Sixteen patients completed the first year of the follow-up. Generalized tonic-clonic seizures were completely controlled in 10 (62.5%); more than 50% of reduction in 4 (25.0%) and less than 50% in 2 (12.5%). Myoclonia were controlled in 11 (68.8%) and persisted in 5 (31.2%) patients. Absence seizures were present in 5 (22.7%) of whom 2 (9.0%) showed more than 50% of seizure reduction while 3 (13.6%) presented worsening. Discontinuations were due to inadequate seizure control and adverse events (N=4), low compliance and loss of follow-up (N=2) and subject choice (N=1). CONCLUSION: TPM showed to be an effective and well-tolerated drug in the treatment of JME. Although frequently observed, TPM side effects were tolerable and the drug could be maintained in the majority of patients.

OBJETIVO: Avaliar a eficácia e tolerabilidade do topiramato (TPM) na epilepsia mioclônica juvenil (EMJ). MÉTODO: Avaliamos a resposta terapêutica e efeitos colaterais do TPM em 22 pacientes (18 mulheres) com idades entre 13 e 53 anos. A dose alvo utilizada foi até 200 mg/dia. Os pacientes foram divididos em 3 grupos no início do tratamento: aqueles com controle das crises mas que apresentavam efeitos colaterais (n=4); com crises não controladas (n=15) e com EMJ recém diagnosticada (n=3). RESULTADOS: Dezesseis pacientes completaram o primeiro ano de acompanhamento. Crises tônico-clonicas generalizadas foram completamente controladas em 10 (62,5%), tiveram redução maior de 50% em 4 (25,0%) e menor de 50% em 2 (12,5%). Mioclonias foram controladas em 11 (68,8%) e persistiram em 5 (31.2%) pacientes. As crises de ausências, presentes em 5 (22,7%) pacientes, tiveram redução maior do que 50% em 2 (9,0%) e agravamento em 3 (13,6%). A retirada do estudo foi devida principalmente ao controle inadequado das crises e efeitos colaterais indesejáveis (n=4), pouca adesão e perda do seguimento (n=2) e escolha do paciente (n=1). CONCLUSÃO: TPM foi considerada droga eficaz e bem tolerada no tratamento da EMJ. Apesar de freqüentemente observados, os efeitos colaterais do TPM foram toleráveis e a medicação pode ser mantida na maioria dos pacientes.

Cerebellar atrophy in an epileptic child: is it due to phenytoin?

A four and half year old epileptic child on phenytoin therapy since one year presented with signs of cerebellar dysfunction. Serum phenytoin level was high (33 mcg/ml) and computerised tomographic scan of the brain showed severe generalised cerebellar atrophy. The cerebellar signs represented drug over dosage and toxicity and persisted long after omission of phenytoin.

Estudo comparativo entre oxcarbazepina e carbamazepina contra crises convulsivas tônico-clônicas induzidas por eletrochoque em ratos / Effects of Oxcarbazepine and Carbamazepine as anticonvulsivants induced by electric shock in rats

O trabalho visa comparar a eficácia anticonvulsivante da oxcarbazepina e da carbamazepina e a relaçao dose-efeito das mesmas. Foram utilizados 64 ratos albinos Wistar divididos em sete grupos, que receberam doses de OCBZ e CBZ em diferentes concentraçöes, sendo submetidos 30 minutos depois a eletrochoque transcorneal de 100V po 0,2 segundos, sendo observado o período de latência e de início das crises convulsivas tônico-clônicas...

Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study.

OBJECTIVE: To compare the efficacy and side effects of phenobarbitone (PB), phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic-clonic convulsions (GTC). DESIGN: Randomized, double blind clinical trial. SETTING: Out-Patients in a tertiary care hospital. PATIENTS: 151 children with GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127 children remained in the study. INTERVENTION: Each child was given one active drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations were done every month. Serum drug levels were assessed periodically. MAIN OUTCOME MEASURES: Recurrence of convulsion and side effects. RESULTS: The proportion of children with recurrence did not differ among the 3 groups. More than one side effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9 (19%) children on SVP and this difference was statistically significant (p < 0.05). Hyperactivity was the major side effect of PB, observed in 22% of children. CONCLUSION: All 3 drugs were equally effective in controlling seizures. Side effects were minimal with SVP followed by PB. Though side effects were more frequent with PHT, most of them disappeared on adjusting drug dosage. Least expensive phenobarbitone may be preferred as the first drug of choice but, only for pre-school children. SVP is advised for school going children.

Compliance monitoring in epileptic patients.

Poor patient compliance is one of the major causes of non responsiveness to antiepileptic drug therapy. Compliance is mostly assessed by self reporting, pill counting and plasma drug level estimation. However, none of them is fool proof. Subtherapeutic plasma drug levels can be due to poor compliance or need for higher dosage. Therefore, in the present study, 20 adult non responsive epileptic patients showing subtherapeutic plasma phenytoin levels inspite of receiving standard phenytoin therapy and history of good compliance were admitted in the clinical pharmacology ward and received supervised drug treatment for five days after which plasma phenytoin levels in 14 patients increased to therapeutic range. All except one (i.e. 9 out of 10) patients showing phenytoin levels < 5 ug/ml inspite of phenytoin dosage of > 300 mg/d and history of good compliance were found to be noncompliant. Hence adult patient receiving greater than or equal to 300 mg/day phenytion and showing phenytoin levels less than or equal to 5 ug/ml should be investigated for possible noncompliance before altering their dosage schedules.

Effect of sodium valproate on serum amylase in epileptics.

Thirty-eight patients of generalised tonic-clonic seizures of epileptics in the age group of 15-30 years were included in this study. Of these 20 were started sodium valproate afresh and 18 already taking it for more than one year prior to inclusion. Serum amylase and serum valproic acid levels were measured in all of them, initially and at every 3 months interval for 9 months. Though no clinical evidence was present, there was significant increase in serum amylase levels in both the groups which has no correlation with dose or serum valproic acid levels.

Need for 25 mg tablets of phenytoin.

Phenytoin is widely used for the treatment of generalized tonic clonic and partial seizures. Monitoring of serum phenytoin levels is essential to optimize therapy. Of 320 patients monitored, 190 patients whose seizures were uncontrolled were followed up before and after dosage adjustment was carried out. Plasma phenytoin estimation was done by HPLC method. Of all the patients receiving the drug, 20% and 8% of patients were finally on dosages requiring 50 and 25 mg fraction administration respectively. Administration of 100 mg fractions resulted in either loss of seizure control or toxicity. This emphasizes the need for providing tablets of 25 mg strength, presently not available in this country.