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1.
Indian J Ophthalmol ; 70(5): 1491-1501, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35502014

RESUMO

Topiramate-induced acute angle closure (TiAAC) is a potentially vision-threatening side effect of topiramate (TPM) use. The purpose of this article is to review demographic characteristics, clinical features, and management options of TiAAC. A systematic literature search of all reported cases and case series of TiAAC was conducted in the following search engines: PubMed, Web of Science, Google Scholar, Elsevier, and EBSCO. Seventy-three publications describing 77 cases were included. 58 (75.3%) patients were female, and the mean age was 34.88 ± 11.21 years (range, 7-57). The most commonly reported indication of TPM use was migraine headache (59.7%), and the mean duration from starting treatment until the onset of angle closure was 14.1 ± 31.5 days. All cases were managed by immediate cessation of TPM and topical therapy. In addition, systemic medications (carbonic anhydrase inhibitors, hyperosmotic agents, and steroids) were used in 51 patients (66.2%). A laser and/or surgical intervention was performed in 10 patients (13%). After commencement of treatment, the mean duration until the resolution of TiAAC was 3.9 ± 3.6 days (range, 1-18). The findings of our study present a summary of the current body of evidence provided by case reports and case series on TiAAC. In conclusion, the onset of angle closure following TPM use peaks at 2 weeks after initiating treatment, and in most cases, successful management can be achieved by discontinuing TPM and initiating appropriate medical therapy.


Assuntos
Glaucoma de Ângulo Fechado , Transtornos de Enxaqueca , Doença Aguda , Adulto , Anticonvulsivantes/efeitos adversos , Feminino , Frutose/efeitos adversos , Glaucoma de Ângulo Fechado/induzido quimicamente , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Topiramato/efeitos adversos , Adulto Jovem
2.
JAMA Netw Open ; 5(4): e226484, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385086

RESUMO

Importance: Anticonvulsant mood stabilizer treatment is associated with an increased risk of weight gain, but little is known about the risk of developing type 2 diabetes (T2D). Objective: To evaluate the comparative safety of anticonvulsant mood stabilizers on risk of T2D in adults and children by emulating a target trial. Design, Setting, and Participants: This observational cohort study used data from IBM MarketScan (2010-2019), with a 5-year follow-up period. The nationwide sample of US commercially insured patients included children (aged 10-19 years) and adults (aged 20-65 years) who initiated anticonvulsant mood stabilizer treatment. Data were analyzed from August 2020 to May 2021. Exposures: Initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate. Main Outcomes and Measures: Onset of T2D during follow-up. Weighted pooled logistic regression was used to estimate the association of initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate with the risk of developing T2D. Inverse probability weights were used to control for confounding and loss to follow-up by measured baseline and time-varying covariates. Results: The analysis included 274 206 adults (159 428 women [58%]; mean [SD] age, 39.9 [13.2] years) and 74 005 children (38 672 girls [52%]; mean [SD] age, 15.6 [2.6] years) who initiated an anticonvulsant mood stabilizer. In adults, initiation of valproate was associated with an increased risk of developing T2D compared with initiation of lamotrigine (5-year risk difference [RD], 1.17%; 95% CI, 0.66% to 1.76%). The number needed to harm was 87 patients initiating valproate for 1 patient to develop T2D within 5 years compared with initiation of lamotrigine. Point estimates were similar when evaluating the association of treatment continuation (5-year RD, 1.99%; 95% CI, -0.64% to 5.31%). The estimated association was smaller and more variable comparing carbamazepine and oxcarbazepine to lamotrigine. In children, RDs were much smaller and more variable (5-year RD for initiation of oxcarbazepine vs lamotrigine, 0.29%; 95% CI, -0.12% to 0.69%; 5-year RD for initiation of valproate vs lamotrigine, 0.18%; 95% CI, -0.09% to 0.49%). Conclusions and Relevance: In this cohort study, valproate was associated with the highest risk of developing T2D in adults. The comparative safety was generally similar in children, but estimates were small and variable. In the absence of randomized trials, emulating target trials within health care databases can generate the age-specific drug safety data needed to inform treatment decision-making.


Assuntos
Anticonvulsivantes , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Lamotrigina/uso terapêutico , Pessoa de Meia-Idade , Oxcarbazepina/uso terapêutico , Ácido Valproico/efeitos adversos , Adulto Jovem
4.
J Trop Pediatr ; 68(3)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35459951

RESUMO

BACKGROUND: In newly diagnosed neurocysticercosis (NCC) with seizures, the choice of anti-seizure medication (ASM) seems to be arbitrary due to a lack of comparative studies. Although oxcarbazepine (OXC) is often considered efficacious for focal seizures in NCC, due to adverse effects, newer ASMs like levetiracetam (LCM) and lacosamide are also being explored. METHODS: This study was performed by case record review of children with newly diagnosed solitary viable parenchymal NCC aged 4-18years who received lacosamide and OXC at least for 12 weeks between August 2019 and April 2021, from a prospective registry of a tertiary care teaching hospital in north India. Seizure control, electroencephalographic abnormalities, resolution of inflammatory granulomas and adverse effects were compared between two arms at 12 and 24 weeks. RESULTS: Total 31 (8.3 ± 4.7 years, 19 boys) and 72 (8.6 ± 4.2 years, 43 boys) completed at least 12 weeks follow-up in LCM and OXC groups, out of which 2 and 51 completed at least 24 weeks follow-up in LCM and OXC groups, respectively. The occurrence of breakthrough seizure was comparable in both arms at 12 and 24 weeks (1/31 and 2/22 in lacosamide group vs. 2/72 and 4/51 in OXC group, p = 0.66 and 0.59, respectively). Patients receiving OXC had more frequent treatment-emergent adverse events (p = 0.0001) and four patients required discontinuation due to severe adverse events (SAEs), while none in the lacosamide group had SAEs. CONCLUSIONS: Lacosamide appears to be efficacious and safe for achieving seizure freedom in patients with solitary viable parenchymal neurocysticercosis.


Assuntos
Epilepsias Parciais , Neurocisticercose , Anticonvulsivantes/efeitos adversos , Criança , Epilepsias Parciais/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Feminino , Humanos , Lacosamida/uso terapêutico , Levetiracetam/uso terapêutico , Masculino , Neurocisticercose/induzido quimicamente , Neurocisticercose/complicações , Neurocisticercose/tratamento farmacológico , Oxcarbazepina/efeitos adversos , Convulsões/tratamento farmacológico , Convulsões/etiologia , Resultado do Tratamento
5.
Pediatr Neurol ; 130: 53-59, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35364461

RESUMO

BACKGROUND: Fanconi syndrome (FS) can be of primary or secondary origin. Some cases of FS secondary to the use of sodium valproate (VPA) have been described, mostly in children with severe psychomotor retardation who are fed by feeding device. The objetive of this study was to describe patients treated for this entity in our center, comparing them against the published literature. METHODS: Descriptive study of our patients and those found in the literature. Epidemiologic and clinical data were collected. RESULTS: We describe seven patients (three to 17 years old) with severe psychomotor retardation and undergoing treatment with VPA. Four presented pathologic fractures before the diagnosis of FS, and in three patients the diagnosis was reached due to abnormal laboratory findings. A review of the published cases was carried out and, including our sample, a total of 42 patients were studied: 51.3% were male, and the median age at diagnosis of FS was 6 years. Severe psychomotor retardation was found in 92.8% of patients, 78% carried a feeding device, and 77.5% received treatment with several antiepileptic drugs. The mean duration of VPA treatment was 5.7 years (range 2 to 7.5 years). Fifteen patients (37.5%) had bone complications. The resolution time of FS after discontinuation of drug therapy ranged from two to 19 months (median 4 months). CONCLUSIONS: FS related to VPA is a rare complication, but it should be considered in patients with epilepsy, especially if they have severe psychomotor retardation, are users of feeding devices, and receive other antiepileptic treatments in addition to VPA.


Assuntos
Epilepsia , Síndrome de Fanconi , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/tratamento farmacológico , Feminino , Humanos , Masculino , Ácido Valproico/efeitos adversos
6.
JAMA ; 327(13): 1269-1281, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380580

RESUMO

Importance: Epilepsy affects approximately 65 million people worldwide. Persistent seizures are associated with a 20% to 40% risk of bodily injuries (eg, fractures, burns, concussions) over 12-month follow-up. The primary goal of epilepsy treatment is to eliminate seizures while minimizing adverse effects of antiseizure drugs (ASDs). Observations: An epileptic seizure is defined as a sudden occurrence of transient signs and symptoms caused by abnormal and excessive or synchronous neuronal activity in the brain. Focal and generalized epilepsy are the 2 most frequent types of epilepsy; diagnosis is based on the type of seizures. There are 26 US Food and Drug Administration-approved medications for epilepsy, of which 24 have similar antiseizure efficacy for focal epilepsy and 9 have similar efficacy for generalized epilepsy. The decision to initiate an ASD should be individualized, but should be strongly considered after 2 unprovoked seizures or after 1 unprovoked seizure that occurred during sleep and/or in the presence of epileptiform activity on an electroencephalogram and/or in the presence of a structural lesion on the brain magnetic resonance imaging. The ASDs must be selected based on the seizure and epilepsy types, the epilepsy syndrome, and the adverse effects associated with the drug. For focal epilepsy, oxcarbazepine and lamotrigine are first-line therapy, while levetiracetam can be also considered if there is no history of psychiatric disorder. For generalized epilepsy, the selection of the ASD is based on the type of epilepsy syndrome and the patient's sex, age, and psychiatric history. Seizure freedom is achieved in approximately 60% to 70% of all patients. A total of 25% to 50% of patients also experience neurologic, psychiatric, cognitive, or medical disorders, such as mood, anxiety, and attention deficit disorders and migraines. For these patients, selecting an ASD should consider the presence of these disorders and concomitant use of medications to treat them. ASDs with cytochrome P450 enzyme-inducing properties (eg, carbamazepine, phenytoin) may worsen comorbid coronary and cerebrovascular disease by causing hyperlipidemia and accelerating the metabolism of concomitant drugs used for their treatment. They can also facilitate the development of osteopenia and osteoporosis. Conclusions and Relevance: Epilepsy affects approximately 65 million people worldwide and is associated with increased rates of bodily injuries and mortality when not optimally treated. For focal and generalized epilepsy, selection of ASDs should consider the seizure and epilepsy types and epilepsy syndrome, as well as the patient's age and sex, comorbidities, and potential drug interactions.


Assuntos
Anticonvulsivantes , Epilepsia , Convulsões , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Síndromes Epilépticas/tratamento farmacológico , Humanos , Convulsões/tratamento farmacológico
7.
Artigo em Inglês | MEDLINE | ID: mdl-35457375

RESUMO

OBJECTIVE: To investigate the occurrence of adverse effects of antiepileptic drugs (AEDs) in pediatric epileptic patients on mono- or polytherapy. METHOD: We evaluated eighty consecutive patients that met the following inclusion criteria: aged ≤18 years; diagnosed with epilepsy for at least one year; a stable dose of AED for at least three months; verbal consent to participation in the study. Patients were asked if they had experienced any adverse drug reaction (ADR) related to the AED. Afterward, regardless of the answer, they were interviewed based on a detailed semi-structured questionnaire about the presence of ADRs associated with the AED. The data were analyzed regarding the use of monotherapy or polytherapy. RESULTS: Ninety-seven percent of the patients reported having experienced ADRs related to AEDs. The greatest number of seizures affected the group of patients treated with monotherapy (both at baseline and at followup), but the greatest number of ADRs were observed among patients treated with polytherapy. In patients on monotherapy, the most frequent ADRs reported at baseline included fatigue and somnolence, and among patients with polytherapy, it was fatigue and hair loss. CONCLUSION: Children on polytherapy were significantly more likely to develop ADRs compared to those on monotherapy, but a statistically significant improvement in seizure frequency was also observed in the group of patients on polytherapy. Pharmacovigilance is very important in children with AEDs, so that ADRs can be identified early and managed appropriately.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsia , Anticonvulsivantes/efeitos adversos , Criança , Epilepsia/epidemiologia , Fadiga , Humanos , Farmacovigilância , Convulsões/induzido quimicamente
8.
Neurosci Lett ; 778: 136620, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35395326

RESUMO

Allopurinol, a uric-acid-lowering medication, has shown its efficacy in several studies suggesting that allopurinol can be prescribed as adjunctive cure meant for intractable epilepsy. The exact mechanism of allopurinol is still unknown. This study evaluates allopurinol's effect on seizure threshold, seizure incidence, and mortality rate in mice models. Moreover, the possible involvement of nitric oxide (NO) pathway and N-methyl-D-aspartate (NMDA) receptors are investigated. To evaluate the effect of allopurinol on seizure, we used the pentylenetetrazole (PTZ)-induced seizure along with maximal electroshock (MES)-induced seizure. To assess the underlying mechanism behind the allopurinol activity, we used nitric oxide synthase (NOS) substrate (L-arginine), NOS inhibitors (L-NAME, aminoguanidine, 7-nitroindazole), and NMDA receptor antagonist (MK-801). Intraperitoneal allopurinol administration at a dose of 50 mg/kg in mice showed a significant (p < 0.001) anti-convulsant activity in the PTZ-induced seizure. Even though pre-treatment with L-Arginine (60 mg/kg) potentiates allopurinol's anti-convulsant effect in the PTZ-induced seizure, pre-treatment with L-NAME (10 mg/kg), aminoguanidine (100 mg/kg), and 7-nitroindazole (30 mg/kg) reversed the anti-convulsant effect of allopurinol in the PTZ-induced seizure. In addition, pre-treatment with MK-801 also decreased the anti-convulsant effect of allopurinol in the PTZ-induced seizure. While allopurinol at a dose of 50 mg/kg and 100 mg/kg did not induce protection against seizure incidence in the MES-induced seizure, it revealed a remarkable effect in reducing the mortality rate in the MES-induced seizure. Allopurinol increases the seizure threshold in PTZ-induced seizure and enhances the survival rate in MES-induced seizure. Allopurinol exerts its anti-convulsant effect, possibly through targeting NO pathway and NMDA receptors.


Assuntos
Pentilenotetrazol , Receptores de N-Metil-D-Aspartato , Alopurinol/efeitos adversos , Animais , Anticonvulsivantes/efeitos adversos , Arginina/farmacologia , Arginina/uso terapêutico , Convulsivantes , Maleato de Dizocilpina , Eletrochoque , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Camundongos , NG-Nitroarginina Metil Éster/efeitos adversos , Óxido Nítrico/metabolismo , Pentilenotetrazol/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo
9.
Epilepsy Behav ; 130: 108671, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35381495

RESUMO

OBJECTIVES: To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. METHODS: We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. RESULTS: Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. CONCLUSION: The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. TRIAL REGISTRATION NUMBER: CTRI/2017/12/010906.


Assuntos
Anticonvulsivantes , Epilepsia , Adulto , Anticonvulsivantes/efeitos adversos , Benzodiazepinas , Clobazam/uso terapêutico , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
10.
Neurosurg Focus ; 52(4): E3, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35364580

RESUMO

OBJECTIVE: The natural history of seizure risk after brain tumor resection is not well understood. Identifying seizure-naive patients at highest risk for postoperative seizure events remains a clinical need. In this study, the authors sought to develop a predictive modeling strategy for anticipating postcraniotomy seizures after brain tumor resection. METHODS: The IBM Watson Health MarketScan Claims Database was canvassed for antiepileptic drug (AED)- and seizure-naive patients who underwent brain tumor resection (2007-2016). The primary event of interest was short-term seizure risk (within 90 days postdischarge). The secondary event of interest was long-term seizure risk during the follow-up period. To model early-onset and long-term postdischarge seizure risk, a penalized logistic regression classifier and multivariable Cox regression model, respectively, were built, which integrated patient-, tumor-, and hospitalization-specific features. To compare empirical seizure rates, equally sized cohort tertiles were created and labeled as low risk, medium risk, and high risk. RESULTS: Of 5470 patients, 983 (18.0%) had a postdischarge-coded seizure event. The integrated binary classification approach for predicting early-onset seizures outperformed models using feature subsets (area under the curve [AUC] = 0.751, hospitalization features only AUC = 0.667, patient features only AUC = 0.603, and tumor features only AUC = 0.694). Held-out validation patient cases that were predicted by the integrated model to have elevated short-term risk more frequently developed seizures within 90 days of discharge (24.1% high risk vs 3.8% low risk, p < 0.001). Compared with those in the low-risk tertile by the long-term seizure risk model, patients in the medium-risk and high-risk tertiles had 2.13 (95% CI 1.45-3.11) and 6.24 (95% CI 4.40-8.84) times higher long-term risk for postdischarge seizures. Only patients predicted as high risk developed status epilepticus within 90 days of discharge (1.7% high risk vs 0% low risk, p = 0.003). CONCLUSIONS: The authors have presented a risk-stratified model that accurately predicted short- and long-term seizure risk in patients who underwent brain tumor resection, which may be used to stratify future study of postoperative AED prophylaxis in highest-risk patient subpopulations.


Assuntos
Anticonvulsivantes , Neoplasias Encefálicas , Assistência ao Convalescente , Anticonvulsivantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Humanos , Alta do Paciente , Estudos Retrospectivos , Convulsões/etiologia
11.
Seizure ; 98: 57-70, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35427849

RESUMO

BACKGROUND: Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs). OBJECTIVE: The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study. RESULTS: A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital. CONCLUSIONS: Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.


Assuntos
Epilepsia , Leite Humano , Anticonvulsivantes/efeitos adversos , Aleitamento Materno , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Etossuximida/uso terapêutico , Feminino , Humanos , Lactente , Lactação , Fenobarbital/uso terapêutico , Primidona/uso terapêutico , Revisões Sistemáticas como Assunto
12.
Seizure ; 98: 87-94, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35453064

RESUMO

PURPOSE: Report final data from adolescent (12-<18 years) and adult (≥18 years) patients from PROVE (NCT03208660), a multicenter, retrospective, non-interventional, Phase IV study to assess retention, efficacy, safety, and dosing of perampanel in patients with epilepsy during routine clinical care. METHODS: Data were retrospectively collected from medical/pharmacy records of patients in the US initiating perampanel after January 1, 2014, according to treating clinicians' recommendation. Retention rate was the primary efficacy endpoint. Secondary endpoints included median percent changes in seizure frequency, seizure-freedom rates, investigator's impression of seizure effect, and treatment-emergent adverse events (TEAEs). RESULTS: The Safety Analysis Set (SAS) included 294 adolescents and 1157 adults (median maximum perampanel dose, 6.0 mg/day). In patients eligible for inclusion in the retention rate analysis, 24-month retention rates were 53.5% (n=91/170) in adolescents and 47.8% (n=354/741) in adults. In patients with available efficacy data during Months 10-12, median percent seizure frequency reductions were 79.3% (n=20) in adolescents and 70.8% (n=92) in adults. Most patients in the SAS with seizure-effect data experienced an improvement in seizures at the last follow-up time point (adolescents, 51.4% [n=128/249]; adults, 52.3% [n=506/967]). TEAEs occurred in 113 adolescents (38.4%; most common, aggression [6.5%]) and 512 adults (44.3%; most common, dizziness [9.2%]). CONCLUSION: Perampanel demonstrated favorable retention rates and sustained efficacy (up to 2 years) in adolescent and adult patients during routine clinical care; no new safety signals were observed. GOV IDENTIFIER: NCT03208660 (https://clinicaltrials.gov/ct2/show/NCT03208660).


Assuntos
Anticonvulsivantes , Epilepsia , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Humanos , Nitrilas , Piridonas/efeitos adversos , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Resultado do Tratamento
13.
Seizure ; 98: 8-12, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35395505

RESUMO

Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the 'Prevent' pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance. An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021. The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old. Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual.


Assuntos
Epilepsias Parciais , Epilepsia , Anticonvulsivantes/efeitos adversos , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Gravidez , Reino Unido , Ácido Valproico/efeitos adversos
14.
J Healthc Eng ; 2022: 3789516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422974

RESUMO

Objectives: Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Methods: In this study, patients with status epilepticus in the Intensive Care Unit of the Department of Neurology of Qujing First People's Hospital were collected and treated with levetiracetam injection, continuous bedside EEG monitoring (cEEG) technology, and quantitative EEG (qEEG) technique. The inhibitory effects of different doses of levetiracetam injection and sodium valproate on abnormal discharge, the improvement of clinical symptoms, the incidence of adverse reactions, and prognosis were monitored, analyzed, and compared. Results: Compared with the experimental group of sodium valproate, 1000 mg/d levetiracetam group and 1500 mg/d levetiracetam group had a high probability of successful symptom control and a short control time. The patients had a low recurrence rate and a long recurrence time, and the probability of abnormal discharge in EEG was low. Conclusions: The recording results showed that levetiracetam could significantly inhibit the abnormal discharge of patients. Compared with sodium valproate, high-dose levetiracetam is a drug with a rapid effect, good effect, and long action time.


Assuntos
Epilepsia , Ácido Valproico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Levetiracetam/efeitos adversos , Levetiracetam/uso terapêutico , Fenitoína/efeitos adversos , Ácido Valproico/uso terapêutico
15.
Seizure ; 98: 51-56, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35421622

RESUMO

Topiramate (TPM) is widely used as monotherapy or add-on therapy in adults and children (aged 2 to 16 years) with primary generalized tonic-clonic seizures or focal-onset seizures. TPM has also expanded its treatment spectrum to other seizure types and epileptic encephalopathies. Moreover, TPM has beneficial effects in some comorbidities of epilepsy such as migraine/headache and obesity. Interestingly, it also exhibited neuroprotective effects in several preclinical studies. The most common side effects of TPM are generally mild to moderate, including somnolence, dizziness, fatigue, insomnia and weight loss, which may be reduced through starting with a low dose and slowing titration to effective dosages. The mechanisms underlying the antiepileptic effect and adverse reactions of TPM have been extensively studied in the past 14 years since the last comprehensive review of TPM. Multiple mechanisms including but not limited to: (1) blockade of voltage-gated Na+ channels, (2) inhibition of voltage-gated Ca2+ channels, (3) inhibition of glutamate-mediated neurotransmission, (4) inhibition of carbonic anhydrase isoenzyme, as well as (5) enhancement of GABA-mediated neurotransmission are involved in its antiepileptic effect. In this review, we aim to summarize the mechanisms, clinical benefits and adverse reactions of TPM in epilepsy treatment, and to briefly discuss the prospects of TPM.


Assuntos
Epilepsia Generalizada , Epilepsia , Adulto , Anticonvulsivantes/efeitos adversos , Criança , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Frutose/efeitos adversos , Humanos , Convulsões/tratamento farmacológico , Topiramato/efeitos adversos
16.
Isr Med Assoc J ; 24(4): 253-257, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35415985

RESUMO

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS). OBJECTIVES: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal. METHODS: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy. RESULTS: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient's sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women. CONCLUSIONS: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal.


Assuntos
Epilepsia Mioclônica Juvenil , Síndrome de Abstinência a Substâncias , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Epilepsia Mioclônica Juvenil/induzido quimicamente , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Ácido Valproico/efeitos adversos
17.
Continuum (Minneap Minn) ; 28(2): 399-427, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35393964

RESUMO

PURPOSE OF REVIEW: Issues pertaining to women with epilepsy have advanced with a better understanding of multidirectional influences among hormones, seizures, and antiseizure medications, as well as pregnancy-related concerns around fertility, seizure destabilization, and antiseizure medication-associated teratogenicity. This article highlights important developments in this field and reviews best practices in the management of women with epilepsy. RECENT FINDINGS: Important external hormonal influences may impact women with epilepsy particularly in the context of gender-affirming medications, hormonal replacement therapy, and fertility therapies. Fertility for women with epilepsy is influenced by multiple variables; however, in the absence of preexisting fertility issues, epilepsy per se is not associated with significantly impaired fertility. Once women with epilepsy are pregnant, the majority have a stable course. Antiseizure medication use in pregnancy is associated with major congenital malformations 2 to 5 times that of the general population and is highest with high-dose (≥1500 mg or greater total daily) valproate. Carefully considered changes in drug choice and dose may mitigate these risks. Therapeutic drug monitoring plays an important role in pregnancy care, and under expert supervision, women with epilepsy in pregnancy have similar seizure risks as women with epilepsy who are not pregnant. As women with epilepsy age, bone health and menopause may further be impacted by seizures and antiseizure medications. SUMMARY: The care of women with epilepsy is a multifaceted discipline that recognizes the life-long impact of sex and gender influences on epilepsy care.


Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/efeitos adversos , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Humanos , Menopausa , Gravidez , Complicações na Gravidez/tratamento farmacológico , Convulsões/tratamento farmacológico
18.
Neurosci Lett ; 776: 136574, 2022 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-35271996

RESUMO

Valproate (VPA) and levetiracetam (LEV), the two broad spectrum antiseizure drugs with antiabsence effects were previously tested for their antiepileptogenic effects when administered in the early postnatal period and revealed possible modification of the epileptogenic process though the effect being not persistent. The aim of this study was to investigate the effects of in utero exposure to these drugs on the absence epilepsy seizures of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats on electroencephalogram (EEG) which are characterised by bilateral, symmetrical, and synchronized spike-and-wave discharges (SWDs). Considering LEV was proposed as a safer drug of choice in pregnancy, its effects on the newborn histopathology of GAERS was also investigated. Adult female GAERS were randomly grouped as VPA-(400 mg/kg/day), LEV- (100 mg/kg/day), and saline-treated. The drugs were injected into the animals intraperitoneally starting before pregnancy until parturition. The lungs, kidneys, and brains of the LEV-exposed newborns were evaluated histologically to be compared with unexposed naïve Wistar and GAERS newborns. Rest of the VPA-, LEV-, and saline-exposed offsprings were taken for EEG recordings on postnatal day 90. VPA or LEV did not show significant effect on mean cumulative duration and mean number of SWDs on EEG. The lungs of the LEV-exposed offsprings showed thickened alveolar epithelium in most regions, suggesting incomplete development of the alveoli. The renal examination revealed dilated Bowman's spaces in some renal corpuscles, which may be interpreted as a deleterious effect of LEV on the kidney. In addition, brain examination of LEV- and saline-exposed groups revealed irregularities in cortical thickness compared to Wistar control group. Lack of significant difference on SWD parameters may indicate that the mechanism responsible for the antiepileptogenic effects of VPA and LEV may not be operating in the prenatal period. The detrimental effect of LEV exposure observed in our study on the lungs and the kidneys of the newborns should be investigated by further studies with advanced molecular and biochemical techniques.


Assuntos
Levetiracetam , Efeitos Tardios da Exposição Pré-Natal , Ácido Valproico , Animais , Anticonvulsivantes/efeitos adversos , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/genética , Feminino , Levetiracetam/efeitos adversos , Gravidez , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico , Ácido Valproico/efeitos adversos
19.
Cochrane Database Syst Rev ; 3: CD011501, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35285519

RESUMO

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30% of individuals with epilepsy continue to have epileptic seizures despite treatment with an antiepileptic drug. These patients are classified as drug-resistant and require treatment with a combination of multiple antiepileptic drugs. Brivaracetam is a third-generation antiepileptic drug that is a high-affinity ligand for synaptic vesicle protein 2A. In this review we investigated the use of brivaracetam as add-on therapy for epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of brivaracetam when used as add-on treatment for people with drug-resistant epilepsy. SEARCH METHODS: For the latest update we searched the following databases on 7 September 2021: the Cochrane Register of Studies (CRS Web); MEDLINE (Ovid) 1946 to 3 September 2021. CRS Web includes randomised controlled trials (RCTs) and quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: We searched for parallel-group RCTs that recruited people of any age with drug-resistant epilepsy. We accepted studies with any level of blinding (double-blind, single-blind, or unblinded). DATA COLLECTION AND ANALYSIS: In accordance with standard Cochrane methodological procedures, two review authors independently assessed trials for inclusion before evaluating trial quality and extracting relevant data. The primary outcome to be assessed was 50% or greater reduction in seizure frequency. Secondary outcomes were: seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse events, the proportion of participants who experienced any adverse events, and drug interactions. We used an intention-to-treat population for all primary analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: We did not identify any new studies for this update, therefore the results and conclusions of the review are unchanged. The previous review included six studies involving a total of 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. Study participants were aged 16 to 80 years. Treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. Details on the method used for allocation concealment and how blinding was maintained were insufficient in one study each. One study did not report all outcomes prespecified in the trial protocol, and there were discrepancies in reporting in a further study. Participants receiving brivaracetam add-on were more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-certainty evidence). Participants receiving brivaracetam were more likely to attain seizure freedom; however, the evidence is of low certainty (RR 5.89, 95% CI 2.30 to 15.13; 6 studies). The incidence of treatment withdrawal for any reason was slightly greater for participants receiving brivaracetam compared to those receiving placebo (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-certainty evidence). The risk of participants experiencing one or more adverse events did not differ significantly following treatment with brivaracetam compared to placebo (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-certainty evidence). However, participants receiving brivaracetam did appear to be more likely to withdraw from treatment due to adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-certainty evidence). AUTHORS' CONCLUSIONS: When used as add-on therapy for individuals with drug-resistant epilepsy, brivaracetam may be effective in reducing seizure frequency and may aid patients in achieving seizure freedom. However, add-on brivaracetam is probably associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the included studies involved participants under the age of 16, and all studies were of short duration. Consequently, the findings of this review are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, as well as assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and in other age groups.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia Generalizada , Adulto , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada , Epilepsia Generalizada/tratamento farmacológico , Humanos , Pirrolidinonas , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico
20.
Epilepsy Behav ; 129: 108627, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35240507

RESUMO

Planning pregnancy is very important for women with epilepsy (WWE), because of the potential teratogenic effects and neurodevelopmental disorders of different antiseizure medications (ASMs). Nevertheless, contraception in WWE can be challenging due to the existence of drug interactions between ASMs and hormonal contraception. The aim of this study was to assess women's knowledge of potential interactions between their ASMs and contraceptive options. The second objective was to assess neurologist's knowledge of the potential interactions between ASMs and contraceptive methods. An anonymous online survey was proposed to reproductive-age WWE during consultation with their neurologist. Another online survey was proposed to neurologists. These surveys were performed through a French regional medical network. A total of 79 patients agreed to respond to the survey. Forty-nine women used lamotrigine alone or in combination, 15 used an enzyme-inducing ASM alone or in combination, 13 used non-enzyme-inducing ASM and 2 used both lamotrigine and an enzyme-inducing ASM. Half of the WWE had mistaken beliefs about interactions between their ASM and contraception. Among them, 35% of the women treated with an enzyme-inducing ASM were unaware of a potential decreased efficacy of hormonal contraception. Moreover, 51% of the women who were taking lamotrigine did not know that combined hormonal contraception might decrease the efficacy of their ASM. On the other hand, 64.5% of WWE without an enzyme-inducing ASM wrongly thought that their ASM can decrease their hormonal contraceptive efficacy. A total of 20 neurologists answered the online survey. It revealed specific gaps concerning interactions between ASM and contraceptives; in fact, 35% of answers concerning the identification of specific enzyme-inducing ASMs were wrong. This study therefore highlights the need for educational efforts for both WWE and their physicians regarding drug interactions between ASMs and hormonal contraceptives.


Assuntos
Epilepsia , Médicos , Anticonvulsivantes/efeitos adversos , Anticoncepção/métodos , Anticoncepcionais/uso terapêutico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez
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