RESUMO
OBJECTIVES: The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy. METHODS: Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)). RESULTS: Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy. CONCLUSION: STP seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of STP in adult patients with pharmacoresistant focal epilepsy.
Assuntos
Anticonvulsivantes , Epilepsias Parciais , Adulto , Anticonvulsivantes/uso terapêutico , Dioxolanos , Epilepsias Parciais/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECT: Epilepsy is a major comorbidity in children with hydrocephalus (HC) and has a serious impact on their developmental outcomes. There are variable influencing factors, thus the individual risk for developing epilepsy remains unclear. Our aim was to analyse risk factors for developing epilepsy in children with shunted HC. METHODS: A retrospective, single-centre analysis of 361 patients with the diagnosis of HC was performed. Age at HC diagnosis, shunt treatment, development of epilepsy, epilepsy course, and the aetiology of HC were considered. The influence of shunt therapy, including its revisions and complications, on the development of epilepsy was investigated. RESULTS: One-hundred forty-three patients with HC (n = 361) had a diagnosis of epilepsy (39.6%). The median age at the first manifestation of epilepsy was 300 days (range:1-6791; Q1:30, Q3: 1493). The probability of developing epilepsy after HC decreases with increasing age. The most significant influence on the development of epilepsy is that of the HC itself and its underlying aetiology (HR 5.9; 95%-CI [3-10.5]; p < 0.001). Among those, brain haemorrhage is associated with the highest risk for epilepsy (HR 7.9; 95%-CI [4.2-14.7]; p < 0.01), while shunt insertion has a lower influence (HR 1.5; 95%-CI [0.99; 2.38]; p = 0.06). The probability of epilepsy increases stepwise per shunt revision (HR 2.0; p = 0.03 after 3 or more revisions). Five hundred days after the development of HC, 20% of the children had a diagnosis of epilepsy. Shunt implantation at a younger age has no significant influence on the development of epilepsy nor does sex. CONCLUSION: Children with HC are at high risk for developing epilepsy. The development of epilepsy is correlated mainly with HC's underlying aetiology. The highest risk factor for the development of epilepsy seems to be brain haemorrhage. The age at shunt implantation appears to be unrelated to the development of epilepsy, while structural brain damage at a young age, shunt revisions and complications are independent risk factors. The onset of epilepsy is most likely to take place within the first 500 days after the diagnosis of HC.
Assuntos
Derivações do Líquido Cefalorraquidiano/efeitos adversos , Epilepsia/etiologia , Hidrocefalia/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Nearly 10 years after its introduction into the market, the significance of lacosamide in genetic generalized epilepsies is still unclear. Its new mode of action may qualify lacosamide as a therapeutic agent in this entity, but only a limited number of cases have been published so far. AIM: To describe the efficacy of lacosamide as treatment in a patient with the absence status epilepticus. METHOD: We report on a 28-year-old woman with genetic generalized epilepsy who suffered recurrent absence status epilepticus during video-EEG-monitoring. After treatment failure of first- and second-line medication, lacosamide was administered. The outcome in this patient was evaluated, and a systematic literature review was performed for the use of lacosamide in the absence status epilepticus. RESULTS: After application of 400 mg lacosamide intravenously, the absence status epilepticus terminated within 30 minutes. No further seizures or epileptiform discharges reoccurred until the end of video-EEG-Monitoring 3 days later. CONCLUSIONS: The role of lacosamide as a therapeutic option in patients with the absence status epilepticus is unclear. Only two cases have been reported so far with conflicting results. Further randomized controlled studies are required to validate the relevance of lacosamide as treatment for status epilepticus in genetic generalized and the absence epilepsy.
Assuntos
Acetamidas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Adulto , Feminino , Humanos , Lacosamida , Convulsões/tratamento farmacológicoRESUMO
Brivaracetam is the latest antiepileptic drug to be approved for adjunctive therapy in focal epilepsy and has a high affinity as a SV2A ligand. The aim of this review article is to summarize the data from the pivotal studies in which more than 2000 patients received brivaracetam. A significant median reduction in seizures from 30.5 % to 53.1 % for 50 mg/day, from 32.5 % to 37.2 % for 100 mg/day and 35.6 % for 200 mg/day could be demonstrated. Overall brivaracetam appears to be well-tolerated, with fatigue, dizziness and somnolence being the main adverse side effects. An immediate change from levetiracetam to brivaracetam at a conversion ratio of 10:1 to 15:1 seems feasible and could alleviate behavioral side effects related to treatment with levetiracetam. A swift permeability into brain tissue and a faster onset of action compared to levetiracetam suggest that brivaracetam could be useful in emergency situations.
Assuntos
Distúrbios do Sono por Sonolência Excessiva/induzido quimicamente , Tontura/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Fadiga/induzido quimicamente , Pirrolidinonas/administração & dosagem , Pirrolidinonas/efeitos adversos , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Quimioterapia Adjuvante , Distúrbios do Sono por Sonolência Excessiva/prevenção & controle , Tontura/prevenção & controle , Relação Dose-Resposta a Droga , Epilepsias Parciais/diagnóstico , Medicina Baseada em Evidências , Fadiga/prevenção & controle , Humanos , Resultado do TratamentoRESUMO
Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.
Assuntos
Anticonvulsivantes/uso terapêutico , Indústria Farmacêutica/legislação & jurisprudência , Epilepsia/prevenção & controle , Marketing de Serviços de Saúde/legislação & jurisprudência , Avaliação de Resultados em Cuidados de Saúde/legislação & jurisprudência , Garantia da Qualidade dos Cuidados de Saúde/legislação & jurisprudência , Anticonvulsivantes/normas , Aprovação de Drogas/economia , Aprovação de Drogas/legislação & jurisprudência , Alemanha , Regulamentação Governamental , Reforma dos Serviços de Saúde/economia , Reforma dos Serviços de Saúde/legislação & jurisprudência , Humanos , Legislação de Medicamentos , Marketing de Serviços de Saúde/economia , Avaliação de Resultados em Cuidados de Saúde/economia , Garantia da Qualidade dos Cuidados de Saúde/economiaRESUMO
PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure-freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve.
Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Fenilenodiaminas/uso terapêutico , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Carbamatos/efeitos adversos , Criança , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia/efeitos dos fármacos , Feminino , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fenilenodiaminas/efeitos adversos , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Centros de Atenção Terciária , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To determine whether stiripentol (STP) might be a treatment option in super-refractory status epilepticus (SRSE). METHODS: Medical records of patients treated due to a status epilepticus in Marburg between January 2013 and June 2014 were reviewed for administration of STP. Primary outcome measures were resolution of SE after initiation of STP. RESULTS: Five adult patients were started with STP due to SRSE. The median age was 78 years (interquartile range [IQR] 11 years), and four patients were female. The median duration of SRSE before initiation of STP was 39 days (IQR 16 days), and the median number of anticonvulsants used before was 6 (IQR 1). SRSE ceased in three patients within 2-4 days after the start of STP. In two patients, SRSE continued after administration of STP and further escalation of anticonvulsant regimen. Both were switched eventually to supportive care only. None serious side effects were observed while on STP. CONCLUSIONS: Based on our presented cases and previous experimental animal data, STP may prove useful in treating super-refractory SE. Prospective trials are warranted to examine the efficacy of the STP in adults with refractory SE and to examine whether earlier treatment leads to better control of SE.
Assuntos
Anticonvulsivantes/uso terapêutico , Dioxolanos/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Cuidados Críticos , Dioxolanos/administração & dosagem , Relação Dose-Resposta a Droga , Eletroencefalografia , Feminino , Humanos , Masculino , Estado Epiléptico/complicações , Resultado do TratamentoRESUMO
Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged ≥ 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.
Assuntos
Anticonvulsivantes/uso terapêutico , Estimulação Encefálica Profunda/tendências , Eletroencefalografia/tendências , Epilepsia/diagnóstico , Epilepsia/terapia , Imageamento por Ressonância Magnética/tendências , Procedimentos Neurocirúrgicos/tendências , HumanosRESUMO
Minocycline, a tetracycline family antibiotic, is known to inhibit microglial activation and proinflammatory cytokine release in animal models. Experimental data show that these immune processes may play a role in epilepto- and ictogenesis. We present the case of a patient with marked reduction in seizure frequency during minocycline therapy with severe symptomatic epilepsy due to an astrocytoma.
Assuntos
Anticonvulsivantes/uso terapêutico , Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Epilepsia/tratamento farmacológico , Minociclina/uso terapêutico , Astrocitoma/radioterapia , Astrocitoma/cirurgia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Epilepsia/etiologia , Humanos , Masculino , Melanoma/complicações , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/complicaçõesRESUMO
"Classic" and "newer" antiepileptic drugs (AEDs) were compared in an epidemiological survey regarding patient's acceptance of AEDs, quality of life (QoL), and employment. Data from 907 outpatients, 45.9% female (mean age: 44.8 ± 17.9 years), were evaluated by 90 neurologists in private practices, who were also involved in a non-interventional study by Sanofi-Aventis Deutschland GmbH, regarding medication, seizure type, illness duration, employment, patients' acceptance of AEDs (4-point scale where 1=very good), and QoL (6-point scale where 1=very good). Among the patients, 69.7% were on monotherapy, 25.4% were taking two AEDs, and 4.9% were taking more than two AEDs. Patient's acceptance of AEDs (mean ± SD=1.65 ± 0.62) and QoL (2.34 ± 0.89) were "good." Among patients aged 18-65 years, 68.6% were employed. QoL and acceptance were lower with polytherapy. Older age and polytherapy were associated with lower probability of employment. No differences emerged between "classic" and "newer" AED monotherapy. Polytherapy-associated lower QoL could be due to severity of illness or adverse effects of treatment.
Assuntos
Emprego , Epilepsia/psicologia , Cooperação do Paciente/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Emprego/estatística & dados numéricos , Epilepsia/tratamento farmacológico , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Primary brain tumors and metastases are common causes of symptomatic epilepsy. Seizures, neurological and neuropsychological deficits can interfere with driving ability. The present paper aims to systematically review the incidence of epileptic seizures in brain tumor patients and to discuss driving ability in the context of the current German guidelines and expert opinions. METHODS: To evaluate the incidence of epileptic seizures which occur at the beginning and in the course of the disease, we performed a systematic literature research in PubMed from 1960 to 2007. Additionally on the basis of this data we performed a survey collecting expert opinions regarding the driving ability of brain tumor patients from members of the German working groups "Arbeitsgemeinschaft für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie" (Working Group for Presurgical Epilepsy Diagnostics and Operative Epileptic Therapy) and "Neuroonkologische Arbeitsgemeinschaft" (Neuro-oncological Working Group). RESULTS: The incidence of epileptic seizures depends on the entity, dignity and localization of the tumor. The driving ability of brain tumor patients is not explicitly regulated in Germany. Of the interviewed experts 72% judged the guidelines to be precise enough and 44% did not want to deprive the patients of their driving ability without a first seizure, independent of the individual risk. DISCUSSION: The available studies are methodologically insufficient and show that a further evaluation is necessary to assess the driving ability. Possible restrictions of the driving ability in patients with a high risk of seizures in the course of the disease have to take into account the balance between individual rights and the interests of the general public.
Assuntos
Condução de Veículo/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Epilepsia/epidemiologia , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
At the moment atypical Parkinson syndromes have unfavorable prognoses and show little response to dopaminergic medication. Early differential diagnosis of these disorders from idiopathic Parkinson syndrome is of pivotal clinical relevance. In case of future causal, neuroprotective therapeutic strategies, early diagnosis will allow a timely start of therapy. In the early stage of disease, it might be difficult clinically to distinguish multiple system atrophy, progressive supranuclear palsy, and corticobasal ganglionic degeneration from idiopathic Parkinson syndrome. Additional electrophysiological, imaging, and nuclear medical investigations may support the clinical diagnosis. During disease progression clinical signs indicative of an atypical Parkinson syndrome should always warrant reevaluation of the diagnosis.