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1.
Crit Care Med ; 51(12): 1754-1765, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37638780

RESUMO

OBJECTIVES: Seizures and status epilepticus (SE) are frequent complications of acute subdural hematoma (aSDH) associated with increased morbidity and mortality. Therefore, we aimed to evaluate whether invasive subdural electroencephalogram recording leads to earlier seizure detection and treatment initiation in patients with aSDH. DESIGN: Prospective, single-center, cohort trial. SETTING: Neurologic and neurosurgical ICUs of one academic hospital in Germany. PATIENTS: Patients with aSDH undergoing surgical treatment. In total, 76 patients were enrolled in this study, 31 patients (40.8%) were assigned to the invasive electroencephalogram (iEEG) monitoring group and 45 patients (59.2%) to control group. INTERVENTIONS: The electrode group was implanted with a subdural strip electrode providing up to 7 days of real-time electroencephalogram recording in the neurointensive care unit, whereas the control group received regular normal surface electroencephalograms during the 7-day period. The primary outcomes were the prevalence and time to seizures and SE occurrence. Secondary outcomes included neurologic outcomes assessed using the Glasgow Outcome Scale (GOS) at discharge and 6-month follow-up and the prevalence of focal structural epilepsy within 2 years after discharge. MEASUREMENTS AND MAIN RESULTS: The trial was stopped after a study committee meeting when the prespecified criteria were met. The iEEG and control groups were well-matched for clinical characteristics at admission. Frequencies of seizures and SE detection were significantly higher in the iEEG group than in the control group (61% vs 15.6%; p < 0.001 and 38.7% vs 11.1%; p = 0.005). Time to seizure and SE detection was significantly earlier (median 29.2 vs 83.8 hr; p = 0.018 and 17.2 vs 83.8 hr; p = 0.033) in the iEEG group than in the control group. Favorable outcomes (GOS 4-5) were more frequently achieved in the iEEG group than in the control group (58% vs 31%; p = 0.065). No significant differences were detected in long-term mortality or post-traumatic epilepsy. CONCLUSIONS: Invasive subdural electroencephalogram monitoring is valuable and safe for early seizure/SE detection and treatment and might improve outcomes in the neurocritical care of patients with aSDH.


Assuntos
Hematoma Subdural Agudo , Estado Epiléptico , Humanos , Estudos Prospectivos , Resultado do Tratamento , Hematoma Subdural/diagnóstico , Convulsões/diagnóstico , Convulsões/epidemiologia , Eletroencefalografia , Hematoma Subdural Agudo/epidemiologia , Hematoma Subdural Agudo/cirurgia , Estado Epiléptico/diagnóstico , Eletrodos , Estudos Retrospectivos
2.
Epilepsy Behav ; 116: 107715, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33493802

RESUMO

PURPOSE: To describe the patients' characteristics, surgical ratio, and outcomes following epilepsy surgery at the newly established Epilepsy Center Frankfurt Rhine-Main. METHODS: We retrospectively studied the first 100 consecutive patients, including adult (n = 77) and pediatric (n = 23) patients, with drug-resistant epilepsy who underwent resective or ablative surgical procedures at a single, newly established epilepsy center. Patient characteristics, seizure and neuropsychological outcomes, histopathology, complications, and surgical ratio were analyzed. RESULTS: The mean patient age was 28.8 years (children 10.6 years, adults 34.2 years). The mean epilepsy duration was 11.9 years (children 3.9 years, adults 14.3 years), and the mean follow-up was 1.5 years. At the most recent visit, 64% of patients remained completely seizure free [Engel IA]. The rates of perioperative complications and unexpected new neurological deficits were 5%, each. The proportion of patients showing deficits in one or more cognitive domains increased six months after surgery and decreased to presurgical proportions after two years. Symptoms of depression were significantly decreased and quality of life was significantly increased after surgery. The surgical ratio was 25.3%. CONCLUSION: Similar postsurgical outcomes were achieved at a newly established epilepsy center compared with long-standing epilepsy centers. The lower time to surgery may reflect a general decrease in time to surgery over the last decade or the improved accessibility of a new epilepsy center in a previously underserved area. The surgical ratio was not lower than reported for established centers.


Assuntos
Epilepsia , Qualidade de Vida , Adulto , Criança , Eletroencefalografia , Epilepsia/cirurgia , Seguimentos , Humanos , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Resultado do Tratamento
3.
NMR Biomed ; 33(2): e4203, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31797463

RESUMO

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug-resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients. On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM-WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map. The resulting CE- and/or SM-enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces. In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM-WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.


Assuntos
Meios de Contraste/química , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/diagnóstico , Adulto , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Adulto Jovem
4.
Epilepsy Behav ; 91: 94-98, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29941212

RESUMO

Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Mutations in the TSC1 or TSC2 genes lead to the dysregulation of the mechanistic target of rapamycin (mTOR) pathway. This mTOR pathway hyperactivation is associated with several processes resulting in epileptic conditions. The occurrence of seizures and their treatment outcomes seem to play a crucial role in cognitive and behavioral developments in patients with TSC. Mechanistic target of rapamycin inhibitors have been proven to be effective in epilepsy treatment in individuals with TSC. Specifically, because of their disease-modifying mechanism of action, they have the capability to prevent epileptogenesis in patients with TSC. This article will provide an overview of the current evidence of and delineate future perspectives for mTOR inhibitors and their role in preventing epileptogenesis.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Epilepsia/etiologia , Epilepsia/metabolismo , Previsões , Humanos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento , Esclerose Tuberosa/complicações , Esclerose Tuberosa/metabolismo
5.
Epilepsy Behav ; 91: 86-89, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29752000

RESUMO

Epilepsies are a common and chronic neurological disorder characterized by sustained risk of recurrent seizures. Because of paroxysmal and often unpredictable occurrence of seizures, patients with uncontrolled epilepsy are subject to disease-specific restrictions in daily life, such as their career choice or specific work limitations. According to German law and many other European and international guidelines, driving is strictly prohibited in patients with uncontrolled epilepsy so as to increase active and passive safety in public road traffic. Nevertheless, a significant percentage of patients probably do not comply with these legal restrictions and drive on a regular basis. For this study, we analyzed a representative German cohort with 302 patients (mean age: 45.0 years ±â€¯16.4; 48% male) with established epilepsy to identify the number of patients driving without permission. Overall, 58.6% (n = 177) of patients had a driving license, 71.1% (n = 69/97) of patients were in seizure remission, and 52.7% (n = 108/205) of patients had uncontrolled epilepsy. Among patients in seizure remission, 54.6% (n = 53/97) reported regular driving while, among patients with uncontrolled epilepsy, 15.1% (n = 31/205) reported driving on a regular basis. No patient in the cohort stated driving without a valid license. Permanent employment, freelance work, the absence of a relevant disability, and living alone were identified as significant risk factors, which underlines the already existing evidence for the importance of a possible restricted access to the labor market as motive for disregarding legal driving restrictions. In our opinion, specialized and generally available social counseling with a special focus on vocational and career guidance is urgently needed to improve compliance with epilepsy-caused driving restrictions and the underlying reasons for violating these rules. In addition, more effort has to be spent on improving diagnostics and treatment of epilepsy to reduce the number of patients with uncontrolled seizures. Comprehensive introduction of self-driving vehicles may also help to improve mobility of patients with refractory epilepsy.


Assuntos
Condução de Veículo/psicologia , Epilepsia Resistente a Medicamentos/psicologia , Emprego/psicologia , Cooperação do Paciente/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude , Estudos de Coortes , Aconselhamento/métodos , Epilepsia Resistente a Medicamentos/epidemiologia , Epilepsia Resistente a Medicamentos/terapia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Convulsões/epidemiologia , Convulsões/psicologia , Convulsões/terapia , Adulto Jovem
6.
Epilepsy Behav ; 91: 30-37, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29907526

RESUMO

INTRODUCTION: Stereoelectroencephalography (sEEG) is a diagnostic procedure for patients with refractory focal epilepsies that is performed to localize and define the epileptogenic zone. In contrast to grid electrodes, sEEG electrodes are implanted using minimal invasive operation techniques without large craniotomies. Previous studies provided good evidence that sEEG implantation is a safe and effective procedure; however, complications in asymptomatic patients after explantation may be underreported. The aim of this analysis was to systematically analyze clinical and imaging data following implantation and explantation. RESULTS: We analyzed 18 consecutive patients (mean age: 30.5 years, range: 12-46; 61% female) undergoing invasive presurgical video-EEG monitoring via sEEG electrodes (n = 167 implanted electrodes) over a period of 2.5 years with robot-assisted implantation. There were no neurological deficits reported after implantation or explantation in any of the enrolled patients. Postimplantation imaging showed a minimal subclinical subarachnoid hemorrhage in one patient and further workup revealed a previously unknown factor VII deficiency. No injuries or status epilepticus occurred during video-EEG monitoring. In one patient, a seizure-related asymptomatic cross break of two fixation screws was found and led to revision surgery. Unspecific symptoms like headaches or low-grade fever were present in 10 of 18 (56%) patients during the first days of video-EEG monitoring and were transient. Postexplantation imaging showed asymptomatic and small bleedings close to four electrodes (2.8%). CONCLUSION: Overall, sEEG is a safe and well-tolerated procedure. Systematic imaging after implantation and explantation helps to identify clinically silent complications of sEEG. In the literature, complication rates of up to 4.4% in sEEG and in 49.9% of subdural EEG are reported; however, systematic imaging after explantation was not performed throughout the studies, which may have led to underreporting of associated complications.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletrodos Implantados/normas , Eletroencefalografia/normas , Complicações Pós-Operatórias , Cuidados Pré-Operatórios/normas , Cirurgia Vídeoassistida/normas , Adolescente , Adulto , Criança , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Eletrodos Implantados/efeitos adversos , Eletroencefalografia/efeitos adversos , Eletroencefalografia/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/efeitos adversos , Cuidados Pré-Operatórios/instrumentação , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/cirurgia , Técnicas Estereotáxicas/efeitos adversos , Técnicas Estereotáxicas/normas , Espaço Subdural/diagnóstico por imagem , Espaço Subdural/cirurgia , Cirurgia Vídeoassistida/efeitos adversos , Adulto Jovem
7.
Epilepsy Behav ; 98(Pt A): 88-95, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31301455

RESUMO

OBJECTIVE: The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of real-world evidence on medicine utilization of patients with DS in Europe. METHODS: Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe. RESULTS: The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed. SIGNIFICANCE: This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common AED combinations being in line with clinical guidelines/best practice, there is no discernable impact of best treatment on seizure frequency. We find a higher use of bromide in Germany compared with other real-world evidence in Europe.


Assuntos
Anticonvulsivantes/administração & dosagem , Prescrições de Medicamentos , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/epidemiologia , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Clobazam/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Topiramato/administração & dosagem , Ácido Valproico/administração & dosagem
8.
Epilepsia ; 59(8): 1549-1556, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29943451

RESUMO

OBJECTIVE: The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice. METHODS: A multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017. RESULTS: A total of 61 patients (mean age = 29.8, range = 9-90 years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure-free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long-term 50% responder rate was present in 17 patients (28%; 11 seizure-free [18%]) for >6 months and in 14 patients (23%; 10 seizure-free [16%]) for >12 months. Treatment-emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200-300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus. SIGNIFICANCE: Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV-induced adverse events.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia Generalizada/tratamento farmacológico , Pirrolidinonas/administração & dosagem , Resultado do Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Adulto Jovem
9.
Epilepsia ; 58(7): 1208-1216, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28480518

RESUMO

OBJECTIVE: To evaluate factors predicting efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. METHODS: A multicenter, retrospective cohort study recruiting all patients who started BRV between February and November 2016 with observation time between 3 and 12 months. RESULTS: Of a total of 262 patients (mean age 40, range 5-81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were unclassified. The length of exposure to BRV ranged from 1 day to 12 months, with a median retention time of 6.1 months, resulting in a total exposure time to BRV of 1,504 months. The retention rate was 79.4% at 3 months and 75.8% at 6 months. Efficacy at 3 months was 41.2% (50% responder rate) with 14.9% seizure-free for 3 months and, at 6 months, 40.5% with 15.3% seizure-free. Treatment-emergent adverse events were observed in 37.8% of the patients, with the most common being somnolence, dizziness, and behavioral adverse events (BAEs). BAE that presented under previous levetiracetam (LEV) treatment improved upon switch to BRV in 57.1% (20/35) and LEV-induced somnolence improved in 70.8% (17/24). Patients with BAE on LEV were more likely to develop BAE on BRV (odds ratio [OR] 3.48, 95% confidence interval [CI] 1.53-7.95). SIGNIFICANCE: BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Vigilância de Produtos Comercializados , Pirrolidinonas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Substituição de Medicamentos , Quimioterapia Combinada , Eletroencefalografia/efeitos dos fármacos , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Estudos de Viabilidade , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinonas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Epilepsy Behav ; 70(Pt A): 177-181, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28427029

RESUMO

PURPOSE: We aimed to ascertain the possible use of brivaracetam (BRV) as an option for treatment of status epilepticus (SE). METHODS: A review of medical records was carried out to detect BRV administration in SE patients treated in Frankfurt and Greifswald during the period February 2016 to January 2017. The primary outcome question concerned SE resolution after BRV initiation. RESULTS: During that period, BRV was started with eleven adult patients with SE. Five of these were female, and the median age was 64 (interquartile range [IQR] 21years). The median SE duration before BRV initiation was 5days (IQR 9days); the median number of previous anticonvulsants used was 4 (IQR 5). Initial BRV doses ranged between 50mg and 400mg (median 100mg), titrated to a daily dose of 100 to 400mg (median 200mg). There was a cessation of SE in the first 24h of BRV in three patients (27%). While taking BRV, no serious side effects were seen. CONCLUSION: Based on these cases and previous data from animal experiments, BRV may prove useful in SE treatment, and trials would be warranted to examine BRV's efficacy in treating SE and how this efficacy might be influenced by co-administration with levetiracetam.


Assuntos
Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/epidemiologia , Hospitais Universitários , Pirrolidinonas/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Hospitais Universitários/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Epilepsy Behav ; 76: 7-12, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28917498

RESUMO

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1].


Assuntos
Biomarcadores , Encéfalo/patologia , Epilepsia/terapia , Medicina de Precisão , Pesquisa Translacional Biomédica , Anticonvulsivantes/uso terapêutico , Barreira Hematoencefálica , Lesões Encefálicas/patologia , Epigenômica , Epilepsia/diagnóstico , Epilepsia/genética , Variação Genética , Humanos , Pesquisa Translacional Biomédica/tendências
12.
Epilepsy Behav ; 76: 13-18, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28917501

RESUMO

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1].


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Medicina de Precisão , Barreira Hematoencefálica , Encéfalo/patologia , Lesões Encefálicas/patologia , Epigenômica , Marcadores Genéticos/genética , Variação Genética , Humanos , Medicina de Precisão/tendências , Pesquisa Translacional Biomédica , Resultado do Tratamento
13.
Epilepsia ; 56(9): 1408-14, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26216711

RESUMO

OBJECTIVE: To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring. METHODS: Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ. RESULTS: In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p = 0.009). SIGNIFICANCE: Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic-clonic seizures for 24 h following in-MDZ.


Assuntos
Moduladores GABAérgicos/administração & dosagem , Midazolam/administração & dosagem , Convulsões/tratamento farmacológico , Administração Intranasal , Adolescente , Adulto , Idoso , Criança , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Recidiva , Convulsões/cirurgia , Gravação em Vídeo , Adulto Jovem
15.
Epilepsia ; 55(2): 362-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24417206

RESUMO

OBJECTIVE: SCN1A encodes the alpha subunit of the voltage-gated sodium channel and plays a crucial role in several epilepsy syndromes. The common SCN1A splice-site polymorphism rs3812718 (IVS5N+5 G>A) might contribute to the pathophysiology underlying genetic generalized epilepsies and is associated with electrophysiologic properties of the channel and the effect of sodium-channel blocking antiepileptic drugs. We assessed the effects of the rs3812718 genotype on cortical excitability at baseline and after administration of carbamazepine in order to investigate the mechanism of this association. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied in 92 healthy volunteers with the homozygous genotypes AA or GG of rs3812718 at baseline and after application of 400 mg of carbamazepine or placebo in a double-blind, randomized, crossover design. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP) were determined. RESULTS: At baseline there was no significant difference in any TMS parameter. Genotype GG was associated with a higher carbamazepine-induced increase in CSP duration as compared to AA (multivariate analysis of covariance [MANCOVA], p = 0.013). An expected significant increase in RMT was genotype independent. SIGNIFICANCE: We found that the rs3812718 genotype modifies the effect of carbamazepine on CSP duration (mainly reflecting modulation of γ-aminobutyric acid (GABA)ergic inhibition), but not on RMT (mainly reflecting modulation of voltage-gated sodium channels). This provides evidence that rs3812718 affects the pharmacoresponse to carbamazepine via an effect on GABAergic cortical interneurons. Our results also confirm that TMS is useful to investigate the effect of genetic variants on cortical excitability and pharmacoresponse.


Assuntos
Anticonvulsivantes/farmacologia , Carbamazepina/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Farmacogenética/métodos , Sítios de Splice de RNA/genética , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Resultado do Tratamento , Adulto Jovem
16.
Int J Neurosci ; 123(4): 278-82, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23215817

RESUMO

We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the central nervous system, the patient presented with a left mesiotemporal electroencephalogram focus and left hippocampal sclerosis. This is the first case, which reports an association between mesial temporal lobe epilepsy and spinocerebellar ataxia type 13. This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies.


Assuntos
Epilepsia do Lobo Temporal/complicações , Canais de Potássio Shaw/genética , Degenerações Espinocerebelares/complicações , Eletroencefalografia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Ataxias Espinocerebelares/congênito , Degenerações Espinocerebelares/genética , Degenerações Espinocerebelares/cirurgia
17.
Epilepsia Open ; 8(2): 497-508, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36896643

RESUMO

OBJECTIVE: The phenotypic and genotypic spectrum of adult patients with epilepsy and intellectual disability (ID) is less clear than in children. We investigated an adult patient cohort to further elucidate this and inform the genetic testing approach. METHODS: Fifty-two adult patients (30 male, 22 female) with epilepsy, at least mild ID and no known genetic or acquired cause were included and phenotyped. Variants identified through exome sequencing were evaluated using ACMG criteria. Identified variants were compared with commercially available gene panels. Cluster analysis of two features, age at seizure onset and age at ascertainment of cognitive deficits, was performed. RESULTS: Median age was 27 years (range 20-57 years) with median seizure onset at 3 years and median ascertainment of cognitive deficits at 1 year. Likely pathogenic/pathogenic variants were identified in 16/52 patients (31%) including 14 (27%) single nucleotide variants and 2 (4%) copy number variants. Simulated yield of commercial gene panels varied between 13% in small (≤144 genes) and 27% in large panels (≥1478 genes). Cluster analysis (optimal number 3 clusters) identified a cluster with early seizure onset and early developmental delay (developmental and epileptic encephalopathy, n = 26), a cluster with early developmental delay but late seizure onset (ID with epilepsy, n = 16) and a third cluster with late ascertainment of cognitive deficits and variable seizure onset (n = 7). The smaller gene panels particularly missed the genes identified in the cluster with early ascertainment of cognitive deficits and later onset of epilepsy (0/4) as opposed to the cluster with developmental and epileptic encephalopathy (7/10). SIGNIFICANCE: Our data indicates that adult patients with epilepsy and ID represent a heterogeneous cohort that includes grown-up patients with DEE but also patients with primary ID and later onset of epilepsy. To maximize diagnostic yield in this cohort either large gene panels or exome sequencing should be used.


Assuntos
Epilepsia Generalizada , Epilepsia , Deficiência Intelectual , Criança , Humanos , Adulto , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Deficiência Intelectual/genética , Epilepsia/diagnóstico , Epilepsia/genética , Testes Genéticos , Convulsões/genética
18.
J Neurol Neurosurg Psychiatry ; 83(11): 1093-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22595362

RESUMO

BACKGROUND: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. METHODS: A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. RESULTS: The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs. LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). CONCLUSIONS: There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00242606.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Piracetam/análogos & derivados , Triazinas/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Criança , Diagnóstico Precoce , Feminino , Humanos , Lamotrigina , Levetiracetam , Masculino , Pessoa de Meia-Idade , Piracetam/efeitos adversos , Piracetam/uso terapêutico , Qualidade de Vida , Triazinas/efeitos adversos
19.
Epilepsy Behav ; 23(4): 451-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22381385

RESUMO

This study evaluated the resource use of patients with epilepsy in the German district of Marburg-Biedenkopf. A cross-sectional cohort of consecutive adults with epilepsy, irrespective of seizure severity, duration of illness and epilepsy syndrome, was investigated in all health-care sectors. Costs of inpatient and outpatient treatment were derived from billing data of participating hospitals and office-based physicians. Data on socioeconomic status, course of epilepsy and further direct and indirect costs were recorded using patient questionnaires. We enrolled 366 patients from the district of Marburg-Biedenkopf and calculated annual epilepsy-specific costs of €7738 per patient. Direct costs contributed 31.1% (€2406) and indirect costs 68.9% (€5332) of the total costs. Direct medical costs were mainly due to hospitalization (33.2% of total direct costs) and anticonvulsants (26.7%). Costs of admissions were due to status epilepticus (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and seizure-related injuries (8.8%). Indirect costs were mainly due to early retirement (38.0%), unemployment (35.9%) and days off due to seizures (26.2%). The mean costs of epilepsy found in our study were lower than those found in studies conducted at European epilepsy centers due to the inclusion of patients in all health-care sectors.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Epilepsia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/economia , Antieméticos/uso terapêutico , Estudos de Coortes , Custos e Análise de Custo , Estudos Transversais , Eletroencefalografia , Epilepsia/economia , Epilepsia/epidemiologia , Epilepsia/terapia , Feminino , Alemanha/epidemiologia , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Gravação em Vídeo , Adulto Jovem
20.
Neurology ; 99(3): e221-e233, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35851549

RESUMO

BACKGROUND AND OBJECTIVES: Pathogenic STXBP1 variants cause a severe early-onset developmental and epileptic encephalopathy (STXBP1-DEE). We aimed to investigate the natural history of STXBP1-DEE in adults focusing on seizure evolution, the presence of movement disorders, and the level of functional (in)dependence. METHODS: In this observational study, patients with a minimum age of 18 years carrying a (likely) pathogenic STXBP1 variant were recruited through medical genetics departments and epilepsy centers. Treating clinicians completed clinical questionnaires and performed semistructured video examinations while performing tasks from the (modified) Unified Parkinson Disease Rating Scale when possible. RESULTS: Thirty adult patients were included for summary statistics, with video recordings available for 19 patients. The median age at last follow-up was 24 years (range 18-58 years). All patients had epilepsy, with a median onset age of 3.5 months. At last follow-up, 80% of adults had treatment-resistant seizures despite long periods of seizure freedom in 37%. Tonic-clonic, focal, and tonic seizures were most frequent in adults. Epileptic spasms, an unusual feature beyond infancy, were present in 3 adults. All individuals had developmental impairment. Periods of regression were present in 59% and did not always correlate with flare-ups in seizure activity. Eighty-seven percent had severe or profound intellectual disability, 42% had autistic features, and 65% had significant behavioral problems. Video examinations showed gait disorders in all 12 patients able to walk, including postural abnormalities with external rotation of the feet, broad-based gait, and asymmetric posture/dystonia. Tremor, present in 56%, was predominantly of the intention/action type. Stereotypies were seen in 63%. Functional outcome concerning mobility was variable ranging from independent walking (50%) to wheelchair dependence (39%). Seventy-one percent of adults were nonverbal, and all were dependent on caregivers for most activities of daily living. DISCUSSION: STXBP1-DEE warrants continuous monitoring for seizures in adult life. Periods of regression are more frequent than previously established and can occur into adulthood. Movement disorders are often present and involve multiple systems. Although functional mobility is variable in adulthood, STXBP1-DEE frequently leads to severe cognitive impairments and a high level of functional dependence. Understanding the natural history of STXBP1-DEE is important for prognostication and will inform future therapeutic trials.


Assuntos
Epilepsia , Transtornos dos Movimentos , Proteínas Munc18 , Atividades Cotidianas , Adolescente , Adulto , Eletroencefalografia , Humanos , Lactente , Pessoa de Meia-Idade , Transtornos dos Movimentos/genética , Proteínas Munc18/genética , Mutação , Convulsões/genética , Adulto Jovem
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