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[PMID]:29320603
[Au] Autor:McTague A; Martland T; Appleton R
[Ad] Endereço:Molecular Neurosciences, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
[Ti] Título:Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.
[So] Source:Cochrane Database Syst Rev;1:CD001905, 2018 01 10.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs. This is an update of a Cochrane Review first published in 2002 and updated in 2008. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsant drugs used to treat any acute tonic-clonic convulsion of any duration, including established convulsive (tonic-clonic) status epilepticus in children who present to a hospital or emergency medical department. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Group's Specialised Register (23 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to 23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International Clinical Trials Registry Platform (ICTRP, 23 May 2017). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. MAIN RESULTS: The review includes 18 randomised trials involving 2199 participants, and a range of drug treatment options, doses and routes of administration (rectal, buccal, nasal, intramuscular and intravenous). The studies vary by design, setting and population, both in terms of their ages and also in their clinical situation. We have made many comparisons of drugs and of routes of administration of drugs in this review; our key findings are as follows:(1) This review provides only low- to very low-quality evidence comparing buccal midazolam with rectal diazepam for the treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690 children). However, there is uncertainty about the effect and therefore insufficient evidence to support its use. There were no included studies which compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants were shown to lead to similar rates of seizure cessation as intravenous anticonvulsants, e.g. intranasal lorazepam appears to be as effective as intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high-quality evidence) and intranasal midazolam was equivalent to intravenous diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality evidence).(3) Intramuscular midazolam also showed a similar rate of seizure cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105 children; low-quality evidence).(4) For intravenous routes of administration, lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality evidence. Furthermore, we found no statistically significant or clinically important differences between intravenous midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In general, intravenously-administered anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish intravenous access.(5) There is limited evidence from a single trial to suggest that intranasal lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160 children; moderate-quality evidence).(6) Adverse side effects were observed and reported very infrequently in the included studies. Respiratory depression was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of respiratory depression between the different anticonvulsants or their different routes of administration; but when pooled, three studies (439 children) provided moderate-quality evidence that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).Much of the evidence provided in this review is of mostly moderate to high quality. However, the quality of the evidence provided for some important outcomes is low to very low, particularly for comparisons of non-intravenous routes of drug administration. Low- to very low-quality evidence was provided where limited data and imprecise results were available for analysis, methodological inadequacies were present in some studies which may have introduced bias into the results, study settings were not applicable to wider clinical practice, and where inconsistency was present in some pooled analyses. AUTHORS' CONCLUSIONS: We have not identified any new high-quality evidence on the efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic convulsion that would inform clinical practice. There appears to be a very low risk of adverse events, specifically respiratory depression. Intravenous lorazepam and diazepam appear to be associated with similar rates of seizure cessation and respiratory depression. Although intravenous lorazepam and intravenous diazepam lead to more rapid seizure cessation, the time taken to obtain intravenous access may undermine this effect. In the absence of intravenous access, buccal midazolam or rectal diazepam are therefore acceptable first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion that has lasted at least five minutes. There is no evidence provided by this review to support the use of intranasal midazolam or lorazepam as alternatives to buccal midazolam or rectal diazepam.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsia Tônico-Clônica/tratamento farmacológico
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Administração Oral
Administração Retal
Anticonvulsivantes/administração & dosagem
Criança
Diazepam/administração & dosagem
Seres Humanos
Injeções Intramusculares
Injeções Intravenosas
Lorazepam/administração & dosagem
Midazolam/administração & dosagem
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD001905.pub3


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[PMID]:28464258
[Au] Autor:Vorderwülbecke BJ; Kowski AB; Kirschbaum A; Merkle H; Senf P; Janz D; Holtkamp M
[Ad] Endereço:Department of Neurology, Epilepsy-Center Berlin-Brandenburg, Charité - University Medicine Berlin, Berlin, Germany.
[Ti] Título:Long-term outcome in adolescent-onset generalized genetic epilepsies.
[So] Source:Epilepsia;58(7):1244-1250, 2017 07.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Until now, it has been unclear if the three subsyndromes of adolescent-onset generalized genetic epilepsy (GGE) differ in long-term prognosis. Therefore, this study aimed to compare long-term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic seizures alone (EGTCS). METHODS: This retrospective study is based on the archive of an institutional tertiary care outpatient clinic for adult patients with epilepsy. Charts of 870 epilepsy outpatients were reviewed among whom 176 had adolescent-onset GGE (53 JAE, 66 JME, 57 EGTCS). Median patient age at investigation was 60 years; median follow-up time was 42.5 years. If possible, GGE patients were additionally interviewed on psychosocial and clinical variables. RESULTS: Age at first seizure was significantly higher in EGTCS patients (median 18 years) than in patients with JAE or JME (14 years each; p ≤ 0.001). Long-term seizure outcome hardly differed between the three subsyndromes. At the end of follow-up, 60% of all patients were in 5-year terminal seizure remission, and in 14%, epilepsy even had resolved (>10 years without seizures, >5 years without pharmacotherapy). Twenty percent of patients had persistent seizures during the last year of follow-up. Across all patients, 23% reported a psychiatric comorbidity, 87% had married, and 57% had achieved university entrance qualification. SIGNIFICANCE: Long-term outcome was shown to be highly similar across all subsyndromes of adolescent-onset GGE. Even in a selection of difficult-to-treat epilepsy patients still attending an adult epilepsy clinic, most become seizure-free. To confirm these findings, prospective studies are needed.
[Mh] Termos MeSH primário: Epilepsia Tipo Ausência/diagnóstico
Epilepsia Tipo Ausência/genética
Epilepsia Generalizada/diagnóstico
Epilepsia Generalizada/genética
Epilepsia Tônico-Clônica/diagnóstico
Epilepsia Tônico-Clônica/genética
Epilepsia Mioclônica Juvenil/diagnóstico
Epilepsia Mioclônica Juvenil/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Anticonvulsivantes/uso terapêutico
Epilepsia Tipo Ausência/tratamento farmacológico
Epilepsia Generalizada/tratamento farmacológico
Epilepsia Tônico-Clônica/tratamento farmacológico
Feminino
Seres Humanos
Masculino
Meia-Idade
Epilepsia Mioclônica Juvenil/tratamento farmacológico
Prognóstico
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180107
[Lr] Data última revisão:
180107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13761


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[PMID]:28980702
[Au] Autor:Halford JJ; Sperling MR; Nair DR; Dlugos DJ; Tatum WO; Harvey J; French JA; Pollard JR; Faught E; Noe KH; Henry TR; Jetter GM; Lie OV; Morgan LC; Girouard MR; Cardenas DP; Whitmire LE; Cavazos JE
[Ad] Endereço:Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, U.S.A.
[Ti] Título:Detection of generalized tonic-clonic seizures using surface electromyographic monitoring.
[So] Source:Epilepsia;58(11):1861-1869, 2017 Nov.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit (EMU) of an investigational wearable surface electromyographic (sEMG) monitoring system for the detection of generalized tonic-clonic seizures (GTCSs). METHODS: One hundred ninety-nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video-electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. RESULTS: For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61-0.87) of the GTCSs, with a positive predictive value (PPV) of 0.03 and a mean false alarm rate (FAR) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88-1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. SIGNIFICANCE: Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.
[Mh] Termos MeSH primário: Eletromiografia/métodos
Epilepsia Tônico-Clônica/diagnóstico
Epilepsia Tônico-Clônica/fisiopatologia
Monitorização Ambulatorial/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Criança
Pré-Escolar
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13897


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[PMID]:28778447
[Au] Autor:André A; Félix A; Shamasna M; Nzwalo H; Basílio C
[Ad] Endereço:Neurology Department, Algarve Hospital Center, Portugal. Electronic address: alandre@chalgarve.min-saude.pt.
[Ti] Título:Neuroendocrine tumour metastatic brain disease during immunosuppressive treatment for paraneoplastic GABA receptor antibodies encephalitis: Is immunosuppression always beneficial?
[So] Source:J Neuroimmunol;310:66-68, 2017 Sep 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Limbic autoimmune encephalitis (LE) should be considered in any patient with acute or subacute neuropsychiatric manifestations, without other common causes of encephalitis. Y-Aminobutyric-acid-B-receptor (anti-GABA R) antibodies are rarely encountered in association with LE. CASE REPORT: A 74-year-old patient presented with a progressive cognitive degradation and generalized tonic-clonic seizures, with positive anti-GABA R. He declined under immunosuppression treatment. Control magnetic resonance revealed brain lesions, which became positive for pulmonary neuroendocrine tumour metastatic disease. CONCLUSION: The occurrence of diversified neurological manifestations of an underling tumour is difficult to manage. We speculate if in some cases, immunosuppression can itself facilitate tumour progression.
[Mh] Termos MeSH primário: Autoanticorpos/sangue
Imunossupressores/uso terapêutico
Encefalite Límbica
Neoplasias Pulmonares/patologia
Receptores de GABA-B/imunologia
[Mh] Termos MeSH secundário: Adenocarcinoma/patologia
Adenocarcinoma/cirurgia
Idoso
Encéfalo/diagnóstico por imagem
Encéfalo/patologia
Neoplasias Encefálicas/patologia
Neoplasias Encefálicas/cirurgia
Transtornos Cognitivos/etiologia
Epilepsia Tônico-Clônica/diagnóstico por imagem
Epilepsia Tônico-Clônica/etiologia
Seres Humanos
Encefalite Límbica/diagnóstico por imagem
Encefalite Límbica/etiologia
Encefalite Límbica/patologia
Sistema Límbico/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Immunosuppressive Agents); 0 (Receptors, GABA-B)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


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[PMID]:28555759
[Au] Autor:Peng W; Danison JL; Seyal M
[Ad] Endereço:Department of Neurology, University of California, Davis, Sacramento, California, U.S.A.
[Ti] Título:Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic-clonic seizures in sleep and wakefulness.
[So] Source:Epilepsia;58(8):1409-1414, 2017 Aug.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic-clonic seizures (GTCS) in sleep. Postictal generalized electroencephalography (EEG) suppression (PGES), postictal immobility, and periictal respiratory dysfunction are potential risk factors for SUDEP. We sought to determine whether there was a difference in respiratory dysfunction, PGES, and postictal immobility for GTCS occurring during wakefulness or sleep. METHODS: We retrospectively analyzed video-EEG telemetry data in the epilepsy-monitoring unit. Patients' state at seizure onset and seizure characteristics were identified. Respiratory parameters and heart rate were recorded. Presence and duration of PGES and time to first postictal nonrespiratory movement were recorded. RESULTS: There were 165 seizures in 67 patients. There was no significant difference in the duration of postictal immobility in GTCS occurring out of wakefulness or sleep (p = 0.280). Oxygen desaturation nadir (p = 0.572) and duration of oxygen desaturation were not significantly different for GTCS starting during sleep or wakefulness (p = 0.992). PGES occurred more frequently when seizure onset was in sleep than in wakefulness (p = 0.004; odds ratio [OR] 2.760). There was no difference in the duration of PGES between the two groups. SIGNIFICANCE: PGES occurs more commonly after GTCS in sleep than in wakefulness but, in the epilepsy-monitoring unit (EMU), a patient's state at seizure onset does not affect the degree of respiratory dysfunction or duration of postictal immobility. In sleep, outside the hospital setting, GTCS are likely to go unnoticed. Postictal immobility in prone patients prevents head repositioning and unimpeded air exchange. A positive feedback cycle ensues with increasing respiratory distress, potentiating postictal immobility and PGES and eventually leading to asystole. Our findings suggest that the high incidence of nocturnal SUDEP may be related to the unsupervised environment during sleep rather than the severity of sleep-related respiratory dysfunction or PGES duration in the immediate postictal period.
[Mh] Termos MeSH primário: Ondas Encefálicas/fisiologia
Epilepsia Tônico-Clônica/complicações
Transtornos Respiratórios/etiologia
Sono
Vigília
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Morte Súbita/etiologia
Eletroencefalografia
Epilepsia Tônico-Clônica/epidemiologia
Feminino
Frequência Cardíaca/fisiologia
Seres Humanos
Masculino
Meia-Idade
Oximetria
Transtornos Respiratórios/epidemiologia
Estudos Retrospectivos
Estatísticas não Paramétricas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13805


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[PMID]:28481729
[Au] Autor:Coppola G; Piccorossi A; Operto FF; Verrotti A
[Ad] Endereço:a Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery , University of Salerno , Salerno , Italy.
[Ti] Título:Anticonvulsant drugs for generalized tonic-clonic epilepsy.
[So] Source:Expert Opin Pharmacother;18(9):925-936, 2017 Jun.
[Is] ISSN:1744-7666
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities. Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide. Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsia Tônico-Clônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetamidas/administração & dosagem
Acetamidas/efeitos adversos
Acetamidas/uso terapêutico
Anticonvulsivantes/administração & dosagem
Anticonvulsivantes/efeitos adversos
Epilepsia Generalizada/tratamento farmacológico
Feminino
Frutose/administração & dosagem
Frutose/efeitos adversos
Frutose/análogos & derivados
Frutose/uso terapêutico
Seres Humanos
Isoxazóis/administração & dosagem
Isoxazóis/efeitos adversos
Isoxazóis/uso terapêutico
Masculino
Piracetam/administração & dosagem
Piracetam/efeitos adversos
Piracetam/análogos & derivados
Piracetam/uso terapêutico
Piridonas/administração & dosagem
Piridonas/efeitos adversos
Piridonas/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Resultado do Tratamento
Triazinas/administração & dosagem
Triazinas/efeitos adversos
Triazinas/uso terapêutico
Ácido Valproico/administração & dosagem
Ácido Valproico/efeitos adversos
Ácido Valproico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Acetamides); 0 (Anticonvulsants); 0 (Isoxazoles); 0 (Pyridones); 0 (Triazines); 0H73WJJ391 (topiramate); 230447L0GL (etiracetam); 30237-26-4 (Fructose); 459384H98V (zonisamide); 563KS2PQY5 (lacosamide); 614OI1Z5WI (Valproic Acid); H821664NPK (perampanel); U3H27498KS (lamotrigine); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE
[do] DOI:10.1080/14656566.2017.1328499


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[PMID]:28387951
[Au] Autor:Jobst BC; Kapur R; Barkley GL; Bazil CW; Berg MJ; Bergey GK; Boggs JG; Cash SS; Cole AJ; Duchowny MS; Duckrow RB; Edwards JC; Eisenschenk S; Fessler AJ; Fountain NB; Geller EB; Goldman AM; Goodman RR; Gross RE; Gwinn RP; Heck C; Herekar AA; Hirsch LJ; King-Stephens D; Labar DR; Marsh WR; Meador KJ; Miller I; Mizrahi EM; Murro AM; Nair DR; Noe KH; Olejniczak PW; Park YD; Rutecki P; Salanova V; Sheth RD; Skidmore C; Smith MC; Spencer DC; Srinivasan S; Tatum W; Van Ness P; Vossler DG; Wharen RE; Worrell GA; Yoshor D; Zimmerman RS; Skarpaas TL; Morrell MJ
[Ad] Endereço:Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, U.S.A.
[Ti] Título:Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.
[So] Source:Epilepsia;58(6):1005-1014, 2017 Jun.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.
[Mh] Termos MeSH primário: Córtex Cerebral/fisiopatologia
Estimulação Encefálica Profunda/métodos
Epilepsia Resistente a Medicamentos/fisiopatologia
Epilepsia Resistente a Medicamentos/terapia
Terapia por Estimulação Elétrica/métodos
Eletroencefalografia
Neocórtex/fisiopatologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Mapeamento Encefálico
Estimulação Encefálica Profunda/instrumentação
Terapia por Estimulação Elétrica/instrumentação
Eletrodos Implantados
Epilepsias Parciais/fisiopatologia
Epilepsias Parciais/terapia
Epilepsia Parcial Complexa/fisiopatologia
Epilepsia Parcial Complexa/terapia
Epilepsia Motora Parcial/fisiopatologia
Epilepsia Motora Parcial/terapia
Epilepsia Tônico-Clônica/fisiopatologia
Epilepsia Tônico-Clônica/terapia
Estudos de Viabilidade
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13739


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[PMID]:27976799
[Au] Autor:Nolan SJ; Marson AG; Weston J; Tudur Smith C
[Ad] Endereço:Department of Biostatistics, University of Liverpool, Block F, Waterhouse Building, 1-5 Brownlow Hill, Liverpool, UK, L69 3GL.
[Ti] Título:Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual participant data review.
[So] Source:Cochrane Database Syst Rev;12:CD001904, 2016 12 15.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This is an updated version of the original Cochrane Review, first published in Issue 1, 2003 and updated in 2015. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenobarbitone are commonly used broad-spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first-line treatment for partial onset seizures, and is used in the USA and Europe. Phenobarbitone is no longer considered a first-line treatment because of concerns over associated adverse events, particularly documented behavioural adverse events in children treated with the drug. However, phenobarbitone is still commonly used in low- and middle-income countries because of its low cost. No consistent differences in efficacy have been found between carbamazepine and phenobarbitone in individual trials; however, the confidence intervals generated by these studies are wide, and therefore, synthesising the data of the individual trials may show differences in efficacy. OBJECTIVES: To review the time to withdrawal, remission, and first seizure of carbamazepine compared with phenobarbitone when used as monotherapy in people with partial onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: For the latest update, we searched the following databases on 18 August 2016: the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid, from 1946), the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov), and the World Health Organization International Clinical Trials Registry Platform (ICTRP). Previously we also searched SCOPUS (from 1823) as an alternative to Embase, but this is no longer necessary, because randomised controlled trials (RCTs) and quasi-RCTs in Embase are now included in CENTRAL. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. SELECTION CRITERIA: RCTs in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of carbamazepine monotherapy versus phenobarbitone monotherapy. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'adverse events'. We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), with the generic inverse variance method used to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 836 participants out of 1455 eligible individuals from six out of 13 trials; 57% of the potential data. For remission outcomes, HR > 1 indicated an advantage for phenobarbitone, and for first seizure and withdrawal outcomes, HR > 1 indicated an advantage for carbamazepine.The main overall results (pooled HR adjusted for seizure type, 95% CI) were HR 1.50 for time to withdrawal of allocated treatment (95% CI 1.15 to 1.95; P = 0.003); HR 0.93 for time to achieve 12-month remission (95% CI 0.72 to 1.20; P = 0.57); HR 0.99 for time to achieve six-month remission (95% CI 0.80 to 1.23; P = 0.95); and HR 0.87 for time to first seizure (95% CI 0.72 to 1.06; P = 0.18). Results suggest an advantage for carbamazepine over phenobarbitone in terms of time to treatment withdrawal and no statistically significant evidence between the drugs for the other outcomes. We found evidence of a statistically significant interaction between treatment effect and seizure type for time to first seizure recurrence (Chi² test for subgroup differences P = 0.03), where phenobarbitone was favoured for partial onset seizures (HR 0.76, 95% CI 0.60 to 0.96; P = 0.02) and carbamazepine was favoured for generalised onset seizures (HR 1.23, 95% CI 0.88 to 1.77; P = 0.27). We found no evidence of an interaction between treatment effect and seizure type for the other outcomes. However, methodological quality of the included studies was variable, with 10 out of the 13 included studies (4 out of 6 studies contributing IPD) judged at high risk of bias for at least one methodological aspect, leading to variable individual study results, and therefore, heterogeneity in the analyses of this review. We conducted sensitivity analyses to examine the impact of poor methodological aspects, where possible. AUTHORS' CONCLUSIONS: Overall, we found evidence suggestive of an advantage for carbamazepine in terms of drug effectiveness compared with phenobarbitone (retention of the drug in terms of seizure control and adverse events) and evidence suggestive of an association between treatment effect and seizure type for time to first seizure recurrence (phenobarbitone favoured for partial seizures and carbamazepine favoured for generalised seizures). However, this evidence was judged to be of low quality due to poor methodological quality and the potential impact on individual study results (and therefore variability (heterogeneity) present in the analysis within this review), we encourage caution when interpreting the results of this review and do not advocate that the results of this review alone should be used in choosing between carbamazepine and phenobarbitone. We recommend that future trials should be designed to the highest quality possible with considerations for allocation concealment and masking, choice of population, choice of outcomes and analysis, and presentation of results.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Carbamazepina/uso terapêutico
Epilepsias Parciais/tratamento farmacológico
Epilepsia Generalizada/tratamento farmacológico
Fenobarbital/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Criança
Epilepsia Tônico-Clônica/tratamento farmacológico
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Indução de Remissão
Convulsões/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 33CM23913M (Carbamazepine); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD001904.pub3


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[PMID]:27922722
[Au] Autor:Nolan SJ; Sudell M; Tudur Smith C; Marson AG
[Ad] Endereço:Department of Biostatistics, University of Liverpool, Block F, Waterhouse Building, 1-5 Brownlow Hill, Liverpool, UK, L69 3GL.
[Ti] Título:Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review.
[So] Source:Cochrane Database Syst Rev;12:CD012065, 2016 12 06.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance. It is important that the choice of AED for an individual is based on the highest-quality evidence available regarding the potential benefits and harms of various treatments. It is also important to compare the efficacy and tolerability of AEDs appropriate to given seizure types.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs. OBJECTIVES: To assess the effects of topiramate monotherapy versus carbamazepine monotherapy for epilepsy in people with partial-onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (14 April 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2016) and MEDLINE (Ovid, 1946 to 14 April 2016). We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators. SELECTION CRITERIA: Randomised controlled trials in children or adults with partial-onset seizures or generalised-onset tonic-clonic seizures with or without other generalised seizure types with a comparison of monotherapy with either topiramate or carbamazepine. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to first seizure post randomisation', 'time to 6-month remission, 'time to 12-month remission' and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and used the generic inverse variance method to obtain the overall pooled HRs and 95% CIs. MAIN RESULTS: IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and withdrawal outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results, given as pooled HR adjusted for seizure type (95% CI) were: for time to withdrawal of allocated treatment 1.16 (0.98 to 1.38); time to first seizure 1.11 (0.96 to 1.29); and time to 6-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (0.71 to 1.00).The results of this review are applicable mainly to individuals with partial-onset seizures; 85% of included individuals experienced seizures of this type at baseline. For individuals with partial-onset seizures, a statistically significant advantage for carbamazepine was shown for time to withdrawal of allocated treatment (HR 1.20, 95% CI 1.00 to 1.45) and time to 12-month remission (HR 0.84, 95% CI 0.71 to 1.00). No statistically significant differences were apparent between the drugs for other outcomes and for the limited number of individuals with generalised-onset tonic-clonic seizures with or without other generalised seizure types or unclassified seizures.The most commonly reported adverse events with both drugs were drowsiness or fatigue, 'pins and needles' (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the withdrawal rate from the trial. Hence, we judged the evidence for the primary outcome of treatment withdrawal to be moderate for individuals with partial-onset seizures and low for individuals with generalised-onset seizures. For efficacy outcomes (first seizure, remission), we judged the evidence from this review to be high for individuals with partial-onset seizures and moderate for individuals with generalised-onset or unclassified seizures. AUTHORS' CONCLUSIONS: For individuals with partial-onset seizures, there is evidence that carbamazepine is less likely to be withdrawn and that 12-month remission will be achieved earlier than with topiramate. No differences were found between the drugs in terms of the outcomes measured in the review for individuals with generalised tonic-clonic seizures with or without other seizure types or unclassified epilepsy; however, we encourage caution in the interpretation of these results due to the small numbers of participants with these seizure types.We recommend that future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Carbamazepina/uso terapêutico
Epilepsias Parciais/tratamento farmacológico
Epilepsia Tônico-Clônica/tratamento farmacológico
Frutose/análogos & derivados
[Mh] Termos MeSH secundário: Anticonvulsivantes/efeitos adversos
Carbamazepina/efeitos adversos
Epilepsia Generalizada/tratamento farmacológico
Frutose/efeitos adversos
Frutose/uso terapêutico
Seres Humanos
Quimioterapia de Indução
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 0H73WJJ391 (topiramate); 30237-26-4 (Fructose); 33CM23913M (Carbamazepine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170203
[Lr] Data última revisão:
170203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161207
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012065.pub2


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[PMID]:27841445
[Au] Autor:Nolan SJ; Tudur Smith C; Weston J; Marson AG
[Ad] Endereço:Department of Biostatistics, University of Liverpool, Block F, Waterhouse Building, 1-5 Brownlow Hill, Liverpool, UK, L69 3GL.
[Ti] Título:Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review.
[So] Source:Cochrane Database Syst Rev;11:CD001031, 2016 11 14.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2006 of the Cochrane Database of Systematic Reviews.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment up to 70% of individuals with active epilepsy have the potential to become seizure-free and to go into long-term remission shortly after starting drug therapy with a single antiepileptic drug (AED) in monotherapy.The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance. It is important that the choice of AEDs for an individual is made using the highest quality evidence regarding the potential benefits and harms of the various treatments. It is also important that the effectiveness and tolerability of AEDs appropriate to given seizure types are compared to one another.Carbamazepine or lamotrigine are first-line recommended treatments for new onset partial seizures and as a first- or second-line treatment for generalised tonic-clonic seizures. Performing a synthesis of the evidence from existing trials will increase the precision of the results for outcomes relating to efficacy and tolerability and may assist in informing a choice between the two drugs. OBJECTIVES: To review the time to withdrawal, remission and first seizure with lamotrigine compared to carbamazepine when used as monotherapy in people with partial onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: The first searches for this review were run in 1997. For the most recent update we searched the Cochrane Epilepsy Group Specialized Register (17 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 17 October 2016) and MEDLINE (Ovid, 1946 to 17 October 2016). We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators. SELECTION CRITERIA: Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures comparing monotherapy with either carbamazepine or lamotrigine. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was time to withdrawal of allocated treatment and our secondary outcomes were time to first seizure post-randomisation, time to six-month, 12-month and 24-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: We included 13 studies in this review. Individual participant data were available for 2572 participants out of 3394 eligible individuals from nine out of 13 trials: 78% of the potential data. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine and for first seizure and withdrawal outcomes a HR < 1 indicated an advantage for lamotrigine.The main overall results (pooled HR adjusted for seizure type) were: time to withdrawal of allocated treatment (HR 0.72, 95% CI 0.63 to 0.82), time to first seizure (HR 1.22, 95% CI 1.09 to 1.37) and time to six-month remission (HR 0.84, 95% CI 0.74 to 0.94), showing a significant advantage for lamotrigine compared to carbamazepine for withdrawal but a significant advantage for carbamazepine compared to lamotrigine for first seizure and six-month remission. We found no difference between the drugs for time to 12-month remission (HR 0.91, 95% CI 0.77 to 1.07) or time to 24-month remission (HR 1.00, 95% CI 0.80 to 1.25), however only two trials followed up participants for more than one year so the evidence is limited.The results of this review are applicable mainly to individuals with partial onset seizures; 88% of included individuals experienced seizures of this type at baseline. Up to 50% of the limited number of individuals classified as experiencing generalised onset seizures at baseline may have had their seizure type misclassified, therefore we recommend caution when interpreting the results of this review for individuals with generalised onset seizures.The most commonly reported adverse events for both of the drugs across all of the included trials were dizziness, fatigue, gastrointestinal disturbances, headache and skin problems. The rate of adverse events was similar across the two drugs.The methodological quality of the included trials was generally good, however there is some evidence that the design choice of masked or open-label treatment may have influenced the withdrawal rates of the trials. Hence, we judged the quality of the evidence for the primary outcome of treatment withdrawal to be moderate for individuals with partial onset seizures and low for individuals with generalised onset seizures. For efficacy outcomes (first seizure, remission), we judged the quality of evidence to be high for individuals with partial onset seizures and moderate for individuals with generalised onset seizures. AUTHORS' CONCLUSIONS: Lamotrigine was significantly less likely to be withdrawn than carbamazepine but the results for time to first seizure suggested that carbamazepine may be superior in terms of seizure control. A choice between these first-line treatments must be made with careful consideration. We recommend that future trials should be designed to the highest quality possible with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Carbamazepina/uso terapêutico
Epilepsias Parciais/tratamento farmacológico
Epilepsia Tônico-Clônica/tratamento farmacológico
Triazinas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Anticonvulsivantes/efeitos adversos
Carbamazepina/efeitos adversos
Criança
Epilepsia Generalizada/tratamento farmacológico
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Recidiva
Triazinas/efeitos adversos
Suspensão de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Triazines); 33CM23913M (Carbamazepine); U3H27498KS (lamotrigine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161115
[St] Status:MEDLINE



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