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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]:28452419
[Au] Autor:Joshi S; Rajasekaran K; Williamson J; Kapur J
[Ad] Endereço:Department of Neurology, University of Virginia, Charlottesville, Virginia, U.S.A.
[Ti] Título:Neurosteroid-sensitive δ-GABA receptors: A role in epileptogenesis?
[So] Source:Epilepsia;58(3):494-504, 2017 03.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We determined the role of the neurosteroid-sensitive δ subunit-containing γ-aminobutyric acid A receptors (δ-GABARs) in epileptogenesis. METHODS: Status epilepticus (SE) was induced via lithium pilocarpine in adult rats, and seizures were assessed by continuous video-electroencephalography (EEG) monitoring. Finasteride was administered to inhibit neurosteroid synthesis. The total and surface protein expression of hippocampal δ, α4, and γ2 GABAR subunits was studied using biotinylation assays and Western blotting. Neurosteroid potentiation of the tonic currents of dentate granule cells (DGCs) was measured by whole-cell patch-clamp technique. Finally, the effects of inhibiting N-methyl-d-aspartate receptors (NMDARs) during SE on the long-term plasticity of δ-GABARs, neurosteroid-induced modulation of tonic current, and epileptogenesis were studied. RESULTS: The inhibition of neurosteroid synthesis 4 days after SE triggered acute seizures and accelerated the onset of chronic recurrent spontaneous seizures (epilepsy). The down-regulation of neurosteroid-sensitive δ-GABARs occurred prior to the onset of epilepsy, whereas an increased expression of the γ2-GABAR subunits occurred after seizure onset. MK801 blockade of NMDARs during SE preserved the expression of neurosteroid-sensitive δ-GABARs. NMDAR blockade during SE also prevented the onset of spontaneous seizures. SIGNIFICANCE: Changes in neurosteroid-sensitive δ-GABAR expression correlated temporally with epileptogenesis. These findings raise the possibility that δ-GABAR plasticity may play a role in epileptogenesis.
[Mh] Termos MeSH primário: Epilepsia do Lobo Temporal/fisiopatologia
Neurotransmissores/fisiologia
Receptores de GABA-A/fisiologia
Estado Epiléptico/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Giro Denteado/fisiopatologia
Modelos Animais de Doenças
Maleato de Dizocilpina/farmacologia
Regulação para Baixo/efeitos dos fármacos
Regulação para Baixo/fisiologia
Eletroencefalografia/efeitos dos fármacos
Feminino
Finasterida/farmacologia
Hipocampo/fisiopatologia
Compostos de Lítio
Masculino
Plasticidade Neuronal/efeitos dos fármacos
Plasticidade Neuronal/fisiologia
Neurônios/efeitos dos fármacos
Neurônios/fisiologia
Neurotransmissores/antagonistas & inibidores
Técnicas de Patch-Clamp
Pilocarpina
Ratos
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
Gravação em Vídeo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lithium Compounds); 0 (Neurotransmitter Agents); 0 (Receptors, GABA-A); 0 (Receptors, N-Methyl-D-Aspartate); 01MI4Q9DI3 (Pilocarpine); 57GNO57U7G (Finasteride); 6LR8C1B66Q (Dizocilpine Maleate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13660


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[PMID]:29443785
[Au] Autor:Warraich S; Ali A; Nizami A; Bakhiet M
[Ad] Endereço:King Hamad University Hospital, Al Sayh.
[Ti] Título:Can endotracheal intubation be the first step in management of nonconvulsive status epilepticus?: A case report.
[So] Source:Medicine (Baltimore);97(7):e9950, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Nonconvulsive status epilepticus (NCSE) is prolonged seizure activity without motor manifestations. Clinically, there are certain examination findings, in addition to elements of history, that help differentiate it from other encephalopathies. When diagnosing NCSE, the physician faces significant difficulties due to inconsistent clinical presentation and somewhat nonspecific electroencephalogram (EEG) criteria. PATIENT CONCERNS: To highlight the problems faced when dealing with such a patient, a case of a 29-year-old male who presented with an altered state of consciousness is put forth for the reader. Only after an extensive laboratory and radiological workup had ruled out other causes, an eventual diagnosis was established when clinical features were correlated with suggestive EEG results. DIAGNOSES: The diagnosis that was reached was NCSE. INTERVENTIONS: The initial therapeutic interventions generally deployed in such a scenario ultimately failed and consequently the patient had to be sedated and intubated, while being kept on antiepileptic medication. OUTCOMES: This measure resulted in satisfactory recovery. LESSONS: Accordingly, we recommend consideration of NCSE in any unconscious patient whose presentation cannot be explained by other disorders. Furthermore, we suggest moving directly to utilizing anesthetic agents and endotracheal intubation, together with anti-epileptic drugs, in the treatment regimen in order to optimize patient outcomes.
[Mh] Termos MeSH primário: Intubação Intratraqueal
Estado Epiléptico/terapia
[Mh] Termos MeSH secundário: Adulto
Anticonvulsivantes/uso terapêutico
Eletroencefalografia
Seres Humanos
Masculino
Estado Epiléptico/complicações
Estado Epiléptico/diagnóstico
Estado Epiléptico/tratamento farmacológico
Inconsciência/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009950


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[PMID]:28460320
[Au] Autor:Redecker J; Wittstock M; Rösche J
[Ad] Endereço:Department of Neurology, University of Rostock, Germany.
[Ti] Título:The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined?
[So] Source:Epilepsy Behav;71(Pt A):35-38, 2017 Jun.
[Is] ISSN:1525-5069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We explored the influence of four different efficacy criteria on the results of observational studies concerning the treatment of status epilepticus (SE) and its subtypes. We compared and contrasted the results of four different efficacy criteria for the effectiveness of phenytoin, valproate, levetiracetam, and lacosamide. Criterion 1=the last antiepileptic drug (AED) administered before SE termination. Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication. Criterion 3=the last drug introduced into the antiepileptic therapy or increased in dose within 24h before termination of the SE without changes in the co-medication. Criterion 4=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE even allowing changes in the co-medication. We used two-tailed χ -tests with the Yates adjustment for small samples to evaluate statistical differences between efficacy rates of different AEDs in the entire group and in subgroups of SE according to the second level of subdivisions in axis 1 and according to axis 2 of the new ILAE classification. A total of 145 treatment episodes in 124 patients (47 male, 77 female) were evaluated. There were 23 significant differences in efficacy according to the different criteria. Only criteria 1 and 3 led to significant results in our analysis. When incorporating theoretical considerations and the results of this study, criterion 3 seems to be the most appropriate measure for the evaluation of efficacy of an AED in the treatment of SE, because it seems to be more reasonable than criterion 1.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Estado Epiléptico/diagnóstico
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetamidas/administração & dosagem
Administração Intravenosa
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Comportamentos Relacionados com a Saúde
Seres Humanos
Masculino
Meia-Idade
Fenitoína/administração & dosagem
Piracetam/administração & dosagem
Piracetam/análogos & derivados
Estudos Retrospectivos
Resultado do Tratamento
Ácido Valproico/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Acetamides); 0 (Anticonvulsants); 230447L0GL (etiracetam); 563KS2PQY5 (lacosamide); 614OI1Z5WI (Valproic Acid); 6158TKW0C5 (Phenytoin); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28449208
[Au] Autor:Maggio N; Shavit Stein E; Segal M
[Ad] Endereço:Department of Neurology, The Chaim Sheba Medical Center, Tel HaShomer, Israel.
[Ti] Título:Complex modulation by stress of the effect of seizures on long term potentiation in mouse hippocampal slices.
[So] Source:Hippocampus;27(8):860-870, 2017 Aug.
[Is] ISSN:1098-1063
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stress has a profound effect on ability to express neuronal plasticity, learning, and memory. Likewise, epileptic seizures lead to massive changes in brain connectivity, and in ability to undergo long term changes in reactivity to afferent stimulation. In this study, we analyzed possible long lasting interactions between a stressful experience and reactivity to pilocarpine, on the ability to produce long term potentiation (LTP) in a mouse hippocampus. Pilocarpine lowers paired pulse potentiation as well as LTP in CA1 region of the mouse hippocampal slice. When stress experience precedes exposure to pilocarpine, it protects the brain from the lasting effect of pilocarpine. When stress follows pilocarpine, it exacerbates the effect of the drug, to produce a long lasting reduction in LTP. These changes are accompanied by a parallel change in blood corticosterone level. A single exposure to selective mineralo- or gluco-corticosterone (MR and GR, respectively) agonists and antagonists can mimic the stress effects, indicating that GR's underlie the lasting detrimental effects of stress whereas MRs are instrumental in counteracting the effects of stress. These studies open a new avenue of understanding of the interactive effects of stress and epileptic seizures on brain plasticity.
[Mh] Termos MeSH primário: Hipocampo/fisiopatologia
Potenciação de Longa Duração/fisiologia
Estado Epiléptico/patologia
Estado Epiléptico/fisiopatologia
Estresse Psicológico/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/farmacologia
Atropina/farmacologia
Corticosterona/sangue
Diazepam/farmacologia
Modelos Animais de Doenças
Estimulação Elétrica
Hipocampo/efeitos dos fármacos
Técnicas In Vitro
Potenciação de Longa Duração/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Agonistas Muscarínicos/toxicidade
Antagonistas Muscarínicos/farmacologia
Pilocarpina/toxicidade
Estado Epiléptico/induzido quimicamente
Estado Epiléptico/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Muscarinic Agonists); 0 (Muscarinic Antagonists); 01MI4Q9DI3 (Pilocarpine); 7C0697DR9I (Atropine); Q3JTX2Q7TU (Diazepam); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1002/hipo.22736


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[PMID]:28741690
[Au] Autor:Faught E; Laliberté F; Wang Z; Barghout V; Haider B; Lejeune D; Germain G; Choi J; Wagh A; Duh MS
[Ad] Endereço:Emory University School of Medicine, Atlanta, Georgia, U.S.A.
[Ti] Título:Health care resource utilization before and after perampanel initiation among patients with epilepsy in the United States.
[So] Source:Epilepsia;58(10):1742-1748, 2017 10.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The purpose of this study was to evaluate changes in health care resource utilization following the initiation of perampanel for the treatment of epilepsy in the United States. METHODS: Health care claims from Symphony Health's Integrated Dataverse database between December 2012 and November 2015 were analyzed. Patients newly initiated on perampanel, having ≥1 epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 345.xx, ICD-10-CM code G40.xxx) or nonfebrile convulsion (ICD-9-CM code 780.39, ICD-10-CM code R56.9) diagnosis, and having ≥6 months of baseline and observation periods were included. Patients <12 years old at perampanel initiation were excluded. RESULTS: Of the 2,508 perampanel patients included in the study, the mean [median] (±standard deviation [SD]) age was 35.8 [34] (±16.0) years and 56.2% were female. The mean [median] (±SD) observation duration was 459.8 [462] (±146.3) days in the postperampanel period. The postperampanel period was associated with significantly lower rates of all health care resource utilization outcomes than the pre-period. For the post- versus pre-period, perampanel users had 42.3 versus 53.8 overall hospitalizations per 100 person-years (rate ratio [RR] = 0.80, p < 0.001) and 1,240.2 versus 1,343.8 outpatient visits per 100 person-years (RR = 0.91, p < 0.001). Epilepsy-related hospitalizations and outpatient visits were 25.2 versus 33.6 per 100 person-years (RR = 0.76, p < 0.001) and 327.0 versus 389.0 per 100 person-years (RR = 0.84, p < 0.001), respectively. Additionally, a significantly lower rate of status epilepticus in the post-period (1.8 events per 100 person-years) was observed compared to the pre-period (4.4 events per 100 person-years; RR = 0.43, p < 0.001). The monthly time trend of hospitalizations showed an increasing trend leading up to the initiation of perampanel, after which the hospitalizations decreased steadily. SIGNIFICANCE: Use of perampanel for the treatment of epilepsy was associated with significant reduction in all-cause and epilepsy-related health care resource utilization, including hospitalizations, especially for status epilepticus, and outpatient visits.
[Mh] Termos MeSH primário: Assistência Ambulatorial/utilização
Anticonvulsivantes/uso terapêutico
Epilepsia/tratamento farmacológico
Hospitalização/estatística & dados numéricos
Piridonas/uso terapêutico
Estado Epiléptico/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Criança
Feminino
Serviços de Saúde/utilização
Seres Humanos
Masculino
Meia-Idade
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Pyridones); H821664NPK (perampanel)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13857


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[PMID]:28448686
[Au] Autor:Gallentine WB; Shinnar S; Hesdorffer DC; Epstein L; Nordli DR; Lewis DV; Frank LM; Seinfeld S; Shinnar RC; Cornett K; Liu B; Moshé SL; Sun S; FEBSTAT Investigator Team
[Ad] Endereço:Department of Pediatrics (Neurology), Duke Children's Hospital, Durham, North Carolina, U.S.A.
[Ti] Título:Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.
[So] Source:Epilepsia;58(6):1102-1111, 2017 06.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1ß levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1ß and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1ß, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1ß or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).
[Mh] Termos MeSH primário: Biomarcadores/sangue
Dano Encefálico Crônico/sangue
Citocinas/sangue
Hipocampo/diagnóstico por imagem
Hipocampo/fisiopatologia
Convulsões Febris/sangue
Estado Epiléptico/sangue
[Mh] Termos MeSH secundário: Dano Encefálico Crônico/diagnóstico por imagem
Criança
Pré-Escolar
Epilepsia do Lobo Temporal/sangue
Feminino
Seres Humanos
Lactente
Recém-Nascido
Proteína Antagonista do Receptor de Interleucina 1/sangue
Interleucina-1beta/sangue
Interleucina-6/sangue
Interleucina-8/sangue
Masculino
Fatores de Risco
Convulsões Febris/diagnóstico por imagem
Estado Epiléptico/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Interleukin 1 Receptor Antagonist Protein); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (Interleukin-8)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180107
[Lr] Data última revisão:
180107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13750


  8 / 6842 MEDLINE  
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[PMID]:29182639
[Au] Autor:Neumann AM; Abele J; Kirschstein T; Engelmann R; Sellmann T; Köhling R; Müller-Hilke B
[Ad] Endereço:Institute of Immunology, University of Rostock, Rostock, Germany.
[Ti] Título:Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice.
[So] Source:PLoS One;12(11):e0187330, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4-5 weeks old C57BL/6 mice. Brains were removed at days 1-4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0-3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention.
[Mh] Termos MeSH primário: Ácido Micofenólico/farmacologia
Pilocarpina/farmacologia
Estado Epiléptico/induzido quimicamente
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Imunofenotipagem
Camundongos
Camundongos Endogâmicos C57BL
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Estado Epiléptico/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
01MI4Q9DI3 (Pilocarpine); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0187330


  9 / 6842 MEDLINE  
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[PMID]:29050394
[Au] Autor:Altwegg-Boussac T; Schramm AE; Ballestero J; Grosselin F; Chavez M; Lecas S; Baulac M; Naccache L; Demeret S; Navarro V; Mahon S; Charpier S
[Ad] Endereço:Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
[Ti] Título:Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.
[So] Source:Brain;140(9):2381-2398, 2017 Sep 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli.
[Mh] Termos MeSH primário: Córtex Cerebral/citologia
Córtex Cerebral/fisiologia
Neurônios/fisiologia
Estado Epiléptico/fisiopatologia
Tiopental/farmacologia
Inconsciência/fisiopatologia
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Adolescente
Adulto
Idoso
Animais
Encéfalo/efeitos dos fármacos
Encéfalo/fisiologia
Estudos de Casos e Controles
Estimulação Elétrica
Eletroencefalografia
Potenciais Evocados/fisiologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Vias Neurais/fisiologia
Células Piramidais/fisiologia
Ratos
Estado Epiléptico/tratamento farmacológico
Tiopental/uso terapêutico
Inconsciência/induzido quimicamente
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
JI8Z5M7NA3 (Thiopental)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx175


  10 / 6842 MEDLINE  
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[PMID]:28960278
[Au] Autor:Bölsterli BK; Gardella E; Pavlidis E; Wehrle FM; Tassinari CA; Huber R; Rubboli G
[Ad] Endereço:Division of Clinical Neurophysiology, University Children's Hospital Zurich, Zurich, Switzerland.
[Ti] Título:Remission of encephalopathy with status epilepticus (ESES) during sleep renormalizes regulation of slow wave sleep.
[So] Source:Epilepsia;58(11):1892-1901, 2017 Nov.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: In previous studies, we showed an altered overnight decrease of non-rapid-eye-movement (NREM) sleep slow waves in children with encephalopathy related to status epilepticus during sleep (ESES). Here, we test the hypothesis that these alterations renormalize after remission of ESES. Because overnight decrease of slow waves has been linked to brain recovery and cognition, we investigate whether cognitive outcome is related to overnight changes of slow waves. METHODS: We performed a retrospective analysis of longitudinal overnight electroencephalography (EEG) in 10 patients with idiopathic ESES. Automated slow wave detection and calculation of slope of slow waves during the first and last hour of NREM sleep were employed. Intraindividual comparisons were undertaken of the slope during active phase and after remission of ESES, and between patients after remission of ESES and healthy controls. Explorative analysis of the relationship between slow wave slope and cognitive outcome was performed. RESULTS: The slope of slow waves did not decrease significantly across the night during active ESES, particularly at the spike focus. After remission of ESES, the slope decreased significantly overnight. Compared to controls, there was no difference in overnight slope decrease. Association between slope and neuropsychological outcome showed best cognitive outcome after remission in those children (n = 3) who showed some degree of slope decline during active ESES. SIGNIFICANCE: This study provides evidence that alterations of overnight changes of NREM-sleep slow waves during active ESES are reversible when ESES resolves, and that the severity of neuropsychological compromise might be related to the extent of slow wave impairment during ESES. Our findings suggest that analysis of slow waves might serve as a prognostic factor regarding cognitive outcome. ESES may serve as disease model of pathologic slow wave sleep and our results might be expanded to epilepsies with spike wave activation in slow wave sleep not only in children but also in adults.
[Mh] Termos MeSH primário: Encefalopatias/fisiopatologia
Eletroencefalografia/tendências
Transtornos do Sono-Vigília/fisiopatologia
Sono/fisiologia
Estado Epiléptico/fisiopatologia
[Mh] Termos MeSH secundário: Encefalopatias/diagnóstico
Criança
Pré-Escolar
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Remissão Espontânea
Estudos Retrospectivos
Transtornos do Sono-Vigília/diagnóstico
Estado Epiléptico/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:170930
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13910



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