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1.
Epilepsy Behav ; 121(Pt A): 108041, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082317

RESUMO

Identification of the language dominant hemisphere is an essential part of the evaluation of potential pediatric epilepsy surgery patients. Historically, language dominance has been determined using the intracarotid amobarbitol procedure (IAP), but use of functional Magnetic Resonance Imaging (fMRI) scanning is becoming more common. Few studies examine the correspondence between fMRI and IAP in pediatric samples. The current study examined the agreement of hemispheric lateralization as determined by fMRI and IAP in a consecutive sample of 10 pediatric patients with epilepsy evaluated for epilepsy surgery. Data showed a strong correlation between IAP and fMRI lateralilty indices (r=.91) and 70% agreement in determination of hemispheric dominance, despite increased demonstration of bilateral or atypical language representation in this pediatric sample. Clinical implications and interpretation challenges are discussed.


Assuntos
Epilepsia , Idioma , Amobarbital , Mapeamento Encefálico , Córtex Cerebral , Criança , Tomada de Decisão Clínica , Dominância Cerebral , Epilepsia/diagnóstico por imagem , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética
2.
Acta Neurol Scand ; 144(5): 585-591, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34132388

RESUMO

BACKGROUND: Anti-seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear. AIMS OF THE STUDY: To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment. METHODS: Fifty-nine adult patients with drug-resistant epilepsy (mean age = 36.1, SD = 11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post-surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed. RESULTS: Total IAP memory score was associated with total ASM drug load (r = -0.30, p = 0.02) and seizure frequency (r = -0.25, p = 0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r = -0.33, p = 0.04). The number of current ASMs was not related to IAP memory score (r = -0.16, p = 0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p > 0.07). CONCLUSIONS: Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Preparações Farmacêuticas , Adulto , Amobarbital , Epilepsia/tratamento farmacológico , Epilepsia do Lobo Temporal/cirurgia , Lateralidade Funcional , Humanos , Injeções Intra-Arteriais , Memória
4.
Braz J Anesthesiol ; 71(3): 288-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33839177

RESUMO

Wada test is an invasive procedure used in the preoperative evaluation for epilepsy surgery to determine language lateralization, postoperative risk of amnesia syndrome, and to assess the risk of memory deficits. It involves injection of amobarbital into internal carotid artery of the affected hemisphere followed by the healthy hemisphere to shut down brain function. We performed an observational study evaluating the density spectral array (DSA) of the bilateral bispectral index VISTA™ Monitoring System (BVMS) in 6 patients with drug-resistant epilepsy undergoing Wada test. DSA revealed the presence of bifrontal alpha waves in absence of loss of consciousness in all patients.


Assuntos
Epilepsia , Memória , Amobarbital , Humanos , Hipnóticos e Sedativos , Idioma
5.
Rev. neurol. (Ed. impr.) ; 72(5): 151-156, 1 mar., 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-202074

RESUMO

INTRODUCCIÓN: La prueba de Wada consiste en la inhibición selectiva y reversible de un hemisferio cerebral mediante la inyección intracarotídea de amobarbital con el objetivo de evaluar la lateralidad del lenguaje y la memoria. Existen otros fármacos anestésicos, como el propofol, como alternativa para la prueba. OBJETIVO: El objetivo del estudio fue describir la tolerabilidad y los efectos adversos (EA) del uso de propofol para la prueba de Wada durante el estudio prequirúrgico de pacientes con epilepsia farmacorresistente. PACIENTES Y MÉTODOS: Se seleccionó a pacientes con diagnóstico de epilepsia estructural farmacorresistente consecutivos, quienes se sometieron a la prueba de Wada durante el estudio prequirúrgico en el período de junio de 2012 a mayo de 2019. Los pacientes fueron evaluados de manera retrospectiva. Los EA se describieron según la clasificación de Mikuni, modificada por Curot. Se analizaron las variables de sexo, edad, lateralidad del foco epiléptico, lateralidad del lenguaje, sustrato lesional, etiología y dosis de propofol administrada en busca de significación estadística. RESULTADOS: Se estudió a un total de 74 pacientes, de los cuales 40 eran hombres (54%). Cuarenta y siete pacientes (63,5%) tuvieron al menos un EA. La dosis media de propofol fue de 9,23 mg. Los EA más frecuentes fueron lagrimeo, sudoración y ojo rojo, correspondientes al grupo I (57%). Un paciente desarrolló estado epiléptico convulsivo, EA importante no descrito anteriormente durante la prueba de Wada. CONCLUSIÓN: La realización de la prueba de Wada con propofol ocasiona frecuentes efectos adversos leves, los cuales no impiden su finalización. Describimos un caso de estado epiléptico convulsivo como único EA grave


INTRODUCTION: The Wada test consists of the selective and reversible inhibition of a cerebral hemisphere by intracarotid injection of amobarbital in order to evaluate the laterality of language and memory. However, there are other anesthetic drugs such as propofol, as an alternative for the test. OBJECTIVE: The objective of the study was to describe the tolerability and adverse effects (AE) of the use of propofol for the Wada test, during the presurgical study of patients with drug-resistant epilepsy. METHODS: Consecutive patients with a diagnosis of drug-resistant structural epilepsy were selected who underwent the Wada test during the pre-surgical study in the period from June 2012 to May 2019. The patients were retrospectively evaluated. The AE were described according to the Mikuni classification, modified by Curot. The variables of sex, age, epileptic foci laterality, language laterality, lesional substrate, etiology and dose of administered Propofol were analyzed for any statistical significance. RESULTS: A total of 74 patients, 40 men (54%), were studied. Forty-seven patients (63.5%) had at least one AE. The mean dose of propofol was 9.23 mg. The most frequent AE were tearing, sweating and red eye, corresponding to group I (57%). One patient developed convulsive status epilepticus, an important AE not previously described during the Wada test. CONCLUSION: Performing the Wada test with propofol causes frequent mild adverse effects, which do not prevent its completion. We describe a case of convulsive status epilepticus as the only serious AE


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Propofol/farmacologia , Hipnóticos e Sedativos/farmacologia , Cérebro/efeitos dos fármacos , Epilepsia Resistente a Medicamentos/diagnóstico , Estudos Retrospectivos , Período Pré-Operatório , Estado Epiléptico/diagnóstico , Amobarbital/farmacologia , Fatores de Risco
6.
Spine J ; 21(6): 1021-1030, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33610806

RESUMO

BACKGROUND: Mounting evidence that oxidative stress contributes to the pathogenesis of intervertebral disc (IVD) degeneration (IDD) suggests that therapies targeting oxidative stress may slow or prevent disease progression. PURPOSE: The objective of this study was to investigate the inhibitory effects of amobarbital (Amo) on the mitochondria of nucleus pulposus (NP) cells under tert-butyl hydrogen peroxide (tBHP)-induced oxidative stress or in NP tissues under oxidative stress from tissue injury as a means of identifying therapeutic targets for IDD. STUDY DESIGN/SETTING: We tested the effects inhibiting mitochondria, a major source of oxidants, with Amo in NP cells subjected to two different forms of insult: exposure to tBHP, and physical injury induced by disc transection. N-acetylcysteine (NAC), an antioxidant known to protect NP cells, was compared to the complex I inhibitor, Amo. METHODS: NP cells were pre-treated for 2 hours with Amo, NAC, or both, and then exposed to tBHP for 1 hour. Apoptosis, necrosis, and reactive oxygen species (ROS) production were assessed using confocal microscopy and fluorescent probes (Annexin V, propidium iodide, and MitoSox Red, respectively). The activation of mitogen-activated protein kinases (MAPKs) involved in oxidative stress responses were interrogated by confocal imaging of immunofluorescence stains using phospho-specific antibodies to extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38. Mitochondrial function was assessed by imaging JC-1 staining, a probe for membrane potential. RESULTS: Amo was modestly more protective than NAC by some measures, while both agents improved mitochondrial function and lowered tBHP-induced apoptosis, necrosis, and ROS production. Activation of MAPK by tBHP was significantly suppressed by both drugs. Physically injured IVDs were treated immediately after transection with Amo or NAC for 24 hours, and then stained with dihydroethidium (DHE), a fluorescent probe for ROS production. Immunofluorescence was used to track the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor that induces the expression of antioxidant genes. Amo and NAC significantly reduced ROS production and increased Nrf2 expression. CONCLUSION: These findings suggest that the progression of IDD may be forestalled by Amo via protection of NP cells from oxidative stress following IVD injury. CLINICAL SIGNIFICANCE: This study will define the extent to which a novel, minimally invasive procedure targeting oxidative stress in NP cells can augment surgical interventions intended to retard IVD degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Preparações Farmacêuticas , Amobarbital/metabolismo , Apoptose , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/prevenção & controle , Estresse Oxidativo , Preparações Farmacêuticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Laryngoscope ; 131(7): 1570-1577, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32857885

RESUMO

OBJECTIVES: Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and/or trachea due to scar tissue. Patients with type 2 diabetes mellitus (T2DM) are over 8 times more likely to develop iLTS and represent 26% to 53% of all iLTS patients. In this investigation, we compared iLTS scar-derived fibroblasts in patients with and without T2DM. STUDY DESIGN: Controlled ex vivo study. METHODS: iLTS scar fibroblasts were isolated and cultured from subglottic scar biopsies in iLTS patients diagnosed with or without type 2 diabetes (non-T2DM). Fibroblast proliferation, fibrosis-related gene expression, and metabolic utilization of oxidative phosphorylation (OXPHOS) and glycolysis were assessed. Contractility was measured using a collagen-based assay. Metabolically targeted drugs (metformin, phenformin, amobarbital) were tested, and changes in fibrosis-related gene expression, collagen protein, and contractility were evaluated. RESULTS: Compared to non-T2DM, T2DM iLTS scar fibroblasts had increased α-smooth muscle actin (αSMA) expression (8.2× increased, P = .020), increased contractility (mean 71.4 ± 4.3% vs. 51.7 ± 16% Δ area × 90 minute-1 , P = .016), and reduced proliferation (1.9× reduction at 5 days, P < .01). Collagen 1 (COL1) protein was significantly higher in the T2DM group (mean 2.06 ± 0.19 vs. 0.74 ±.44 COL1/total protein [pg/µg], P = .036). T2DM iLTS scar fibroblasts had increased measures of OXPHOS, including basal respiration (mean 86.7 vs. 31.5 pmol/minute/10 µg protein, P = .016) and adenosine triphosphate (ATP) generation (mean 97.5 vs. 25.7 pmol/minute/10 µg protein, P = .047) compared to non-T2DM fibroblasts. Amobarbital reduced cellular contractility; decreased collagen protein; and decreased expression of αSMA, COL1, and fibronectin. Metformin and phenformin did not significantly affect fibrosis-related gene expression. CONCLUSION: T2DM iLTS scar fibroblasts demonstrate a myofibroblast phenotype and greater contractility compared to non-T2DM. Their bioenergetic preference for OXPHOS drives their increased contractility, which is selectively targeted by amobarbital. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1570-1577, 2021.


Assuntos
Cicatriz/patologia , Diabetes Mellitus Tipo 2/complicações , Laringoestenose/patologia , Miofibroblastos/patologia , Estenose Traqueal/patologia , Adulto , Idoso , Amobarbital/farmacologia , Biópsia , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cicatriz/etiologia , Constrição Patológica/etiologia , Constrição Patológica/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético , Feminino , Glote/citologia , Glote/lesões , Glote/patologia , Glicólise/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Doença Iatrogênica , Intubação Intratraqueal/efeitos adversos , Laringoestenose/etiologia , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Miofibroblastos/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Fenformin/farmacologia , Fenformin/uso terapêutico , Cultura Primária de Células , Traqueia/citologia , Traqueia/lesões , Traqueia/patologia , Estenose Traqueal/etiologia , Traqueostomia/efeitos adversos , Adulto Jovem
9.
Epilepsy Behav ; 113: 107551, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33246234

RESUMO

OBJECTIVE: Due to supply shortage, amobarbital, the traditional anesthetic agent in Wada testing, was replaced by methohexital in many epilepsy centers. This study aimed to compare the two barbiturates to identify possible advantages or disadvantages of methohexital as compared to amobarbital with regard to the adequacy of language and memory testing during the Wada test. METHODS: Data from 75 patients with temporal lobe epilepsy who underwent bilateral Wada tests using either amobarbital (n = 53) or methohexital (n = 22) as part of presurgical work-up were analyzed retrospectively. The two subgroups were compared regarding hemispheric language and memory lateralization results and Wada testing characteristics, and the adequacy of language and memory testing was assessed. RESULTS: We observed shorter durations of motor-, speech-, and EEG recovery after each injection in patients receiving methohexital compared to amobarbital. In addition, significantly more items could be presented during effective hemispheric inactivation in the methohexital group. Moreover, significant correlations of Wada memory scores with standard neuropsychological memory test scores could be found in the methohexital group. SIGNIFICANCE: Our findings confirm that methohexital is not only equally suitable for Wada testing but has several advantages over amobarbital. Wada testing can be performed more efficiently and under more constant hemispheric inactivation using methohexital. Furthermore, the adequacy of language and memory testing during the Wada test might be affected by the anesthetic agent used.


Assuntos
Amobarbital/farmacologia , Anestésicos/farmacologia , Epilepsia do Lobo Temporal/diagnóstico , Lateralidade Funcional , Hipnóticos e Sedativos/farmacologia , Memória/efeitos dos fármacos , Metoexital/farmacologia , Fala/efeitos dos fármacos , Adolescente , Adulto , Anestésicos/uso terapêutico , Cérebro/efeitos dos fármacos , Cérebro/fisiopatologia , Criança , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Idioma , Testes de Linguagem , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Teste do Limiar de Recepção da Fala , Adulto Jovem
10.
Molecules ; 25(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172092

RESUMO

Wuhan, China was the epicenter of the first zoonotic transmission of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) in December 2019 and it is the causative agent of the novel human coronavirus disease 2019 (COVID-19). Almost from the beginning of the COVID-19 outbreak several attempts were made to predict possible drugs capable of inhibiting the virus replication. In the present work a drug repurposing study is performed to identify potential SARS-CoV-2 protease inhibitors. We created a Quantitative Structure-Activity Relationship (QSAR) model based on a machine learning strategy using hundreds of inhibitor molecules of the main protease (Mpro) of the SARS-CoV coronavirus. The QSAR model was used for virtual screening of a large list of drugs from the DrugBank database. The best 20 candidates were then evaluated in-silico against the Mpro of SARS-CoV-2 by using docking and molecular dynamics analyses. Docking was done by using the Gold software, and the free energies of binding were predicted with the MM-PBSA method as implemented in AMBER. Our results indicate that levothyroxine, amobarbital and ABP-700 are the best potential inhibitors of the SARS-CoV-2 virus through their binding to the Mpro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Inibidores de Proteases/farmacologia , SARS-CoV-2/enzimologia , Amobarbital/farmacologia , Antivirais/química , Sítios de Ligação , Simulação por Computador , Humanos , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Inibidores de Proteases/química , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , SARS-CoV-2/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Software , Termodinâmica , Tiroxina/farmacologia
11.
Clin Neuropharmacol ; 43(6): 185-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32969970

RESUMO

OBJECTIVE: The use of amobarbital in the Wada test varied between epilepsy centers, with no unified dosing or protocols available in the literature to standardize its use. We aimed to determine the dose of amobarbital in the presurgical evaluations of patients with temporal lobe epilepsy. METHODS: A retrospective study of patients with temporal lobe epilepsy seen between January 2004 and December 2018 in King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia, was conducted, and those who successfully underwent a Wada test were studied. A neuropsychologist or a neurologist will assess the memory and language, using standardized testing. RESULTS: A total of 90 patients were studied. The mean age was 30 years (range, 16-52 years), where 49 (57%) of them were men. All patients had a routine neurological examination, including language and memory. The average dose of amobarbital given was 10.1.1 mg (range, 65.7-150 mg). There was no statistical difference between the dosing given to patients who passed or failed the memory testing (101.4 mg vs 94.7 mg, P = 0.1). Multivariate regression analysis showed that amobarbital dose needed an adjustment to patient's weight only for those older than 30 years, (P < 0.05; 95% confidence interval, 0.1-0.5), where an increase in the dose by 0.3 mg·kg·y was required to execute Wada test successfully. CONCLUSION: It was only the patient's age that could influence the modification of Amobarbital dose in the Wada test, yet establishing a universal protocol is challenging because of the lack of well-defined dose determinants.


Assuntos
Amobarbital/administração & dosagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipnóticos e Sedativos/administração & dosagem , Adolescente , Adulto , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Adulto Jovem
12.
Neurology ; 94(23): 1028-1031, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467130

RESUMO

Treatment of functional symptoms has a long history, and interventions were often used in soldiers returning from battle. On the 75th anniversary of the end of the Second World War, I review the portrayal of neurology in documentary film. Two documentaries were released in 1946 and 1948 (Let There Be Light and Shades of Gray, respectively), which showed a number of soldiers with functional neurology including paralysis, stuttering, muteness, and amnesia. The films showed successful treatments with hypnosis and sodium amytal by psychoanalytic psychiatrists. These documentaries link neurology with psychiatry and are remarkable examples of functional neurology and its treatment on screen.


Assuntos
Distúrbios de Guerra/história , Medicina Militar/história , Filmes Cinematográficos/história , Neurologia/história , Transtornos Somatoformes/história , Transtornos de Estresse Pós-Traumáticos/história , II Guerra Mundial , Adulto , Amobarbital/uso terapêutico , Distúrbios de Guerra/psicologia , Distúrbios de Guerra/reabilitação , Distúrbios de Guerra/terapia , Diagnóstico Diferencial , Seguimentos , História do Século XX , História do Século XXI , Humanos , Hipnose/história , Histeria/história , Masculino , Simulação de Doença/diagnóstico , Militares , Neurologia/educação , Transtornos Somatoformes/psicologia , Transtornos Somatoformes/reabilitação , Transtornos Somatoformes/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/reabilitação , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos
13.
Clin Neuroradiol ; 30(4): 691-704, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31960077

RESUMO

PURPOSE: To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in a predominantly pediatric cohort. METHODS: Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23 fMRI examinations (in total 117 fMRI task sessions) of 23 patients (age range 10.0-23.0 years) with drug-refractory epilepsies. RESULTS: The ROIs were considered valid when they showed activation in more than 25% of all sessions for the respective task and never showed false lateralization (in comparison to gold standards). Thus, 13 valid, task-specific ROIs were identified: 5 ROIs for the WCT (frontal operculum, inferior frontal gyrus, middle frontal gyrus, intraparietal sulcus, cerebellum), 3 ROIs for the VIT (frontal operculum, inferior frontal gyrus, middle frontal gyrus), 3 ROIs for the SYT (frontal operculum, inferior frontal gyrus, temporal language area) and 2 ROIs for the BST (inferior frontal gyrus, middle frontal gyrus). CONCLUSION: Clinical fMRI using the battery of four tasks is a valid tool for lateralizing language in children, adolescents and young adults. Each task proved to be specifically useful, which confirms that applying different tasks increases the probability of diagnosing language dominance in presurgical candidates.


Assuntos
Mapeamento Encefálico , Epilepsia , Idioma , Imageamento por Ressonância Magnética , Adolescente , Adulto , Amobarbital , Criança , Epilepsia/diagnóstico por imagem , Lateralidade Funcional , Humanos , Adulto Jovem
14.
J Neurointerv Surg ; 12(2): 165-169, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31320550

RESUMO

BACKGROUND: The selective posterior cerebral artery (PCA) amobarbital test, or PCA Wada test, is used to predict memory impairment after epilepsy surgery in patients who have previously had a failed internal carotid artery (ICA) amobarbital test. METHODS: Medical records from 2012 to 2018 were retrospectively reviewed for all patients with seizures who underwent a selective PCA Wada test at our institution following a failed or inconclusive ICA Wada test. Standardized neuropsychological testing was performed before and during the Wada procedure and postoperatively in patients who underwent resection. RESULTS: Thirty-three patients underwent a selective PCA Wada test, with no complications. Twenty-six patients with medically refractory epilepsy had a seizure focus amenable to selective amygdalohippocampectomy (AHE). Six patients (23%, n=26) had a failed PCA Wada test and did not undergo selective AHE, seven (27%) declined surgical resection, leaving 13 patients who underwent subtemporal selective AHE. Hippocampal sclerosis was found in all 13 patients (100%). Twelve patients (92%) subsequently underwent formal neuropsychological testing and all were found to have stable memory. Ten patients (77%) were seizure-free (Engel Class I), with average follow-up of 13 months. CONCLUSION: The selective PCA Wada test is predictive of memory outcomes after subtemporal selective AHE in patients with a failed or inconclusive ICA Wada test. Furthermore, given the low risk of complications and potential benefit of seizure freedom, a selective PCA Wada test may be warranted in patients with medically intractable epilepsy who are candidates for a selective AHE and who have a prior failed or inconclusive ICA Wada test.


Assuntos
Amobarbital/farmacologia , Tonsila do Cerebelo/cirurgia , Hipocampo/cirurgia , Memória/efeitos dos fármacos , Testes Neuropsicológicos , Artéria Cerebral Posterior/efeitos dos fármacos , Adulto , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Masculino , Memória/fisiologia , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Artéria Cerebral Posterior/fisiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Valor Preditivo dos Testes , Estudos Retrospectivos
15.
Epilepsy Res ; 156: 106150, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31239182

RESUMO

PURPOSE: To review our experience with the Etomidate speech test (EST) for lateralizing language in children undergoing epilepsy surgery evaluation METHODS: This retrospective study included children (<18 years) with drug refractory focal epilepsy undergoing EST for bilateral or poorly reliable language representation on functional MRI. Data for consecutive children who underwent EST between January 2013 to June 2017 were reviewed. RESULTS: Twenty-one children (mean age at EST, 13.1 ±â€¯4.4 years) were studied, with 19-right hemispheric and 20 left hemispheric injections. Six patients had neurological co-morbidities. Duration of ipsilateral EEG slowing was sufficient for speech testing in all children with a single bolus of Etomidate per carotid artery. Language was lateralized to one hemisphere in 17 (80.9%) and bilateral in two cases. EST was unsuccessful in two patients because of diffuse EEG slowing. Contralateral transient frontal EEG slowing was seen in 14 (73.7%) cases. EST was well tolerated in all the patients. CONCLUSIONS: The EST was found to be successful and safe in lateralizing language in most of our drug refractory pediatric epilepsy cohort.


Assuntos
Epilepsia/fisiopatologia , Etomidato/farmacologia , Memória/efeitos dos fármacos , Fala/efeitos dos fármacos , Adolescente , Adulto , Amobarbital , Criança , Epilepsia/tratamento farmacológico , Etomidato/efeitos adversos , Feminino , Lateralidade Funcional/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Humanos , Idioma , Masculino , Memória/fisiologia , Reprodutibilidade dos Testes
16.
Hist Psychiatry ; 30(3): 352-358, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31144519

RESUMO

In the early 1930s, American neurologist and psychiatrist William Bleckwenn used sodium amytal to render catatonic patients responsive, so that he could engage in talk therapy. Bleckwenn found a new, 'off-label' use for this anaesthetic and anxiolytic medication in psychiatry and, in doing so, allowed for important discoveries in the diagnosis and treatment of catatonia. Pharmacological textbooks reveal a 'label', while the Index-Catalogue of the Library of the Surgeon-General's Office reveals explorations 'off label' of barbiturates. The 'off-label' use of barbiturates facilitated talk therapy, heralding an important shift in psychopharmacy. Drugs previously only used as chemical restraints became a form of treatment for specific psychiatric diseases. The current strictures against off-label prescribing are overprescriptive and close off innovative new uses.


Assuntos
Amobarbital/história , Hipnóticos e Sedativos/história , Uso Off-Label/história , Amobarbital/uso terapêutico , Barbitúricos/história , Barbitúricos/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/história , Feminino , História do Século XX , Humanos , Hiperidrose/tratamento farmacológico , Hiperidrose/história , Hipnóticos e Sedativos/uso terapêutico , Masculino
17.
Epilepsia ; 59(12): 2305-2317, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30374948

RESUMO

OBJECTIVE: The European Union-funded E-PILEPSY project was launched to develop guidelines and recommendations for epilepsy surgery. In this systematic review, we aimed to assess the diagnostic accuracy of functional magnetic resonance imaging (fMRI), Wada test, magnetoencephalography (MEG), and functional transcranial Doppler sonography (fTCD) for memory and language decline after surgery. METHODS: The literature search was conducted using PubMed, Embase, and CENTRAL. The diagnostic accuracy was expressed in terms of sensitivity and specificity for postoperative language or memory decline, as determined by pre- and postoperative neuropsychological assessments. If two or more estimates of sensitivity or specificity were extracted from a study, two meta-analyses were conducted, using the maximum ("best case") and the minimum ("worst case") of the extracted estimates, respectively. RESULTS: Twenty-eight papers were eligible for data extraction and further analysis. All tests for heterogeneity were highly significant, indicating large between-study variability (P < 0.001). For memory outcomes, meta-analyses were conducted for Wada tests (n = 17) using both memory and language laterality quotients. In the best case, meta-analyses yielded a sensitivity estimate of 0.79 (95% confidence interval [CI] = 0.67-0.92) and a specificity estimate of 0.65 (95% CI = 0.47-0.83). For the worst case, meta-analyses yielded a sensitivity estimate of 0.65 (95% CI = 0.48-0.82) and a specificity estimate of 0.46 (95% CI = 0.28-0.65). The overall quality of evidence, which was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology, was rated as very low. Meta-analyses concerning diagnostic accuracy of fMRI, fTCD, and MEG were not feasible due to small numbers of studies (fMRI, n = 4; fTCD, n = 1; MEG, n = 0). This also applied to studies concerning language outcomes (Wada test, n = 6; fMRI, n = 2; fTCD, n = 1; MEG, n = 0). SIGNIFICANCE: Meta-analyses could only be conducted in a few subgroups for the Wada test with low-quality evidence. Thus, more evidence from high-quality studies and improved data reporting are required. Moreover, the large between-study heterogeneity underlines the necessity for more homogeneous and thus comparable studies in future research.


Assuntos
Epilepsia/cirurgia , Transtornos da Linguagem/etiologia , Testes de Linguagem , Imageamento por Ressonância Magnética/métodos , Magnetoencefalografia/métodos , Transtornos da Memória/etiologia , Complicações Pós-Operatórias/psicologia , Ultrassonografia Doppler Transcraniana/métodos , Amobarbital , Humanos , Sensibilidade e Especificidade
18.
Am J Physiol Heart Circ Physiol ; 314(4): H787-H795, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29351463

RESUMO

Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.


Assuntos
Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Amobarbital/farmacologia , Animais , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Preparação de Coração Isolado , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Oxirredução , Proteômica/métodos
19.
Epilepsy Behav ; 78: 25-29, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29169082

RESUMO

OBJECTIVE: The intracarotid sodium amytal procedure (the "Wada test") has for many years been the gold standard for language and memory lateralization and remains an important part of presurgical analysis for patients with medically intractable seizures. Due to shortages in the key sedative (amobarbital), neuropsychologists have turned to alternatives such as propofol. Our aim was to investigate the safety and efficacy of propofol relative to amobarbital in the Wada test. METHODS: We performed a retrospective review of the 97 Wada procedures performed at University of Iowa Hospitals and Clinics from 2007 through mid-2015. RESULTS: Propofol produced similar lateralization rates as amobarbital for both language and memory. Similar rates of patients in each group went on to have the resection surgery. With regard to safety, there were no differences found in average rate or severity of adverse effects. None of the demographic characteristics reviewed were predictive of increased risk for either drug. SIGNIFICANCE: These findings support previous studies indicating that propofol is as safe and efficacious as amobarbital, and can continue to be used in Wada procedures with confidence.


Assuntos
Amobarbital/administração & dosagem , Epilepsia/cirurgia , Hipnóticos e Sedativos/uso terapêutico , Monitorização Neurofisiológica Intraoperatória/métodos , Cuidados Pré-Operatórios/métodos , Propofol/administração & dosagem , Adolescente , Adulto , Idoso , Amobarbital/efeitos adversos , Anestésicos Intravenosos , Criança , Epilepsia/diagnóstico , Feminino , Lateralidade Funcional , Humanos , Hipnóticos e Sedativos/farmacologia , Idioma , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/efeitos adversos , Propofol/efeitos adversos , Estudos Retrospectivos
20.
Epilepsy Behav ; 76: 89-100, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28923498

RESUMO

PURPOSE: A previous study showed that assessment of language laterality could be improved by adding grammar tests to the recovery phase of the intracarotid amobarbital procedure (IAP) (Polczynska et al. 2014). The aim of this study was to further investigate the extent to which grammar tests lateralize language function during the recovery phase of the IAP in a larger patient sample. METHODS: Forty patients with drug-resistant epilepsy (14 females, thirty-two right-handed, mean age 38.5years, SD=10.6) participated in this study. On EEG, 24 patients had seizures originating in the left hemisphere (LH), 13 in the right hemisphere (RH), and 4 demonstrated mixed seizure origin. Thirty participants (75%) had bilateral injections, and ten (25%) had unilateral injections (five RH and five LH). Based on results from the encoding phase, we segregated our study participants to a LH language dominant and a mixed dominance group. In the recovery phase of the IAP, the participants were administered a new grammar test (the CYCLE-N) and a standard language test. We analyzed the laterality index measure and effect sizes in the two tests. KEY FINDINGS: In the LH-dominant group, the CYCLE-N generated more profound language deficits in the recovery phase than the standard after injection to either hemisphere (p<0.001). At the same time, the laterality index for the grammar tasks was still higher than for the standard tests. Critically, the CYCLE-N administered in the recovery phase was nearly as effective as the standard tests given during the encoding phase. SIGNIFICANCE: The results may be significant for individuals with epilepsy undergoing IAP. The grammar tests may be a highly efficient measure for lateralizing language function in the recovery phase.


Assuntos
Amobarbital/administração & dosagem , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Lateralidade Funcional/efeitos dos fármacos , Moduladores GABAérgicos/administração & dosagem , Testes de Linguagem , Idioma , Adulto , Amobarbital/farmacologia , Amobarbital/uso terapêutico , Encéfalo/efeitos dos fármacos , Artéria Carótida Interna , Epilepsia Resistente a Medicamentos/diagnóstico , Feminino , Lateralidade Funcional/fisiologia , Humanos , Injeções Intra-Arteriais , Linguística , Masculino , Pessoa de Meia-Idade , Convulsões
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