ABSTRACT
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.
Subject(s)
Epilepsy , Memory , Amobarbital , Humans , Hypnotics and Sedatives , LanguageABSTRACT
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.
Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Coronavirus 3C Proteases/antagonists & inhibitors , Drug Discovery/methods , Drug Repositioning/methods , Protease Inhibitors/pharmacology , SARS-CoV-2/enzymology , Amobarbital/pharmacology , Antiviral Agents/chemistry , Binding Sites , Computer Simulation , Humans , Machine Learning , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Protease Inhibitors/chemistry , Protein Binding , Quantitative Structure-Activity Relationship , SARS-CoV-2/drug effects , Small Molecule Libraries/chemistry , Software , Thermodynamics , Thyroxine/pharmacologyABSTRACT
INTRODUCTION: An appropriate localization of ictal onset zone in refractory temporal lobe epilepsy favors an adequate outcome associated with surgical treatment. When video-electroencephalogram (video-EEG) and magnetic resonance imaging do not provide accurate data to locate ictal onset zone, the use of subdural or deep intracranial electrodes is indicated. Hippocampal electrode placement could generate functional changes in an unaffected hippocampus. AIM: To describe mnesic changes in patients admitted for epilepsy surgery, with previous bilateral hippocampal implantation using depth electrodes. PATIENTS AND METHODS: We identified eight patients undergoing video-EEG using bilateral hippocampal electrodes. Verbal and nonverbal mnesic performance was evaluated before/after the procedure. The following aspects were considered for the analysis: memory lateralization according to intracarotid amobarbital test (Wada test), invasive ictal onset zone, side of resection and pattern of electrocorticographic dissemination. RESULTS: In patients with memory dominance, contralateral to the ictal onset zone, there was an improvement in verbal and nonverbal memory, suggesting that invasive recordings did not impair mnesic skills of the unaffected hippocampus. In patients with bilateral representation of memory, ipsilateral mnesic impairment was associated with the resection. Contralateral improvement in memory was seen when the right side was resected, as opposed to no changes with resections made on the left side, indicating that electrode implantation of unaffected hippocampus did not generate a functional decline. CONCLUSIONS: Based on the preservation of verbal and nonverbal memory after depth electrode placement, invasive recordings of the hippocampus seem to be safe.
Subject(s)
Electrodes, Implanted , Epilepsy, Temporal Lobe/surgery , Hippocampus/surgery , Memory Disorders/prevention & control , Mental Recall/physiology , Pattern Recognition, Visual/physiology , Postoperative Complications/prevention & control , Preoperative Care/methods , Verbal Learning/physiology , Adult , Aged , Amobarbital , Anterior Temporal Lobectomy , Carotid Artery, Internal , Dominance, Cerebral , Electrodes, Implanted/adverse effects , Electroencephalography , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/psychology , Female , Functional Laterality , Hippocampus/physiopathology , Humans , Injections, Intra-Arterial , Male , Memory Disorders/etiology , Memory Disorders/physiopathology , Middle Aged , Neuropsychological Tests , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Postoperative Complications/psychology , Young AdultABSTRACT
O Teste de Wada continua sendo um exame frequentemente utilizado, para a avaliação qualitativa e quantitativa da lateralidade das funções de linguagem e das funções de memória verbal, e do possível déficit residual, uma vez que simula o efeito da cirurgia na investigação pré-operatória de candidatos a lobectomia temporal. No Brasil, há consideráveis dificuldades impostas pelas autoridades sanitárias para obtenção do Amytal (amobarbital sódico). Descreve o protocolo do Teste de Wada realizado com Brevital (methoexital sódico) em dois candidatos a lobectomia temporal, comentar sua eficácia e suas diferenças em relação ao realizado com o Amytal. Relatou-se o uso do Brevital em dois pacientes submetidos a determinação da lateralidade da linguagem e da memória através de protocolo adaptado pata tal. O Brevital, um anestésico de ação curta, mostrou-se eficiente em ambos os casos como substituto ao Amytal. O Brevital pode ser utilizado no Brasil para a realização do Teste de Wada, com a vantagem de possibilitar um exame mais breve, assim como uma investigação abrangente das funções de memória
Subject(s)
Amobarbital , Anterior Temporal Lobectomy , Epilepsy, Temporal Lobe/therapy , Memory , Chemical PhenomenaABSTRACT
O Teste de Wada (TW) é parte integrante da avaliação pré-cirúrgica para epilepsias de difícil controle. O TW não é padronizado e os protocolos diferem em vários aspectos, incluindo tipos de estímulos para avaliação de memória, tempo de apresentação e metodologia de avaliação. O objetivo deste estudo foi contribuir no estabelecimento de parâmetros para utilização TW para a população brasileira, investigando o desempenho de 100 controles normais, sem medicação. Dois modelos (Modelos A e B) foram utilizados, baseados no Procedimento de Montreal e adaptadas do protocolo de Gail Risse (MEG-MN,EUA). Foram observadas as proporções de acerto dos sujeitos normais para os modelos de TW, em seguida, os dois modelos foram comparados entre si. Os resultados demonstraram que os dois modelos são similares mas, observaram-se significativas diferenças entre os tipos de estímulos. Os resultados sugerem que tipos de estímulos podem influenciar os resultados do TW e esses dados devem ser considerados na construção de modelos e comparações entre diferentes protocolos.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Amobarbital , Epilepsy/physiopathology , Functional Laterality , Language , Memory/physiology , Neuropsychological Tests/standards , Amobarbital/pharmacology , Brazil , Brain/drug effects , Case-Control Studies , Educational Status , Language Tests , Sex Distribution , Visual PerceptionABSTRACT
The Wada Test (WT) is part of the presurgical evaluation for refractory epilepsy. The WT is not standardized and the protocols differ in important ways, including stimulus type of material presented for memory testing, timing of presentations and methods of assessment. The aim of this study was to contribute to establish parameters for a WT to Brazilian population investigating the performance of 100 normal subjects, without medication. Two parallel models were used based on Montreal Procedure adapted from Gail Risse's (MEG-MN,EUA) protocol. The proportions of correct responses of normal subjects submitted to two parallel WT models were investigated and the two models were compared. The results showed that the two models are similar but significant differences among the stimulus type were observed. The results suggest that the stimulus type may influence the results of the WT and should be considered when constructing models and comparing different protocols.
Subject(s)
Amobarbital , Epilepsy/physiopathology , Functional Laterality/physiology , Language Tests , Memory/physiology , Neuropsychological Tests/standards , Adolescent , Adult , Amobarbital/pharmacology , Brain/drug effects , Brazil , Case-Control Studies , Educational Status , Female , Humans , Male , Middle Aged , Sex Distribution , Visual PerceptionABSTRACT
The intracarotid sodium amytal test (ISAT or Wada Test) is a commonly performed procedure in the evaluation of patients with clinically refractory epilepsy candidates to epilepsy surgery. Its goal is to promote selective and temporary interruption of hemispheric functioning, seeking to define language lateralization and risk for memory compromise following surgery. Behavioral modification is expected during the procedure. Even though it may last several minutes, in most cases it is subtle and easily manageable. We report a series of patients in whom those reactions were unusually bizarre, including agitation and aggression. Apart of the obvious technical difficulties (patients required physical restraining) those behaviors potentially promote testing delay or abortion and more importantly, inaccurate data. We reviewed those cases, seeking for features that might have predicted their occurrence. Overall, reactions are rare, seen in less than 5% of the ISAT procedures. The barbiturate effect, patients' psychiatric profiles, hemisphere dominance or selectiveness of the injection were not validated as predictors. Thorough explanation, repetition and simulation may be of help in lessening the risk of those reactions.
Subject(s)
Amobarbital/adverse effects , Behavior/drug effects , Epilepsy/physiopathology , Hypnotics and Sedatives/adverse effects , Psychoses, Substance-Induced/etiology , Adolescent , Adult , Brain Neoplasms/physiopathology , Carotid Arteries , Epilepsy, Temporal Lobe/physiopathology , Female , Glioma/physiopathology , Humans , Injections, Intra-Arterial , Male , Parietal Lobe , Predictive Value of Tests , Retrospective StudiesABSTRACT
O teste do amital sódico intracarotídeo (TASI ou teste de Wada) é procedimento comum na avaliação de pacientes portadores de epilepsia clinicamente refratária candidatos a cirurgia de epilepsia. Tem por objetivo promover interrupção seletiva e temporária da função hemisferial, definindo lateralização de linguagem e risco de comprometimento de memória no pós-operatório. São esperadas mudanças comportamentais durante o teste, as quais podem durar vários minutos, porém, em geral, são sutis e facilmente manejáveis. Relatamos uma série de casos em que ocorreram comportamentos pouco usuais, bizarros, incluindo agitação e agressividade. Estes comportamentos comprometem o teste (paciente deve ser contido), podendo levar a atrasos ou mesmo abortamento do mesmo, além de produzir dados menos confiáveis. Os casos foram revisados, visando a definição de preditores de sua ocorrência. Estas reações são raras (5% dos casos). Efeito barbitúrico, perfil psiquiátrico, dominância cerebral e seletividade da injeção não puderam ser validados como preditores. Explicações detalhadas, repetição e simulações podem ser utéis na prevenção deste tipo de ocorrência.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Amobarbital/pharmacology , Behavior/drug effects , Epilepsy/physiopathology , Hypnotics and Sedatives/pharmacology , Brain Neoplasms/physiopathology , Brain Neoplasms/surgery , Carotid Arteries , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/surgery , Epilepsy/surgery , Glioma/physiopathology , Glioma/surgery , Injections, Intra-Arterial , Parietal Lobe , Predictive Value of TestsABSTRACT
A lobectomia temporal anterior (LTA) é reconhecidamente um tratamento eficaz para epilepsias de lobo temporal de difícil controle. O teste de Wada (TW) é parte da investigação pré-cirúrgica para epilepsia, mas sua capacidade de previsão ainda é discutida. Os resultados no TW para reserva, capacidade e assimetria foram comparados com os resultados nos testes de aprendizagem de lista de palavras de Rey e figura complexa de Rey de 34 pacientes com epilepsia de lobo temporal unilateral submetidos a lobectomia temporal anterior (10 a direita 24 esquerda). A análise demonstrou que reserva e capacidade no TW não são suficientemente sensíveis para prever déficit de memória pós operatório./The anterior temporal lobectomy (ATL) is recognized as an effective treatment for the refractory temporal lobe epilepsy. The Wada test (WT) is part of the pre-surgical assessment but its predictive value is still debated. The WT results for reserve, capacity and asymmetry were compared with pre and post surgery scores on Rey auditory verbal learning test and Rey complex figure test of 34 unilateral temporal lobe epilepsy patients submitted anterior temporal lobectomy (10 right and 24 left). Analysis showed that the WT reserve and capacity scores were not sensitive enough to predict post surgery memory deficits.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Amobarbital , Epilepsy, Temporal Lobe/surgery , Memory Disorders/diagnosis , Prognosis , Sensitivity and SpecificitySubject(s)
Humans , Male , Adult , Amobarbital , Language Tests , Propofol , Craniocerebral Trauma , Functional Laterality , Injections, Intra-Arterial , Memory , Neuropsychological TestsSubject(s)
Humans , Female , Adult , Amobarbital/therapeutic use , Anesthetics, Intravenous , Cerebrum/drug effects , Neuropsychological Tests , PropofolABSTRACT
The intracarotid amobarbital procedure was carried out in 8 male and 7 female candidates to temporal lobectomy, and a female candidate to frontal lesionectomy, aged 18-50 (mean 32.5) years. Language and memory were tested after injection in each hemisphere. Both were measured by the Montreal procedure. In 9 patients language and memory were evaluated with the Seattle procedure too. In 12 patients the left hemisphere was dominant for language; three had bilateral dominance. In 1 patient the Seattle procedure demonstrated the dominant hemisphere by relatively slowness of speech during the drug effect in the left hemisphere. Memory was defined to be in the left hemisphere in 12 patients, in the right in 2, bilateral in 1 and in another lateralization was not possible. In 1 patient memory dominance was determined by the Montreal protocol alone because of lack of cooperation. These early results indicate that the methods may be complementary for determination of language and memory dominance in epilepsy surgery candidates.
Subject(s)
Amobarbital/pharmacology , Epilepsy/surgery , Neuropsychological Tests , Adolescent , Adult , Female , Functional Laterality , Humans , Language Tests , Male , Memory/drug effects , Middle AgedABSTRACT
The intracarotid amobarbital procedure was carried out in 8 male and 7 female candidates to temporal lobectomy, and a female candidate to frontal lesionectomy, aged 18-50 (mean 32.5) years. Language and memory were tested after injection in each hemisphere. Both were measured by the Montreal procedure. In 9 patients language and memory were evaluated with the Seattle procedure too. In 12 patients the left hemisphere was dominant for language; three had bilateral dominance. In 1 patient the Seattle procedure demonstrated the dominant hemisphere by relatively slowness of speech during the drug effect in the left hemisphere. Memory was defined to be in the left hemisphere in 12 patients, in the right in 2, bilateral in 1 and in another lateralization was not possible. In 1 patient memory dominance was determined by the Montreal protocol alone because of lack of cooperation. These early results indicate that the methods may be complementary for determination of language and memory dominance in epilepsy surgery candidates.
Subject(s)
Adult , Middle Aged , Female , Humans , Adolescent , Amobarbital/pharmacology , Epilepsy/surgery , Neuropsychological Tests , Functional Laterality , Language Tests , Memory/drug effectsABSTRACT
Este estudo discute os resultados obtidos no teste de amital sódico (TAS) intracarotídeo e seu valor prognóstico e de lateralizaçäo em pacientes com epilepsia do lobo temporal (ELT) e esclerose mesial temporal (EMT). Dezoito pacientes foram submetidos ao TAS. Quinze possuíam epilepsias bitemporais e 3 unilaterais. Todos os pacientes possuíam EMT na RMN e em 1 existia uma calcificaçäo hipocampal contralateral. Nove pacientes bitemporais passaram a injeçäo ipsilateral à EMT e 4 falharam bilateralmente. Um paciente bitemporal passou bilateralmente. Sete pacientes bitemporais passaram a injeçäo ipsilateral à EMT e falharam do outro lado. Dois pacientes unitemporais tiveram este mesmo comportamento. Um paciente unitemporal falhou bilateralmente no TAS. Globalmente, 56 por cento dos pacientes apresentaram o padräo passa ipsi-/falha contralateral no TAS. Oito pacientes foram operados, estäo sem crises e näo tiveram déficits adicinonais de memória. Muitos pacientes com ELT possuem o padräo passa ipsi-/falha contralateral no TAS. Isto deve representar fator de lateralizaçäo e prognóstico relevante
Subject(s)
Humans , Animals , Amobarbital , Epilepsy, Temporal Lobe/diagnosis , Temporal Lobe/pathology , Carotid Artery, Internal , Electroencephalography , Epilepsy, Temporal Lobe/pathology , Functional Laterality , Hippocampus/pathology , Injections, Intra-Arterial , Magnetic Resonance Imaging , Memory Disorders , Prognosis , SclerosisABSTRACT
This study discusses the results from the IAP and its lateralizing and prognostic value in patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). Eighteen patients were submitted to the IAP. Fifteen had bitemporal and 3 unitemporal lobe epilepsies. All patients had MTS on MRI and in one there was an unrelated lesion in the contralateral hippocampus. Nine bitemporal patients passed after the injection ipsilateral to the MTS and 4 failed bilaterally. One bitemporal passed bilaterally. Seven of these bitemporal patients passed an injection ipsilateral to MTS and failed on contralateral injection. Two of the unitemporal lobe patients passed the ipsilateral injection and failed the contralateral one. One of the unitemporal lobe patients failed bilaterally the IAP. Overall, 56% of the group disclosed the pass ipsi-/fail contralateral pattern in the IAP. Eight patients were operated, are seizure free and had no additional memory deficit. Many patients with TLE were found to have the pass ipsi-/fail contralateral pattern in the IAP. This might prove to be of lateralizing and prognostic value in such cases.
Subject(s)
Amobarbital , Epilepsy, Temporal Lobe/diagnosis , Temporal Lobe/pathology , Animals , Carotid Artery, Internal , Electroencephalography , Functional Laterality , Hippocampus/pathology , Humans , Injections, Intra-Arterial , Memory Disorders , Prognosis , SclerosisABSTRACT
We report on a right-handed bilingual patient with a left perisylvian arteriovenous malformation that caused a mild naming deficit evident only on formal language testing in both languages. Sodium amytal injected in the left carotid artery (Wada test) before surgery resulted in speech arrest for both languages. Following surgery for removal of the lesion she developed additional deficits in her native language without alteration in her second language. Selective impairment in one language after surgery demonstrates that each language has different anatomical representation within the perisylvian dominant area.
Subject(s)
Hematoma/physiopathology , Language Disorders/etiology , Parietal Lobe/physiopathology , Postoperative Complications , Temporal Lobe/physiopathology , Temporal Lobe/surgery , Adult , Amobarbital , Arteriovenous Malformations/complications , Arteriovenous Malformations/diagnosis , Bolivia/ethnology , Dominance, Cerebral , Epilepsy, Generalized/etiology , Epilepsy, Generalized/physiopathology , Female , Hematoma/complications , Humans , Language Disorders/diagnosis , Language Disorders/physiopathology , Magnetic Resonance Imaging , Neuropsychological Tests , United StatesABSTRACT
We performed a selective Wada test on a bilingual patient. While a left middle cerebral artery (MCA) injection produced global aphasia for both (Spanish and English) languages, the patient could only speak Spanish (his mother tongue) 1 min after he started to speak English. No language disturbances were observed after a right MCA amytal injection. These findings suggest that all of a multilingual's languages are stored within the verbal-dominant perisylvian region, and while the second language may be organized within the central Sylvian core, the first language may be better represented in more distal perisylvian areas.
Subject(s)
Amobarbital , Aphasia/diagnosis , Dominance, Cerebral/physiology , Embolization, Therapeutic , Intracranial Arteriovenous Malformations/therapy , Language , Adult , Angiography, Digital Subtraction , Aphasia/physiopathology , Cerebral Angiography , Humans , Male , Neuropsychological Tests , Speech Perception/physiologyABSTRACT
Soon after treatment of a right basotemporal vascular malformation using an embolization procedure, a 25-year-old patient developed an acute episode of mania. Two months later the patient was still manic, and a second embolization was scheduled. Before it was conducted, a Wada test was carried out to determine speech dominance. No changes in manic symptoms were observed after amytal injections into the left middle cerebral, right frontopolar, or right middle cerebral arteries. This finding suggests that secondary mania may not be the result of "release" of the left hemisphere following a right hemisphere lesion but instead may be related to specific disturbances within the right hemisphere.