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Background: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA)., Methods: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial., Results: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance., Conclusions: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects., (© 2024. The Author(s).)

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF 6 and [Ru(L)(dppe) 2 ]PF 6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane and bipy = 2,2'-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV-vis and IR spectroscopies, and two by X-ray crystallography. The 31 P{ 1 H} NMR spectra of the complexes with the general formula [Ru(L)(dppe) 2 ]PF 6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF-7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe) 2 ]PF 6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe) 2 ]PF 6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 (M pro ) 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 M pro 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 M pro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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) (Połczyńska 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

TNF-α/cycloheximide (CHX)-induced apoptosis of the mouse intestinal epithelial cell line MODE-K corresponds with the production of reactive oxygen species (ROS). The aim of the study is to investigate the sources of ROS production contributing to apoptotic cell death during TNF-α/CHX-induced oxidative stress in MODE-K cells. Total ROS or mitochondrial superoxide anion production was measured simultaneously with cell death in the absence or presence of pharmacological inhibitors of various ROS-producing systems, and of ROS scavengers/antioxidants. The influence of TNF-α/CHX on mitochondrial membrane potential (Ψ(m)) and cellular oxygen consumption was also studied. TNF-α/CHX time-dependently increased intracellular total ROS and mitochondrial superoxide anion production in MODE-K cells, starting from 2h. Inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) by a pan-NOX inhibitor (VAS-2870) and a specific inhibitor of Rac1 (NSC23766) significantly reduced TNF-α/CHX-induced total ROS and cell death levels. The mitochondrial electron transport chain inhibitors, amytal (IQ site of complex I) and TTFA (Qp site of complex II) showed a pronounced decrease in TNF-α/CHX-induced total ROS, mitochondrial superoxide anion and cell death levels. TNF-α/CHX treatment caused an immediate decrease in mitochondrial respiration, and a loss of Ψ(m) and increase in mitochondrial dysfunction from 1 h on. The results suggest that mitochondria and NOX are the two major sources of ROS overproduction during TNF-α/CHX-induced cell death in MODE-K cells, with superoxide anions being the major ROS species. Particularly, the quinone-binding sites of mitochondrial complex I (site I(Q)) and complex II (site Qp) seem to be the major sites of mitochondrial ROS production., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: Excess mitochondrial reactive oxygen species (mROS) play a vital role in cardiac ischemia reperfusion (IR) injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection., Methods: Isolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion., Results: Phosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion., Conclusion: Our results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury.

129 Wada procedures were reviewed to examine the suitability of propofol (n=54) as a replacement to amobarbital (n=75) for use as an anaesthetic in the Wada test. Suitability was considered with respect to length of hemiplegia induced, the frequency of side effects and patient memory scores. Data was retrospectively collected from records of patients who had undergone the Wada procedure between 2004 and 2009 in Beaumont Hospital, Dublin. No significant differences were found between the two drugs on any of the measures. The results suggest that propofol represents a suitable alternative to amobarbital for use in the Wada procedure., (Copyright © 2012. Published by Elsevier Ltd.)

Introduction: The Wada test has been the gold standard for testing cerebral language localisation during presurgical investigation in the past decades. However, during the last few years a shift has occurred in epilepsy surgery programmes towards the use of non-invasive methods, predominantly functional MRI (fMRI). However, Wada tests are still performed, albeit in a considerably smaller number of patients at many epilepsy centres., Methods: A retrospective monocentric analysis of remaining clinical indications for performing a Wada procedure was undertaken. The clinical data of patients who participated in Wada tests (42 hemispheric and 8 superselective procedures) during recent years were retrospectively evaluated., Results: Reasons for conducting a Wada test were (1) a patient's inability to perform the fMRI task due to agitation, mental disablement, or perceptual impairment, (2) validation of atypical, inconclusive or not clearly lateralised language activation shown with fMRI, (3) evaluation of propagation of ongoing interictal bilateral epileptiform EEG activity, (4) region selective testing of language and other cognitive functions, or (5) assessment of motor localisation. Patients who were not able to perform the fMRI task or in whom fMRI did not provide interpretable results were significantly younger (p<0.05)., Conclusion: It is argued that fMRI is eligible to replace Wada tests in the majority of patients who are compliant with clearly lateralised language localisation, but in patients who are agitated or mentally impaired as well as in the case of the above-mentioned specific clinical indications and bilateral fMRI activations, Wada tests still provide additional information. Additionally, non-invasive methods less sensitive to movement artefacts are discussed as possible alternatives for these patients.

Cardiac ischemia damages the mitochondrial electron transport chain and the damage persists during reperfusion. Ischemic postconditioning (PC), applied during early reperfusion, decreases cardiac injury. This finding suggests that the ischemia-damaged mitochondria can be regulated to decrease cardiac injury. The reversible blockade of electron transport during ischemia prevents damage to mitochondria. We propose that the targets of PC cytoprotective signaling are mitochondria damaged by ischemia. Thus, if ischemia-mediated mitochondrial damage is prevented, PC at the onset of reperfusion will not result in additional protection. Isolated, Langendorff-perfused adult rat hearts underwent 25-minute global ischemia and 30-minute reperfusion. Amobarbital (2.5 mM) was used to reversibly inhibit electron transport during ischemia. PC (6 cycles of 10-second ischemia-reperfusion) was applied at the onset of reperfusion. Subsarcolemmal and interfibrillar mitochondria were isolated after reperfusion. Blockade of electron transport with amobarbital only during ischemia preserved oxidative phosphorylation and decreased myocardial injury. PC, after untreated ischemia, decreased cardiac injury without improvement of oxidative phosphorylation. Blockade of electron transport during ischemia or PC improved calcium tolerance and inner membrane potential in subsarcolemmal mitochondria after reperfusion. In hearts treated with amobarbital before ischemia, PC did not provide further protection. Thus, PC protects myocardium via the regulation of ischemia-damaged mitochondria during early reperfusion.

Myocardial ischemia damages the electron transport chain and augments cardiomyocyte death during reperfusion. To understand the relationship between ischemic mitochondrial damage and mitochondrial-driven cell death, the isolated perfused heart underwent global stop-flow ischemia with and without mitochondrial protection by reversible blockade of electron transport. Ischemic damage to electron transport depleted bcl-2 content and favored mitochondrial permeability transition (MPT). Reversible blockade of electron transport preserved bcl-2 content and attenuated calcium-stimulated mitochondrial swelling. Thus, the damaged electron transport chain leads to bcl-2 depletion and MPT opening. Chemical inhibition of bcl-2 with HA14-1 also dramatically increased mitochondrial swelling, augmented by exogenous H(2)O(2) stress, indicating that bcl-2 depleted mitochondria are poised to undergo MPT during the enhanced oxidative stress of reperfusion., (Copyright © 2011. Published by Elsevier B.V.)

Awareness of deficits is often impaired following disruption of the right hemisphere. Intracarotid anesthetic procedures (IAPs) represent a unique method by which we can assess functioning of each hemisphere in isolation. We used this technique to explore deficits of awareness of specific functions-motor ability, naming, and comprehension-in patients with temporal lobe epilepsy. Some patients were injected with amobarbital, whereas others were injected with etomidate. We found that injection into the right hemisphere, or epileptogenic focus in the right hemisphere following injection in the left, resulted in the lowest levels of motor awareness. We also found a higher level of awareness for expressive language deficits and less awareness for receptive language deficits. Comparison of etomidate and amobarbital suggested more awareness following injection of etomidate. We discuss how these findings contribute to our understanding of the right hemisphere's special role in awareness, and how research in other disorders and in comparative neurology has shaped our conceptualization of the neuroanatomy of insight., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In this paper, the results of studies that have used the intracarotid sodium amytal (amobarbital) test to examine hemispheric lateralization of emotional expression has been reviewed. The important findings are that the emotional states are dissociated from the neurological effects (aphasia, hemiplegia), and occur later, when the electroencephalogram (EEG) is showing evidence of activation. The effects of left hemisphere barbiturization are less clear than those of the right hemisphere, and there is good concordance that the latter lead to states of alteration in mood or euphoria.

Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15min followed by 30min stop-flow ischemia at 37 degrees C. Amobarbital (2.5mM) or azide (5mM) was used to block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase., (Published by Elsevier Inc.)

Purpose: Some patients with pharmacoresistant epilepsy undergoing the Wada test experience transient shivering. The purpose of this study was to investigate various clinical and radiographic characteristics of these individuals to delineate underlying mechanisms of this phenomenon., Methods: A systematic review of prospectively collected information on patients undergoing the Wada test was performed. All demographic, clinical, and radiographic information was obtained and reviewed by the appropriate expert in the field; statistical analysis was performed to determine the predictors of transient shivering., Results: A total of 120 consecutive carotid artery injections in 59 patients were included in the study. Shivering was observed in 46% of the patients, and it was not significantly affected by gender, age, location of epileptogenic zone, brain lesion on magnetic resonance imaging (MRI), side of the first injection, duration of the hemiparesis, or excess slow wave activity on electroencephalography (EEG). However, shivering was more likely to follow sodium amobarbital injection if there was no filling of the posterior circulation on cerebral angiogram., Discussion: Transient shivering during the Wada test is common. A transient but selective functional lesion of the anterior hypothalamus produced by the effects of sodium amobarbital may result in disinhibition of the posterior hypothalamus and other brainstem thermoregulatory centers, thereby inducing transient shivering.

Introduction: Methohexital has replaced amobarbital during Wada testing at many centers. The objective of our study was to compare the use of methohexital and amobarbital during Wada testing regarding language and memory lateralization quotients as well as speech arrest times., Methods: A chart review of 582 consecutive patients undergoing 1041 Wada-procedures was performed (left=60, right=63, bilateral=459). Language lateralization was calculated based on duration of speech arrest using a laterality index, defined as (L-R)/(L+R). Memory lateralization was expressed as percentage of retained objects and laterality quotient., Results: Language and memory lateralization revealed a similar distribution with amobarbital and methohexital. Speech arrest after left and right-sided injection was significantly longer in the amobarbital group as compared to the methohexital group. Language lateralization did not differ in the two groups. Percentage of retained memory items was higher in the methohexital group and there were fewer presented test items in the methohexital group., Discussion: Language and memory testing during the Wada test can successfully be performed with methohexital instead of amobarbital. The shorter half-life of methohexital allows repeated injections and shorter interhemispheric testing intervals, but also shortens the testing window.

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.

Purpose: To assess the prevalence and attributes of atypical language lateralization (ALL) in patients with left mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS)., Methods: We recruited consecutive patients with left MTLE-HS, who had undergone resective surgery and had pathologically proven HS. Based on the Wada test, language lateralization was classified into typical (left hemispheric) or atypical (right hemispheric or codominant). We assessed the attributes of patients with ALL using univariate and multivariate analyses., Results: Of 124 patients with left MTLE-HS, 23 (18.5%) had ALL. ALL occurred more frequently in patients with severe initial precipitating injury (IPI), early onset of epilepsy, and a short latent period between IPI and onset of habitual seizures. ALL was more common in patients with bitemporal and extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On multivariate analyses, the age at onset of habitual seizures <6 years, atypical IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities independently predicted ALL. The likelihood of ALL was very low ( approximately 1%) when all of these four risk factors were absent, whereas it was very high (>95%), if any three or all four of them were present., Conclusions: ALL occurs in one-fifth of patients with left MTLE-HS. ALL is more frequent in those with structural or functional extrahippocampal involvement and early onset of epilepsy interrupting the development of normal language networks. Because ALL is uncommon in those with damage/dysfunction restricted to the hippocampus, the hippocampus itself may have only a limited role in determining language lateralization.

Succinate-containing derivatives of 3-hydroxypyridine, mexidol and proxypin, serve as succinate donors for the respiratory chain and contribute to activation of the succinate oxidase pathway of oxidation. Under conditions of hypoxia, these changes promote recovery of aerobic energy production, normalization of intracellular ATP concentration, and development of the antihypoxic effect. Succinate-free analogues of the test compounds exhibit no such properties. Both agents are considered as energotropic substances. The specific effect of these compounds is manifested in direct interaction with the respiratory chain and normalization of ATP synthesis under conditions of hypoxia/ischemia. The test compounds can be used for the correction of energy metabolism disorders during acute oxygen deficiency. Moreover, they can be used for the treatment of associated functional disturbances.

Purpose: This work examines the efficacy of functional magnetic resonance imaging (fMRI) for language lateralization using a comprehensive three-task language-mapping approach. Two localization methods and four different metrics for quantifying activation within hemisphere are compared and validated with Wada testing. Sources of discordance between fMRI and Wada lateralization are discussed with respect to specific patient examples., Methods: fMRI language mapping was performed in patients with epilepsy (N = 40) using reading sentence comprehension, auditory sentence comprehension, and a verbal fluency task. This was compared with the Wada procedure using both whole-brain and midline exclusion-based analyses. Different laterality scores were examined as a function of statistical threshold to investigate the sensitivity to threshold effects., Results: For the lateralized patients categorized by Wada, fMRI laterality indices (LIs) were concordant with the Wada procedure results in 83.87% patients for the reading task, 83.33% patients for the auditory task, 76.92% patients for the verbal fluency task, and in 91.3% patients for the conjunction analysis. The patients categorized as bilateral via the Wada procedure showed some hemispheric dominance in fMRI, and discrepancies between the Wada test findings and the functional laterality scores arose for a range of reasons., Discussion: Discordance was dependent upon whether whole-brain or midline exclusion method-based lateralization was calculated, and in the former case the inclusion of the occipital and other midline regions often negatively influenced the lateralization scores. Overall fMRI was in agreement with the Wada test in 91.3% of patients, suggesting its utility for clinical use with the proper consideration given to the confounds discussed in this work.

Purpose: To examine distributed patterns of language processing in healthy controls and patients with epilepsy using magnetoencephalography (MEG), and to evaluate the concordance between laterality of distributed MEG sources and language laterality as determined by the intracarotid amobarbital procedure (IAP)., Methods: MEG was performed in 10 healthy controls using an anatomically constrained, noise-normalized distributed source solution (dynamic statistical parametric map, dSPM). Distributed source modeling of language was then applied to eight patients with intractable epilepsy. Average source strengths within temporoparietal and frontal lobe regions of interest (ROIs) were calculated, and the laterality of activity within ROIs during discrete time windows was compared to results from the IAP., Results: In healthy controls, dSPM revealed activity in visual cortex bilaterally from approximately 80 to 120 ms in response to novel words and sensory control stimuli (i.e., false fonts). Activity then spread to fusiform cortex approximately 160-200 ms, and was dominated by left hemisphere activity in response to novel words. From approximately 240 to 450 ms, novel words produced activity that was left-lateralized in frontal and temporal lobe regions, including anterior and inferior temporal, temporal pole, and pars opercularis, as well as bilaterally in posterior superior temporal cortex. Analysis of patient data with dSPM demonstrated that from 350 to 450 ms, laterality of temporoparietal sources agreed with the IAP 75% of the time, whereas laterality of frontal MEG sources agreed with the IAP in all eight patients., Discussion: Our results reveal that dSPM can unveil the timing and spatial extent of language processes in patients with epilepsy and may enhance knowledge of language lateralization and localization for use in preoperative planning.

Purpose: Magnetoencephalography (MEG)/magnetic source imaging (MSI) is a noninvasive functional neuroimaging procedure used to localize language-specific regions in the brain. The Wada test, or intracarotid amobarbital procedure (IAP), is the gold standard in determining speech/language lateralization for presurgical planning, although it is invasive and associated with morbidity. The purpose of this study is to provide further validation on the use of MSI for presurgical language lateralization by comparing results against the IAP., Methods: The sample consisted of 35 patients with epilepsy and/or brain tumor undergoing presurgical evaluation at the Minnesota Epilepsy Group. All patients received both an IAP and MSI to determine hemispheric language dominance. For MSI, a 148-channel MEG system was used to record activation of language-specific cortex by an auditory word-recognition task., Results: The MSI and IAP were concordant in determining language in the hemisphere to be treated in 86% of the cases with sensitivity and specificity values of 80% and 100%, respectively., Conclusions: The results from this study are consistent with prior research findings comparing functional neuroimaging procedures to the IAP in determining language lateralization in presurgical patients. The current study provides an important replication and support for Papanicolaou et al.'s findings in 2004 using a consecutive clinical sample from a different institution. An unusually high rate of atypical IAP language cases in this sample and differences between the two procedures are believed to explain the noted discrepancies. MSI is a viable noninvasive alternative to the IAP in the presurgical determination of language lateralization.

The intracarotid amobarbital procedure (IAP) has for over 50 years been an important component of the presurgical investigation of patients with epilepsy who are candidates for surgical intervention as treatment for their seizures. Owing to increasing frequency and duration of amobarbital shortages, alternatives for this drug have been sought and implemented, but until now only the drug was changed, while the basic procedure remained essentially the same as that used with amobarbital. This paper describes the Montreal Neurological Institute experience using etomidate in place of amobarbital and introducing a significant change in the procedure: after an initial bolus injection, an infusion is used to maintain the level of hemianesthesia during critical test times. Results of 28 patients tested with this procedure are compared to results from 40 patients tested in the standard IAP.

The Neurovisceral Integration Model is based on the premise of significant central nervous system-peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1-10 of inactivation) [Roy's Root (10,59)=0.378, p=0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system-peripheral nervous system relationships.

Data from lesion studies suggest that the ability to perceive speech sounds, as measured by auditory comprehension tasks, is supported by temporal lobe systems in both the left and right hemisphere. For example, patients with left temporal lobe damage and auditory comprehension deficits (i.e., Wernicke's aphasics), nonetheless comprehend isolated words better than one would expect if their speech perception system had been largely destroyed (70-80% accuracy). Further, when comprehension fails in such patients their errors are more often semantically-based, than-phonemically based. The question addressed by the present study is whether this ability of the right hemisphere to process speech sounds is a result of plastic reorganization following chronic left hemisphere damage, or whether the ability exists in undamaged language systems. We sought to test these possibilities by studying auditory comprehension in acute left versus right hemisphere deactivation during Wada procedures. A series of 20 patients undergoing clinically indicated Wada procedures were asked to listen to an auditorily presented stimulus word, and then point to its matching picture on a card that contained the target picture, a semantic foil, a phonemic foil, and an unrelated foil. This task was performed under three conditions, baseline, during left carotid injection of sodium amytal, and during right carotid injection of sodium amytal. Overall, left hemisphere injection led to a significantly higher error rate than right hemisphere injection. However, consistent with lesion work, the majority (75%) of these errors were semantic in nature. These findings suggest that auditory comprehension deficits are predominantly semantic in nature, even following acute left hemisphere disruption. This, in turn, supports the hypothesis that the right hemisphere is capable of speech sound processing in the intact brain.

The cellular ATP concentration was tested for its effect on fatty acid biosynthesis from glucose in hepatocytes. ATP was manipulated by adding increasing concentrations of cycloheximide, amytal, atractyloside, 2,4-dinitrophenol or adenosine. A slight decrease in cellular ATP coincided with a stimulation of fatty acid biosynthesis whereas a further lowering of cellular ATP resulted in a gradual inhibition. Increasing the cellular ATP level by titration with adenosine had the opposite effect. These results are in line with the suggestion that fatty acid biosynthesis from glucose is an energy-yielding process which is stimulated by a moderate drop in cellular ATP.

Epilepsy surgery has been proved to be efficacious, safe and cost-effective in developing countries. However, the success of epilepsy surgery depends on selecting suitable candidates based on the available resources and technologies. Some of the challenges to provide appropriate surgical treatment for epilepsy patients in developing countries include providing human and technological resources and developing realistic presurgical protocols. Detection of ideal candidates for epilepsy surgery is possible for well-trained epileptologists with the help of basic investigative technologies, for example, magnetic resonance imaging (MRI) and electroencephalography (EEG). Patients with potentially epileptogenic, well-circumscribed lesions on MRI and patients with mesial temporal lobe epilepsy (MTLE) are reasonable candidates for surgery. Palliative epilepsy surgeries include corpus callosotomy and other disconnections. These operations are feasible in developing countries with a knowledgeable team consisting of an epileptologist, neurosurgeon and technicians and with using MRI and EEG as basic investigative technologies.

Aim: Damage to the mitochondrial electron transport chain (ETC) occurs during ischaemia. Blockade of electron flow in the ETC just before ischaemia with the reversible complex I inhibitor amobarbital protects isolated mitochondria against ischaemic damage and preserves oxidative phosphorylation and cytochrome c content. We hypothesized that brief amobarbital perfusion just before ischaemia would improve cardiac recovery and decrease infarct size after ischaemia and reperfusion (IR) by preserving the mitochondrial redox state and reducing mitochondrial superoxide (O(2)(-*)) generation, in turn would decrease mitochondrial Ca(2+) accumulation (mt[Ca(2+)])., Methods: Guinea pig Langendorff-perfused hearts were treated with Krebs Ringer solution (KR; untreated) or amobarbital (2.5 mM) in KR for 1 min immediately before 30 min of no flow, global ischaemia, followed by reperfusion without additional treatment. Cardiac function, mitochondrial NADH, FAD, mt[Ca(2+)], and O(2)(-*) levels were assessed during the 1 min perfusion period and throughout IR., Results: Amobarbital perfusion alone before ischaemia significantly increased O(2)(-*) levels and NADH, without altering FAD, and decreased mt[Ca(2+)]. During ischaemia, mitochondrial NADH was higher, O(2)(-*) levels were lower, and mt[Ca(2+)] was less elevated in the amobarbital group. On reperfusion O(2)(-*) levels and mt[Ca(2+)] were significantly reduced, NADH-FAD redox state was preserved and cardiac function was markedly improved in the amobarbital group; infarct size was smaller in the amobarbital group compared to the untreated group., Conclusion: Temporary blockade of mitochondrial complex I activity by amobarbital protects hearts by reducing production of O(2)(-*) and mtCa(2+) loading during IR injury.

Purpose: Noninvasive tests that accurately localize seizure onset provide great value in the presurgical evaluation of patients with intractable epilepsy. This study examined the diagnostic utility of three expressive language disturbances in lateralizing language-dominant (DOM) temporal lobe complex partial seizures: (1) the postictal language delay (PILD; time taken to correctly read a test phrase out loud immediately following seizures); (2) the production of postictal phonemic paraphasic errors (PostPE); and (3) interictal phonemic paraphasic errors (InterPE)., Methods: All 60 subjects underwent inpatient video/EEG monitoring and had surgically confirmed temporal lobe epilepsy (TLE). We determined the presence and number of PostPE and, PILD times (in s) for 212 seizures, and InterPE on the Boston Naming Test (BNT). Each technique's diagnostic usefulness was evaluated via logistic regression and ROC curve analysis. Sensitivity, specificity, positive predictive value and negative predictive values were computed., Results: PILD, PostPE and InterPE production were equally effective and accurate in lateralizing DOM seizure onset. Patients with DOM TLE had a longer PILD and committed more PostPE and InterPE than those with nondominant (NDOM) TLE. Respective sensitivity and specificity values were as follows: PILD (84%, 86%), PostPE (94%, 64%), and InterPE (97%, 86%). No single predictor was significantly better but a combination model yielded enough incremental utility to collectively outperform each separate predictor model., Conclusions: Interictal language testing is as accurate as postictal language testing in predicting DOM lateralization of TLE. Clinicians should also attend to the quality of errors produced during interictal and postictal language testing.

As a major co-morbidity of Parkinson's disease (PD), depression is associated with the loss of serotonergic neurons. Our recent study has shown that midbrain dopaminergic neurons are particularly vulnerable to microtubule-depolymerizing agents including rotenone, an environmental toxin linked to PD. Here we show that rotenone also selectively killed serotonergic neurons in midbrain neuronal cultures. Its selective toxicity was significantly decreased by the microtubule-stabilizing drug taxol and mimicked by microtubule-depolymerizing agents such as colchicine and nocodazole. Microtubule depolymerization induced by rotenone or colchicine caused vesicle accumulation in the soma and killed serotonergic neurons through a mechanism dependent on serotonin metabolism in the cytosol. Blocking serotonin synthesis or degradation, as well as application of antioxidants, significantly reduced the selective toxicity of rotenone or colchicine. Inhibition of vesicular sequestration of serotonin exerted a selective toxicity on serotonergic neurons that was mitigated by blocking serotonin metabolism. Over-expression of parkin, a protein-ubiquitin E3 ligase that strongly binds to microtubules, greatly attenuated the selective toxicity of rotenone or colchicine. The protective effects of parkin were abrogated by its PD-linked mutations. Together, our results suggest that rotenone and parkin affect the survival of serotonergic neurons by impacting on microtubules in opposing manners.

We describe two patients who underwent intracarotid amobarbital procedure (IAP) postoperatively following temporal lobectomy (one right temporal and one left temporal lobectomy), prompted by consideration of reoperation for persistent, intractable seizures. IAP memory score, consisting of the percentage of correctly recognized dually encoded stimuli, was calculated for each hemisphere. Both patients performed well on the IAP baseline memory assessment prior to injections, and both were left hemisphere dominant for language. The IAP memory results were consistent with the postoperative neuropsychological memory evaluation in that the patient who had undergone nonlanguage-dominant temporal resection performed within normal limits, while the patient who had undergone language-dominant temporal resection performed poorly, although not completely amnestic, on memory testing. Injection of the nonsurgical, presumably healthy, hemisphere resulted in complete failure of memory in both patients, implying that baseline memory was dependent on the functional integrity of the nonsurgical hemisphere, inactivation of which led to complete memory disruption. Secondly, the hippocampus in the nonlanguage-dominant hemisphere was able to support memory to some extent, if not completely, when it functioned in isolation without the influence of the language-dominant hemisphere during the IAP. These findings are discussed in the context of functional reserve and adequacy models.

Purpose: Neuropsychological assessment can be of assistance in determining seizure lateralization in cases where EEG and MRI findings do not provide clear lateralizing data. While several studies have examined the lateralizing value of individual neuropsychological measures, clinicians are still in need of a statistically sound method that permits the incorporation of multiple neuropsychological variables to predict seizure lateralization in the individual patient., Method: The present study investigated the lateralizing value of several commonly used neuropsychological measures in a large sample of patients (n = 217) who eventually underwent surgical resection to treat their epilepsy. Side of surgery was used to operationally define seizure lateralization. A comparison of the relative utility of a multivariate versus univariate approach to predict seizure lateralization was conducted in temporal epilepsy cases., Results: The results provide evidence for the incremental validity of neuropsychological measures, other than memory and IQ tests, in the prediction of seizure lateralization in patients with medically intractable epilepsy. These data indicate that a multivariate approach increases the accuracy of prediction of seizure lateralization for temporal lobe epilepsy cases., Conclusion: This study supports the use of a multivariate approach using neuropsychological measures to predict seizure lateralization in temporal epilepsy surgical candidates. Regression formulas are provided to enhance the clinical utility of these findings.

The cognitive outcome of the surgical removal of an epileptic focus depends on the assessment of the localisation and functional capacity of language and memory areas which need to be spared by the neurosurgeon. Traditionally, presurgical evaluation of epileptic patients has been achieved by means of the intracarotid amobarbital test assisted by neuropsychological measures. However, the advent of neuroimaging techniques has provided new ways of assessing these functions by means of non-invasive or minimally invasive methods, such as anatomical and functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, transcranial magnetic stimulation, functional transcranial Doppler monitoring, magnetoencephalography and near infrared spectroscopy. This paper aims at comparing and evaluating the traditional and recent preoperative approaches from a neuropsychological perspective.

Background: Our aim was to identify different states of energy metabolism in the perfused isolated vertebrate retina by simultaneous recordings of light-evoked changes of transretinal potential (TRP) and spectroscopic changes related to oxidation of pyridine nucleotides., Methods: Isolated retinas were obtained from R.esc. and superfused. For each setting, three experiments were performed. Eighteen retinas were used. TRP as a response to light stimulation was recorded simultaneously with stimulus-induced transmission shift at 350 nm. These responses were recorded under normal conditions, under withdrawal of oxygen and glucose, and after addition of electron transport inhibitors and uncouplers of oxidative phosphorylation., Results: Under normal conditions, TRP was strongly correlated with transmission shift after light stimulation. Without oxygen, amplitudes of stimulus-related TRP decreased and response related increase of transmission at 350 nm was reduced. The retina showed a much higher general absorption of the analyzing light. During glucose lack, an overall increase in transmission at 350 nm could be observed. The addition of Amytal yielded a specific reduction of the OFF components. Cyanide attenuated the ON and OFF components. Dinitrophenol yielded a considerable loss of the electrical ON response. Transmission change was affected less than electrical signal. Chlorophenylhydrazine induced a reproducible reduction of electrical responses, with a relative increase of transmission shift at 350 nm., Conclusion: In the isolated perfused retina, different states of energy metabolism and their specific impact on neuroretinal responses can be examined by simultaneous recordings of stimulus-related neuronal activity and spectroscopic changes.

Purpose: The aim of this study was to compare the utility of baseline neuropsychological measures and scores from the intracarotid amobarbital procedure (IAP) in the prediction of postoperative memory decline in temporal lobe epilepsy surgery patients., Methods: Logistic regression analyses were used to determine the relation between demographic variables, baseline neuropsychological scores, and scores from the IAP (using mixed verbal and nonverbal stimuli) and postoperative deterioration in verbal learning and verbal recall in 91 patients (48 right, RTL; 43 left, LTL) who had undergone a standard anterior temporal lobe resection for the relief of medically intractable epilepsy and who had been followed up 1 year postoperatively., Results: In the RTL group, the IAP scores were not significant predictors of a postoperative decline in verbal learning or recall. In the LTL group, postoperative decline in verbal learning was associated with good preoperative baseline scores, an older age at the time of surgery, and an unexpected asymmetry on the IAP. Baseline neuropsychological scores and scores from the IAP were associated with a significant postoperative decline in verbal recall in the LTL group., Conclusions: Scores from the IAP using mixed stimuli were not helpful in the prediction of postoperative verbal memory decline in RTL patients. The significance of IAP scores in predicting verbal memory deficits in LTL patients may be task specific.

Rationale: Our goal was to determine the frequency of repeated intracarotid amobarbital test (IAT) at our center and to estimate the retest reliability of the IAT for both language and memory lateralization., Methods: A total of 1,249 consecutive IATs on 1,190 patients were retrospectively reviewed for repeat tests., Results: In 4% of patients the IAT was repeated in order to deliver satisfactory information on either language or memory lateralization. Reasons for repetition included obtundation and inability to test for memory lateralization, inability to test for language lateralization, no hemiparesis during first test, no aphasia during first test, atypical vessel filling, and bleeding complications from the catheter insertion site. Language lateralization was reproduced in all but one patient. Repeated memory test results were less consistent across tests, and memory lateralization was unreliable in 63% of the patients., Discussion: In spite of test limitations by a varying dose of amobarbital, crossover of amobarbital from one side to the other, testing of both hemispheres on the same day, practice effects, unblinded observers, fluctuating cooperation of the patients, and a biased sample of patients language lateralization was reproduced in all but one patient. In contrast, repeated memory test results were frequently contradictory. Memory results on IAT therefore seem much less robust than the results of language testing. Gain of reliable information versus the risks of complications and failed tests has to be considered when a patient is subjected to an IAT.

Purpose: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra- and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children., Methods: Thirty children (4.7 - 14.9 years) and 18 adult controls (18-59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test., Results: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p<0.05). This threshold, demonstrated by survival and chi2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p<0.05)., Conclusions: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group.

The intracarotid amobarbital procedure or Wada test has been the gold standard for lateralization of language dominance before epilepsy surgery. It is based on deactivation of language cortex with intracarotid anesthesia. However, it is an invasive test with risks and discomforts, and it also has limitations. There has been great interest in replacing the Wada test with a noninvasive procedure. One alternative, repetitive magnetic stimulation works by deactivating language cortex, but most other promising alternatives are based on brain activation. Functional magnetic resonance imaging (fMRI), 15O-water positron emission tomography, single photon emission computerized tomography, transcranial Doppler, and near infrared spectroscopy detect hemodynamic responses to language cortex activation, while magnetoencephalography more directly measures event-related physiological activation. Some of the techniques also provide localization of language functions, whereas the Wada test is strictly a lateralization method. Based on widespread availability, fMRI will likely be the most widely used alternative.

False-positive (FP) errors during recognition memory testing often interfere with interpretation of Wada test results. This study examined which clinical and neuropsychological variables provide the best prediction of these errors. Fifty-six patients completed the Wada test and the California Verbal Learning Test (CVLT). Subjects with three or more FP errors on the recognition trials of the CVLT were nearly twice as likely to exhibit FP responding during the Wada test. Further analysis indicates that FP errors during the Wada test appear to be the primary result of a stable and liberal response-bias rather than a result of any other neurological or procedure-related factor.

Purpose: To examine the effects of illness duration on the neural processing of memory in patients with temporal lobe epilepsy (TLE) by using functional MRI., Methods: Twenty-three TLE patients (16 left, seven right) performed a complex visual scene-encoding task during functional MRI. Region-of-interest (ROI) analyses were used to quantity functional activation in the mesial temporal and frontal lobes. The patients' verbal and visual memory performances were evaluated by standardized neuropsychological tests. Analyses included group comparison and correlations of duration of epilepsy with functional activation and memory performance., Results: Compared with normal controls, TLE patients demonstrated reduced activation bilaterally in the mesial temporal lobe (p=0.003), and the reduction was more pronounced on the ipsilateral side of the seizure focus. Moreover, a longer duration of illness was associated with fewer voxels activated in both the left (p=0.038) and right (p=0.017) mesial temporal lobe. Furthermore, the duration of illness was found to be significantly and negatively correlated with both verbal (p=0.020) and visual (p=0.000) memory functioning., Conclusions: TLE seems to affect the memory processes in the mesial temporal lobes progressively (i.e., the longer the duration of illness, the lower the brain activation). In turn, the reduction of brain activation negatively affects memory functioning. Finally, the reduction is not limited to the side of seizure but also is observed in the contralateral hemisphere.

Purpose: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT)., Methods: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient., Results: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult., Conclusions: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.

Purpose: To evaluate speech recognition in patients with focal intractable epilepsy and surgical resections in the nondominant (right) hemisphere., Methods: Speech recognition was tested prospectively, under different listening conditions, in 22 patients with right temporal lobe (11 patients) or extra-temporal lobe epilepsy. All were left-hemisphere dominant for language on preoperative intracarotid sodium amobarbital testing., Results: All patients demonstrated normal auditory recognition of words and environmental sounds before and after surgery. However, when real-world listening conditions were simulated by using acoustically degraded (filtered) words, patients with temporal lobe epilepsy performed significantly worse than patients with frontal or parietooccipital lobe epilepsy before and after surgery (p<0.0001)., Conclusions: Patients with intractable right temporal lobe epilepsy are at risk for speech recognition impairments in real-world listening environments, independent of surgery. The impact of speech recognition difficulties on verbal communication, coupled with the prevalence of adverse listening environments, underscores the importance of testing speech recognition under different listening conditions in patients with intractable right temporal lobe epilepsy.

Purpose: To evaluate the prevalence and mechanism of ictal speech in patients with language-dominant, left temporal lobe seizures., Methods: We retrospectively reviewed the video-EEG telemetry records for the presence of ictal speech in 96 patients with surgically proven left temporal lobe epilepsy and studied the seizure-propagation patterns in three patients who required intracranial EEG recordings for seizure localization., Results: Ictal speech preservation was observed in five patients. One patient's seizures demonstrated rapid propagation of the ictal discharges to the contralateral temporal area where the seizure evolved, resembling a nondominant temporal lobe seizure. The other two patients had ictal discharges that remained confined to the inferomesial temporal areas, sparing language cortex., Conclusions: Preservation of speech in complex partial seizures of language-dominant, left temporal lobe origin is rare. Based on intracranial EEG recordings, the likely mechanism underlying this potentially misleading clinical finding is the preservation of language areas due to limited seizure-propagation patterns.

Purpose: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions., Methods: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected)., Results: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization., Conclusions: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.