The Optimal Dose of Amobarbital in the Wada Test for the Presurgical Evaluation of Patients With Temporal Lobe Epilepsy.

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

The safety and efficacy of propofol as a replacement for amobarbital in intracarotid Wada testing of presurgical patients with epilepsy.

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

Assessment of grammar optimizes language tasks for the intracarotid amobarbital procedure.

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

Comparing the Intracarotid Amobarbital Test and Functional MRI for the Presurgical Evaluation of Language in Epilepsy.

Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE). However, such surgery frequently causes deficits in language function, especially if performed on the dominant hemisphere. In recent years, the intracarotid amobarbital test (IAT) has been gradually replaced by functional magnetic resonance imaging (fMRI) in the preoperative identification of language areas to estimate the risk of postoperative language decline. In this paper, we review the neural substrates for language processing, how language impairment can result both from TLE itself and from surgical attempts to treat it. Subsequently, we discuss the strengths and limitations of, and current indications for fMRI and IAT during the preoperative workup, both by discussion of the studies that have evaluated them individually and through meta-analysis of data from 31 studies deemed eligible for analysis. Electrocortical stimulation mapping (ESM) is also discussed, as is the usefulness of the novel technique of resting-state fMRI. Finally, surgical techniques designed to avoid or reduce language decline in patients at risk are explored.

Menstrual cycle corrupts reliable and valid assessment of language dominance: Consequences for presurgical evaluation of patients with epilepsy.

PURPOSE: Functional transcranial Doppler sonography (fTCD) is a valid and non-invasive tool for determining language dominance, e.g. in the context of presurgical evaluations. Beyond this, fTCD might be an ideal tool to study dynamics in language dominance over time. However, an essential prerequisite would be a high test-retest reliability. This was addressed in the present study. METHODS: Test-retest reliability of hemispheric hemodynamics during open speech was determined in 11 male and 11 female healthy volunteers using the Animation Description Paradigm. Expressive language dominance was assessed weekly over an interval of 4-5 weeks. RESULTS: Internal consistency of the four measurements was excellent (split-half reliability 0.85-0.95), but test-retest reliability of the lateralization index was poor to moderate (rtt=0.37-0.74). Controlling for gender, test-retest reliabilities were better in men (rtt=0.67-0.78) as compared to women (rtt=0.04-0.70). When arranging the assessments in women around day one of menstruation - all were on contraceptives - a significant shift from left hemisphere dominance toward bilaterality (t=2.2 p=0.04) was evident around menstruation with significant reversal afterwards (t=-3.4 p=0.005). CONCLUSION: A high intraindividual variability of language dominance patterns is indicated in women when assessed repeatedly by fTCD. Menstrual cycle appeared to be the source of inconsistency. The finding challenges the use of non-deactivating methods for language dominance assessment in epilepsy. Support for this is demonstrated with a female patient with epilepsy in whom language dominance assessed by repeated fMRI and fTCD varied concordantly with cycle but not so the repeated intracarotidal amobarbital test.

Application of envelope trend to analyze early EEG changes in the frontal regions during intracarotid amobarbital procedure in children.

BACKGROUND: Intracarotid amobarbital procedure (IAP) is acknowledged as the gold standard test for language lateralization. EEG is performed routinely during IAP to monitor the anesthetization of a brain hemisphere. Here, we studied the correlation between the early EEG changes using envelope trend and the clinical outcome of IAP. METHOD: Fifty consecutive patients underwent IAP at Texas Children's Hospital (2004-2009). Intracarotid amobarbital procedure was considered "complete" or "incomplete" based on the outcome if the procedure was completed or aborted due to behavior changes. Envelope trend was used to calculate the median EEG amplitude changes within the first 60s of IAP. Statistical analysis was performed to determine the role of EEG changes and clinical features on the procedure outcome. RESULTS: Only 30 IAP-EEG files were available for review. Amobarbital was administered at the dose of 60-150mg (mean: 110±20). The intracarotid amobarbital procedure was recorded as complete in 23 patients and incomplete in 7 patients. EEG changes occurred within the first few seconds following amobarbital injection. Following amobarbital injection, focal slowing was present in the ipsilateral frontal region or both ipsilateral and contralateral frontal regions. Elapsed time to the first EEG change or duration and change in median EEG amplitude in the ipsilateral frontal regions were indifferent between the complete and incomplete groups (p>0.05). However, the median amplitude changes between the ipsilateral and contralateral frontal regions within each group were found significant only in the complete group (p<0.05), suggesting ipsilateral without contralateral frontal slowing. Other than age at the time of IAP (p=0.03), none of the other clinical features correlated with the clinical outcome of IAP (p>0.05). CONCLUSION: Early EEG changes during IAP using envelope trend may predict successful completion of the IAP test. Younger children are at risk of behavioral changes during IAP.

Is it time to replace the Wada test and put awake craniotomy to sleep?

The question we address here is whether the invasive presurgical brain mapping approaches of direct cortical stimulation and of the Wada procedure can be replaced by noninvasive functional neuroimaging methods (functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], transcranial magnetic stimulation and [TMS]). First, we outline the reasons for contemplating such a replacement. Second, we present evidence to the effect that the efficacy of the invasive and noninvasive methods, while suboptimal, is comparable. Third, we discuss additional advantages of noninvasive presurgical brain mapping and conclude that there are no longer compelling reasons for opting for invasive mapping in many if not most cases provided that the non-invasive methods are available.

Changes in bilateral bispectral index VISTA monitoring system during Wada test.

The Wada test is a procedure used in the preoperative assessment before epilepsy surgery in order to determine language lateralization, to assess the post-operative risk of an amnesia syndrome, and to evaluate the risk of material-specific memory deficits, in particular verbal memory deficits. This test involves inserting a cannula into the internal carotid artery via the femoral artery, and then to inject amobarbital to shut down brain function, usually in one of the brain hemispheres. The bilateral bispectral index (BIS) VISTA™ monitoring system (BVMS) was used to detect changes in EEG, and in the power spectrum distribution using the density spectral array (DSA) of both hemispheres. We describe a patient with an agenesis of the A1 segment of the right anterior cerebral artery, scheduled for a Wada test, in whom the BVMS demonstrated its potential value.

Sensitivity and specificity of Ankara University Cerebral Dominance Inventory in comparison with the Wada test.

We aimed to examine the sensitivity and specificity of the Ankara University Cerebral Dominance Inventory (AUCDI) in determining left cerebral dominance compared with the Wada test. The AUCDI and Wada test were applied to 49 patients referred to Ankara University for epilepsy surgery. Hand, foot and 'total' preference scores were specified according to the results of the inventory. Thirty-eight of the patients had left cerebral dominance and 11 had atypical cerebral dominance for language. 86 % of the patients were right-handed and 43 % were right-footed. When compared with the results of the Wada test, the sensitivity of the AUCDI for each 'total preference', and hand and foot preference was 90, 95 and 50 % and specificity was 46, 46 and 82 %, respectively. The percentage of right-footed patients was low when compared with the other studies. This difference might result from the method used for assessing foot preference by the actual demonstration of the task rather than just asking about the performance. The AUCDI was found to be sensitive in terms of 'total preference' and hand preference, and specific in terms of foot preference for determining the left hemisphere dominance in patients preferring the right side. It was a cheap and noninvasive alternative to the Wada test, appropriate for clinical bedside evaluation.

Naming outcome after left or right temporal lobectomy in patients with bilateral language representation by Wada testing.

OBJECTIVE: This study aimed to examine language outcome after left or right anterior temporal lobectomy (ATL) in patients with epilepsy with bilateral language representation on intracarotid sodium amobarbital (Wada) testing. METHODS: Twenty-two patients with epilepsy with bilateral language (Wada laterality index between -50 and 50) underwent right ATL (RATL, n=10) or left ATL (LATL, n=12). All the patients were administered the Boston Naming Test preoperatively and six months postoperatively. RESULTS: Left anterior temporal lobectomy patients showed greater postoperative naming decline than RATL patients. Group differences were also observed on subtests of the Wada test. Performance on the Wada naming and comprehension subtests was better in the nonsurgical hemisphere than in the surgical hemisphere in the RATL group, but there was no difference between the nonsurgical and the surgical hemisphere naming and comprehension performance in the LATL group. CONCLUSIONS: Left anterior temporal lobectomy patients with bilateral language are at greater risk for naming decline than RATL patients with bilateral language. This difference may be due to relatively better naming and comprehension abilities in the nonsurgical hemisphere in the RATL group.

Who needs a Wada test? Present clinical indications for amobarbital procedures.

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.

The intracarotid amobarbital procedure: when is it worth repeating?

PURPOSE: Despite the reported diagnostic value of the intracarotid amobarbital procedure (IAP) or "Wada test" for determining hemispheric lateralization and memory functioning, it has never undergone formal reliability testing because a prospective test-retest study design is neither feasible nor ethical. However, some patients require repeat testing for clinical purposes, a circumstance that allows for exploration of issues related to reliability. The current investigation sought to: (1) evaluate the frequency of and reasons for repeated IAPs and (2) describe the test-retest reliability of repeated IAPs in a large tertiary epilepsy center. METHODS: A 10-year review (2001-2011) of the New York University Langone Medical Center Comprehensive Epilepsy Center patient registry revealed 630 IAPs. Review of medical records identified 20 individuals who underwent two or more IAPs on separate days. Because IAPs repeated due to technical problems should be considered separate from IAPs repeated for other reasons because these IAPs likely included a change in the procedure (e.g., lower medication dose) in an attempt to ameliorate the complication, patients were grouped accordingly. Six patients underwent repeated IAPs due to technical complication and 14 patients underwent a repeated IAP due to other reasons (e.g., unexpected memory outcome, reconsideration of surgery years after a previous surgical work-up in which no surgery was performed, and/or consideration of a second surgery). Given that data obtained from injections ipsilateral to a seizure focus are sometimes considered in a manner clinically different from data obtained from injections contralateral to the seizure focus, memory outcome was classified relative to the side of identified seizure focus. The degree to which language and memory data were consistent across repeated IAPs was examined. KEY FINDINGS: Language functioning was consistently lateralized across IAPs in all but one case. Among the six patients who experienced technical problems in the first IAP, three were fully participatory in the second procedure such that valid data were obtained. For the other three, the technical problem recurred with no change in outcome across procedures. Among the 14 patients with repeated IAPs due to other reasons, 79% of the available ipsilateral and 73% of the contralateral pass/fail outcomes were consistent across procedures. No difference between ipsilateral or contralateral injections was observed for the likelihood of a change in results (p = 0.57). SIGNIFICANCE: Our data identified overall high reliability for both the ipsilateral and contralateral sides with repeated IAP testing. Results indicated that although patients for whom a correctable technical problem was identified during the IAP may benefit from a repeat study, there is little benefit to repeating the IAP in patients with discordant or unexpected results (i.e., results are not likely to change). These data support the overall reliability of both the language and memory data obtained from the IAP.

The contribution of posterior circulation to memory function during the intracarotid amobarbital procedure.

The purpose of this study was to evaluate the contribution of posterior circulation to memory function by comparing memory scores between patients with and without a foetal-type posterior cerebral artery (FTP) during the intracarotid amobarbital procedure (IAP) in epilepsy patients. Patients undergoing bilateral IAP between January 2004 and January 2010 were retrospectively included. Pre-test angiograms were assessed for the presence of a FTP. Memory function scores (% correct) after right and left injections were obtained. Functional significance of FTP was affirmed by relative occipital versus parietal EEG slow-wave increase during IAP. Memory and EEG scores were compared between patients with and without FTP (Mann-Whitney U test). A total of 106 patients were included, 73 with posterior cerebral arteries (PCA) without FTP ('non-FTP'), 28 patients with unilateral FTP and 5 with a bilateral FTP. Memory scores were lower when amytal was injected to the hemisphere contralateral to the presumed seizure focus (on the right decreasing from 98.3 to 59.1, and on the left decreasing from 89.1 to 72.4; p < 0.001). When IAP was performed on the side of FTP memory scores were significantly lower (70.8) compared to non-FTP (82.0; p = 0.02). Relative occipital EEG changes were 0.44 for FTP cases and 0.36 for non-FTP patients (p = 0.01). A relationship between vasculature and brain function was demonstrated by lower memory scores and more slow-wave activity on occipital EEG during IAP in patients with foetal-type PCA compared to patients with non-FTP. This suggests an important contribution of brain areas supplied by the PCA to memory function.

Clinical magnetoencephalography for neurosurgery.

Noninvasive neuroimaging aids in surgical planning and in counseling patients about possible risks of surgery. Magnetoencephalography (MEG) performs the most common types of surgical planning that the neurosurgeon faces, including localization of epileptic discharges, determination of the hemispheric dominance of verbal processing, and the ability to locate eloquent cortex. MEG is most useful when it is combined with structural imaging, most commonly with structural magnetic resonance (MR) imaging and MR diffusion imaging. This article reviews the history of clinical MEG, introduces the basic concepts about the biophysics of MEG, and outlines the basic neurosurgical applications of MEG.

Transient shivering during Wada test provides insight into human thermoregulation.

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.

Detained and drugged: a brief overview of the use of pharmaceuticals for the interrogation of suspects, prisoners, patients, and POWs in the US.

Using medical literature citations, Congressional hearings, and declassified documents this paper examines the uses of pharmaceuticals in the interrogation of vulnerable populations. From the use of IV relaxants on criminal suspects during the 1920s to the Global War on Terror, the nexus of drugs, testing, and interrogations will be explored in both the domestic and international contexts.

Intracarotid amobarbital procedure and etomidate speech and memory test.

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.

Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

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.

Threshold-independent functional MRI determination of language dominance: a validation study against clinical gold standards.

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.

Memory performance is related to language dominance as determined by the intracarotid amobarbital procedure.

OBJECTIVE: The goal of this study was to explore the relationship between language and memory lateralization in patients with epilepsy undergoing the intracarotid amobarbital procedure. METHODS: In 386 patients, language lateralization and memory lateralization as determined by laterality index (LI) were correlated with each other. RESULTS: Language lateralization and memory lateralization were positively correlated (r=0.34, P<0.01). Correlations differed depending on the presence and type of lesion (chi(2)=7.98, P<0.05). LIs correlated significantly higher (z=2.82, P<0.05) in patients with cortical dysplasia (n=41, r=0.61, P<0.01) compared with the group without lesions (n=90, r=0.16, P>0.05), with patients with hippocampal sclerosis falling between these two groups. Both memory (P<0.01) and language (P<0.01) LIs were higher in right- compared with left-sided lesions. CONCLUSION: Correlation of language and memory is more pronounced in patients with structural lesions as compared with patients without lesions on MRI.