Hippocampal memory function as reflected by the intracarotid sodium methohexital Wada test

The intracarotid amobarbital procedure (IAP) determines lateralization of memory function for predicting the risk of amnesia after epilepsy surgery. Shortages of amobarbital led to its substitution with sodium methohexital in the intracarotid methohexital procedure (IMP). We compared IAP scores (32 patients) with IMP scores (20 patients). Wada ipsilateral and contralateral memory scores were analyzed and compared, as was the relationship of these scores to the results of standard neuropsychological memory tests. There was no significant difference in Wada contralateral memory scores (first injection) between the IAP and IMP. Differences between the IAP and IMP in memory scores for the hemisphere ipsilateral to the epileptogenic focus (second injection) were significant (P = 0.01), patients who underwent the IMP manifesting a higher ipsilateral memory reserve. IAP scores related better to standard neuropsychological memory test scores than did IMP scores. The anesthetic drug used in Wada testing may affect lateralized memory assessment and prediction of postsurgical memory changes.     

Effects of topiramate on memory performance on the intracarotid amobarbital (Wada) test

We evaluated the effects of topiramate (TPM) on memory function in the intracarotid amobarbital (Wada) test in nine patients with mesial temporal lobe epilepsy (MTLE) whose antiepileptic drugs (AEDs) included TPM and compared their scores with those of 16 patients with MTLE on AEDs not including TPM. Sodium amobarbital was injected first into the hemisphere ipsilateral to the seizure focus and then into a contralateral site, and the patients were tested for naming and memorization. There was no statistical difference in percentage memory scores between the two patient groups following the contralateral injection. After the ipsilateral injection, however, TPM patients had significantly lower percentage memory scores compared with non-TPM patients (P < 0.02). We conclude that a possible adverse effect of TPM on memory performance should be considered when evaluating the Wada test memory scores of patients on TPM therapy.     

Contralateral EEG slowing and amobarbital distribution in Wada test: an intracarotid SPECT study

PURPOSE: To relate the occurrence of contralateral electroencephalogram slowing (CES) to amobarbital distribution, we performed electroencephalogram (EEG) monitoring and intracarotid single photon emission computed tomography (SPECT) during an intracarotid amobarbital procedure (IAP). METHODS: IAP was performed on 22 patients with temporal lobe epilepsy. CES was defined as the occurrence of significant EEG slowing on the contralateral hemisphere (>50% of the ipsilateral hemisphere slowing) after amobarbital injection. To map the distribution of the amobarbital, we injected a mixture of amobarbital and (99m)technetium-ethylcysteinate dimer (99mTc-ECD) into the internal carotid artery and performed a brain SPECT 2 h later. In the SPECT images, regions of interest were determined by ipsilateral and contralateral anterior cerebral artery territories (iACA, cACA), ipsilateral and contralateral middle cerebral artery territories (iMCA, cMCA), and ipsilateral and contralateral posterior cerebral artery territories (iPCA, cPCA), as well as ipsilateral and contralateral anterior and posterior mesial temporal regions (iAMT, cAMT, iPMT, cPMT). The perfusion of amobarbital was interpreted visually in each region. RESULTS: Amobarbital was distributed in the iMCA in all the patients; in the iACA in 20 (90.9%) patients; in the iAMT in 14 (63.5%); and in the iPCA and iPMT in only two (9.1%). CES was observed in 13 (59.1%) patients. Cross-perfusion of amobarbital in limited areas of the cACA were observed in only four of 13 patients. Wada retention memory scores (WRMS) showed no significant difference between the CES- (n = 9) and CES+ (n = 13) groups. CONCLUSIONS: Amobarbital rarely perfused the iPCA territory and the iPMT region and was rarely delivered to the contralateral hemisphere. The occurrence of CES was not related to the cross-perfusion of amobarbital. CES appears to be produced by a transient functional disconnection from the ipsilateral hemisphere.     

Wada Memory Disparities Predict Seizure Laterality and Postoperative Seizure Control

Summary: We examined the efficacy of a memory difference score (DS: right minus left hemisphere memory) during the Wada test (intracarotid amobarbital procedure, IAP) for predicting seizure laterality and postoperative seizure outcome in 70 left speech dominant patients from two epilepsy centers. DS ≥2, after addition of 1 point to the left hemisphere injection score to account for aphasia, were noted in 71. 4% of patients and correctly predicted surgery side for 98. 0% of these patients. The DS related significantly to seizure outcome at 1–year follow-up (p < 0.002) and correctly predicted 80% of patients who were The Wada test, or intracarotid amobarbital procedure (IAP), is traditionally used to determine the laterality of language dominance and to assess the memory competence in the hemisphere contralateral to the proposed temporal lobectomy in an effort to avoid postoperative amnesia (1–6). Ipsilateral memory testing (adequacy of the hemisphere ipsilateral to anticipated resection) also is frequently examined. The validity of IAP memory testing as a measure of temporal lobe function is demonstrated by correlating IAP memory scores of the affected hemisphere with hippocampal cell counts (7,8) and with hippocampal volume assessed by magnetic resonance imaging (MRI) (9). The disparity between ipsilateral and contralateral memory scores is often predictive of seizure focus laterality (1 1–18). However, most studies have examined group means rather than the utility of the DS for predicting the seizure focus in specific patients. To date, only Loring et al. (9) have reported Presented in part at the Annual Meeting of the International Neuropsychological Society, Galveston, Texas, February 1993. seizure-free. Patients whose DS did not correctly predict seizure laterality more frequently required invasive studies to establish seizure onset. The relationship of the DS to laterality did not differ significantly by class of IAP memory stimuli. When seizures originate from the temporal lobe, the IAP memory DS predicts seizure laterality by assessing the functional adequacy of the involved hemisphere and is predictive of seizure control.     

Memory following intracarotid amobarbital injection contralateral to hippocampal damage

We examined the relationship between memory performance and hippocampal damage in temporal lobe epileptics undergoing the intracarotid amobarbital sodium procedure (IAP). Overall memory performance in the course of IAP was correlated with seizure lateralization. The hemisphere of seizure focus had impaired IAP memory in 63% (19/30) of the patients. The IAP memory performance following perfusion of the hemisphere contralateral to severe hippocampal lesions was impaired in five of six patients. These patients also exhibited hypometabolism of the impaired temporal lobe as determined independently by positron emission tomography. The single patient with a severely damaged hippocampus who did not demonstrate IAP memory impairment with contralateral hemisphere injection did not exhibit perfusion of the ipsilateral posterior cerebral artery with amobarbital. Memory performance following intracarotid amobarbital injection contralateral to a less severely damaged hippocampus was impaired in 14 of 24 patients and was not related to extent of hippocampal damage, temporal lobe hypometabolism of labeled glucose, perfusion of the ipsilateral posterior cerebral artery, hemispheric language dominance, or order of injection. These results indicate that impaired memory performance during IAP may reflect severe hippocampal damage and/or epileptogenic abnormality.     

Asymmetries in the Effect of Side of Seizure Onset on Recognition Memory Following Intracarotid Amobarbital Injection

Summary: Purpose : To assess inter hemispheric differences in recognition memory for objects during the intracarotid amobarbital sodium procedure (IAP).
Methods : The recognition memory for real objects of patients with either right (RTLE, n = 28) or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after left and right intracarotid amobarbital sodium injection.
Results : There were no differences between groups on baseline performance. Performance following injection ipsilateral to the side of seizure focus was relatively lower for the LTLE as compared with the RTLE group, but this difference did not reach statistical significance. However, performance following injection contralateral to the side of seizure focus was significantly lower for the RTLE as compared with the LTLE group. Within-group differences in performance after ipsilateral as compared with contralateral injection were significant for the RTLE but not the LTLE group. The difference in inter hemispheric asymmetry in IAP memory performance between RTLE and LTLE groups was reflected in decreased ability to classify LTLE patients as compared with RTLE patients about side of seizure onset, using a clinically applicable decision rule.
Conclusions : Recognition memory during the IAP for real objects, simultaneously named and presented visually during encoding, is mediated effectively by both the left and right hemisphere when there is no seizure focus present. However, memory appears to be more vulnerable to the presence of a seizure focus in the right as compared with the left hemisphere.     

Seizures during intracarotid methohexital and amobarbital testing

BackgroundMethohexital and amobarbital have been used as agents for Wada testing in the presurgical evaluation of patients with epilepsy. Previous experience with methohexital as an anesthetic indicates that methohexital may decrease seizure threshold and may trigger seizures.MethodsA retrospective chart review of 760 intracarotid amobarbital and methohexital tests was performed to determine the frequency of seizures associated with preoperative intracarotid barbiturate testing for language and memory lateralization.ResultsSixteen patients (2.1%) who had seizures were found. In 3 patients, seizures occurred prior to barbiturate injection, and in 13, following barbiturate injection. After injection of amobarbital, 4 of 538 patients (0.7%) had a seizure. Nine of 222 patients had a seizure after methohexital injection (4.1%) (P = 0.001).ConclusionPatients with a previous history of epilepsy may be at higher risk for seizures after methohexital injection as compared with amobarbital injection.     

Intracarotid Amobarbital Procedure: II. Lateralizing Value in Evaluation for Temporal Lobectomy

The intracarotid amobarbital procedure (IAP) was assessed for lateralizing value in 37 patients who later had temporal lobectomy for intractable epilepsy. Among patients who failed IAP memory testing on one side (defined as a retention score for test items at least 20% lower on one side than the other), significantly more patients failed the injection contralateral (16 of 20, 80%) than ipsilateral (4 of 20, 20%) to the side of later resection (p = 0.008). In addition, preoperative EEG evidence of bilateral temporal epileptogenicity was significantly more frequent among patients who failed the ipsilateral IAP injection (2 of 4, 50%) than among patients who passed the ipsilateral IAP injection (2 of 33, 6%) (p = 0.050). Finally, failure of the contralateral IAP injection involved significantly more severe amnesia for test items (median retention score 25%) than did failure of the ipsilateral injection (median retention score 59%) (p = 0.047). Profoundly low retention scores less than 33% occurred only with contralateral injection. These findings suggest that the IAP has some adjunctive lateralizing value for the epileptogenic hemisphere in patients with temporal lobe epilepsy, especially when the retention score with one injection is profoundly low.     

The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure

The intracarotid amobarbital sodium (Amytal) procedure (IAP) was performed for 46 patients with temporal lobe epilepsy (21 with left seizure foci; 25 with right seizure foci). After anteromedial temporal lobectomy, neuronal densities were established for hippocampal subfields CA1, CA2, and CA3; the hilum; and the dentate granule cell layer. Intracarotid amobarbital procedure memory results were related to CA3 neuronal loss only. Patients who did not demonstrate memory after injection contralateral to the seizure focus had significantly fewer cells in CA3 than patients who did. Additionally, a significant correlation was observed between the intracarotid amobarbital procedure memory examination raw score after injection contralateral to the seizure focus and CA3 cell density. Using chi 2 analysis, significant differences were documented in the frequency with which memory was demonstrated after injection contralateral to the seizure focus for groups of patients classified by degree of CA3 neuronal loss. This finding supports prior research showing subfield specificity in some memory processes.     

Does the Intracarotid Amobarbital Procedure Predict Global Amnesia After Temporal Lobectomy?

PURPOSE: The intracarotid amobarbital procedure (IAP) is widely used to help predict who might be at risk for postoperative amnesia after unilateral temporal lobectomy for intractable seizures. We describe the memory outcome in 10 patients who underwent standard temporal lobectomy, including mesial temporal structures, despite failing the memory portion of the IAP after injections both ipsilateral and contralateral to the resected seizure focus. METHODS: Data for seven of the study subjects were obtained through a retrospective review of patients assessed on a surgical epilepsy unit during a 15-year period who failed the Montreal Neurological Institute IAP memory protocol after both ipsilateral and contralateral injections and subsequently underwent unilateral temporal lobectomy. More recently, we have studied temporal lobectomy patients who failed the Medical College of Georgia memory protocol after both ipsilateral and contralateral injections (n = 3). Preoperative and postoperative memory test scores were compared, and data regarding seizure outcome and self-perception of postoperative memory were collected. RESULTS: At follow-up, none of the patients presented with a pattern indicative of a global amnesia, and 80% demonstrated >90% improvement in their seizure disorder or were seizure-free. CONCLUSIONS: These findings indicate that bilateral memory failure on the IAP does not preclude the removal of an epileptogenic temporal lobe or a successful surgical outcome. In addition, the findings raise questions regarding the validity of the IAP and the possibility that memory may be reorganized in patients with a long history of temporal lobe epilepsy.     

The role of the intracarotid amobarbital procedure in predicting verbal memory decline after temporal lobe resection

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.     

Wada difference a day makes: interpretive cautions regarding same-day injections.

OBJECTIVE: To determine whether memory scores after second intracarotid amobarbital procedure (IAP) injections are affected by the time between the first and second injections. METHODS: Sixty-two patients received their second IAP injection on the day after the first injection. Forty-three other patients received the second injection on the same day as the first injection. Both groups underwent similar IAP protocols and memory assessments, except for the timing of the second injection. RESULTS: The second IAP memory scores in the two-day group were significantly higher (p < 0.05) than those in the one-day group. Timing of second injection was a significant correlate of second memory scores, but amobarbital dosage, first IAP memory score, and pre-IAP measures of memory and intelligence were not significant correlates. CONCLUSION: One-day and two-day IAP protocols do not result in similar memory scores after the second injection. Nineteen percent of a subset of patients in the one-day protocol were misclassified, in terms of IAP memory ratings, because of the deleterious effect of having both injections on the same day. It is recommended that correction scores be considered, for some patients who receive two IAP injections on one day, to approximate what the second IAP memory score would have been had the second injection occurred on a second day.     

Intracarotid amobarbital procedure: I. Prediction of decreased modality-specific memory scores after temporal lobectomy.

To assess predictive value of the intracarotid amobarbital procedure (IAP) for decreased postoperative modality-specific memory, we studied 37 temporal lobectomy patients with intractable partial epilepsy who were selected for operation independent of preoperative IAP findings. When ipsilateral IAP failure was defined by an absolute method as a retention score less than 67%, the results were not associated with decreased modality-specific memory after operation. When ipsilateral IAP failure was defined by a comparative method as a retention score at least 20% lower after ipsilateral than contralateral injection, the results showed greater differences between groups, but differences still did not achieve statistical significance. Four left-resection patients who failed the ipsilateral IAP had a median postoperative change in the Wechsler Memory Scale-Revised (WMS-R) Verbal Memory Index score of -14%, whereas 16 left-resection patients who passed the ipsilateral IAP had a mean postoperative change in the WMS-R Verbal Memory Index score of -7.5% (p = 0.12). These results suggested that the IAP interpreted comparatively may be a helpful adjunctive test in assessment of relative risk for modality-specific memory dysfunction after temporal lobectomy, but larger series of operated patients are needed to confirm this possibility. In this series, complete amnesia was not noted after ipsilateral injection, even in patients with postoperative modality-specific memory decline.     

Interpretation of Wada memory test for lateralization of seizure focus by use of (99m)technetium-HMPAO SPECT

PURPOSE: Although the intracarotid amobarbital procedure (IAP) or Wada test is useful in lateralizing seizure focus in patients with temporal lobe epilepsy (TLE), the results of the IAP memory test are frequently nonlateralizing. An insufficient suppression of the medial temporal region contralateral to the seizure focus may contribute to the failure of lateralization. We tried to correlate IAP memory results with the functional changes in the contralateral medial temporal region as measured by single photon emission computed tomography (SPECT) during IAP. METHODS: We performed a (99m)technetium-(Tc) hexamethylene-propylene-amine-oxime (HMPAO) brain SPECT in 19 medial TLE patients during a contralateral IAP (sodium amobarbital injected contralateral to the seizure focus). Regional cerebral blood flow (rCBF) was measured in the contralateral medial temporal region. The amount of decrease in the rCBF was calculated by subtracting the previous measurement from the one obtained with the interictal SPECT. RESULTS: Ten (53%) patients passed and nine (47%) failed the contralateral IAP. The mean percentage decrease in rCBF was 5.3+/-5.3%. There was a significant negative correlation between a decrease in the rCBF and the IAP memory-retention score by Spearman correlation (p = -0.53: p<0.021). Patients with smaller decreases in rCBF (<5%) more frequently passed the contralateral IAP memory test than did those with larger decreases (80 vs. 22%; p<0.023). CONCLUSIONS: We suggest that an insufficient suppression of the contralateral medial temporal function is partly responsible for nonlateralizing IAP memory tests. An IAP-SPECT may be useful in interpreting IAP memory tests for the lateralization of seizure focus in TLE patients.     

The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy

We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option.     

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: the limits of material specificity

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.     

Sodium methohexital (brevital) as an anesthetic in the Wada test

PURPOSES: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures). METHODS: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal). RESULTS: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital. CONCLUSIONS: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation.     

Contralateral Cerebral Blood Flow Velocity Changes after Intracarotid Amobarbital Injection

BACKGROUND AND PURPOSE: The intracarotid amobarbital procedure (IAP) leads to a prompt decrease in ipsilateral middle cerebral artery (MCA) mean blood flow velocity (MFV). Little is known about contralateral MFV changes. METHODS: The authors investigated bilateral MCA MFV using transcranial Doppler sonography (TCD) in 8 patients with epilepsy undergoing IAP. Measurements were excluded from analysis if angiography revealed any signs of interhemispheric cross-flow. RESULTS: With in 64 seconds after amobarbital injection, ipsilateral MFV decreased to a mean of 44.4% +/- 7.5% of baseline value (P < .01). In the absence of interhemispheric cross-flow and within 68 seconds, contralateral MFV decreased to 83.1% +/- 7.9% (P < .01). CONCLUSIONS: The observed decrease of contralateral MFV was not caused by amobarbital cross-perfusion. A possible underlying mechanism may be interhemispheric deafferentation.     

The intracarotid amobarbital or Wada test: unilateral or bilateral?

Objective – In the Netherlands, presurgical screening for temporal lobe epilepsy (TLE) includes the intracarotid amobarbital procedure (IAP), consisting of two consecutive injections of amobarbital, ipsilateral and contralateral to the epileptic focus. We studied whether a bilateral IAP has added value to a unilateral, ipsilateral IAP. Methods – This population‐based study included 183 consecutive patients referred for screening for TLE surgery who underwent bilateral IAP. Using multivariable modeling, we assessed the added value of bilateral IAP on the decision for surgery, resection size, amygdalohippocampectomy, post‐operative seizure freedom, memory performance, and IQ change. Results – Given the results from the unilateral IAP, the bilateral IAP had added prognostic value for postoperative change in verbal memory (P < 0.01) and verbal IQ (P < 0.01), especially if patients had a left‐sided focus. In contrast, information provided by the contralateral IAP was not associated with decision‐making or surgical strategy. Conclusions – A bilateral IAP has added value in predicting post‐operative verbal memory and IQ. A bilateral IAP is currently not used to guide surgical strategy, but may be used for this purpose when verbal capacity is of particular concern in patients with a left‐sided focus. In other cases, IAP is best performed unilaterally.     

Comparison of the intracarotid amobarbital procedure and interictal cerebral 18-fluorodeoxyglucose positron emission tomography scans in refractory temporal lobe epilepsy.

The relationship between interictal focal hypometabolism determined by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty-five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety-five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side.