Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test

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.     

Risk factors for unsuccessful testing during the intracarotid amobarbital procedure in preadolescent children

PURPOSE: Identification of risk factors for unsuccessful testing during intracarotid amobarbital procedure (IAP) in preadolescent children. METHODS: A pediatric IAP protocol was attempted in 42 candidates for epilepsy surgery (5-12 years old; mean, 10 years) based on the ability to pass a practice test. Language dominance was defined by marked asymmetry until first verbal response and paraphasic errors. Intact hemispheric memory was defined by recall of >/=60% of test items. The odds ratios of baseline variables (age at IAP, Full-Scale IQ, side of disease, age at seizure onset, amobarbital dose) were calculated for various IAP outcomes. RESULTS: IAPs were accomplished in 40 children. Language dominance was established in 25 (62.5%) of 40 patients: all 21 focal resection candidates were left language dominant; four hemispherectomy candidates had intact language after injection of the damaged hemisphere. In 12 (30%) of 40 patients, language testing failed because of agitation or obtundation. Compared with the 21 children with language dominance established by bilateral IAP, these 12 children had lower mean Full-Scale IQ (66.4 vs. 87.9; p = 0.014), and more frequently, the epileptogenic lesion in the left hemisphere (presumed dominant by right-handedness; 78 vs. 33%; p = 0.04). Excluding hemispherectomy candidates (intentionally only one injection), memory testing could not be completed in 13 (36%) of 36 children because of obtundation or agitation. These children were significantly younger than the 23 (64%) of 36 with successful bilateral memory testing (mean age, 107.6 vs. 128.7 months; p = 0. 006). The eight (25%) of 32 children with failing retention scores after ipsilateral injection had lower Full-Scale IQ than did the 24 (75%) patients who passed (mean, 59.6 vs. 81.7 months; p = 0.03). CONCLUSIONS: The IAP successfully established hemispheric language dominance and memory representation for just under two thirds of the preselected preadolescent children. Risk factors for unsuccessful testing included low Full-Scale IQ (especially <80), young age (especially <10 years), and seizures arising from the left hemisphere presumed dominant by right-handedness.     

Repeated intracarotid amobarbital tests

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.     

Relation Between Intracarotid Amobarbital Memory Asymmetry Scores and Hippocampal Sclerosis in Patients Undergoing Anterior Temporal Lobe Resections

Summary: The intracarotid amobarbital procedure (IAP) is used to evaluate memory function preoperatively in candidates for anterior temporal lobe resections (ATL). We examined IAP memory asymmetry scores in 30 patients undergoing ATL (17 R, 13 L), as a function of the presence (HS+) or absence (HS−) of hippocampal sclerosis. Ictal onset zones were determined by extraoperative recording with subdural strip electrodes in all but 3 patients in whom magnetic resonance imaging (MRI) scan showed HS. MRI scans were otherwise normal. All patients were left hemisphere dominant for language except 1, in whom language was represented bilaterally. IAP memory testing involved presentation of eight subjects during anesthesia of each hemisphere, followed by recognition testing after patients recovered from amobarbital effects. A score of 1 was given for each correctly recognized object, and 0.5 was deducted for each false-positive identification. There were 16 foils. A total asymmetry score was calculated, which was positive if there was agreement between the direction of the symmetry and side of operation and negative if reversed. The mean asymmetry score for HS- (n = 8) was 0.9; that for HS+ (n = 22) was 4.1 (p < 0.01). IAP memory performance provided lateralizing information (asymmetry score 2 + or −2) in 73% of cases; among these, the lateralization was correct in 91%. Our data indicate that IAP memory asymmetry predicts both laterality of ictal onset and the presence of HS.     

Functional MRI and Wada studies in patients with interhemispheric dissociation of language functions

Rare patients with chronic epilepsy show interhemispheric dissociation of language functions on intracarotid amobarbital (Wada) testing. We encountered four patients with interhemispheric dissociation in 490 consecutive Wada language tests. In all cases, performance on overt speech production tasks was supported by the hemisphere contralateral to the seizure focus, whereas performance on comprehension tasks was served by the hemisphere with the seizure focus. These data suggest that speech production capacity is more likely to shift hemispheres than is language comprehension. Wada and fMRI language lateralization scores were discordant in three of the four patients. However, the two methods aligned more closely when Wada measures loading on comprehension were used to calculate lateralization scores. Thus, interhemispheric dissociation of language functions could explain some cases of discordance on Wada/fMRI language comparisons, particularly when the fMRI measure used is not sensitive to speech production processes.     

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.     

One center's experience with complications during the Wada test

This study aimed to define the number and type of complications associated with the Wada test at an academic medical center for comparison to previous reports. We performed a retrospective review of medical records for patients who underwent the Wada test at the University of Michigan between April 1991 and June 2013. Information was collected regarding the angiography procedure and the immediate postoperative period to assess for both clinical and angiographic complications. A total of 436 patients were identified who underwent the Wada procedure between April 1991 and June 2013, and 431 patients were included in the final analysis. Twenty‐five patients (5.8%) had notable clinical events associated with the Wada test. Nine patients (2.1%) had clinical events meeting criteria for complication, which included seizures, status epilepticus, internal carotid artery vasospasm, inadvertent injection of anesthetic in the external carotid artery, and transient encephalopathy. No complications were associated with significant morbidity or mortality. This retrospective review of patients undergoing the Wada test found significantly fewer associated complications in comparison to previously published studies, with no patients experiencing long‐term morbidity. The Wada test should be considered a safe diagnostic tool for lateralizing language and memory.     

Intracarotid amobarbital (Wada) test for language dominance: correlation with results of cortical stimulation

Eighty-eight patients had bilateral intracarotid amobarbital (Wada) testing to determine hemispheric dominance for language in preparation for epilepsy surgery, as well as unilateral extraoperative cortical electrical stimulation using subdural electrode arrays. In none of the patients with left dominance by Wada testing were language areas found with right-sided stimulation, but two patients with right dominance by Wada testing had language areas mapped on the left side. These findings suggest that left dominance by Wada testing is strong evidence for exclusive lateralization of language function in the left hemisphere, but there is concern about the ability of the Wada test to exclude the possibility of some left-sided language function despite apparent right-sided dominance. Patients with left dominance on Wada testing do not need cortical stimulation before extensive right temporal lobectomy, but we believe that patients with right or bilateral dominance on Wada testing should have cortical stimulation for localization of language areas if extensive left or right temporal or frontal resection is planned.     

The role of the intracarotid amobarbital procedure in evaluation of patients for epilepsy surgery

PURPOSE: To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy. METHODS: We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance. RESULTS: Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection. CONCLUSIONS: In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.     

Intracarotid amobarbital procedure in post-temporal lobectomy patients

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.     

Material-specific memory changes after anterior temporal lobectomy as predicted by the intracarotid amobarbital test

Summary: Purpose: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material‐specific aspects of IAT memory and material‐specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? Methods: Seventy left hemisphere language‐dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. Results: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. Conclusions: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.     

Selective Amobarbital Test for the Determination of Language Function in Patients with Epilepsy with Frontal and Posterior Temporal Brain Lesions

Summary: Purpose: Selective amobarbital tests with selective temporary inactivation of the left frontal operculum and/or the left parietotemporal cortex were performed in 5 patients with left-hemispheric epileptogenic lesions in or adjacent to classical Broca's and/or Wemicke's aréa. The aim was to assess language functions in these brain regions before surgery, to tailor the surgery according to the individual functional importance of these brain regions, and to predict postoperative outcome. Methods: Amobarbital was injected by transfemoral selective catheterization of the arteries supplying the target areas. Along with neuropsychological and neurological testing during the amobarbital procedure, EEG recordings were performed in all patients, and [^199mTc]HMPAO-single photon emission computed tomography (SPECT) in 2 patients. Results: After the amobarbital injection into the left frontal opercular region, there was no recognizable language dysfunction in 3 patients. In these 3 patients, the lesions in or adjacent to the frontal operculum were completely resected without postoperative language impairment. In the remaining 2 patients, temporary language impairment after the amobarbital injection into the left frontoopercular and Wemicke's region, respectively, suggested language functions in these areas. Surgery was restricted to the left mesiotemporal lobe in 1 patient. In the other patient, the tumor infiltrating the frontal operculum was restrictively resected. Postoperatively, the fist patient had no language impairment, but the latter had transient global aphasia, from which she recovered. Conclusions: Selective temporary amobarbital inactivation of brain regions that may be associated with language has clearly indicated the presence or absence of language functions in these regions. The test contributed substantially to planning of the surgical approach in each patient. The predictive alue of the amobarbital test was demonstrated by the postoperative outcome.     

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.     

Prediction of seizure-onset laterality by using Wada memory asymmetries in pediatric epilepsy surgery candidates

PURPOSE: Because the capacity of intracarotid amobarbital (Wada) memory assessment to predict seizure-onset laterality in children has not been thoroughly investigated, three comprehensive epilepsy surgery centers pooled their data and examined Wada memory asymmetries to predict side of seizure onset in children being considered for epilepsy surgery. METHODS: One hundred fifty-two children with intractable epilepsy underwent Wada testing. Although the type and number of memory stimuli and methods varied at each institution, all children were presented with six to 10 items soon after amobarbital injection. After return to neurologic baseline, recognition memory for the stimuli was assessed. Seizure onset was determined by simultaneous video-EEG recordings of multiple seizures. RESULTS: In children with unilateral temporal lobe seizures (n = 87), Wada memory asymmetries accurately predicted seizure laterality to a statistically significant degree. Wada memory asymmetries also correctly predicted side of seizure onset in children with extra-temporal lobe seizures (n = 65). Although individual patient prediction accuracy was statistically significant in temporal lobe cases, onset laterality was incorrectly predicted in < or =52% of children with left temporal lobe seizure onset, depending on the methods and asymmetry criterion used. There also were significant differences between Wada prediction accuracy across the three epilepsy centers. CONCLUSIONS: Results suggest that Wada memory assessment is useful in predicting side of seizure onset in many children. However, Wada memory asymmetries should be interpreted more cautiously in children than in adults.     

fMRI: Applications in Epilepsy

Summary:  Functional MRI (fMRI) methods use currently standard MRI scanning hardware to detect changes in regional blood flow and metabolism that accompany regional brain activation. Major applications of fMRI in epilepsy include the localization of task-correlated language and memory function, and the localization of ictal and paroxysmal phenomena. Language lateralization by fMRI provides comparable results to intracarotid amobarbital testing, and memory lateralization by fMRI also shows promise. The recent development of methodologies to allow interpretable electroencephalographic data to be recorded during MRI scanning has opened up new opportunities for combining the spatial resolution of imaging with the temporal resolution of electrophysiology in seizure localization.     

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.     

Wada memory performance predicts seizure outcome after epilepsy surgery in children

PURPOSE: Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children. METHODS: One hundred fifty-six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty-eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II-IV) at follow-up (mean follow-up interval, 2.3 years). RESULTS: Seizure-free children recalled 19.3% more Wada memory items after ipsilateral injection than did non-seizure-free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure-free children recalled 27.7% more items after ipsilateral injection than did non-seizure-free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01). CONCLUSIONS: Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.     

Transient oromotor deficits in children with benign childhood epilepsy with central temporal spikes

PURPOSE: To describe transient oromotor deficits in benign childhood epilepsy with centrotemporal spikes (BCECTS), an idiopathic age-specific epileptic syndrome with a benign course. METHODS: Five children with BCECTS and intermittent dysarthria and drooling not in the context of typical clinical seizures are presented. RESULTS: The periods of oromotor deficits correlated with increased seizure frequency in all children. Concomitant EEGs that were recorded during periods of dysarthria in four of the children revealed focal electrographic seizures. The reported children did not differ from other patients with BCECTS in any other respect. CONCLUSIONS: Transient oromotor dysfunction is a rare ictal phenomenon that occurs in children with BCECTS with no other unique clinical features.