Atypical hemispheric language dominance in left temporal lobe epilepsy as a result of the reorganization of language functions

Hemispheric language dominance, as determined by intracarotid short-acting barbiturate injections (Wada testing), was retrospectively evaluated in 44 right-handed patients with medically intractable left (n=26) or right (n=18) temporal lobe epilepsy (TLE). Atypical hemispheric language dominance (right or bilateral) was revealed in 13.6% of all patients investigated. A significantly higher rate of deviance from complete left hemisphere dominance was observed in left TLE (23.1%) than in right TLE (0%). Patient age at the time of seizure onset was proven a critical variable affecting atypical speech development in left TLE. The mean patient age at the time of seizure onset in left TLE patients with atypical language representation was 5.61 years, but was 13.13 years in patients with left hemisphere language dominance. Our results strongly support the influential impact of epileptiform activity spreading from the left temporal lobe structures on the reorganization of language functions in patients with early brain injury.     

Ictal vomiting in partial seizures of temporal lobe origin

We report 3 cases presenting ictal vomiting during partial seizures of temporal lobe origin. Two patients had complex partial seizures accompanying vomiting characteristics. Ictal vomiting occurred early in the course of the seizure when rhythmic discharges involved predominantly the left hemisphere, the language dominance hemisphere. The other patient had ictal vomiting in simple partial seizures which originated from the right temporal lobe or the language nondominant side. All 3 patients underwent anterior temporal lobectomy with promising outcomes. Pathologic diagnosis included hippocampal sclerosis in 2 patients and astrocytoma in 1 patient. In our patients, ictal vomiting does not lateralize temporal lobe epilepsy and is not specific to pathology.     

Shift-back of right into left hemisphere language dominance after control of epileptic seizures: evidence for epilepsy driven functional cerebral organization

Atypical, i.e. right hemisphere language dominance is frequently observed in early onset left hemisphere epilepsies. In left mesial temporal lobe epilepsy, where eloquent cortex is not directly involved, it is a matter of debate, to which degree atypical language dominance is driven not only by morphological lesions but also by epileptic dysfunction, and whether atypical dominance is hardwired or not. Taking this as the background this study evaluated the hypothesis that epilepsy driven atypical dominancy might be reversible when seizures are successfully controlled. This was evaluated in patients with left mesial temporal lobe epilepsy, who were atypically language dominant by means of language fMRI before surgery, and became seizure free after left selective amygdalo-hippocampectomy. Three out of 53 consecutive atypically dominant patients with chronic epilepsy fulfilled these criteria. Postoperative follow-up language fMRI indicated reversal of right into left dominance in one patient going along with unexpected losses in verbal memory performance. The two other patients experienced unchanged or even enhancement of the pre-existing dominance pattern, going along with consistent postoperative performance changes in cognition. The data thus provide supporting evidence that atypical language dominance can indeed be functionally driven and moreover that in at least some patients, right hemispheric language can shift-back to the left hemisphere when the driving factor, i.e. seizures, becomes successfully controlled. The results have clinical implications for outcome prediction after brain surgery in atypically dominant patients with epilepsy. However, further research in larger groups of atypically dominant patients is required to identify the conditions under which atypical dominance becomes hardwired and when not.     

Postictal Language Dysfunction in Patients with Right or Bilateral Hemispheric Language Localization

Summary: Purpose : As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non-left (right hemisphere or mixed) language dominance.
Methods : Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) >90% seizure reduction after anterior temporal lobectomy with 2-year minimum follow- follow- up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex.
Results : Two hundred twenty-four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non-left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%).
Conclusions : Postictal language testing accurately identifies patients with non-left language dominance and may be useful in selecting appropriate patients for IAT.     

Study of hemispheric lateralization of language regions by functional MRI. Validation with the Wada test

Language hemispheric dominance can be assessed by the Wada test before temporal lobectomy, in patients with refractory epilepsy of the mesial temporal lobe. Functional MR is a less invasive technique which recently demonstrated the ability to localize some language areas. The aim of this study was to determine if functional MR can be substituted to the Wada test in the determination of language dominance. Seven patients with a refractory epilepsy of the mesial temporal lobe were included. The MR protocol was carried out using a 1.5 T system including 12 axial gradient echo BOLD EPI images. A semantic fluency task, interspersed with rest periods, was used as activation paradigm. An activation of middle and inferior frontal region was found in all patients. It predominated in the left hemisphere in 6 cases and in the right hemisphere in 1 case. The hemispheric and frontal lobe lateralization of the functional MR activation was correlated with the hemispheric language dominance as assessed by the Wada test. In conclusion, functional MR is a promising technique in the determination of language dominance.     

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.     

Lateralization of temporal lobe epilepsy and learning disabilities, as defined by disability-related civil rights law

PURPOSE: Epilepsy research has identified higher rates of learning disorders in patients with temporal lobe epilepsy (TLE). However, most studies have not adequately assessed complex functional adult learning skills, such as reading comprehension and written language. We designed this study to evaluate our predictions that higher rates of reading comprehension, written language, and calculation disabilities would be associated with left TLE versus right TLE. METHODS: Reading comprehension, written language, and calculation skills were assessed by using selected subtests from the Woodcock-Johnson Psycho-Educational Tests of Achievement-Revised in a consecutive series of 31 presurgical patients with TLE. Learning disabilities were defined by one essential criterion consistent with the Americans with Disabilities Act of 1990. Patients had left hemisphere language dominance based on Wada results, left or right TLE based on inpatient EEG monitoring, and negative magnetic resonance imaging (MRI), other than MRI correlates of mesial temporal sclerosis. RESULTS: Higher rates of reading comprehension, written language, and calculation disabilities were associated with left TLE, as compared with right TLE. Nearly 75% of patients with left TLE, whereas fewer than 10% of those with right TLE, had at least one learning disability. CONCLUSIONS: Seizure onset in the language-dominant hemisphere, as compared with the nondominant hemisphere, was associated with higher rates of specific learning disabilities and a history of poor literacy or career development or both. These results support the potential clinical benefits of using lateralization of seizure onset as a predictor of the risk of learning disabilities that, once evaluated, could be accommodated to increase the participation of patients with epilepsy in work and educational settings.     

Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology

Schizophrenia patients vary in right ear advantage (REA) on dichotic listening tests for assessing left hemispheric dominance for language processing. The authors examined if patients with low REA differed from other patients in symptoms and in resting brain metabolism. SPECT was conducted during visual fixation for 9 healthy control subjects and 16 schizophrenia patients: 8 with normal and 8 with diminished REA. REA-diminished patients had greater positive symptoms and lower mental status scores (all P<0.05) and had right middle temporal gyrus hypermetabolism. Both schizophrenia groups had decreased right frontal and increased medial temporal lobe metabolism vs. control subjects. REA-diminished patients had right temporal lobe hypermetabolism under a resting condition (eyes open, visual fixation). Results suggest reduced right ear (left hemisphere) advantage for dichotic word perception in schizophrenia is related to a predisposition to overactivate right temporal lobe regions and to positive symptoms. In contrast, the prefrontal-medial temporal imbalance present in both patient groups may typify the schizophrenia syndrome.     

Right-hemisphere language dominance in temporal lobe epilepsy: clinical and neuropsychological correlates

Prior to and following temporal lobe surgery, patients with right-hemisphere language dominance and focal left temporal lobe epilepsy (RHLD-LTLSz) were compared to right-handed patients with left-hemisphere language dominance and either left temporal lobe epilepsy (LHLD-LTLSz) or right temporal lobe epilepsy (LHLD-RTLSz). The group of RHLD-LTLSz patients had a more consistent history of brain involvement before the age of 5 years and had a higher seizure frequency rating than did either LHLD patient group. Cognitively, RHLD-LTLSz patients did not show significant deficits in psychometric intellectural scores. In addition, they did not demonstrate comparable degrees of verbal memory loss as found either pre- or postoperatively in LHLD-LTLSz patients. The right-handed RHLD-LTLSz and the right-handed LHLD-LTLSz groups both appeared to exhibit bilaterally depressed fine-motor coordination. The left-handed RHLD-LTLSz patients did not show the same motor deficiencies. These latter findings suggest that hemispheric dominance for bilateral motor control may exist independent of language dominance, but not independent of handedness.     

Right-hemisphere language dominancein temporal lobe epilepsy: Clinical and neuropsychological correlates

Abstract

Prior to and following temporal lobe surgery, patients with right-hemisphere language dominance and focal left temporal lobe epilepsy (RHLD-LTLSz) were compared to right-handed patients with left-hemisphere language dominance and either left temporal lobe epilepsy (LHLD-LTLSz) or right temporal lobe epilepsy (LHLD-RTLSz). The group of RHLD-LTLSz patients had a more consistent history of brain involvement before the age of 5 years and had a higher seizure frequency rating than did either LHLD patient group. Cognitively, RHLD-LTLSz patients did not show significant deficits in psychometric intellectual scores. In addition, they did not demonstrate comparable degrees of verbal memory loss as found either pre- or postoperatively in LHLD-LTLSz patients. The right-handed RHLD-LTLSz and the right-handed LHLD-LTLSz groups both appeared to exhibit bilaterally depressed fine-motor coordination. The left-handed RHLD-LTLSz patients did not show the same motor deficiencies. These latter findings suggest that hemispheric dominance for bilateral motor control may exist independent of language dominance, but not independent of handedness.     

Stimulus type affects Wada memory performance

The effects of amytal injection side, seizure focus laterality, and stimulus type (real and line-drawn objects, printed words, and faces) on recognition memory were studied during the Wada procedure. To-be-remembered stimuli were presented during cerebral anesthesia to 35 patients with left temporal lobe epilepsy (LTLE) and 28 patients with right temporal lobe epilepsy (RTLE), all with left hemisphere language dominance. In both groups, recognition of real and line-drawn objects was best after anesthetization of the lesional hemisphere. Recognition of faces was poor after either injection in patients with RTLE, but only after right injection in patients with LTLE. Conversely, recognition of words by patients with LTLE was impaired equally after either injection, but more so after left than right injection in patients with RTLE. The findings suggest that (1) real and line-drawn objects are "dually encoded" and memory accuracy depends on seizure focus laterality, and (2) accuracy in recognition of words and faces is related to seizure focus laterality, but may also depend on the language dominance of the hemisphere being assessed.     

Cortical stimulation mapping and Wada results demonstrate a normal variant of right hemisphere language organization

Purpose: Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed in such patients, as most undergo nondominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathologic process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Furthermore, these data confirm the Wada test findings of atypical dominance. Methods: Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our center between 1974 and 2006. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients. Key Findings: Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus, all of which were common zones where language was identified in the left hemisphere dominant comparison sample. Significance: Results suggest that the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding right hemisphere language sites), and that the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization.     

Memory for objects presented soon after intracarotid amobarbital sodium injections in patients with medically intractable complex partial seizures

We evaluated the abilities of 36 patients with intractable temporal lobe epilepsy and left hemisphere dominance for language to later recognize objects presented in the confusional phase after left intracarotid amobarbital injection. Eighteen of 24 patients with left, but only 4/12 with right, temporal lobe epilepsy recognized at least two-thirds of objects during a post-test. These results demonstrate that the initial muteness and apparent confusion after amobarbital injection do not prohibit the formation of new memories; this gives further support to the idea that consciousness can be retained despite transient disruption of function of the language-dominant hemisphere.     

Cerebral language lateralization: evidence from intracarotid amobarbital testing

Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable.     

Localisation des centres du langage par l'analyse quantifiée de l'EEG (versus test de Wada) dans l'épilepsie temporale chez le droitier

Spectral analysis of the EEG alpha rhythm was studied in nine temporal epileptic right-handed patients in order to predict localization of the speech area. We studied the variation of the spectral power of the alpha rhythm during an activation paradigm previously validated in normal right-handed subjects. Significant alpha power decreases in the left hemisphere during writing with the right hand (as compared to resting) and/or significant alpha power decreases in the right hemisphere during left-hand recognition and classification of cardboard objects (as compared to resting) were considered as consistent with left-hemisphere dominance for language. The results of EEG spectral analysis were compared with those of the Wada test. The left hemisphere was dominant for language according to the Wada test in eight subjects and the right hemisphere in one subject. Six patients had a significant alpha power reduction in the hemisphere concerned during lateralized cognitive tasks, consistent with language localization in the left hemisphere according to the Wada test. The three remaining patients had no significant EEG spectral power variations. A significant decrease of alpha power in the active hemisphere during cerebral activation seems statistically related to left-hemispheric dominance for language in right-handed subjects (hemispheric specialization). However, the localization of the speech area using this electrophysiological method does not appear clinically relevant for a case-by-case decision in individual patients.     

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 effect of seizure focus on regional language processing areas

Purpose: To determine the effect of seizure focus location within the left hemisphere on the expression of regional language dominance. Methods: In this cross‐sectional study we investigated 90 patients (mean age 23.3 ± 12.9 years) with left hemisphere focal epilepsy (mean age onset 11.7 ± 8.3 years). Eighteen patients had a frontal lobe focus and 72 had a temporal lobe focus (43 mesial; 29 neocortical). Subjects performed an auditory word definition language paradigm using 3 Tesla blood oxygen level dependent (BOLD) EPI functional magnetic resonance imaging (fMRI). Data were analyzed in SPM2. Regional laterality indices (LIs) for inferior frontal gyrus (IFG), and Wernicke’s area (WA), were calculated using a bootstrap method. Categorical language dominance and mean LI were analyzed. Key Findings: Mean WA LI was lower for subjects with a mesial temporal focus compared with a frontal focus (p = 0.04). There was a greater proportion of atypical language in WA for subjects with a mesial temporal focus compared with a frontal focus (χ² = 4.37, p = 0.04). WA LI did not differ for subjects with a neocortical focus compared with a mesial focus or a frontal focus. Mean IFG LI and proportion of atypical language in IFG were similar across seizure focus groups. Age and age of onset were not correlated with mean laterality in WA or IFG. Epilepsy duration tended to be negatively correlated with WA LI (r = ?0.18, p = 0.10), but not IFG LI. Significance: Temporal lobe foci have wide‐ranging effects on the distributed language system. In contrast, the effects of a frontal lobe focus appear restricted to anterior rather than posterior language processing areas.     

Effects of anterior temporal lobectomy on language function: A controlled study

This study represents the first prospective controlled investigation of preoperative versus postoperative (6 months) language function in patients who underwent partial resection of the dominant (n = 15) or nondominant (n =14) anterior temporal lobe for treatment of medically refractory epilepsy. Language dominance was confirmed by in tracarotid sodium amytal test. Thirteen of the 15 patients undergoing anterior temporal lobectomy of the dominant hemisphere were operated on under local anesthesia in order to map language and memory functions intraoperatively. Using a standardized language/aphasia battery, we found a significant trend of worse preoperative language function in patients with dominant hemisphere temporal lobe foci in comparison to patients with nondominant foci. Following anterior temporal lobectomy, neither group showed any significant losses in language function, whereas the dominant hemisphere temporal lobe group showed significant improvement in receptive language comprehension and associative verbal fluency.     

Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Language cortex representation: Effects of developmental versus acquired pathology

Relatively little is known about language cortex representation in patients with developmental pathology and epilepsy. We report the results of mapping language by electrical stimulation of chronically implanted subdural electrodes in 34 patients (mean age, 12.2 years) evaluated for epilepsy surgery, 28 of whom had magnetic resonance imaging or histological evidence of developmental tumors or cortical dysplasia. Language cortex was identified in the temporal or frontal lobe of 19 patients (left hemisphere in 17, right hemisphere in 2), and overlapped or bordered the epileptogenic region in 12. Language cortex was not found in the frontal or temporal lobe of 15 patients (left hemisphere in 4, right hemisphere in 11) and was presumed to be contralateral to grid placement. Three patients with left-hemisphere perinatal or postnatal cerebral insults before the age of 5 years had no language in the left hemisphere, while 3 patients with insults between the ages of 6 and 16 years had preserved left-hemisphere language. Developmental lesions and early onset seizures do not displace language cortex from prenatally determined sites, whereas lesions acquired before the age of 5 years may cause language to relocate to the opposite hemisphere, but only when language cortex is destroyed.