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Aaron A. Cohen-Gadol, Michael Westerveld, Juan Alvarez-Carilles, and Dennis D. Spencer

Object. Intracarotid Amytal testing (the Wada test) has been used to lateralize language and identify patients who may be at risk for memory impairment after temporal lobectomy. The goal of this study was to determine the validity of the Wada test in the assessment of pathological conditions of the hippocampus among candidates for epilepsy surgery. The authors examined the correlation between the functional integrity of the hippocampus, measured using the Wada test, and quantitative measures of hippocampal pathology, determined by obtaining volumetric measurements of the hippocampus with the aid of magnetic resonance (MR) imaging.

Methods. The authors reviewed the relationship between memory scores on the Wada test and hippocampal volumes measured on preoperative MR images in 76 patients who underwent anteromedial temporal lobectomy and amygdalohippocampectomy for the treatment of medically refractory temporal lobe epilepsy. The data were analyzed with respect to their usefulness in lateralizing the seizure focus and predicting the long-term postoperative memory outcome.

Right and left hippocampal volume measurements did not correlate with one another (p > 0.1). Similarly, following a left carotid artery injection of Amytal the patients' right hemisphere memory was not significantly related to their left hemisphere memory on the Wada test (p > 0.1). On the other hand, the patients' right hemisphere memory significantly correlated with their right hippocampal volume (r = 0.51; p < 0.001) and their left hemisphere memory significantly correlated with their left hippocampal volume (r = 0.51; p < 0.001). Both right and left hemisphere memory scores correlated with the hippocampal volumetry ratio (r = 0.47 and r = 0.45, respectively; both p < 0.001). Lateralization of a seizure focus based on hippocampal volumetry results was significantly related to lateralization based on the results of the Wada test (r = 0.49; p < 0.01). The disparity between the Wada memory scores on ipsilateral and contralateral sides was significantly and inversely related to the change in verbal memory following temporal lobectomy (r = −0.28; p < 0.02). The preoperative hippocampal volumetry ratio also significantly and inversely correlated with the change in verbal memory after surgery (r = −0.31; p < 0.01).

Conclusions. The Wada memory test may be a valuable method of measuring the functional integrity of the hippocampus. The systematic study of MR imaging—acquired morphological data and Wada-acquired neuropsychological data may increase our understanding of the location of material-specific memory and the selection of eligible candidates for epilepsy surgery.

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Aaron A. Cohen-Gadol, Christopher C. Bradley, Anne Williamson, Jung H. Kim, Michael Westerveld, Robert B. Duckrow, and Dennis D. Spencer

Object. The syndrome of medial temporal lobe epilepsy (MTLE) may occur in patients in whom magnetic resonance (MR) images demonstrate normal findings. In these patients, there is no evidence of hippocampal sclerosis on neuroimaging, and histopathological examination of the resected hippocampus does not reveal significant neuron loss. In this paper the authors describe the distinct clinical features of this MTLE subtype, referred to as paradoxical temporal lobe epilepsy (PTLE).

Methods. The authors selected 12 consecutive patients with preoperative findings consistent with MTLE in whom MR imaging did not demonstrate any hippocampal abnormality. Onset of hippocampal seizure was confirmed by long-term intracranial monitoring. There were six female and six male patients with a mean age of 32 ± 11 years (mean ± standard deviation [SD]) at presentation. These patients' seizure histories, available hippocampal volumetric measurements, and hippocampal cell densities in different subfields were reviewed. Sharp electrode recordings from dentate granule cells that had been maintained in hippocampal slices provided a measure of excitation and inhibition in the tissue. We compared these data with those of a cohort of 50 randomly selected patients who underwent anteromedial temporal resection for medial temporal sclerosis (MTS) during the same time period (1987–1999). The durations of follow up (means ± SDs) for the PTLE and MTS groups were 51 ± 59 months and 88 ± 44 months, respectively.

A history of febrile seizure was present less frequently in the PTLE group (8%) than in the MTS group (34%). Other risk factors for epilepsy such as trauma, meningoencephalitis, or perinatal injuries were present more frequently in the PTLE group (50%) than in the MTS cohort (36%). In patients in the PTLE group the first seizure occurred later in life (mean age at seizure onset 14 years in the PTLE group compared with 9 years in the MTS group, p = 0.09). Ten patients (83%) in the PTLE cohort and 23 patients (46%) in the MTLE cohort had secondary generalization of their seizures. Among patients with PTLE, volumetric measurements (five patients) and randomized blinded visual inspection (seven patients) of the bilateral hippocampi revealed no atrophy and no increased T2 signal change on preoperative MR images. All patients with PTLE underwent anteromedial temporal resection (amygdalohippocampectomy, in five patients on the left side and in seven on the right side). Electrophysiological studies of hippocampal slices demonstrated that dentate granule cells from patients with PTLE were significantly less excitable than those from patients with MTS. The mean pyramidal cell loss in the CA1 subfield in patients in the PTLE group was 20% (range 0–59%) and that in patients in the MTS group was 75% (range 41–90%) (p < 0.001). Maximal neuron loss (mean loss 38%) occurred in the CA4 region in six patients with PTLE (end folium sclerosis). At the last follow-up examination, six patients (50%) in the PTLE group were seizure free compared with 38 patients (76%) in the MTS group.

Conclusions. Clinical PTLE is a distinct syndrome with clinical features and surgical outcomes different from those of MTS.

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Elakkat D. Gireesh, Kihyeong Lee, Holly Skinner, Joohee Seo, Po-Ching Chen, Michael Westerveld, Richard D. Beegle, Eduardo Castillo, and James Baumgartner


The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex.


The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant.


Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6–2.8 years). All patients responded favorably to treatment (Engel class I–III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT.


sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.

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Milena Korostenskaja, Po-Ching Chen, Christine M. Salinas, Michael Westerveld, Peter Brunner, Gerwin Schalk, Jane C. Cook, James Baumgartner, and Ki H. Lee

Accurate language localization expands surgical treatment options for epilepsy patients and reduces the risk of postsurgery language deficits. Electrical cortical stimulation mapping (ESM) is considered to be the clinical gold standard for language localization. While ESM affords clinically valuable results, it can be poorly tolerated by children, requires active participation and compliance, carries a risk of inducing seizures, is highly time consuming, and is labor intensive. Given these limitations, alternative and/or complementary functional localization methods such as analysis of electrocorticographic (ECoG) activity in high gamma frequency band in real time are needed to precisely identify eloquent cortex in children.

In this case report, the authors examined 1) the use of real-time functional mapping (RTFM) for language localization in a high gamma frequency band derived from ECoG to guide surgery in an epileptic pediatric patient and 2) the relationship of RTFM mapping results to postsurgical language outcomes. The authors found that RTFM demonstrated relatively high sensitivity (75%) and high specificity (90%) when compared with ESM in a “next-neighbor” analysis. While overlapping with ESM in the superior temporal region, RTFM showed a few other areas of activation related to expressive language function, areas that were eventually resected during the surgery. The authors speculate that this resection may be associated with observed postsurgical expressive language deficits. With additional validation in more subjects, this finding would suggest that surgical planning and associated assessment of the risk/benefit ratio would benefit from information provided by RTFM mapping.

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Michael Westerveld, Kimberlee J. Sass, Gordon J. Chelune, Bruce P. Hermann, William B. Barr, David W. Loring, Esther Strauss, Max R. Trenerry, Kenneth Perrine, and Dennis D. Spencer

Object. The authors sought to determine the impact of early temporal lobectomy (in patients younger than age 17 years) on intellectual functioning. The efficacy of temporal lobectomy for treating seizures is well established and the procedure is becoming more acceptable as a treatment for children whose seizures are intractable. However, cognitive outcomes of temporal lobectomy in children and adolescents are largely unreported. The present study takes advantage of a unique multicenter collaboration to examine retrospectively intellectual functioning in a large sample of children who underwent temporal lobectomy.

Methods. Intellectual functioning was assessed before and after temporal lobectomy for treatment of medication-resistant seizures in 82 patients at eight centers of epilepsy surgery. All children underwent standard presurgical examinations, including electroencephalography—video monitoring, magnetic resonance (MR) imaging, and neuropsychological testing, at their respective centers.

Forty-three children underwent left temporal lobectomy and 39 underwent right temporal lobectomy. For the entire sample, there were no significant declines in intelligence quotient (IQ) following surgery. Children who underwent left temporal lobectomy demonstrated no significant loss in verbal intellectual functioning and improved significantly in nonverbal intellectual functioning. Children who underwent right temporal lobectomy did not demonstrate significant changes in intellectual functioning. Although group scores showed no change in overall IQ values, an analysis of individual changes revealed that approximately 10% of the sample experienced a significant decline and 9% experienced significant improvement in verbal functioning. Significant improvement in nonverbal cognitive function was observed in 16% of the sample and only 2% of the sample showed significant declines. Risk factors for significant decline included older patient age at the time of surgery and the presence of a structural lesion other than mesial temporal sclerosis on MR imaging.

Conclusions. The present study provides preliminary data for establishing the risk of cognitive morbidity posed by temporal lobectomy performed during childhood. With respect to global intellectual functioning, a slight improvement was significantly more likely to occur than a decline. However, there were several patients in whom significant declines did occur. It will be necessary to study further the factors associated with such declines. In addition, further study of more specific cognitive functions, particularly memory, is needed.