Surgery For Mesial Temporal Lobe Epilepsy Research Articles

The anterior sylvian point as a reliable landmark for the anterior temporal lobectomy in mesial temporal lobe epilepsy: technical note, case series, and cadaveric dissection.

Mesial temporal lobe epilepsy (MTLE) is one of the most prevalent forms of focal epilepsy in surgical series, particularly among adults. Over the decades, different surgical strategies have been developed to address drug-resistant epilepsy while safeguarding neurological and cognitive functions. Among these strategies, anterior temporal lobectomy (ATL), involving the removal of the temporal pole and mesial temporal structures, has emerged as a widely employed technique. Numerous modifications have been proposed to mitigate the risks associated with aphasia, cognitive issues, and visual field defects. Our approach is elucidated through intraoperative and cadaveric dissections, complemented by neuroradiological and cadaveric measurements of key anatomical landmarks. A retrospective analysis of patients with drug-resistant MTLE who were treated using our ATL technique at IRCCS Neuromed (Pozzilli) is presented. A total of 385 patients were treated with our ATL subpial technique anatomically focused on the anterior Sylvian point (ASyP). The mean FU was 9.9 ± 5.4 years (range 1-24). In total, 84%of patients were free of seizures during the last follow-up, with no permanent neurological deficits. Transient defects were as follows: aphasia in 3% of patients, visual field defects in 2% of patients, hemiparesis in 2% of patients, and cognitive/memory impairments in 0.8% of patients. In cadaveric dissections, the ASyP was found at a mean distance from the temporal pole of 3.4 ± 0.2 cm (range 3-3.8) at the right side and 3.5 ± 0.2 cm (3.2-3.9) at the left side. In neuroimaging, the ASyP resulted anterior to the temporal horn tip in all cases at a mean distance of 3.2 ± 0.3 mm (range 2.7-3.6) at the right side and 3.5 ± 0.4 mm (range 2.8-3.8) at the left side. To the best of our knowledge, this study first introduces the ASyP as a reliable and reproducible cortical landmark to perform the ATL to overcome the patients' variabilities, the risk of Meyer's loop injury, and the bias of intraoperative measurements. Our findings demonstrate that ASyP can be a safe cortical landmark that is useful in MTLE surgery because it is constantly present and is anterior to risky temporal regions such as temporal horn and language networks.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Analysis of distribution and localization of proteins of the reelin signalling pathway in mesial temporal lobe epilepsy

Introduction Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE. Materials and Methods Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls (n = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software. Results Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy. Conclusions Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. Nine centers from 3 continents contributed 206 patients operated for drug-resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss-of-function (LoF) variants (odds ratio [OR]=2.6, 95% confidence interval [CI]=1.9-3.5, p= 1.3E-09) and in genes encoding voltage-gated cation channels (OR=2.4, 95% CI=1.4-3.8, p= 2.7E-04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between-group differences. Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision-making and counseling. ANN NEUROL 2022.

Reelin Signaling Pathway and Mesial Temporal Lobe Epilepsy: A Causative Link.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis. The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases. We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases. The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.

Machine learning approaches for imaging-based prognostication of the outcome of surgery for mesial temporal lobe epilepsy.

ObjectivesAround 30% of patients undergoing surgical resection for drug‐resistant mesial temporal lobe epilepsy (MTLE) do not obtain seizure freedom. Success of anterior temporal lobe resection (ATLR) critically depends on the careful selection of surgical candidates, aiming at optimizing seizure freedom while minimizing postoperative morbidity. Structural MRI and FDG‐PET neuroimaging are routinely used in presurgical assessment and guide the decision to proceed to surgery. In this study, we evaluate the potential of machine learning techniques applied to standard presurgical MRI and PET imaging features to provide enhanced prognostic value relative to current practice.MethodsEighty two patients with drug resistant MTLE were scanned with FDG‐PET pre‐surgery and T1‐weighted MRI pre‐ and postsurgery. From these images the following features of interest were derived: volume of temporal lobe (TL) hypometabolism, % of extratemporal hypometabolism, presence of contralateral TL hypometabolism, presence of hippocampal sclerosis, laterality of seizure onset volume of tissue resected and % of temporal lobe hypometabolism resected. These measures were used as predictor variables in logistic regression, support vector machines, random forests and artificial neural networks.ResultsIn the study cohort, 24 of 82 (28.3%) who underwent an ATLR for drug‐resistant MTLE did not achieve Engel Class I (i.e., free of disabling seizures) outcome at a minimum of 2 years of postoperative follow‐up. We found that machine learning approaches were able to predict up to 73% of the 24 ATLR surgical patients who did not achieve a Class I outcome, at the expense of incorrect prediction for up to 31% of patients who did achieve a Class I outcome. Overall accuracies ranged from 70% to 80%, with an area under the receiver operating characteristic curve (AUC) of .75–.81. We additionally found that information regarding overall extent of both total and significantly hypometabolic tissue resected was crucial to predictive performance, with AUC dropping to .59–.62 using presurgical information alone. Incorporating the laterality of seizure onset and the choice of machine learning algorithm did not significantly change predictive performance.SignificanceCollectively, these results indicate that "acceptable" to "good" patient‐specific prognostication for drug‐resistant MTLE surgery is feasible with machine learning approaches utilizing commonly collected imaging modalities, but that information on the surgical resection region is critical for optimal prognostication.

Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry.

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy.Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded.Outcomes: The collected data will be used for establishing standardized reference values (“benchmarks”) for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications.Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials.Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).

Olfactory function in patients with temporal lobe epilepsy; correlation of functional magnetic resonance imaging for olfaction with the laterality of the epileptic focus

The olfactory function shares the same cerebral structures as those involved in the origin and propagation of focal temporal lobe seizures. Likewise, functional magnetic resonance imaging (fMRI) allows the study of olfactory function. This suggests that by quantitatively studying the olfactory function with an olfactory paradigm through fMRI it is possible to identify the functional alteration produced by the epileptic focus. The objective of the present study was to assess the olfactory function in the side of the epileptic focus in patients with mesial temporal lobe epilepsy, using fMRI for smell, and propose a non-invasive diagnostic method for patients candidates to mesial temporal lobe epilepsy surgery. MethodsPatients (n = 18) with clinical diagnosis of mesial temporal lobe epilepsy, refractory to pharmacological treatment: 7 patients (38.9%) with non-invasive studies consistent enough to submit them to anterior temporal lobectomy, and 11 (61.1%) patients where focal onset seizures were identified by stereoelectroencephalography (SEEG) on the left temporal lobe in 5 (27.8%) and in both temporal lobes in 2 (11.1%). Patients were evaluated using EEG, MRI, neuropsychological data, and fMRI with olfactory paradigm. Results of the fMRI were compared with the laterality of the epileptic focus determined by intracranial electroencephalogram recordings through stereotactically placed electrodes, and with post-surgical outcome at one year of follow-up. ResultsfMRI showed a lower olfactory activation in 81.8% concordant with unilateral onset seizures. There were significant differences of olfactory fMRI activation between epileptic and non-epileptic foci. ConclusionFunctional magnetic resonance imaging with an olfactory paradigm may be a non-invasive diagnostic tool to determine the laterality of seizure onset in the mesial temporal lobe.

The role of brain magnetic resonance imaging on the timing of antiepileptic drugs withdrawal following mesial temporal lobe epilepsy surgery.

Objectives:To assess the influence of magnetic resonance imaging (MRI) brain findings on the timing of antiepileptic drugs (AEDs) withdrawal following anterior temporal lobectomy (ATL) in patients with mesial temporal lobe epilepsy (MTLE).Methods:We conducted a retrospective chart review at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia from Jan, 2004 – Dec, 2017 of patients with MTLE who underwent ATL and included patients who had a minimum of 2 years of follow-up. We evaluated the association between the time required to start tapering and discontinuing AEDs after ATL in patients with Engel class I outcomes and their preoperative brain MRI.Results:We studied 64 patients who underwent ATL. The majority of patients (63%) had hippocampal sclerosis (HS) on histopathology. Following ATL, the mean time to start tapering AEDs was 10 months and AEDs were discontinued at a mean of 48 months. Abnormal brain MRI was observed in 53 (83%) patients, with findings suggestive of mesial temporal sclerosis (MTS) accounting for 75% of these abnormalities. The presence of any MRI abnormality was associated with a 10-month earlier tapering of AEDs (p<0.01), and an 18-month earlier complete withdrawal of AEDs (p<0.01). The odds of being seizure-free within the first year were higher if MTS was present in the brain MRI (adjusted OR=16). Similarly, this was associated with seizure freedom after the first year (adjusted OR=14.8, p<0.01). The presence of unilateral temporal IEDs on preoperative EEG were also associated with earlier tapering and discontinuation of AEDs as well as a seizure-free state after ATL surgery (OR=8.5 and 4.2, for the first and second year respectively, p<0.01).Conclusion:Patients with abnormal MRI findings and unilateral IEDs had earlier tapering of AEDs with an overall shorter AED discontinuation plan. Moreover, the presence of MTS on MRI, along with unilateral IEDs, were predictors of seizure freedom following ATL.

Critical area for memory decline after mesial temporal resection in epilepsy patients.

Mesial temporal lobe epilepsy (MTLE) surgery is associated with a risk of memory decline after surgery, but the effect of the extent and locus of temporal resection on postoperative memory function are controversial. The authors' aim in this study was to confirm if selective resection is effective in preserving memory function and identify critical areas for specific memory decline after temporal resection. In this single-center retrospective study, the authors investigated data from patients who underwent unilateral MTLE surgery between 2005 and 2015. Data from 74 MTLE patients (60.8% of whom were female; mean [SD] age at surgery 32 years [8.91 years] and duration of epilepsy 16 years [9.65 years]) with histologically proven hippocampal sclerosis were included. Forty-two patients underwent left-sided surgery. The resection area was manually delineated on each patient's postoperative T1-weighted images. Mapping was performed to see if the resected group, compared with the nonresected group, had worse postoperative memory in various memory domains, including verbal item, verbal associative, and figural memory. Overall, 95.9% had a favorable epilepsy outcome. In verbal item memory, resection of the left lateral temporal area was related to postoperative decline in immediate and delayed recall scores of word lists. In verbal associative memory, resection of the anterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to postoperative decline in immediate recall scores of word pairs. Resection of the posterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to delayed recall scores of the same task. Similarly, in the figural memory, postoperative decline of immediate recall scores was associated with the resection of the anterior part of the right hippocampus, amygdala, parahippocampal area, and superior temporal area, and decline of delayed recall scores was related to resection of the posterior part of the right hippocampus and parahippocampal area. Using voxel-based analysis, which accounts for the individual differences in the resection, the authors found a critical region for postoperative memory decline that is not revealed in the region-of-interest or groupwise comparison. Particularly, resection of the hippocampus was related to associative memory. In both verbal and visual memory, resection of the anterior part of the hippocampus was associated with immediate recall, and resection of the posterior part of the hippocampus was associated with delayed recall. Therefore, the authors' results suggest that selective resection may be effective in preserving postoperative memory decline.

Visual field defects after radiosurgery versus temporal lobectomy for mesial temporal lobe epilepsy: Findings of the ROSE trial

PurposeStereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9–100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. MethodsThis prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. ResultsNo patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. ConclusionThe nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.

T07. Resting-state EEG functional connectivity and outcome following mesial temporal lobe epilepsy surgery

In this study we explore the reorganization of brain functional connectivity in patients with refractory mesial temporal lobe epilepsy that underwent surgery. We carried out a resting-state EEG functional connectivity analysis in a baseline period before and two years after the surgical intervention. Changes in synchronization features and graph theoretical properties were quantified by synchronization likelihood in patients with different surgical outcome, where outcome was defined as seizure-free (good outcome) or not seizure-free (poor outcome) 1 year after surgery. EEG segments were manually selected and included at least 2 min in closed eyes resting state. In all segments, synchronization likelihood (SL) and graph parameters in delta (1–4 Hz), theta (4–7 Hz), alpha1 (8–10 Hz), alpha2 (10–13 Hz), beta1 (13–15 Hz) and beta2 (15–20 Hz) frequency bands were calculated. Results showed that strength of the overall spatial synchronization was different 2 years after surgery in patients that were free of seizures. The change in synchronization was characterized by lower synchronization in alpha 1 but higher synchronization in alpha2. No changes between pre- and 2 years post-surgery periods were present in patients with seizures’ recurrence. Network properties as clustering coefficient and modularity in alpha2, beta1 and beta2 were higher postoperatively in the group free of seizures compared to baseline. Local efficiency was also higher in theta, alpha2 and beta bands. Interestingly the group with seizures’ recurrence showed a higher modularity only in the delta band but the clustering coefficient and the local efficiency were higher in all frequency bands 2 years after surgery. Outcome after surgery is related to a specific reorganization in brain networks as manifested in changes of functional connectivity and network topology. Reorganization toward a small-world network within the alpha2 and beta bands seems to be mediating seizure resolution.

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery

PurposeThe purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. MethodsForty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. Key findingsSix (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. SignificanceImpairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.

Cognitive Outcome after Surgery in Patients with Mesial Temporal Lobe Epilepsy.

The aim of the present study was to evaluate the neuropsychological outcomes of patients with medically intractable unilateral mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) treated either by anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). This was a retrospective study where 67 patients who had undergone surgery for MTLE were evaluated. Thirty-two patients underwent ATL and 35 underwent SAH. All patients underwent a detailed neuropsychological evaluation before and 1 year after surgery. The verbal memory outcome was unchanged after left-sided surgery, whereas learning capacity increased after right-sided surgery (p=0.038). The visual memory outcome improved after right-sided surgery. Improvement of executive functions, particularly in the resistance of interference pattern in the Stroop Test, shortened 5th card time (p=0.000), and decreased corrections (p=0.003), after right-sided surgery and increased attention (p=0.027) after left-sided surgery were observed. After both surgery types, although statistically insignificant, there was a marked decrease in incorrect answers in the Stroop Test, which also showed an improvement in the resistance of interference pattern. Moreover, there was a significant decrease in switching errors with word pairs in the Verbal Fluency Test (p=0.008) after right-sided surgery. When the two sides were compared, we observed that the recall phase of the verbal memory worsened (p=0.018); however, the recognition phase improved (p=0.015) after left-sided surgery. Additionally, the short-term visual memory was better for both sides (p=0.035). Our results showed that patients with left MTLE were not worsened in verbal memory, but despite improved recognition, they have some problems in recalling information and only a minor improvement in attention. Patients with right MTLE improved in their verbal learning capacity, visual memory, and resistance of interference pattern 1 year after surgery. It was thus shown that while epilepsy surgery is associated with some negative cognitive changes, it may also improve some cognitive functions.

Optic Radiation Tractography and Visual Field Deficits in Laser Interstitial Thermal Therapy for Amygdalohippocampectomy in Patients with Mesial Temporal Lobe Epilepsy

Background/Aims: Laser interstitial thermal therapy (LITT) has become an alternative to open-resective surgery for refractory mesial temporal lobe epilepsy (MTLE). Occurrence of visual field defects (VFDs) following open surgery for MTLE is reported at 52-100%. We examined the rate of VFDs following LITT for amygdalohippocampectomy (AHE) and correlated the occurrence of VFDs with damage to the optic radiations, assessed by diffusion tensor tractography (DTI). Methods: We performed a retrospective analysis of 5 patients who underwent LITT-AHE for medically refractory MTLE. We examined the association between VFDs and optic radiation damage by correlating postprocedural visual field testing with qualitative assessment of optic radiation fiber tracts. Results: Postoperative assessments showed that 4 patients had normal visual field testing, and 1 had a right superior quadrantanopsia (20%). We performed 3-dimensional reconstruction of the optic radiation, laser probe trajectory, and ablation volume. Damage to Meyer's loop was determined consistent with the VFD. Conclusions: Short-term follow-up in our series suggests that laser ablation AHE may be associated with a lower rate of VFD than has been reported for open AHE. Our results suggest that incorporating optic radiation mapping through DTI may preoperatively help to minimize the risk of VFD following laser ablation AHE.

Introduction: Epilepsy surgery

This issue of Neurosurgical Focus is devoted to epilepsy surgery and includes a variety of topics ranging from technical nuances to edge-of-the-envelope interventions that are just beginning to find their place in surgical management. Eleven papers are included. Some of the new findings and methods that we think will interest readers involve magnetoencephalography (MEG), stereoelectroencephalography (SEEG), and a-methyl-l-tryptophan (AMT)–PET, as well as novel ways of coregistering preand postoperative MR images. We also include a review of optogenetics as it could apply to excitation or inhibition of neural circuits still being studied in animal models. Other reports consider more standard, but no less relevant, issues: complications and specific etiologies such as new-onset refractory status epilepticus and hypothalamic hamartoma. In the report, “Tissue localization during resective epilepsy surgery,” the authors describe methods they use for localization of specific brain regions and implantable electrodes as well as tissue removed by coregistering preand postoperative information from MRI, including functional MRI (fMRI), allowing for the correlation of anatomy, pathology (even at a molecular level), and outcome. Similarly, new methodology for localization is considered in “Correlation between magnetoencephalography-based ‘clusterectomy’ and postoperative seizure freedom,” in which the authors describe using clustering of MEG-derived information from interictal spikes to guide resections, particularly for extratemporal foci. Another report, “Complications after mesial temporal lobe epilepsy surgery via inferior temporal gyrus approach,” considers related complications, which in the authors’ hands showed very acceptable risks. The report, “Seizure control after subtotal lesional resection,” includes the description of a single case as well as a comprehensive literature review of tailored subtotal resection for lesional epilepsy. Also included in this issue is a valuable review of hemispherectomy, “Hemispherectomy: historical review and recent technical advances.” As the title indicates, this paper expands the discussion to more novel imaging and surgical strategies. Another report continues the discussion of hemispherectomy and hemispherotomy—“Disconnective surgery in posterior quadrantic epilepsy: experience in a consecutive series of 10 patients”—but restricts considerations to temporal parietooccipital resections and disconnections accordingly. Stereoelectroencephalography is discussed in the report, “Stereoelectroencephalography for continuous twodimensional cursor control in a brain-machine interface,” in which the methodology of analyzing information from specially designed depth electrodes, each with multiple contacts, is presented. The relevance to localization for epilepsy as well as to brain-machine interfaces is considered. “Optogenetics in epilepsy” presents an overview of futuristic methodology, induction of ion channels using viral vectors, and the use of light to stimulate or inhibit neural circuits. The authors review the work done in animal models and their relevance to human seizures. Several reports consider specific etiologies: inflammation and hypothalamic hamartomas (the latter discussed in 2 parts). “Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus” presents a single case and reviews the topic, including a discussion of more standard methods for localization coregistered with molecular information from AMT-PET. The paired reports on hypothalamic hamartomas review this entity in detail as well as management strategies. Epilepsy surgery sits at the juncture of classic anatomical neurosurgery and functional neurosurgery. Surgery to treat epilepsy also provides us with an opportunity to understand neuronal networks. The papers in this issue illustrate some of the issues, challenges, and exciting developments in the field. (http://thejns.org/doi/abs/10.3171/2013.4.FOCUS13138)

Visual field defects after radiosurgery for mesial temporal lobe epilepsy

Gamma knife radiosurgery (RS) may be an alternative to open surgery for mesial temporal lobe epilepsy (MTLE), but morbidities and the anticonvulsant mechanisms of RS are unclear. Examination of visual field defects (VFDs) after RS may provide evidence of the extent of a postoperative fixed lesion. VFDs occur in 52-100% of patients following open surgery for MTLE. This multicenter prospective trial of RS enrolled patients with unilateral hippocampal sclerosis and concordant video-electroencephalography (EEG) findings. Patients were randomized to low (20 Gy) or high (24 Gy) doses delivered to the amygdala, hippocampal head, and parahippocampal gyrus. Postoperative perimetry were obtained at 24 months after RS. Visual field defect ratios (VFDRs) were calculated to quantify the degree of VFDs. Results were contrasted with age, RS dose and 50% isodose volume, peak volume of radiation-induced change at the surgical target, quality of life measurements, and seizure remission. No patients reported visual changes and no patients had abnormal bedside visual field examinations. Fifteen (62.5%) of 24 patients had postoperative VFDs, all homonymous superior quadrantanopsias. None of the VFDs were consistent with injury to the optic nerve or chiasm. Clinical diagnosis of VFDs correlated significantly with VFDRs (p = 0.0005). Patients with seizure remission had smaller (more severe) VFDRs (p = 0.04). No other variables had significant correlations. VFDs appeared after RS in proportions similar to historical comparisons from open surgery for MTLE. The nature of VFDs was consistent with lesions of the optic radiations. The findings support the hypothesis that the mechanism of RS involves some degree of tissue damage and is not confined entirely to functional changes in neuromodulation.

Serious Adverse Effects of Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy

Gamma knife radiosurgery (GKRS) for mesial temporal lobe epilepsy (MTLE) has been proposed as an alternative to surgical resection. We report serious adverse effects of the treatment after follow-up periods over 9 years in 11 patients treated with GKRS between 1997 and 2000. The target volume of the entorhinoamygdalohippocampectomy area was 4.8-17.1 ml. Marginal dose of 20-25 Gy to the 50% isodose was delivered. One patient was drowned after suffering seizure 7 months after GKRS. Two patients did not show any reduction in seizure frequency over 9 and 18 months. Both patients requested open surgery and became seizure-free postoperatively. Four of the other eight patients were classified as Engel's class I within 4 years after GKRS. One of the four patients experienced symptomatic radiation-induced cerebral edema transiently, one developed radiation necrosis and required surgery 5 years after GKRS, and one developed cognitive impairment with hemiparesis 10 years after GKRS. Magnetic resonance (MR) imaging showed a large cyst in the irradiated temporal lobe. This patient recovered fully after the cyst excision. Only one patient became seizure-free and antiepileptic drug-free without symptomatic radiation-induced complications. However, MR imaging revealed abnormal enhancement, cyst formation, and diffuse white matter change in the irradiated temporal lobe 9 years after GKRS. GKRS for MTLE causes adverse effects of delayed seizure remission and symptomatic radiation-induced complications. Therefore, GKRS cannot be considered as an ideal alternative to surgery for MTLE. Long-term follow-up studies including MR imaging with contrast medium are required for the patients even after successful control of seizures.

Memory outcome after temporal lobe epilepsy surgery: corticoamygdalohippocampectomy versus selective amygdalohippocampectomy

The aim of this study was to compare IQ and memory outcomes at the 1-year follow-up in patients with medically refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis. All patients were treated using a corticoamygdalohippocampectomy (CAH) or a selective amygdalohippocampectomy (SelAH). The data of 256 patients who underwent surgery for MTLE were retrospectively evaluated. One hundred twenty-three patients underwent a CAH (63 [right side] and 60 [left side]), and 133 underwent an SelAH (61 [right side] and 72 [left side]). A comprehensive neuropsychological test battery was assessed before and 1 year after surgery, and the results were compared between the surgical procedures. Furthermore, seizure outcome was compared using the Engel classification scheme. At 1-year follow-up, there was no statistically significant difference between the surgical approaches with respect to seizure outcome. Overall, IQ scores showed improvement, but verbal IQ decreased after left SelAH. Verbal memory impairment was seen after left-sided resections especially in cases of SelAH, and nonverbal memory decreased after right-sided resection, especially for CAH. Left-sided resections produced some improvement in nonverbal memory. Older age at surgery, longer duration of seizures, greater seizure frequency before surgery, and poor seizure control after surgery were associated with poorer memory. Both CAH and SelAH can lead to several cognitive impairments depending on the side of the surgery. The authors suggest that the optimal type of surgical approach should be decided on a case-by-case basis.

Long-term seizure outcome after mesial temporal lobe epilepsy surgery: corticalamygdalohippocampectomy versus selective amygdalohippocampectomy

Resection strategies for the treatment of temporal lobe epilepsy (TLE) are a matter of discussion, and little information is available. The aim of this study was to compare seizure outcomes at the 5-year follow-up in patients with medically refractory unilateral mesial TLE (MTLE) due to hippocampal sclerosis (HS) who were treated using a cortical amygdalohippocampectomy (CorAH) or a selective AH (SelAH). The authors obtained data from 100 adult patients who underwent surgery for MTLE. Fifty patients underwent a CorAH and 50 underwent an SelAH. Seizure control achieved with each technique was compared using the Engel classification scheme. Overall, at the 5-year follow-up, favorable (Engel Classes I and II) seizure outcomes were noted in 82 and 90% of patients who had undergone CorAH and SelAH, respectively. Furthermore, 40% of the patients who had undergone a CorAH and 58% of those who had undergone an SelAH were seizure free (Engel Class Ia). There was no statistically significant difference between the 2 surgical approaches in terms of seizure outcome at the 5-year follow-up (p = 0.38). Both CorAH and SelAH can lead to similar favorable seizure control in patients with MTLE/HS. However, the authors suggest that the transcortical selective approach has the great advantage of minimizing or completely abolishing the impact of dividing several venous and arterial adhesions which are tedious, time consuming, and, at times, associated with some degree of cerebral swelling.