Temporal Lobe Epilepsy Surgery Research Articles

A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery

PurposeTo establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). Patients and Methods234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). ResultsEight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95%CI: 0.59-0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. ConclusionsA PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.

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.

Mass Spectrometric Imaging of Anionic Phospholipids Desorbed from Human Hippocampal Sections: Discrimination between Temporal and Nontemporal Lobe Epilepsies.

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, often accompanied by hippocampal sclerosis. The molecular processes underlying this epileptogenesis are poorly understood. To examine the lipid profile, 39 fresh frozen sections of the human hippocampus obtained from epilepsy surgery for TLE (n = 14) and non-TLE (control group; n = 25) patients were subjected to desorption electrospray ionization mass spectrometry imaging in the negative ion mode. In contrast to our earlier report that showed striking downregulation of positively charged phospholipids (e.g., phosphatidylcholine and phosphatidylethanolamine, etc.) in the TLE hippocampus, this study finds complementary upregulation of negatively charged phospholipids, notably, phosphatidylserine and phosphatidylglycerol. This result may point to an active metabolic pool in the TLE hippocampus that produces these anionic phospholipids at the expense of the cationic phospholipids. This metabolic shift could be due to the dysregulation of the Kennedy and CDP-DG pathways responsible for biosynthesizing these lipids. Thus, this study further opens up opportunities to investigate the molecular hallmarks and potential therapeutic targets for TLE.

Verbal episodic memory in children undergoing temporal lobe epilepsy surgery: a one-year follow-up study.

Verbal episodic memory (VEM) is often unimpaired in children with focal epilepsy undergoing left temporal lobe resections, unlike what we might expect in the adult brain. The latter findings suggest that epileptiform activity in early life disrupts memory system lateralization, leading to the development of bilateral memory representation. The present study aims to analyze whether the laterality of epilepsy is a major predictor for post-operative VEM prognosis in pediatric temporal lobe epilepsy (TLE) surgery. This research also pretends to provide evidence about the relationship of VEM performance with other relevant demographical and clinical factors such as sex, age at onset of seizures, age at surgery and duration of epilepsy, as well as to study the impact of presurgical VEM performance on postsurgical outcomes. Pre-operative and one-year follow-up post-operative word-list recall scores from 25 children who underwent TLE surgery (left-sided, n = 11; right-sided, n = 14) were extracted from the Hospital Sant Joan de Deu database and were retrospectively analyzed. No significant presurgical intergroup differences were found when comparing VEM scores by laterality of epilepsy (p > 0.5). Looking at the left TLE group, a high negative correlation was found between the onset age and the pre-operative long-term free recall score (rho = -0.72, p = 0.01). No significant pre- to post-operative intragroup changes were found regarding VEM performance, regardless of epilepsy laterality (left TLE group, p > 0.56; right TLE group, p > 0.12). The laterality of epilepsy does not show to be a significant factor in and of itself regarding presurgical VEM outcome and its prognosis one year after surgery, thus supporting the bilateral memory representation hypothesis. Furthermore, a younger age at onset of seizures seems to be related with a better pre-operative VEM performance, likely due to a more efficient reorganization of memory system induced by a greater brain plasticity at lower ages; however, this relationship has been only reported for the left-sided epilepsies in our sample.

32 Prediction of Seizure Outcome with Presurgical IAT, MRI, and PET in Patients with Temporal Lobe Epilepsy Undergoing Surgery

Objective:Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.Participants and Methods:Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.Results:Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).Conclusions:Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Performance of hippocampal radiomics models based on T2-FLAIR images in mesial temporal lobe epilepsy with hippocampal sclerosis

PurposePreoperative identification of hippocampal sclerosis (HS) is crucial to successful surgery for mesial temporal lobe epilepsy (MTLE). We aimed to investigate the diagnostic performance of hippocampal radiomics models based on T2 fluid-attenuated inversion recovery (FLAIR) images in MTLE with HS. MethodsWe analysed 210 cases, including 172 HS pathology-confirmed cases (100 magnetic resonance imaging [MRI]-positive cases [MRI + HS], 72 MRI-negative HS cases [MRI − HS]), and 38 healthy controls (HC). The hippocampus was delineated slice by slice on an oblique coronal plane by a T2-FLAIR sequence, perpendicular to the hippocampus’s long axis, to obtain a three-dimensional region of interest. Radiomics were processed using Artificial Intelligence Kit software; logistic regression radiomics models were constructed. The model evaluation indexes included the area under the curve (AUC), accuracy, sensitivity, and specificity. ResultsThe respective AUC, accuracy, sensitivity, and specificity were 0.863, 81.4%, 78.0%, and 84.6% between the MRI − HS and HC groups in the training set and 0.855, 75.0%, 68.2%, and 81.8% in the test set; 0.975, 95.0%, 92.9%, and 98.0% between the MRI + HS and HC groups in the training set and 0.954, 88.7%, 90.0%, and 87.0% in the test set; and 0.912, 84.3%, 83.3%, and 86.5% between the MTLE and HC groups in the training set and 0.854, 79.7%, 80.8%, and 77.3% in the test set. The AUC values of the comparative radiomics models were > 0.85, indicating good diagnostic efficiency. ConclusionThe hippocampal radiomics models based on T2-FLAIR images can help diagnose MTLE with HS. They can be used as biological markers for MTLE diagnosis.

Temporal Lobe Surgery for Epilepsy in a Resource-Limited Vietnamese Cohort

Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September2022. The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate.

Psychiatric changes after stereotactic laser amygdalohippocampotomy for medial temporal lobe epilepsy

PurposeStereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for drug-resistant temporal lobe epilepsy (TLE) that has comparable rates of seizure freedom to traditional open resective TLE surgery. The objective of this study was to determine psychiatric outcome (i.e., depression and anxiety changes, psychosis) after SLAH, to explore possible contributory factors to these changes, and to determine the prevalence of de novo psychopathology. MethodsWe explored mood and anxiety in 37 adult patients with TLE undergoing SLAH using the Beck psychiatric symptoms scales (i.e., Beck Depression Inventory-II [BDI-II] and Beck Anxiety Inventory [BAI]) preoperatively and 6 months following surgery. Multivariable regression analysis was conducted to identify predictors of worse depression or anxiety symptoms following SLAH. The prevalence of de novo psychopathology following SLAH was also determined. ResultsWe found a significant decrease in BDI-II (mean decline from 16.3 to 10.9, p = 0.004) and BAI (mean decline from 13.3 to 9.0, p = 0.045) scores following SLAH at the group level.While the rate of resolution of depression (from 62% to 49%) did not achieve statistical significance (p = 0.13, McNemar’s), the rate of resolution of anxiety (from 57% to 35%) was statistically significant (p = 0.03, McNemar’s). The de novo rate of psychopathology (i.e., new onset depression or anxiety) following SLAH was 1 of 7 (14%). Using a metric of meaningful change rather than complete symptom resolution, 16 of 37 (43%) patients experienced improvement in depression and 6 of 37 (16%) experienced worsening. For anxiety, 14 of 37 (38%) experienced meaningful improvement and 8 of 37 (22%) experienced worsening. Baseline performance on the Beck Scales was the only factor contributing to outcome status. DiscussionIn one of the first studies to evaluate psychiatric outcomes after SLAH, we found promising overall trends toward stability or significant improvement in symptom burden at the group level for both depression and anxiety. There was also a significant improvement in clinical anxiety, though the decrease in clinical depression was not significant, likely owing to the limitations of sample size. SLAH may improve overall psychiatric symptoms, similarly to traditional resective TLE surgery, but de novo psychopathology and postoperative psychiatric morbidity remain significant issues, and larger samples are necessary to determine causal contributory factors.

SHORT-TERM SURGICAL OUTCOMES IN PATIENTS WITH DRUG-RESISTANT EPILEPSY DUE TO LESIONAL TEMPORA

Objectives: To describe the outcome of 35 cases of drug-resistant epilepsy due to the lesional temporal lobe surgery at Vietduc University Hospital from May 2018 to September 2022. Methods: A prospective description combined with retrospective, longitudinal follow-up of all patients diagnosed with drug resistance due to lesional temporal lobe epilepsy undergoing surgery at Vietduc University Hospital was conducted. Results: 35 cases of intractable lesional temporal lobe epilepsy surgery, male/female 1.5/1, partial seizures with loss of consciousness accounted for 99%, and 2/3 of cases occurred without aura. Seizure-free (post-operation 1 month) (Engel I) accounted for 74.3%, and the remaining (25.7%) had improved seizures (Engel 2, 3). Complications after surgery accounted for 17.1%, and there were no cases of death. Conclusion: Surgical treatment for drug resistance due to lesional temporal lobe epilepsy is safe and very effective, with a low complication rate.

Long-term Remission and Resolution of Epilepsy following Surgery for Drug Resistant Lesional Temporal Lobe Epilepsy. (P2-1.001)

<h3>Objective:</h3> To determine the long-term seizure freedom and resolution of epilepsy in patients with drug resistant Temporal Lobe Epilepsy (TLE) and a clear-cut MRI lesion. <h3>Background:</h3> The long-term seizure free outcomes following surgery for TLE varied widely from 41% – 80% following surgery for TLE. <h3>Design/Methods:</h3> In a retrospective, longitudinal cohort study, we analysed the presurgical, surgical and post-surgical parameters to determine the seizure freedom and resolution of epilepsy in patients with ‘drug resistant lesional TLE with at least 10 years or more of post-surgery follow-up. The Study period was from June 2001 to 2012 <h3>Results:</h3> Of the 259 patients who formed the study population, 46% were women. The duration of follow-up ranged from 10 to 21 years. The average age at surgery was 25.80 ± 11.32 yrs; 49% had an aura, 61% had only hypomotor seizures and 38% had psychiatric comorbidity. The commonest pathology was hippocampal sclerosis(70%) followed by tumoral lesions and focal cortical dysplasia; 9.8% had acute post-operative seizures. At latest follow-up 75.6% were seizure free of which 52% had resolution of epilepsy. Presence of an aura , hippocampal sclerosis and longer time to first post-operative seizure were strong predictors for resolution of epilepsy while acute post-operative seizures and an abnormal post-surgery EEG at 1 year were predictors of persistent seizures. On survival analysis, the time to first seizure was significantly early in patients with persistent seizures. Seizure freedom both at three and five years predicted seizure freedom at 10 years. <h3>Conclusions:</h3> Resective surgery for drug resistant lesional TLE was associated with higher rate of seizure-freedom in ~75% and resolution of epilepsy in 52.15% even at long term follow-up. Longer time to first seizure, presence of aura at presentation and hippocampal sclerosis are strong predictors for resolution of epilepsy. APOS and abnormal Post-Surgery inter-ictal EEG are predictors of unfavourable outcome. <b>Disclosure:</b> Dr. Sattaluri has nothing to disclose. Dr. Patil has nothing to disclose. Dr. Choudhary has nothing to disclose. Dr. Vooturi has nothing to disclose.

Distinguishing TLE and TLE+ using magnetoencephalography virtual sensors (P8-9.010)

<h3>Objective:</h3> This study observes whether user-defined virtual sensors (UDvs) beamforming, using expert reader analysis, is superior to the conventional equivalent current dipole (ECD) for non-invasively differentiating between TLE and TLE+. This could result in decreased failure rates in temporal lobe epilepsy surgery and improved seizure-free outcomes. <h3>Background:</h3> Temporal lobe epilepsy (TLE) is the most common seizure disorder. 44% of TLE+ pediatric patients that undergo resective surgery fail to achieve seizure freedom. It is imperative to identify TLE vs TLE+ in children pre-surgically, since the invasive monitoring plan to identify the seizure onset zone (SOZ) would differ. <h3>Design/Methods:</h3> Ten patients who underwent magnetoencephalography (MEG) as part of non-invasive pre-surgical evaluation and intracranial electroencephalography (iEEG) monitoring were included in this retrospective analysis. Five patients each were assigned to two groups: TLE and TLE+. Virtual sensors were placed symmetrically in the bilateral mesial temporal structures, temporal gyri, and neighboring structures. We reconstructed virtual sensor waveforms and analyzed three ten-minute segments of MEG recordings to classify them as positive or negative for epileptiform activity. A chart review of iEEG data was also classified as either positive or negative spikes. The primary analysis calculated the sensitivity and specificity of each method to determine the predictive value of UDvs-beamforming. <h3>Results:</h3> Ten patients (mean age 9.8 ± 4.2 years) with TLE or TLE+ were included. Across the ten patients, the UDvs method had a mean sensitivity of 93.1% and specificity of 53.3% compared to the ECD method which had a sensitivity of 71.1% and specificity of 88.3% (P = 0.031, 0.002). <h3>Conclusions:</h3> The ECD method has greater specificity than UDvs while UDvs had greater sensitivity than ECD in determining the presence of interictal epileptic spikes compared to the gold standard, iEEG. Future work will examine increasing sample size, performing connectivity analysis of interictal spikes, and correlating surgical resection with patient outcomes. <b>Disclosure:</b> Miss Hong has nothing to disclose. The institution of Paul Horn has received research support from NIH. Dr. Tenney has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wilson Smith Cochran Dickerson. The institution of Dr. Tenney has received research support from NIH.

Remote effects of temporal lobe epilepsy surgery: Long-term morphological changes after surgical resection.

Epilepsy surgery is an effective treatment for drug-resistant patients. However, how different surgical approaches affect long-term brain structure remains poorly characterized. Here, we present a semiautomated method for quantifying structural changes after epilepsy surgery and compare the remote structural effects of two approaches, anterior temporal lobectomy (ATL), and selective amygdalohippocampectomy (SAH). We studied 36 temporal lobe epilepsy patients who underwent resective surgery (ATL = 22, SAH = 14). All patients received same-scanner MR imaging preoperatively and postoperatively (mean 2 years). To analyze postoperative structural changes, we segmented the resection zone and modified the Advanced Normalization Tools (ANTs) longitudinal cortical pipeline to account for resections. We compared global and regional annualized cortical thinning between surgical treatments. Across procedures, there was significant cortical thinning in the ipsilateral insula, fusiform, pericalcarine, and several temporal lobe regions outside the resection zone as well as the contralateral hippocampus. Additionally, increased postoperative cortical thickness was seen in the supramarginal gyrus. Patients treated with ATL exhibited greater annualized cortical thinning compared with SAH cases (ATL: -0.08 ± 0.11 mm per year, SAH: -0.01 ± 0.02 mm per year, t = 2.99, P = 0.006). There were focal postoperative differences between the two treatment groups in the ipsilateral insula (P = 0.039, corrected). Annualized cortical thinning rates correlated with preoperative cortical thickness (r = 0.60, P < 0.001) and had weaker associations with age at surgery (r = -0.33, P = 0.051) and disease duration (r = -0.42, P = 0.058). Our evidence suggests that selective procedures are associated with less cortical thinning and that earlier surgical intervention may reduce long-term impacts on brain structure.

Structural disconnection relates to functional changes after temporal lobe epilepsy surgery.

Epilepsy surgery consists of surgical resection of the epileptic focus and is recommended for patients with drug-resistant focal epilepsy. However, focal brain lesions can lead to effects in distant brain regions. Similarly, the focal resection in temporal lobe epilepsy surgery has been shown to lead to functional changes distant from the resection. Here we hypothesize that there are changes in brain function caused by temporal lobe epilepsy surgery in regions distant from the resection that are due to their structural disconnection from the resected epileptic focus. Therefore, the goal of this study was to localize changes in brain function caused by temporal lobe epilepsy surgery and relate them to the disconnection from the resected epileptic focus. This study takes advantage of the unique opportunity that epilepsy surgery provides to investigate the effects of focal disconnections on brain function in humans, which has implications in epilepsy and broader neuroscience. Changes in brain function from pre- to post-epilepsy surgery were quantified in a group of temporal lobe epilepsy patients (n = 36) using a measure of resting state functional MRI activity fluctuations. We identified regions with significant functional MRI changes that had high structural connectivity to the resected region in healthy controls (n = 96) and patients based on diffusion MRI. The structural disconnection from the resected epileptic focus was then estimated using presurgical diffusion MRI and related to the functional MRI changes from pre- to post-surgery in these regions. Functional MRI activity fluctuations increased from pre- to post-surgery in temporal lobe epilepsy in the two regions most highly structurally connected to the resected epileptic focus in healthy controls and patients-the thalamus and the fusiform gyrus ipsilateral to the side of surgery (PFWE < 0.05). Broader surgeries led to larger functional MRI changes in the thalamus than more selective surgeries (P < 0.05), but no other clinical variables were related to functional MRI changes in either the thalamus or fusiform. The magnitude of the functional MRI changes in both the thalamus and fusiform increased with a higher estimated structural disconnection from the resected epileptic focus when controlling for the type of surgery (P < 0.05). These results suggest that the structural disconnection from the resected epileptic focus may contribute to the functional changes seen after epilepsy surgery. Broadly, this study provides a novel link between focal disconnections in the structural brain network and downstream effects on function in distant brain regions.

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery. We studied 127 patients who underwent TLE surgery from 2010 to 2019. Neuropsychological testing included picture naming, semantic fluency, and phonemic verbal fluency, performed preoperatively and 3 and 12 months postoperatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (postoperative scores minus preoperative scores). Functional MRI was used to determine language lateralization. The arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, middle longitudinal fasciculus (MLF), and uncinate fasciculus were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing coregistered preoperative and postoperative T1 MRI scans, were used as exclusion regions on preoperative tractography to estimate the percentage of preoperative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent sample t tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively. Language-dominant and language-nondominant resections were treated separately for picture naming because postoperative outcomes were significantly different between these groups. In language-dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI decline at 3 months. Damage to the inferior frontal subfasciculus of the IFOF was related to change at 3 months. In language-nondominant hemisphere resections, increased MLF resection was associated with RCI decline at 3 months, and damage to the anterior subfasciculus was related to change at 3 months. Language-dominant and language-nondominant resections were treated as 1 cohort for semantic and phonemic fluency because there were no significant differences in postoperative decline between these groups. Postoperative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency. We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.

The Determiners of Temporal Lobe Epilepsy Surgery Outcome in a Developing Country

Background: Epilepsy surgery has become a successful treatment option for patients with drug-resistant epilepsies. Objectives: This study aimed to assess temporal lobe epilepsy (TLE) surgery outcome and its association with epilepsy duration, the presence of pre-surgical generalized tonic-clonic seizure (GTCS), and brain MRI findings. Materials &amp; Methods: This retrospective study was performed from 2016 to 2020 at Loghman-Hakim Hospital, Tehran, Iran. The patients’ demographic data, epilepsy type, duration, frequency, brain image findings, the selected surgical approaches, and histopathological findings were collected. The post-operative seizure outcome was expressed one year according to the proposed International League Against Epilepsy (ILAE) classification system. The independent sample t-test, chi-square, and one-way analysis of variance were applied to analyze the differences between variables in terms of quantitative and categorical data. Results: A total number of 69 TLE surgeries were enrolled in our study. No differences were found in the surgical outcome base on the ILAE classification system of patients with lesional vs non-lesional MRIs (P=0.834). In patients with mesial temporal sclerosis, no correlation was found between the surgical approaches including selective amygdalohippocampectomy, anterior temporal lobectomy, and post-operative seizure outcome (P=0.142). Seven patients (10.1%) developed post-operative functional seizures. Conclusion: In our study, the epilepsy duration and the presence of GTCSs before surgery had no effect on the surgery outcome. In patients with mesial temporal sclerosis, amygdalohippocampectomy, and anterior temporal lobectomy did not confer different surgical outcomes. TLE patients with normal MRI showed similar surgical outcomes as lesional patients. A significantly high proportion of our patients developed functional seizures, postoperatively.

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.

Avoidance of Pitfalls and Complications During Surgery for Temporal Lobe Epilepsy.

Anterior temporal lobectomy with amygdalohippocampectomy is the most common epilepsy surgery, which, in cases of mesial temporal lobe epilepsy caused by mesial temporal sclerosis, usually leads to improvements in seizure control, cognitive function, and quality of life. Nevertheless, while the primary goal of intervention is achieved in a large majority of patients, a small number of them, unfortunately, encounter complications. Some morbidity is nonspecific and may be noted after any craniotomy (e.g., surgical site infections, meningitis, bone flap osteomyelitis, and operative site or craniotomy-related hematomas). On the other hand, certain complications are specifically associated with surgery for temporal lobe epilepsy and can be discussed from the etiological standpoint: mechanical injuries of the brain; injury of eloquent neuronal structures; arterial and venous injuries; cerebral venous thrombosis; remote cerebellar hemorrhage; and postoperative hydrocephalus, seizures, and psychiatric disorders. In many cases, these complications are manifested in the early postoperative period by alterations of consciousness and a focal neurological deficit, and it may require immediate decisions on their appropriate management.

The impact of temporal lobe epilepsy surgery on picture naming and its relationship to network metric change

BackgroundAnterior temporal lobe resection (ATLR) is a successful treatment for medically-refractory temporal lobe epilepsy (TLE). In the language-dominant hemisphere, 30%- 50% of individuals experience a naming decline which can impact upon daily life. Measures of structural networks are associated with language performance pre-operatively. It is unclear if analysis of network measures may predict post-operative decline. MethodsWhite matter fibre tractography was performed on preoperative diffusion MRI of 44 left lateralised and left resection individuals with TLE to reconstruct the preoperative structural network. Resection masks, drawn on co-registered pre- and post-operative T1-weighted MRI scans, were used as exclusion regions on pre-operative tractography to estimate the post-operative network. Changes in graph theory metrics, cortical strength, betweenness centrality, and clustering coefficient were generated by comparing the estimated pre- and post-operative networks. These were thresholded based on the presence of the connection in each patient, ranging from 75% to 100% in steps of 5%. The average graph theory metric across thresholds was taken.We incorporated leave-one-out cross-validation with smoothly clipped absolute deviation (SCAD) least absolute shrinkage and selection operator (LASSO) feature selection and a support vector classifier to assess graph theory metrics on picture naming decline. Picture naming was assessed via the Graded Naming Test preoperatively and at 3 and 12 months post-operatively and the outcome was classified using the reliable change index (RCI) to identify clinically significant decline. The best feature combination and model was selected using the area under the curve (AUC). The sensitivity, specificity and F1-score were also reported. Permutation testing was performed to assess the machine learning model and selected regions difference significance. ResultsA combination of clinical and graph theory metrics were able to classify outcome of picture naming at 3 months with an AUC of 0.84. At 12 months, change in strength to cortical regions was best able to correctly classify outcome with an AUC of 0.86. Longitudinal analysis revealed that betweenness centrality was the best metric to identify patients who declined at 3 months, who will then continue to experience decline from 3 to 12 months. Both models were significantly higher AUC values than a random classifier. ConclusionOur results suggest that inferred changes of network integrity were able to correctly classify picture naming decline after ATLR. These measures may be used to prospectively to identify patients who are at risk of picture naming decline after surgery and could potentially be utilised to assist tailoring the resection in order to prevent this decline.

Reliable change on the selective reminding test in a series of left-hemisphere language dominant patients with right temporal lobe epilepsy

The Selective Reminding Test (SRT) is widely used in pre-surgical evaluations for people with epilepsy; however, important characteristics such as reliability and stability over time within an epilepsy-specific control cohort are unclear. In this study, we document test–retest reliabilities, practice effects, and Reliable Change Indices (RCI) for this test in a sample of right temporal lobe epilepsy patients who are left hemisphere dominant for language and underwent surgical resection on the right temporal lobe. A sample of 101 adults with a right temporal lobe seizure focus (mean age = 38.5) was administered the SRT pre- and post-right temporal lobe surgery. Test-retest reliabilities were modest (r = 0.44–0.59). Practice effects were minimal (0.25–2.04). Reliable Change Indices were calculated and ranged from 4 to 26 depending on the SRT index. The RCI’s indicate that relatively moderate to large changes on the SRT are needed for a change score to be considered a significant change in an individual’s performance. The RCIs can be used to detect a reliable change in patients undergoing left temporal lobe epilepsy surgery who are at significant risk for verbal memory decline.

Temporal encephalocele: a rare but treatable cause of temporal lobe epilepsy

Although rare, temporal encephalocele is an important causative agent in surgically remediable drug-refractory epilepsy. The ideal treatment for temporal encephalocele remains unclear with a variety of resective surgeries recommended. Here, we analyse patient data on temporal encephalocele with a view to highlighting diagnostic clues and management strategies. Comprehensive databases at Deenanath Mangeshkar Hospital, Pune from January 2015 to June 2019 were reviewed for this observational study. Of 107 temporal lobe epilepsy surgery patients, nine individuals with temporal encephalocele were identified, who formed the study cohort. Their clinical, neuropsychological, EEG, imaging and long-term outcome data were analysed. The study cohort consisted of seven males and two females with a mean age of 22 years. Epilepsy onset age varied from 4.5 to 19 years. Seven patients had focal non-motor seizures with impaired awareness, while two patients had focal motor seizures. Temporal encephalocele detection by MRI was reported in only two patients, and was missed in seven individuals. Three patients underwent standard anterior temporal lobectomy while the remaining six underwent resection of the temporal encephalocele with surrounding temporal pole. Eight patients showed Engel Class I outcome and one showed Class IIa outcome after a mean follow-up duration of 27 months (17-44 months). Histopathology confirmed gliosis in seven, hippocampal sclerosis type I in one and suspicious dyslamination with prominent gliosis in one patient. Six of eight patients reported an improvement in their psychological state (mood, anxiety and motivation) over time. A careful review of MRI in patients with temporal lobe epilepsy is necessary, followed by investigations for the presence of an encephalocele. When temporal lobe epilepsy is associated with encephalocele, tailored resection of the encephalocele and the surrounding temporal pole, sparing mesial temporal structures, demonstrates excellent long-term clinical and neuropsychological outcome.