Drug-resistant Temporal Lobe Epilepsy Research Articles

Daily rhythms in right-sided and left-sided temporal lobe epilepsy

IntroductionEpilepsy is closely related to daily rhythms, such as the sleep–wake cycle. The objective of this study was to evaluate the relationship between drug-resistant temporal lobe epilepsy (TLE) and the...

Long-Term Outcome of Temporal Lobe Epilepsy Surgery in 621 Patients With Hippocampal Sclerosis: Clinical and Surgical Prognostic Factors.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60–70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Quantitative analysis of visually reviewed normal scalp EEG predicts seizure freedom following anterior temporal lobectomy

ObjectiveAnterior temporal lobectomy (ATL) is a widely performed and successful intervention for drug‐resistant temporal lobe epilepsy (TLE). However, up to one third of patients experience seizure recurrence within 1 year after ATL. Despite the extensive literature on presurgical electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities to prognosticate seizure freedom following ATL, the value of quantitative analysis of visually reviewed normal interictal EEG in such prognostication remains unclear. In this retrospective multicenter study, we investigate whether machine learning analysis of normal interictal scalp EEG studies can inform the prediction of postoperative seizure freedom outcomes in patients who have undergone ATL.MethodsWe analyzed normal presurgical scalp EEG recordings from 41 Mayo Clinic (MC) and 23 Cleveland Clinic (CC) patients. We used an unbiased automated algorithm to extract eyes closed awake epochs from scalp EEG studies that were free of any epileptiform activity and then extracted spectral EEG features representing (a) spectral power and (b) interhemispheric spectral coherence in frequencies between 1 and 25 Hz across several brain regions. We analyzed the differences between the seizure‐free and non–seizure‐free patients and employed a Naïve Bayes classifier using multiple spectral features to predict surgery outcomes. We trained the classifier using a leave‐one‐patient‐out cross‐validation scheme within the MC data set and then tested using the out‐of‐sample CC data set. Finally, we compared the predictive performance of normal scalp EEG‐derived features against MRI abnormalities.ResultsWe found that several spectral power and coherence features showed significant differences correlated with surgical outcomes and that they were most pronounced in the 10–25 Hz range. The Naïve Bayes classification based on those features predicted 1‐year seizure freedom following ATL with area under the curve (AUC) values of 0.78 and 0.76 for the MC and CC data sets, respectively. Subsequent analyses revealed that (a) interhemispheric spectral coherence features in the 10–25 Hz range provided better predictability than other combinations and (b) normal scalp EEG‐derived features provided superior and potentially distinct predictive value when compared with MRI abnormalities (>10% higher F1 score).SignificanceThese results support that quantitative analysis of even a normal presurgical scalp EEG may help prognosticate seizure freedom following ATL in patients with drug‐resistant TLE. Although the mechanism for this result is not known, the scalp EEG spectral and coherence properties predicting seizure freedom may represent activity arising from the neocortex or the networks responsible for temporal lobe seizure generation within vs outside the margins of an ATL.

Altered Temporal Variations of Functional Connectivity Associated With Surgical Outcomes in Drug-Resistant Temporal Lobe Epilepsy.

BackgroundCurrently, more than one-third of patients with drug-resistant temporal lobe epilepsy (TLE) continue to develop seizures after resection surgery. Dynamic functional network connectivity (DFNC) analyses, capturing temporal properties of functional connectivity during MRI acquisition, may help us identify unfavorable surgical outcomes. The purpose of this work was to explore the association of DFNC variations of preoperative resting-state MRI and surgical outcomes in patients with drug-resistant TLE.MethodsWe evaluated 61 patients with TLE matched for age and gender with 51 healthy controls (HC). Patients with TLE were classified as seizure-free (n = 39) and not seizure-free (n = 16) based on the Engel surgical outcome scale. Six patients were unable to confirm the postoperative status and were not included in the subgroup analysis. The DFNC was calculated using group spatial independent component analysis and the sliding window approach.ResultsDynamic functional network connectivity analyses suggested two distinct connectivity “States.” The dynamic connectivity state of patients with TLE was different from HC. TLE subgroup analyses showed not seizure-free (NSF) patients spent significantly more time in State II compared to seizure-free (SF) patients and HC. Further, the number of transitions from State II to State I was significantly lower in NSF patients. SF patients had compensatory enhancement of DFNC strengths between default and dorsal attention network, as well as within the default network. While reduced DFNC strengths of within-network and inter-network were both observed in NSF patients, patients with abnormally temporal properties and more extension DFNC strength alterations were less likely to receive seizure freedom.ConclusionsOur study indicates that DFNC could offer a better understanding of dynamic neural impairment mechanisms of drug-resistant TLE functional network, epileptic brain network reorganization, and provide an additional preoperative evaluation support for surgical treatment of drug-resistant TLE.

FV 16 Long-term potentiation of synaptic plasticity in the temporal cortex of epilepsy patients – in search of a mechanism for memory impairment

Question: Modification of synaptic strength by neuronal activity underlies memory formation. Thus, long-term potentiation (LTP) of synaptic plasticity by electrical stimulation is an efficient model for studying memory at the neurophysiological level. Patients suffering from chronic epilepsy often present with memory deficits. We were therefore interested whether memory impairment was reflected in impacted LTP of synaptic plasticity in the human cortex of epileptic patients. Methods: We prepared acute human temporal cortex slices from resection specimens obtained during surgery for drug-resistant temporal lobe epilepsy. Extracellular field potential recordings were used to assess the induction of long-term potentiation by a standardized theta-burst stimulation protocol. Results: In the human temporal cortex, LTP was impaired and could only be induced sporadically. In some slices, theta-burst stimulation led to paradoxical induction of long-term depression of synaptic plasticity. By contrast, LTP was enhanced in the presence of a glucocorticoid receptor blocker. Conclusions: LTP induction in acute slices presents an opportunity to study the mechanisms underlying memory impairment in the human cortex. This model is a valuable complement to data from non-invasive recording modalities and stereo EEG, as it offers the unique possibility of pharmacological manipulation of synapses.

Combined quantitative T2 mapping and [18F]FDG PET could improve lateralization of mesial temporal lobe epilepsy

ObjectivesTo investigate whether quantitative T2 mapping is complementary to [18F]FDG PET in epileptogenic zone detection, thus improving the lateralization accuracy for drug-resistant mesial temporal lobe epilepsy (MTLE) using hybrid PET/MR.MethodsWe acquired routine structural MRI, T2-weighted FLAIR, whole brain T2 mapping, and [18F]FDG PET in 46 MTLE patients and healthy controls on a hybrid PET/MR scanner, followed with computing voxel-based z-score maps of patients in reference to healthy controls. Asymmetry indexes of the hippocampus were calculated for each imaging modality, which then enter logistic regression models as univariate or multivariate for lateralization. Stereoelectroencephalography (SEEG) recordings and clinical decisions were collected as gold standard.ResultsRoutine structural MRI and T2w-FLAIR lateralized 47.8% (22/46) of MTLE patients, and FDG PET lateralized 84.8% (39/46). T2 mapping combined with [18F]FDG PET improved the lateralization accuracy by correctly lateralizing 95.6% (44/46) of MTLE patients. The asymmetry indexes of hippocampal T2 relaxometry and PET exhibit complementary tendency in detecting individual laterality, especially for MR-negative patients. In the quantitative analysis of z-score maps, the ipsilateral hippocampus had significantly lower SUVR (LTLE, p < 0.001; RTLE, p < 0.001) and higher T2 value (LTLE, p < 0.001; RTLE, p = 0.001) compared to the contralateral hippocampus. In logistic regression models, PET/T2 combination resulted in the highest AUC of 0.943 in predicting lateralization for MR-negative patients, followed by PET (AUC = 0.857) and T2 (AUC = 0.843).ConclusionsThe combination of quantitative T2 mapping and [18F]FDG PET could improve lateralization for temporal lobe epilepsy.Key Points• Quantitative T2 mapping and18F-FDG PET are complementary in the characterization of hippocampal alterations of MR-negative temporal lobe epilepsy patients.• The combination of quantitative T2 and18F-FDG PET obtained from hybrid PET/MR could improve lateralization for temporal lobe epilepsy.

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.

Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.

Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II+III+IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. Forty-eight patients (mean age = 43±14.2years, range = 21-78) were followed for a mean period of 50±20.7months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to threeseizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.

Intraoperative overlay of optic radiation tractography during anteromesial temporal resection: a prospective validation study.

Anteromesial temporal lobe resection (ATLR) results in long-term seizure freedom in patients with drug-resistant focal mesial temporal lobe epilepsy (MTLE). There is significant anatomical variation in the anterior projection of the optic radiation (OR), known as Meyer's loop, between individuals and between hemispheres in the same individual. Damage to the OR results in contralateral superior temporal quadrantanopia that may preclude driving in 33%-66% of patients who achieve seizure freedom. Tractography of the OR has been shown to prevent visual field deficit (VFD) when surgery is performed in an interventional MRI (iMRI) suite. Because access to iMRI is limited at most centers, the authors investigated whether use of a neuronavigation system with a microscope overlay in a conventional theater is sufficient to prevent significant VFD during ATLR. Twenty patients with drug-resistant MTLE who underwent ATLR (9 underwent right-side ATLR, and 9 were male) were recruited to participate in this single-center prospective cohort study. Tractography of the OR was performed with preoperative 3-T multishell diffusion data that were overlaid onto the surgical field by using a conventional neuronavigation system linked to a surgical microscope. Phantom testing confirmed overlay projection errors of < 1 mm. VFD was quantified preoperatively and 3 to 12 months postoperatively by using Humphrey and Esterman perimetry. Perimetry results were available for all patients postoperatively, but for only 11/20 (55%) patients preoperatively. In 1/20 (5%) patients, a significant VFD occurred that would prevent driving in the UK on the basis of the results on Esterman perimetry. The VFD was identified early in the series, despite the surgical approach not transgressing OR tractography, and was subsequently found to be due to retraction injury. Tractography was also used from this point onward to inform retractor placement, and no further significant VFDs occurred. Use of OR tractography with overlay outside of an iMRI suite, with application of an appropriate error margin, can be used during approach to the temporal horn of the lateral ventricle and carries a 5% risk of VFD that is significant enough to preclude driving postoperatively. OR tractography can also be used to inform retractor placement. These results warrant a larger prospective comparative study of the use of OR tractography-guided mesial temporal resection.

Choroidal artery ischemic events after temporal lobe epilepsy surgery: clinical outcome, quality of life, and surgical pitfalls.

Ischemic events within the territory of the choroidal artery are an important cause of morbidity after temporal lobe epilepsy (TLE) surgery. The aim of the present study was to evaluate the rate of these ischemic events, their clinical presentation, and impact on patients' health-related quality of life (HRQoL) after TLE surgery. Four hundred twenty-two consecutive patients undergoing temporal resections for drug-resistant TLE were retrospectively analyzed. All patients underwent presurgical multidisciplinary assessment using a standard protocol comprising clinical, neuroradiological, neuropsychological, and EEG data. Postoperative complications with corresponding imaging, neurological deficits, and disease-specific HRQoL questionnaires were evaluated. The overall complication rate was 7.8% (n = 33). Fourteen patients (3.3%) suffered from ischemic events causing 6 permanent motor deficits, 3 with permanent aphasias, and 6 visual field defects that exceeded quadrantanopia. In 8 patients with anterior choroidal artery infarction, accounting for 57% of all ischemic events, infarction volume correlated positively with the occurrence of new permanent neurological deficits (8666 vs 1692 mm3, p = 0.032). Despite the occurrence of ischemic events, HRQoL improved in 71% of patients. However, infarction volume showed a negative correlation trend with HRQoL (Pearson's r = -0.390, p = 0.094). There was a trend toward increased risk for ischemic events in patients who underwent selective amygdalohippocampectomy compared to patients who underwent anterior temporal lobectomy or temporal lesionectomy (RR 0.96, 95% CI 0.93-0.99, p = 0.08). Choroidal artery infarctions are rare but relevant complications after TLE surgery, presenting with variable clinical courses ranging from devastating neurological deterioration to complete recovery. Despite the occurrence of postoperative infarction, most patients report improvement of HRQoL after TLE surgery. This study showed that the type of surgery appears to modulate the risk for these ischemic events.

How predictable is heart rate variability in Brazilian patients with drug-resistant mesial temporal lobe epilepsy?

This study aimed to compare heart rate variability (HRV) in patients with drug-resistant mesial temporal lobe epilepsy (MTLE) with healthy controls and to analyze their clinical and sociodemographic variables predictive for HRV. Thirty-nine consecutive patients with drug-resistant MTLE were included in the study. The control group included twenty-seven healthy participants matched by age and gender. Seven HRV indices (HR, RR, rMSSD, SDNN, LF, HF, and LF/HF) were compared between patients and controls. The clinical and sociodemographic variables independently associated with the HRV indices were identified by multiple linear regression. In comparison with controls, the patients with MTLE showed a significant reduction in RR, rMSSD, SDNN, LF, HF, and LF/HF indices (t value 1.97–5.97, p < 0.05). Multiple regression models showed that disease duration predicted 11–22% of the analyzed HRV indices. Time domain indices showed higher association with disease duration than coefficients in frequency domain. Patients with drug-resistant MTLE present cardiac autonomic tone dysfunction, showing a significant reduction in their HRV indices (RR, SDNN, rMSSD, LF, HF, and LF/HF). Disease duration has a negative association with all HRV indices. This study contributes to understanding the relationship between MTLE and the cardiac autonomic tone, with possible implications for sudden unexpected death in epilepsy.

Association Between Microstructural Asymmetry of Temporal Lobe White Matter and Memory Decline After Anterior Temporal Lobectomy.

Risk for memory decline is a substantial concern in patients with temporal lobe epilepsy (TLE) undergoing anterior temporal lobectomy (ATL). Although prior studies have identified associations between memory and integrity of white matter (WM) networks within the medial temporal lobe (MTL) preoperatively, we contribute a study examining whether microstructural asymmetry of deep and superficial WM networks within the MTL predicts postoperative memory decline. Patients with drug-resistant TLE were recruited from 2 epilepsy centers in a prospective longitudinal study. All patients completed preoperative T1 and diffusion-weighted MRI (DWI) as well as preoperative and postoperative neuropsychological testing. Preoperative fractional anisotropy (FA) of the WM directly beneath the neocortex (i.e., superficial WM [SWM]) and of deep WM tracts associated with memory were calculated. Asymmetry was calculated for hippocampal volume and FA of each WM tract or region and examined in linear and logistic regressions with preoperative to postoperative memory change as the primary outcome. Data were analyzed from 42 patients with TLE (19 left TLE [LTLE], 23 right TLE [RTLE]) who underwent ATL. Leftward FA asymmetry of the entorhinal SWM was associated with decline on prose and associative recall in LTLE, whereas leftward FA asymmetry of the uncinate fasciculus (UNC) was associated with decline on prose recall only. After controlling for preoperative memory score and hippocampal volume, leftward FA asymmetry of the entorhinal SWM uniquely contributed to decline in both prose and associative recall (β = -0.46; SE 0.14 and β = -0.68; SE 0.22, respectively) and leftward FA asymmetry of the UNC uniquely contributed to decline in prose recall (β = -0.31; SE 0.14). A model combining asymmetry of hippocampal volume and entorhinal FA correctly classified memory outcomes in 79% of patients with LTLE for prose (area under the curve [AUC] 0.89; sensitivity 82%; specificity 75%) and 81% of patients for associative (AUC 0.79; sensitivity 83%; specificity 80%) recall. Entorhinal SWM asymmetry was the strongest predictor in both models. Preoperative asymmetry of deep WM and SWM integrity within the MTL is a strong predictor of postoperative memory decline in TLE, suggesting that surgical decision-making may benefit from considering each patient's WM network adequacy and reserve in addition to hippocampal integrity. This study provides Class II evidence that preoperative asymmetry of deep WM and SWM integrity within the MTL is a predictor of postoperative memory decline.

Case Report: Multisystem Autoimmune and Overlapping GAD65-Antibody-Associated Neurological Disorders With Beneficial Effect of Epilepsy Surgery and Rituximab Treatment

Glutamic acid decarboxylase (GAD) antibodies are associated with disabling conditions such as stiff person syndrome, temporal lobe epilepsy (TLE), limbic encephalitis, cerebellar ataxia (CA), and ocular movement disorders, which are usually chronic and difficult to treat. GAD-related TLE has poor response to anti-seizure medications and immune therapies, and epilepsy surgery is rarely successful. We report on a 47-year-old female with history of migraine, autoimmune thyroid disease, ankylosing spondylitis, and drug-resistant TLE. A video electroencephalography recorded frequent seizures with temporo-insular semiology, correlating to left temporal epileptiform activity and left mesiotemporal hyperintensity on magnetic resonance imaging. GAD autoimmunity was confirmed by very high GAD antibody titers in serum and cerebrospinal fluid. Steroids, immunoglobulins, and cyclophosphamide had no effect, and selective left amygdalectomy was performed based on very restricted hypermetabolism on positron-emission tomography. After transient seizure freedom, significant epilepsy improvement was observed in spite of memory decline. Transient worsening was noted 1 year later during diabetes mellitus manifestation and 5 years later during presentation of progressive CA, which stabilized on rituximab treatment. We believe this case illustrates the diversity and the frequent overlap of GAD-associated disorders, the need of early and aggressive immunotherapy in severe patients, as well as the possible benefit from epilepsy surgery in some GAD-TLE.

Ictal onset stereoelectroencephalography patterns in temporal lobe epilepsy: type, distribution, and prognostic value.

The aim of this study was to investigate the different ictal onset stereoelectroencephalography patterns (IOPs) in patients with drug-resistant temporal lobe epilepsy (TLE). We examined whether the IOPs relate to different TLE subtypes, MRI findings, and underlying pathologies, and we evaluated their prognostic value for predicting the surgical outcome. We retrospectively analyzed data from patients with TLE who underwent stereoelectroencephalography (SEEG) monitoring followed by surgical resection between January 2018 and January 2020. The SEEG recordings were independently analyzed by two epileptologists. Forty-five patients were included in the study, and 61seizures were analyzed. Five IOPs were identified: low voltage fast activity (LVFA; 44.3%), spike-and-wave activity (16.4%), low frequency high-amplitude periodic spikes (LFPS; 18%), a burst of high-amplitude polyspikes (8.2%), and rhythmic sharp activity at ≤ 13Hz (13.1%). Thirty-two patients were found to have a single IOP, while the other 13 patients had two or more IOPs. All five IOPs were found to occur in the medial temporal lobe epilepsy (MTLE), while four IOPs occurred in the lateral temporal lobe epilepsy (LTLE). The LFPS was a common IOP that could distinguish MTLE from LTLE (x2 = 7.046, p = 0.011). Among the MTLE patients, the LFPS was exclusively seen in cases of hippocampal sclerosis (x2 = 5.058, p = 0.038), while the LVFA was associated with nonspecific histology (x2 = 6.077, p = 0.023). The IOPs were not found to differ according to whether the MRI scans were positive or negative. After surgery, patients achieved the higher seizure-free rate at 81.8% and 77.8%, respectively, if the LFPS and LVFA were the predominant patterns. Multiple IOPs or a negative MRI did not indicate a poor prognosis. Five distinct IOPs were identified in the patients with TLE. The differences found have important clinical implications and could provide complementary information for surgical decision-making, especially in MRI-negative patients.

Volumetric Assessment of Extratemporal Structures in Patients With Temporal Lobe Epilepsy

Background: We assessed the presence of brain volume loss in the extratemporal structures in patients with temporal lobe epilepsy (TLE). The associations between brain volume loss in these structures and epilepsy duration, magnetic resonance imaging (MRI) findings, and occurrence of focal to bilateral tonic-clonic seizures (TCS) were assessed. Methods: In this cross-sectional study, all adult patients with drug-resistant TLE, who were admitted to the epilepsy monitoring unit at Loghman-Hakim Hospital, Tehran, Iran, during 2016-2020, were included. For all the participants, brain MRI was performed and patients with TLE were divided into two subgroups of those with hippocampal sclerosis (TLE-HS) and patients with normal-appearing brain MRI findings (TLE-no). Independent sample t test was applied to compare quantitative variables in the study groups. Pearson correlation test examined the correlation between the clinical and volumetric features. Results: 203 participants (81 patients with TLE and 122 healthy controls) were studied. Compared with healthy controls, patients with TLE showed a decrease in their midbrain (P=0.02) and thalamus (P=0.01) volume. The degree of thalamic atrophy was more significant in TLE-HS (P=0.03). Moreover, the degree of midbrain volume loss was more significant (P=0.07) in patients who had TCS in the past two years (N=31) compared with those who did not (N=50). The volume of the thalamus (r: -0.252, P=0.02) and pallidum (r: -0.255, P=0.02) had inverse correlations with the epilepsy duration. Conclusion: Patients with TLE have lower midbrain and thalamus volume compared with the healthy controls, which may be attributed to the seizure-induced injury. Midbrain atrophy may theoretically increase the risk of sudden unexpected death in epilepsy (SUDEP) because of the enhanced autonomic dysfunction.

Beamforming Seizures from the Temporal Lobe Using Magnetoencephalography.

Surgical treatment of drug-resistant temporal lobe epilepsy (TLE) depends on proper identification of the seizure onset zone (SOZ) and differentiation of mesial, temporolimbic seizure onsets from temporal neocortical seizure onsets. Noninvasive source imaging using electroencephalography (EEG) and magnetoencephalography (MEG) can provide accurate information on interictal spike localization; however, EEG and MEG have low sensitivity for epileptiform activity restricted to deep temporolimbic structures. Moreover, in mesial temporal lobe epilepsy (MTLE), interictal spikes frequently arise in neocortical foci distant from the SOZ, rendering interictal spike localization potentially misleading for presurgical planning. In this study, we used two different beamformer techniques applied to the MEG signal of ictal events acquired during EEG-MEG recordings in six patients with TLE (three neocortical, three MTLE) in whom the ictal source localization results could be compared to ground truth SOZ localizations determined from intracranial EEG and/or clinical, neuroimaging, and postsurgical outcome evidence. Beamformer analysis proved to be highly accurate in all cases and was able to identify focal SOZs in mesial, temporolimbic structures. In three patients, interictal spikes were absent, too complex for dipole modeling, or localized to anterolateral temporal neocortex distant to a mesial temporal SOZ, and thus unhelpful in presurgical investigation. MEG beamformer source reconstruction is suitable for analysis of ictal events in TLE and can complement or supersede the traditional analysis of interictal spikes. The method outlined is applicable to any type of epileptiform event, expanding the information value of MEG and broadening its utility for presurgical recording in epilepsy.

Patient preferences pertaining to treatment options for drug-resistant focal epilepsy

ObjectiveTo determine patient acceptability of benefit-risk trade-offs in selecting treatment options for drug-resistant mesial temporal lobe epilepsy, including open brain surgery, laser ablation (laser interstitial thermal therapy [LITT]), and continued medications. MethodsA discrete-choice experiment survey was developed, consisting of 20 versions that were randomly assigned to respondents. Each version had 8 sets of constructed treatment alternatives, representing open brain surgery, LITT, or continued medical management. For each set, respondents indicated the treatment alternative they would choose first. Treatment alternatives were characterized by varying levels of chance of seizure freedom for at least 2 years (20–70%), risk of 30-day mortality (0–10%), and risk of neurological deficits (0–40%). Respondents’ choices were analyzed using random-parameters logit models to quantify acceptable benefit-risk trade-offs. Preference heterogeneity was evaluated using latent-class analysis. ResultsThe survey was administered to 2 cohorts of adult patients with drug-resistant epilepsy: a Duke cohort identified using diagnostic codes (n = 106) and a web-recruited panel with a self-reported physician diagnosis of drug-resistant epilepsy (n = 300). Based on mean preference weights, respondents who indicated a willingness to consider surgical intervention would accept a reduction in chance of seizure freedom from 70% to a minimum-acceptable benefit (MAB) of 23% if they could undergo LITT rather than open brain surgery. For a reduction in 30-day mortality from 1% to 0%, MAB was 52%. For a reduction in risk of long-term deficits from 10% to 0%, MAB was 39%. Latent-class analysis revealed additional choice patterns identifying respondent groups that more strongly favored continuing medications or undergoing surgery. ConclusionPatients who are receptive to surgery would accept significantly lower treatment effectiveness to undergo a minimally invasive procedure relative to open brain surgery. They also were willing to accept lower treatment benefit to reduce risks of mortality or neurological deficits.

Academic and employment insertion as a factor related to quality of life in patients with drug-resistant temporal lobe epilepsy.

Academic and employment insertion is one of the issues that most concern people with epilepsy, but little is known about its relationship with quality of life. We aimed to analyze the effects of the academic and employment insertion on quality of life, anxiety, depression, social support, and executive functions, and the relationships among these variables in patients with drug-resistant epilepsy. Fifty-nine patients with drug-resistant temporal lobe epilepsy were classified into two groups: with academic or employment insertion (n = 25) and without insertion (n = 34) and underwent a neuropsychological evaluation. Patients with insertion had a significantly better quality of life, lower trait anxiety, and higher social support, and tended to have a lower percentage of errors and higher percent conceptual level responses than those without insertion. Academic/employment insertion had indirect effects on quality of life through its relationship with global social support and trait anxiety. Our findings provide a model for understanding the quality of life in patients with temporal lobe epilepsy for an integral perspective of the patient and points out the key role of increased social support and reduced anxiety associated with academic and employment insertion to improve quality of life. These results could favor the implementation of programs that promote academic or employment reinsertion, considering the relevance of socio-emotional domains.

Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy.

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.

The importance of basal-temporal white matter to pre- and post-surgical naming ability in temporal lobe epilepsy

ObjectiveEmerging research highlights the importance of basal-temporal cortex, centered on the fusiform gyrus, to both pre-surgical naming ability and post-surgical naming outcomes in temporal lobe epilepsy (TLE). In this study, we investigate whether integrity of the white matter network that interconnects this basal region to the distributed language network affects naming ability and risk for post-surgical naming decline. MethodsPatients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-surgical dataset included 50 healthy controls, 47 left TLE (L-TLE), and 41 right TLE (R-TLE) patients. All participants completed pre-surgical T1- and diffusion-weighted MRI (dMRI), as well as neuropsychological tests of auditory and visual naming. Nineteen L-TLE and 18 R-TLE patients underwent anterior temporal lobectomy (ATL) and also completed post-surgical neuropsychological testing. Pre-surgical fractional anisotropy (FA) of the white matter directly beneath the fusiform neocortex (i.e., superficial white matter; SWM) and of deep white matter tracts with connections to the basal-temporal cortex [inferior longitudinal fasciculus (ILF) and inferior frontal occipital fasciculus (IFOF)] was calculated. Clinical variables, hippocampal volume, and FA of each white matter tract or region were examined in linear regressions with naming scores, or change in naming scores, as the primary outcomes. ResultsPre-surgically, higher FA in the bilateral ILF, bilateral IFOF, and left fusiform SWM was associated with better visual and auditory naming scores (all ps < 0.05 with FDR correction). In L-TLE, higher pre-surgical FA was also associated with less naming decline post-surgically, but results varied across tracts. When including only patients with typical language dominance, only integrity of the right fusiform SWM was associated with less visual naming decline (p = .0018). DiscussionAlthough a broad network of white matter network matter may contribute to naming ability pre-surgically, the reserve capacity of the contralateral (right) fusiform SWM may be important for mitigating visual naming decline following ATL in L-TLE. This shows that the study of the structural network interconnecting the basal-temporal region to the wider language network has implications for understanding both pre- and post-surgical naming in TLE.