Drug-resistant Mesial Temporal Lobe Epilepsy Research Articles

Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. At the last available follow-up visit 12.3 ± 6.3years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = -2.341, p = 0.019). SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

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.

Impact of intracranial subclinical seizures on seizure outcomes after SLAH in patients with mesial temporal lobe epilepsy

ObjectiveTo investigate the association between subclinical seizures detected on intracranial electroencephalographic (i-SCSs)recordings and mesial temporal sclerosis (MTS), as well as their impact on surgical outcomes of stereotactic laser amygdalohippocampotomy (SLAH). MethodsA retrospective review was conducted on 27 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) who underwent SLAH. The number of seizures detected on scalp EEG and iEEG was assessed. Patients were followed for a minimum of 3 years after SLAH. ResultsOf the 1715 seizures recorded from mesial temporal regions, 1640 were identified as i-SCSs. Patients with MTS were associated with favorable short- and long-term surgical outcomes. Patients with MTS had a higher number of i-SCSs compared to patients without MTS. The numbers of i-SCSs were higher in patients with Engel I-II outcomes, but no significant statistical difference was found. However, it was observed that patients with MTS who achieved Engel I-II classification had higher numbers of i-SCSs than patients without MTS (P < 0.05). ConclusionPatients with MTS exhibited favorable short-term and long-term surgical outcome after SLAH. A higher number of i-SCSs was significantly associated with MTS in patients with MTLE. The number of i-SCSs tended to be higher in patients with Engel Ⅰ-Ⅱ surgical outcomes. SignificanceThe association between i-SCSs, MTS, and surgical outcomes in MTLE patients undergoing SLAH has significant implications for understanding the underlying mechanisms and identifying potential therapeutic targets to enhance surgical outcomes.

Ultrasound-Navigated Multiple Hippocampal Transections: An Anatomical Study.

Multiple hippocampal transection (MHT) is a surgical technique used for the treatment of drug-resistant mesial temporal lobe epilepsy in situations where standard procedures would pose a high risk for memory deterioration. During MHT, the longitudinal fibers of the hippocampus, implicated in epilepsy spreading, are interrupted, while the transverse memory circuits are spared. The extent of MHT is governed by intraoperative electrocorticography; abolition of epileptic discharges serves as an end point to terminate the transection. In other words, the aim of MHT is not the anatomical completeness of hippocampal transection. In contrast, we hypothesize that only the complete transection of hippocampal cross-section is needed to durably terminate epilepsy, avoiding possible postoperative reorganization of longitudinal pathways. Here, we report an anatomical study designed to evaluate the feasibility of complete transection of hippocampus with the aid of ultrasound neuronavigation and we propose new instruments to reach this goal. Five cadaveric brains were analyzed in this study. MHT was performed on both sides of each brain either with or without ultrasound neuronavigation. The percentage of transected cross-section of the hippocampus was measured using magnetic resonance imaging (MRI) and both sides were compared. The ultrasound-guided MHTs were more likely to achieve complete hippocampal transection compared with the nonnavigated MHT transection (73 vs 58%; p < 0.01). Our study also allowed us to propose specialized transectors to minimize invasivity of this procedure. Completeness of MHT can be better reached with the aid of an ultrasound neuronavigation system; modified instruments for this procedure were also designed.

Metabolic connectivity as a predictor of surgical outcome in mesial temporal lobe epilepsy.

The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HCs), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcomes. FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than 2 years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics. The study showed widespread metabolic network changes in the HS patients as compared to HC. The changes were more extensive in the right HS than in the left HS. Unfavorable surgical outcomes were found in patients with decreased MC within the network including both the lesional and contralesional hippocampus, ipsilesional frontal operculum, and contralesional insula. Favorable outcomes correlated with decreased MC within the network involving both orbitofrontal cortices and the ipsilesional temporal lobe. There are major differences in the metabolic networks of left and right HS, with more extensive changes in right HS. The changes within the metabolic network could help predict surgical outcomes in patients with HS. MC may identify patients with potentially unfavorable outcomes and direct them to a more detailed presurgical evaluation. Metabolic connectivity is a promising method for metabolic network mapping. Metabolic networks in mesial temporal lobe epilepsy are dependent on lateralization of the epileptogenic lobe and could predict surgical outcomes.

Ultrastructural Changes in Brain Tissue in Drug-Resistant Mesial Temporal Lobe Epilepsy in Humans: A Mini-Review

Epilepsy is a group of chronic neurological diseases of the brain characterized by a persistent predisposition to epileptic seizures, affecting more than 70 million people worldwide. Drug-resistance is a key problem in the theory and practice of epileptology. The literature contains many publications devoted to ultrastructural changes in brain tissue in experimental animal models, but the features of ultrastructural changes in human brain tissue in drug-resistant mesial Temporal Lobe Epilepsy (TLE) remain unknown. This brief review presents the current state of the art of problems devoted to the study of the ultrastructure of neurons, glia, and blood vessels in patients with drug-resistant mesial TLE.

Simultaneous high-resolution whole-brain MR spectroscopy and [18F]FDG PET for temporal lobe epilepsy.

Precise lateralizing the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy (mTLE) remains challenging, particularly when routine MRI scans are inconclusive (MRI-negative). This study aimed to investigate the synergy of fast, high-resolution, whole-brain MRSI in conjunction with simultaneous [18F]FDG PET for the lateralization of mTLE. Forty-eight drug-resistant mTLE patients (M/F 31/17, age 12-58) underwent MRSI and [18F]FDG PET on a hybrid PET/MR scanner. Lateralization of mTLE was evaluated by visual inspection and statistical classifiers of metabolic mappings against routine MRI. Additionally, this study explored how disease status influences the associations between altered N-acetyl aspartate (NAA) and FDG uptake using hierarchical moderated multiple regression. The high-resolution whole-brain MRSI data offers metabolite maps at comparable resolution to [18F]FDG PET. Visual examinations of combined MRSI and [18F]FDG PET showed an mTLE lateralization accuracy rate of 91.7% in a 48-patient cohort, surpassing routine MRI (52.1%). Notably, out of 23 MRI-negative mTLE, combined MRSI and [18F]FDG PET helped detect 19 cases. Logistical regression models combining hippocampal NAA level and FDG uptake improved lateralization performance (AUC=0.856), while further incorporating extrahippocampal regions such as amygdala, thalamus, and superior temporal gyrus increased the AUC to 0.939. Concurrent MRSI/PET revealed a moderating influence of disease duration and hippocampal atrophy on the association between hippocampal NAA and glucose uptake, providing significant new insights into the disease's trajectory. This paper reports the first metabolic imaging study using simultaneous high-resolution MRSI and [18F]FDG PET, which help visualize MRI-unidentifiable lesions and may thus advance diagnostic tools and management strategies for drug-resistant mTLE.

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.

Brain but not serum BDNF levels are associated with structural alterations in the hippocampal regions in patients with drug-resistant mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy is the most common type of focal epilepsy, imposing a significant burden on the health care system worldwide. Approximately one-third of patients with this disease who do not adequately respond to pharmacotherapy are considered drug-resistant subjects. Despite having some clues of how such epileptic activity and resistance to therapy emerge, coming mainly from preclinical models, we still witness a scarcity of human data. To narrow this gap, in this study, we aimed to estimate the relationship between hippocampal and serum levels of brain-derived neurotrophic factor (BDNF), one of the main and most widely studied neurotrophins, and hippocampal subfield volumes in patients with drug-resistant mesial temporal epilepsy undergoing neurosurgical treatment. We found that hippocampal (but not serum) BDNF levels were negatively correlated with the contralateral volumes of the CA1 and CA4 subfields, presubiculum, subiculum, dentate gyrus, and molecular layer of the hippocampus. Taken together, these findings are generally in accordance with existing data, arguing for a proepileptic nature of BDNF effects in the hippocampus and related brain structures.

A Consideration of Optimal Head Position in Transsylvian Selective Amygdalohippocampectomy.

Transsylvian selective amygdalohippocampectomy (TSA) is one of the predominant surgical options for drug-resistant mesial temporal lobe epilepsy. The purpose of this article is to highlight the unique features of TSA and determine the setting to perform safe and secure TSA with special reference to the optimal head position. TSA should be performed via a small surgical corridor in the temporal stem that contains functionally important fiber tracts, including the uncinate fasciculus, the inferior fronto-occipital fasciculus, and the optic radiation. Graphical simulations proposed that low-degree (<30°) head rotation had the advantage of sufficiently opening the surgical field in TSA and may help surgical procedures within the limited exposure of the medial temporal structures. Inspection of the surgical videos implied that the collapse of the inferior horn was prevented in low-degree rotation, probably because the deformation due to the brain shift was minimized in the medial temporal structures. A simulation also implied that chin-up position had the advantage of resecting the tail of the hippocampus in a straightforward manner. We suggest that the setting is optimized in TSA with low-degree rotation and chin-up head position.

Differential Expression of the β3 Subunit of Voltage-Gated Ca2+ Channel in Mesial Temporal Lobe Epilepsy

The purpose of this study was to identify and validate new putative lead drug targets in drug-resistant mesial temporal lobe epilepsy (mTLE) starting from differentially expressed genes (DEGs) previously identified in mTLE in humans by transcriptome analysis. We identified consensus DEGs among two independent mTLE transcriptome datasets and assigned them status as “lead target” if they (1) were involved in neuronal excitability, (2) were new in mTLE, and (3) were druggable. For this, we created a consensus DEG network in STRING and annotated it with information from the DISEASES database and the Target Central Resource Database (TCRD). Next, we attempted to validate lead targets using qPCR, immunohistochemistry, and Western blot on hippocampal and temporal lobe neocortical tissue from mTLE patients and non-epilepsy controls, respectively. Here we created a robust, unbiased list of 113 consensus DEGs starting from two lists of 3040 and 5523 mTLE significant DEGs, respectively, and identified five lead targets. Next, we showed that CACNB3, a voltage-gated Ca2+ channel subunit, was significantly regulated in mTLE at both mRNA and protein level. Considering the key role of Ca2+ currents in regulating neuronal excitability, this suggested a role for CACNB3 in seizure generation. This is the first time changes in CACNB3 expression have been associated with drug-resistant epilepsy in humans, and since efficient therapeutic strategies for the treatment of drug-resistant mTLE are lacking, our finding might represent a step toward designing such new treatment strategies.

Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study

BackgroundMagnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and...

Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy

ObjectiveTo determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. MethodsA prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. ResultsTwenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). ConclusionThe results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Burr hole microsurgical subtemporal selective amygdalohippocampectomy.

At present, selective amygdalohippocampectomy (SAH) has become popular in the treatment of drug-resistant mesial temporal lobe epilepsy (TLE). However, there is still an ongoing discussion about the advantages and disadvantages of this approach. The study included a consecutive series of 43 adult patients with drug-resistant TLE, involving 24 women and 19 men (1.8/1). Surgeries were performed at the Burdenko Neurosurgery Center from 2016 to 2019. To perform subtemporal SAH through the burr hole with the diameter of 14mm, we used two types of approaches: preauricular, 25 cases, and supra-auricular, 18 cases. The follow-up ranged from 36 to 78months (median 59months). One patient died 16months after surgery (accident). By the third year after surgery, Engel I outcome was achieved in 80.9% (34 cases) of cases and Engel II in 4 (9.5%) and Engel III and Engel IV in 4 (9.6%) cases. Among the patients with Engel I outcomes, anticonvulsant therapy was completed in 15 (44.1%), and doses were reduced in 17 (50%) cases. Verbal and delayed verbal memory decreased after surgery in 38.5% and 46.1%, respectively. Verbal memory was mainly affected by preauricular approach in comparison with supra-auricular (p = 0.041). In 15 (51.7%) cases, minimal visual field defects were detected in the upper quadrant. At the same time, visual field defects did not extend into the lower quadrant and inside the 20° of the upper affected quadrant in any case. Burr hole microsurgical subtemporal SAH is an effective surgical procedure for drug-resistant TLE. It involves minimal risks of loss of visual field within the 20° of the upper quadrant. Supra-auricular approach, compared to preauricular, results in a reduction in the incidence of upper quadrant hemianopia and is associated with a lower risk of verbal memory impairment.

Hippocampal resection in temporal lobe epilepsy: Do we need to resect the tail?

IntroductionAnteromesial temporal lobe resection is the most common surgical technique used to treat drug-resistant mesial temporal lobe epilepsy, particularly when secondary to hippocampal sclerosis. Structural and functional imaging data suggest the importance of sparing the posterior hippocampus for minimising language and memory deficits. Recent work has challenged the view that maximal posterior hippocampal resection improves seizure outcome. This study was designed to assess whether resection of posterior hippocampal atrophy was associated with improved seizure outcome. MethodsRetrospective analysis of a prospective database of all anteromesial temporal lobe resections performed in individuals with hippocampal sclerosis at our epilepsy surgery centre, 2013–2021. Pre- and post-operative MRI were reviewed by 2 neurosurgical fellows to assess whether the atrophic segment, displayed by automated hippocampal morphometry, was resected, and ILAE seizure outcomes were collected at 1 year and last clinical follow-up. Data analysis used univariate and binary logistic regression. ResultsSixty consecutive eligible patients were identified of whom 70% were seizure free (ILAE Class 1 & 2) at one year. There was no statistically significant difference in seizure freedom outcomes in patients who had complete resection of atrophic posterior hippocampus or not (Fisher’s Exact test statistic 0.69, not significant at p < .05) both at one year, and at last clinical follow-up. In the multivariate analysis only a history of status epilepticus (OR=0.2, 95%CI:0.042–0.955, p = .04) at one year, and pre-operative psychiatric disorder (OR=0.145, 95%CI:0.036–0.588, p = .007) at last clinical follow-up, were associated with a reduced chance of seizure freedom. SignificanceOur data suggest that seizure freedom is not associated with whether or not posterior hippocampal atrophy is resected. This challenges the traditional surgical dogma of maximal posterior hippocampal resection in anteromesial temporal lobe resections and is a step further optimising this surgical procedure to maximise seizure freedom and minimise associated language and memory deficits.

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.

Impairments of Attention and Executive Functions in Patients with Drug-Resistant Mesial Temporal Lobe Epilepsy (MTLE)

Impairments of Attention and Executive Functions in Patients with Drug-Resistant Mesial Temporal Lobe Epilepsy (MTLE)

Sclérose hippocampique associée à l’épilepsie : conséquences cliniques, histopathologie et évolution avec l’âge

Hippocampal sclerosis is the most frequent etiology of patients with drug-resistant mesial temporal lobe epilepsy, which is the most frequent localization for focal epilepsy. Hippocampal sclerosis is the consequence of a cerebral aggression during early childhood, called the initial precipitating event, the most frequent of which are: febrile seizure, intracranial infection, hypoxia, or cranial trauma. The epilepsy onset usually occurs a few years after this event, with an association of focal temporal seizures and rarer secondarily generalized tonic-clonic seizures. Most patients have a drug-resistant focal epilepsy, with a failure of two different and adequate antiepileptic drugs to achieve seizure freedom. Patients also demonstrated with cognitive impairment, with a typical episodic memory impairment affecting both verbal and non-verbal episodic memory. Cognitive impairment is however more diffuse than the sole episodic memory impairment, and also affects language, visuo-spatial processing, and executive functions. With aging, subjects demonstrated a progressive cognitive decline, that appears to parallel the decline associated with normal aging, but starts earlier and from a lower global cognitive functioning with less cognitive reserve. Patients may therefore reach an impairment threshold sooner than healthy subjects, and are much more vulnerable to any other disease that impairs cognitive functioning. Patients exhibited cortical and subcortical atrophy patterns on volumetric brain MRI similar to normal aging in its distribution, but with an earlier pattern of atrophy (4.5 years sooner in patients than in healthy subjects). Hippocampal sclerosis is associated with amyloid and tau deposits inside the hippocampus, which increases with the subjects’ age. Those deposits pattern is close to the one observed in patients with tau / amyloïd neurodegenerative diseases, which demonstrates a bilateral relationship between epilepsy, hippocampal sclerosis, and neurodegenerative diseases. Clinical consequences of such a relationship are yet to be precisely determined.

Volume of hippocampal activation as a determining factor for the lateralisation of the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy

IntroductionApproximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which requires early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE. MethodsWe included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests. ResultsIn patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15 ± 16.48 voxels vs 170.23 ± 17.8 voxels [P < .001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5 ± 3.38 voxels vs 27.8 ± 3.77 voxels in the contralateral hippocampus [P = .048]), showing moderate concordance with conventional tests. ConclusionsThese findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE.

Optimizing deep brain stimulation for the treatment of drug-resistant temporal lobe epilepsy: a pilot study.

The authors sought to determine the antiseizure effects of deep brain stimulation (DBS) of the parahippocampal cortex (PHC) for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE). After a 3-month baseline period, 6 adult patients with drug-resistant MTLE and hippocampal sclerosis (HS) had stereoelectroencephalography (SEEG)-DBS electrodes implanted at the PHC for identification of the seizure onset zone (SOZ). Patients entered an 8-month, randomized, double-blind protocol for DBS, followed by a 12-month open-phase study. Monthly reports of seizure frequency were collected, with separate counting of focal seizures with or without awareness impairment (focal impaired awareness seizures [FIAS] or focal aware seizures [FAS], respectively) and focal evolving to bilateral generalized tonic clonic seizures (GTCS). Stimulation parameters were 130 Hz, 450 μsec, 2.5-3 V, and cyclic stimulation 1 minute on/4 minutes off. The total seizure rate decrement during follow-up was 41% (CI 25%-56%), with better seizure control for GTCS (IQR 19%-20%) and FIAS (IQR 0%-16%), with FAS being less responsive (IQR 67%-236%). No neuropsychological deterioration was observed. PHC DBS induced important antiseizure effects in patients with incapacitating FIAS and GTCS, most likely through blocking the propagation of hippocampal-onset seizures. The PHC target can be easily and safely approached due to positioning away from vascular structures, and there was no evidence of DBS-induced cognitive deterioration.