Unilateral Hippocampal Sclerosis Research Articles

Epileptiform activity contralateral to unilateral hippocampal sclerosis does not cause the expression of brain damage markers.

Patients with epilepsy often ask if recurrent seizures harm their brain and aggravate their epileptic condition. This crucial question has not been specifically addressed by dedicated experiments. We analyze here if intense bilateral seizure activity induced by local injection of kainic acid (KA) in the right hippocampus produces brain damage in the left hippocampus. Adult guinea pigs were bilaterally implanted with hippocampal electrodes for continuous video-electroencephalography (EEG) monitoring. Unilateral injection of 1μg KA in the dorsal CA1 area induced nonconvulsive status epilepticus (ncSE) characterized by bilateral hippocampal seizure discharges. This treatment resulted in selective unilateral sclerosis of the KA-injected hippocampus. Three days after KA injection, the animals were killed, and the brains were submitted to ex vivo magnetic resonance imaging (MRI) and were processed for immunohistochemical analysis. During ncSE, epileptiform activity was recorded for 27.6±19.1hours in both the KA-injected and contralateral hippocampi. Enhanced T1-weighted MR signal due to gadolinium deposition, mean diffusivity reduction, neuronal loss, gliosis, and blood-brain barrier permeability changes was observed exclusively in the KA-injected hippocampus. Despite the presence of a clear unilateral hippocampal sclerosis at the site of KA injection, no structural alterations were detected by MR and immunostaining analysis performed in the hippocampus contralateral to KA injection 3days and 2months after ncSE induction. Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at the same time points confirmed the absence of degenerating cells in the hippocampi contralateral to KA injection. We demonstrate that intense epileptiform activity during ncSE does not cause obvious brain damage in the hippocampus contralateral to unilateral hippocampal KA injection. These findings argue against the hypothesis that epileptiform activity per se contributes to focal brain injuryin previously undamaged cortical regions.

Reduced Interhemispheric White Matter Asymmetries in Medial Temporal Lobe Epilepsy With Hippocampal Sclerosis.

Mesial temporal lobe epilepsy (MTLE), one of the most common types of refractory focal epilepsy, has shown white matter abnormalities both within and beyond the temporal lobe. In particular, the white matter abnormalities in the ipsilateral hemisphere are more obvious than those in the contralateral hemisphere in MTLE, that is, the abnormalities present asymmetrical characteristics. However, very few studies have characterized the white matter microstructure asymmetry in MTLE patients specifically. Thus, we performed diffusion tensor imaging (DTI) to investigate the white matter microstructure asymmetries of patients with MTLE with unilateral hippocampal sclerosis (MTLE-HS). We enrolled 25 MTLE-HS (left MTLE-HS group, n = 13; right MTLE-HS group, n = 12) and 26 healthy controls (HC). DTI data were analyzed by tract-based spatial statistics (TBSS) to test the hemispheric differences across the entire white matter skeleton. We also conducted a two-sample paired t-test for 21 paired region of interests (ROIs) parceled on the basis of the ICBM-DTI-81 white-matter label atlas of bilateral hemispheres to test the hemispheric differences. An asymmetry index (AI) was calculated to further quantify the differences between the left and right paired-ROIs. It was found that the asymmetries of white matter skeletons were significantly lower in the MTLE-HS groups than in the HC group. In particular, the asymmetry traits were moderately reduced in the RMTLE-HS group and obviously reduced in the LMTLE-HS group. In addition, AI was significantly different in the RMTLE-HS group from the LMTLE-HS or HC group in the limbic system and superior longitudinal fasciculus (SLF). The current study found that the interhemispheric white matter asymmetries were significantly reduced in the MTLE-HS groups than in the HC group. The interhemispheric white matter asymmetries are distinctly affected in left and right MTLE-HS groups. The differences in AI among RMTLE-HS, LMTLE-HS, and HC involved the limbic system and SLF, which may have some pragmatic implications for the diagnosis of MTLE and differentiating LMTLE-HS from RMTLE-HS.

Atrophy of the ipsilateral mammillary body in unilateral hippocampal sclerosis shown by thin-slice-reconstructed volumetric analysis.

Conventional volumetric analysis could not detect ipsilateral atrophy of the mammillary body in patients with unilateral hippocampal sclerosis. By using thin-slice-reconstructed volumetric analysis, we investigated whether the mammillary body volume is smaller on the hippocampal sclerosis side than in healthy subjects or the non-hippocampal sclerosis side. This retrospective study included 45 patients with unilateral hippocampal sclerosis and 30 healthy subjects. Three-dimensional T1WI of 1mm thicknesses were oversampled to a thickness of 0.2mm (thin-slice-reconstructed images), and the mammillary bodies were segmented manually to determine mammillary body volume on each side. Mammillary body volumes on the hippocampal sclerosis side were compared with those in healthy subjects or the non-hippocampal sclerosis side. In patients with right hippocampal sclerosis, right mammillary body volume was both significantly smaller than that in healthy subjects (30.3 ± 10.3 vs. 43.3 ± 8.07mm3, P < 0.001) and significantly smaller than the left mammillary body volume in each patient (30.3 ± 10.3 vs. 41.4 ± 10.1mm3, P < 0.001). Similarly, in patients with left hippocampal sclerosis, left mammillary body volume was both significantly smaller than that in healthy subjects (37.7 ± 11.2 vs. 47.0 ± 8.65mm3, P < 0.001) and significantly smaller than right mammillary body volume in each patient (37.7 ± 11.2 vs. 42.5 ± 7.78mm3, P = 0.044). In this study, thin-slice-reconstructed volumetric analysis showed that, in patients with unilateral hippocampal sclerosis, mammillary body volume on the hippocampal sclerosis side is smaller than that in healthy subjects and the non-hippocampal sclerosis side.

Evaluation of dual pathology among drug-resistant epileptic patients with hippocampal sclerosis.

Dual pathology (DP) is defined as simultaneous presence of hippocampal sclerosis (HS) and any other pathology in the brain. Since this is a less probed concept, we aimed to evaluate the frequency and characteristics of DP among drug-resistant epileptic patients with HS. This is a cross-sectional study conducted during 2007-2016 in Kashani Comprehensive Epilepsy Center, Isfahan, Iran. Patients with diagnosis of drug-resistant epilepsy and HS were enrolled in the study, and demographic data, seizure semiology, EEG findings, and MRI findings were collected. We compared these variables between three groups of DP, unilateral HS, and bilateral HS. Of the 200 enrolled cases, 29 patients (14.5%) had DP and 21 patients (10.5%) had bilateral HS; the remaining patients had unilateral HS. The average age of patients with DP was 30.03, and 65.5% of them were male. Patients with DP had more EEG discharges from regional and multi-focal sites compared to unilateral HS (P value < 0.001). Also, complex partial seizure (CPS) was more commonly presented in patients with unilateral HS (96.8%). Comparison of disease characteristics between DP and bilateral HS showed no difference in most categories (P > 0.05). We found DP among 14.5% of our drug-resistant epileptic patients with HS. DP patients mostly presented with CPS and had high proportion of ictal and interictal EEG discharges from regional and multi-focal areas. Gliosis and focal cortical dysplasia were the most common pathologies among DP patients. Patients with DP showed a similar behavior to bilateral HS in many features.

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

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

Prognostic factors determining poor postsurgical outcomes of mesial temporal lobe epilepsy.

ObjectivesTo investigate the long-term postoperative outcomes and predictive factors associated with poor surgical outcomes in mesial temporal lobe epilepsy (MTLE).Materials and methodsWe enrolled patients with MTLE who underwent resective surgery at single university-affiliated hospital. Surgical outcomes were determined using a modified Engel classification at the 2nd and 5th years after surgery and the last time of follow-up.ResultsThe mean duration of follow-up after surgery was 7.6 ± 3.7 years (range, 5.0–21.0 years). 334 of 400 patients (83.5%) were seizure-free at the 5th postoperative year. Significant predictive factors of a poor outcome at the 5th year were a history of generalized tonic clonic (GTC) seizures (odds ratio, OR; 2.318), bi-temporal interictal epileptiform discharge (IED) (OR; 3.107), bilateral hippocampal sclerosis (HS) (OR; 5.471), unilateral HS and combined extra-hippocampal lesion (OR; 5.029), and bi-temporal hypometabolism (BTH) (OR; 4.438). Bi-temporal IED (hazard ratio, HR; 2.186), BTH (HR; 2.043), bilateral HS (HR; 2.541) and unilateral HS and combined extra-hippocampal lesion (HR; 2.75) were independently associated with seizure recurrence. We performed a subgroup analysis of 208 patients with unilateral HS, and their independent predictors of a poor outcome at the 5th year were BTH (OR; 5.838) and tailored hippocampal resection (OR; 11.053).ConclusionThis study demonstrates that 16.5% of MTLE patients had poor long-term outcomes after surgery. Bilateral involvement in electrophysiological and imaging studies predicts poor surgical outcomes in MTLE patients.

The impact of epilepsy duration in a series of patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis

PurposeTo evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). MethodsSeventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus – normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. ResultsForty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = −0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = −0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = −0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). ConclusionOur study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.

Detection of Lesions in Mesial Temporal Lobe Epilepsy by Using MR Fingerprinting.

Purpose To improve diagnosis of hippocampal sclerosis (HS) in patients with mesial temporal lobe epilepsy (MTLE) by using MR fingerprinting and compare with visual assessment of T1- and T2-weighted MR images. Materials and Methods For this prospective study performed between April and November 2016, T1 and T2 maps were obtained and tissue segmentation performed in consecutive patients with drug-resistant MTLE with unilateral or bilateral HS. T1 and T2 maps were compared between 33 patients with MTLE (23 women and 10 men; mean age, 32.6 years; age range, 16-60 years) and 30 healthy participants (20 women and 10 men; mean age, 28.8 years; age range, 18-40 years). Differences in individual bilateral hippocampi were compared by using a Wilcoxon signed rank test, whereas the Wilcoxon rank-sum test was used for difference analysis between healthy control participants and patients with MTLE. Results The diagnosis rate (ie, ratio of HS diagnosed on the basis of a 2.5-minute MR fingerprinting examination compared with standard methods: MRI, electroencephalography, and PET) was 32 of 33 (96.9%; 95% confidence interval: 84.9%, 100%), reflecting improved accuracy of diagnosis (P = 1.92 × 10-12) over routine MR examinations that had a diagnostic rate of 23 of 33 (69.7%; 95% confidence interval: 51.5%, 81.6%). The comparison between atrophic and normal-appearing hippocampus in 33 patients with MTLE and healthy control participants demonstrated that both T1 and T2 values in HS lesions were higher than those of normal hippocampal tissue of healthy participants (T1: 1361 msec ± 85 vs 1249 msec ± 59, respectively; T2: 135 msec ± 15 vs 104 msec ± 9, respectively; P < .0001). Conclusion MR fingerprinting allowed for multiparametric mapping of temporal lobe within 2.5 minutes and helped to identify lesions suspicious for HS in patients with MTLE with improved accuracy.

The phenotype of bilateral hippocampal sclerosis and its management in "real life" clinical settings.

There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P=.002; Fisher's exact test). The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.

Idiothetic signal processing and spatial orientation in patients with unilateral hippocampal sclerosis.

The role of the hippocampus in spatial navigation and the presence of vestibular-responsive neurons in limbic areas are well-established from animal experiments. However, hippocampal spatial processing in humans is not fully understood. Here, we employed real whole body and head-on-trunk rotations to investigate how vestibular signals, either alone or in combination with neck-proprioceptive stimulation, shape the spatial frame of reference in patients with unilateral hippocampal sclerosis (HS). Patients were asked to point in darkness with a light spot, moved on a cylindrical screen by means of a joystick, into their visual straight-ahead direction (VSA), to remember this direction in space, and to revert back to this point after the rotations. Estimates in patients with HS were compared with those of healthy controls and of patients with epilepsy without hippocampal involvement. All groups produced similar errors after low-frequency vestibular stimuli. These errors were eliminated when rotations involved concurrent neck stimulation. Significantly increased variability was observed, however, in both the VSA and reposition estimates after the rotations in patients with HS compared with controls. These results suggest that cognitive processing of idiothetic signals for self-motion perception is inaccurate in patients with HS. Importantly, however, the responses of patients with HS showed no spatial lateralization with regard to right or left HS, suggesting that the underlying neuronal loss attenuates the precision of head-direction signal decoding in a nondirectional manner. Hence, patients are unable to use these signals as efficiently as normal subjects in the construction of a stable head-centric spatial frame of reference. NEW & NOTEWORTHY Spatial perception relies on combined processing of various idiothetic (vestibular and proprioceptive) and allothetic (visual and auditory) sensory signals. Despite the established knowledge of rodent vestibular-hippocampal interactions, human data are lacking. We investigated idiothetic orientational processing in subjects with unilateral hippocampal sclerosis using various combinations of vestibular and proprioceptive stimuli. Hippocampal impairment leads to less accurate, noisy decoding of the signal related to idiothetic orientation. However, patients did not show any lateralized deficits of visual straight-ahead perception or of target/self-displacement perception after idiothetic stimulation.

Longitudinal imaging of Microglia-Astrocyte activation in mouse mesial temporal lobe epilepsy with TSPO PET to identify the best therapeutic time windows

Objectives Mesiotemporal lobe epilepsy (MTLE) is the most common type of drug-resistant partial epilepsy with a specific history which begins by a status epilepticus due to a neurological insult followed by a silent period before the recurrent seizures begin. Once established, these seizures can become resistant to medications. Along this period a specific lesion is often found, described as a unilateral hippocampal sclerosis (HS). Currently it is still challenging to determine when and which drugs can be most effective along the constitution of this epileptic process. Neuroinflammation has been reported to play an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation probes can be potent epilepsy biomarkers. The Translocator Protein 18 kDa (TSPO) expression is associated with neuroinflammatory processes involving reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral hippocampal sclerosis and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that TSPO PET imaging using 18F-DPA-714 TSPO-targeted PET could be a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and follow response to treatment in the mouse model of MTLE. Methods The model was induced by unilateral injection of kainic acid into the right dorsal hippocampus of male C57/Bl6 mice. μPET/CT scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. Results TSPO PET uptake reached the peak at 7 days and mostly correlated with microglial activation whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO which would be related to the increased PET uptake. Our studies suggest that mTOR signal pathways play an important role in the modulation of astrocyte activities. Our hypothesis is that the neurotoxicity during ictogenesis (aggravation phase) could be due to persistent mTOR reactive signaling in astrocytes. Conclusion : on this knowledge of TSPO expression over time in the MTLE model, TSPO PET imaging could be a valuable tool to evaluate efficacy of mTOR treatments.

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with 18 F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS. The model was induced into the right dorsal hippocampus of male C57/Bl6 mice. Micro-PET/computed tomographic scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month, and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. TSPO PET uptake reached peak at 7 days and mostly related to microglial activation, whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO, reflected by a continuing increased PET uptake. TSPO-targeted PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor response to treatment.

Hippocampal Sclerosis in the Oldest Old: A Finnish Population-Based Study.

Background:There are only few population-based studies that have systemically investigated the prevalence of hippocampal sclerosis (HS) in the very old. The frequency of unilateral versus bilateral HS has been rarely studied.Objective:We investigated the prevalence and laterality of HS and its association with other neurodegenerative and vascular pathologies in a population-based sample of very elderly. Furthermore, the concomitant presence of immunoreactivity for TDP-43, p62, and HPtau was studied.Methods:The population-based Vantaa 85+ study includes all inhabitants of the city of Vantaa, who were >85 years in 1991 (n = 601). Neuropathological assessment was possible in 302 subjects. Severity of neuronal loss of CA sectors and subiculum was determined bilaterally by HE- staining. Immunohistochemistry performed using antibodies for TDP-43, p62, and HPtau.Results:Neuronal loss and pathological changes in the hippocampus sector CA1 and subiculum were observed in 47 of the 302 individuals (16%), and 51% of these changes were bilateral. HS without comorbid neurodegenerative pathology was found in 1/47 subjects with HS (2%). Dementia (p < 0.001) and TDP-43 immunopositivity of the granular cell layer of the dentate fascia (p < 0.001) were strongly associated with HS. The CERAD score, immunopositivity for HPtau and p62 in the granular cell layer of the fascia dentate were also associated.Conclusion:HS is prevalent (16%) in the oldest old population, but HS without any comorbid neurodegenerative pathology is rare. The high frequency of unilateral HS (49%) implied that bilateral sampling of hippocampi should be routine practice in neuropathological examination.

Meta-analysis of voxel-based morphometry studies of gray matter abnormalities in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

We aimed to perform a meta-analysis to systematically determine the most consistent regions of gray matter volume (GMV) abnormality in patients of unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), and to reveal the difference of GMV abnormality between the patients with left-sided and right-sided MTLE-HS. A comprehensive and systematic search was performed in PubMed for voxel-based morphometry (VBM) studies of MTLE-HS. A total of 12 MTLE-HS studies, including 9 left-sided MTLE-HS (LMTLE-HS) and 8 right-sided MTLE-HS (RMTLE-HS) studies were included. The activation likelihood estimation (ALE) method was applied in our meta-analysis. Compared to the healthy controls, MTLE-HS patients showed significant GMV decrease in the parahippocampal gyrus, left pulvinar and right pyramis. For LMTLE-HS, the most consistent GMV decrease was detected in the left parahippocampal gyrus. For RMTLE-HS, the most consistent GMV decrease was found in the right parahippocampal gyrus. No shared regions of significant GMV reduction were found between LMTLE-HS and RMTLE-HS either. This meta-analysis revealed that MTLE-HS patients had significant GMV reduction even beyond the hippocampus, and the subtypes showed distinct reduction patterns. Our findings, if were further verified with larger samples, would have implications for the clinical diagnosis of MTLE-HS.

Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study.

To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG). A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16years. Patients were divided into: (1) patients operated on based on routine outpatient EEG information, with >80% of EEGs with unilateral interictal epileptiform discharges (IEDs) ipsilateral to HS or ictal events (n=71); and (2) patients submitted to preoperative VEEG (n=95). To avoid the bias generated by ictal recordings, we performed a subanalysis of: (1) patients without preoperatively ictal recordings (n=80) and (2) patients with ictal recordings in VEEG or routine outpatient EEG (n=86). Groups were similar regarding gender, age at surgery, seizure onset, preoperative seizure frequency, and duration of follow-up. Overall, 136/166 (81.92%) were classified as Engel I seizure outcome, with no difference between groups; 76.84% and 88.73% of patients with and without VEEG, respectively, had Engel I postoperative seizure outcome (P=.77). The time lag until surgery was shorter in the group without VEEG (80 vs 38months; P=.01). Considering ictal recordings, 76.74% of patients with seizures recorded and 87.50% without ictal recordings had Engel I outcome (P=.11). We performed the first prospective study in a tertiary epilepsy center comparing surgical outcomes in unilateral MTLE-HS patients investigated preoperatively with and without VEEG. Based on the surgical outcome, VEEG is not imperative in patients with unilateral MTLE-HS who have compatible semiology and clearly ipsilateralized IEDs evaluated by a multidisciplinary and experienced epilepsy group.

Asymmetric gray matter volume changes in patients with unilateral mesial temporal lobe epilepsy and hippocampal sclerosis: Left- and right-side differences

Asymmetric gray matter volume changes in patients with unilateral mesial temporal lobe epilepsy and hippocampal sclerosis: Left- and right-side differences

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis

ObjectiveThe objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. MethodsThe hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). ResultsThere were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance — the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). SignificanceCornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.

Bilateral cingulum fiber reductions in temporal lobe epilepsy with unilateral hippocampal sclerosis

PurposeTo evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). MethodsTwenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2×2×2mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. ResultsSclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258+81.0) and contralateral side (271+85.6) compared to age-matched controls (447+138). ConclusionFocusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

Laser Interstitial Thermal Therapy for Epilepsy.

MRI-guided laser interstitial thermal therapy (MgLiTT) uses a narrow diameter cannula to stereotactically target and heat deeper cerebral structures. This technique produces a precise lesion in the brain with great reliability because the localized tissue temperature change is monitored in real time. Because MgLiTT minimizes injury to surrounding brain, it appears to have a lower risk of affecting normal neurological function, and because it is done through a burr hole, there is less operative risk, less discomfort, and shorter hospitalizations. It is FDA approved for soft tissue ablation and is being increasingly applied to the surgical treatment of epilepsy, especially when seizures arise from deeper structures such as the hippocampus, amygdala, or discrete dysplastic tissue such as hypothalamic hamartomas. Mesial temporal epilepsy is the most frequently encountered surgically remedial epilepsy suitable for MgLiTT, particularly when there is unilateral hippocampal sclerosis. There is emerging evidence that it can be effective for eliminating seizures in this type of epilepsy, and that it has a lower risk of cognitive deficits than anterior temporal lobectomy.

Atypical handedness in mesial temporal lobe epilepsy.

The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated. We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001). Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.