Mesial Temporal Lobe Structures Research Articles

Seizure and anatomical outcomes of repeat laser amygdalohippocampotomy for temporal lobe epilepsy: A single-institution case series

ObjectiveIn patients with treatment-refractory temporal lobe epilepsy (TLE), a single stereotactic laser interstitial thermotherapy (LITT) procedure is sometimes insufficient to ablate epileptogenic tissue, particularly the medial structures often implicated in TLE. In patients with seizure recurrence after initial ablation, the extent to which a second ablation may achieve improved seizure outcomes is uncertain. The objective of this study was to investigate the feasibility and potential efficacy of repeat LITT amygdalohippocampotomy as a worthwhile strategy for intractable temporal lobe epilepsy by quantifying changes to targeted mesial temporal lobe structures and seizure outcomes. MethodsPatients who underwent two LITT procedures for drug-resistant mesial TLE at our institution were included in the study. Lesion volumes for both procedures were calculated by comparing post-ablation intraoperative sequences to preoperative anatomy. Clinical outcomes after the initial procedure and repeat procedure were classified according to Engel scores. ResultsFive consecutive patients were included in this retrospective case series: 3 with right- and 2 with left-sided TLE. The median interval between LITT procedures was 294 days (range: 227–1918). After the first LITT, 3 patients experienced class III outcomes, 1 experienced a class IV, and 1 experienced a class IB outcome. All patients achieved increased seizure freedom after a second procedure, with class I outcomes (3 IA, 2 IB). ConclusionsRepeat LITT may be sufficient to achieve satisfactory seizure outcomes in some individuals who might otherwise be considered for more aggressive resection or palliative neuromodulation. A larger study to establish the potential value of repeat LITT amygdalohippocampotomy vs. other re-operation strategies for persistent, intractable temporal lobe epilepsy is worth pursuing.

Theta tACS impairs episodic memory more than tDCS

Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer’s disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females; 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippocampus and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.

Whole-brain DTI parameters associated with tau protein and hippocampal volume in Alzheimer's disease.

The causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (Aβ42 ) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole-brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with Aβ42 alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of Aβ42 , phosphorylated tau protein (p-Tau) and total tau (t-Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p-Tau and t-Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early-stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF.

Exoscope improves visualization and extent of hippocampal resection in temporal lobectomy.

Anterior temporal lobectomy (ATL) is a safe and well-validated procedure in the treatment of temporal lobe epilepsy (TLE), but is a challenging technique to master and still confers a risk of morbidity and mortality due to the complex anatomy of the mesial temporal lobe structures. Automated robotic 3D exoscopes have been developed to address limitations traditionally associated with microscopic visualization, allowing for ergonomic, high-definition 3D visualization with hands-free control of the robot. Given the potential advantages of using such a system for visualization of complex anatomy seen during mesial structure resection in ATL, this group sought to investigate impact on the percentage of hippocampal resection in both exoscope and microscope guided procedures. We conducted a retrospective analysis of 20 consecutive patients undergoing standard ATL for treatment of medically refractory TLE at our institution. Using pre-operative and post-operative imaging, the coronal plane cuts in which either the head, body, or tail of the hippocampus appeared were counted. The number of cuts in which the hippocampus appeared were multiplied by slice thickness to estimate hippocampal length. Mean percentage of hippocampal resection was 61.1 (SD 13.1) and 76.5 (SD 6.5) for microscope and exoscope visualization, respectively (p = 0.0037). Use of exoscope for mesial resection during ATL has provided good visualization for those in the operating room and the potential for a safe increase in hippocampal resection in our series. Further investigation of its applications should be evaluated to see if it will improve outcomes.

A Novel Sublabial Anterior Transmaxillary Approach for Medically Refractory Mesial Temporal Lobe Epilepsy: A Comparative Anatomic Study.

Current approaches for mesial temporal lobe epilepsy may result in suboptimal seizure control and cognitive decline. An incomplete treatment of the epileptogenic zone and unnecessary violation of functional cortical and subcortical areas may contribute to suboptimal results. To describe and test the anatomic feasibility of a novel endoscopic anterior transmaxillary (ATM) approach to the temporal lobe and to compare the described technique to other transfacial approaches. Twenty-four cadaveric brain hemispheres fixed in formalin were used to study anterior temporal surface anatomy. Two additional hemispheres were fixed in formalin and then frozen for white matter dissections. Subsequently, bilateral dissections on 4 injected cadaveric heads were used to describe the endoscopic ATM approach and to evaluate various anterior endoscopic corridors for the temporal pole and mesial temporal lobe structures. The ATM approach was considered superior because of direct visualization of the temporal pole and natural alignment with the mesial temporal structures. The mean exposure corridor covered 49.1° in the sagittal plane and 66.2° in the axial plane. The ATM allowed direct access lateral to the maxillary and mandibular nerves with an anterior-posterior trajectory aligned to the longitudinal axis of the hippocampus formation, allowing for a selective amygdalohippocampectomy with preservation of the trigeminal branches and the lateral temporal neocortex. The ATM approach is anatomically feasible, providing a direct and selective approach for the temporal pole and mesial temporal lobe structures, with a substantial angle of visualization because of its direct alignment with the mesial temporal lobe structures.

ID:16352 Differences Between Left and Right Temporal Lobe Epilepsy Using Resting-State Network fMRI and SEEG Connectivity

The most common type of surgical epilepsy is mesial temporal lobe epilepsy (mTLE). Due to rapid contralateral spread, lateralization of mTLE is challenging. Abnormalities have been found in resting-state networks of mTLE patients.1 It is unclear if non-directed/directed connectivity between resting-state networks and mesial temporal lobe structures can aid in lateralization of mTLE patients. Also, it is unknown if directional hippocampal connectivity using fMRI resembles directional connections using stereo-electroencephalography (SEEG).

Serotonin transporter in the temporal lobe, hippocampus and amygdala in SUDEP.

Several lines of evidence link deficient serotonin function and SUDEP. Chronic treatment with serotonin reuptake inhibitors (SRIs) reduces ictal central apnoea, a risk factor for SUDEP. Reduced medullary serotonergic neurones, modulators of respiration in response to hypercapnia, were reported in a SUDEP post‐mortem series. The amygdala and hippocampus have high serotonergic innervation and are functionally implicated in seizure‐related respiratory dysregulation. We explored serotonergic networks in mesial temporal lobe structures in a surgical and post‐mortem epilepsy series in relation to SUDEP risk. We stratified 75 temporal lobe epilepsy patients with hippocampal sclerosis (TLE/HS) into high (N = 16), medium (N = 11) and low risk (N = 48) groups for SUDEP based on generalised seizure frequency. We also included the amygdala in 35 post‐mortem cases, including SUDEP (N = 17), epilepsy controls (N = 10) and non‐epilepsy controls (N = 8). The immunohistochemistry labelling index (LI) and axonal length (AL) of serotonin transporter (SERT)‐positive axons were quantified in 13 regions of interest with image analysis. SERT LI was highest in amygdala and subiculum regions. In the surgical series, higher SERT LI was observed in high risk than low risk cases in the dentate gyrus, CA1 and subiculum (p < 0.05). In the post‐mortem cases higher SERT LI and AL was observed in the basal and accessory basal nuclei of the amygdala and peri‐amygdala cortex in SUDEP compared to epilepsy controls (p < 0.05). Patients on SRI showed higher SERT in the dentate gyrus (p < 0.005) and CA4 (p < 0.05) but there was no difference in patients with or without a psychiatric history. Higher SERT in hippocampal subfields in TLE/HS cases with SUDEP risk factors and higher amygdala SERT in post‐mortem SUDEP cases than epilepsy controls supports a role for altered serotonergic networks involving limbic regions in SUDEP. This may be of functional relevance through reduced 5‐HT availability.

Chapter 19 - The temporal lobes and memory

Since the first description of the case of H.M. in the mid-1950s, the debate over the contribution of the mesial temporal lobe (MTL) to human memory functioning has not ceased to stimulate new experimental work and the development of new theoretical models. The early demonstration that despite their devastating memory loss patients with hippocampal damage are still able to learn a number of visuo-motor and visuo-perceptual skills at a normal rate and to be normally primed by verbal and visual material suggested that the term "memory" is actually an umbrella concept that includes very different brain plasticity phenomena and that MTL damage actually impairs only one of these. Subsequent research, which capitalized on a detailed anatomical description of MTL structures and on the close analysis of memory-related phenomena, tried to define the unique role of the MTL structures in brain plasticity and in the government of human behavior. A first hypothesis identified this role in the conscious forms of memory as opposed to implicit ones. In the last two decades, the emphasis has moved to the relational role of the hippocampus in binding together different pieces of unimodal information to provide unitary, multimodal representations of personal experiences.

A clinically applicable functional MRI memory paradigm for use with pediatric patients

ObjectiveClinically employable functional MRI (fMRI) memory paradigms are not yet established for pediatric patient epilepsy surgery workups. Seeking to establish such a paradigm, we evaluated the effectiveness of memory fMRI tasks we developed by quantifying individual activation in a clinical pediatric setting, analyzing patterns of activation relative to the side of temporal lobe (TL) pathology, and comparing fMRI and Wada test results. MethodsWe retrospectively identified 72 patients aged 6.7–20.9 years with pathology (seizure focus and/or tumor) limited to the TL who had attempted memory and language fMRI tasks over a 9-year period as part of presurgical workups. Memory fMRI tasks required visualization of autobiographical memories in a block design alternating with covert counting. Language fMRI protocols involved verb and sentence generation. Scans were both qualitatively interpreted and quantitatively assessed for blood oxygenation level dependent (BOLD) signal change using region of interest (ROI) masks. We calculated the percentage of successfully scanned individual cases, compared 2 memory task activation masks in cases with left versus right TL pathology, and compared fMRI with Wada tests when available. Patients who had viable fMRI and Wada tests had generally concordant results. ResultsOf the 72 cases, 60 (83%), aged 7.6–20.9 years, successfully performed the memory fMRI tasks and 12 (17%) failed. Eleven of 12 unsuccessful scans were due to motion and/or inability to perform the tasks, and the success of a twelfth was indeterminate due to orthodontic metal artifact. Seven of the successful 60 cases had distorted anatomy that precluded employing predetermined masks for quantitative analysis. Successful fMRI memory studies showed bilateral mesial temporal activation and quantitatively demonstrated: (1) left activation (L-ACT) less than right activation (R-ACT) in cases with left temporal lobe (L-TL) pathology, (2) nonsignificant R-ACT less than L-ACT in cases with right temporal lobe (R-TL) pathology, and (3) lower L-ACT plus R-ACT activation for cases with L-TL versus R-TL pathology. Patients who had viable fMRI and Wada tests had generally concordant results. SignificanceThis study demonstrates evidence of an fMRI memory task paradigm that elicits reliable activation at the individual level and can generally be accomplished in clinically involved pediatric patients. This autobiographical memory paradigm showed activation in mesial TL structures, and cases with left compared to right TL pathology showed differences in activation consistent with extant literature in TL epilepsy. Further studies will be required to assess outcome prediction.

Clinical phenotype modulates brain\u2019s myelin and iron content in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is associated with brain pathology extending beyond temporal lobe structures. We sought to look for informative patterns of brain tissue properties in TLE that go beyond the established morphometry differences. We hypothesised that volume differences, particularly in hippocampus, will be paralleled by changes in brain microstructure. The cross-sectional study included TLE patients (n = 25) from a primary care center and sex-/age-matched healthy controls (n = 55). We acquired quantitative relaxometry-based magnetic resonance imaging (MRI) data yielding whole-brain maps of grey matter volume, magnetization transfer (MT) saturation, and effective transverse relaxation rate R2* indicative for brain tissue myelin and iron content. For statistical analysis, we used the computational anatomy framework of voxel-based morphometry and voxel-based quantification. There was a positive correlation between seizure activity and MT saturation measures in the ipsilateral hippocampus, paralleled by volume differences bilaterally. Disease duration correlated positively with iron content in the mesial temporal lobe, while seizure freedom was associated with a decrease of iron in the very same region. Our findings demonstrate the link between TLE clinical phenotype and brain anatomy beyond morphometry differences to show the impact of disease burden on specific tissue properties. We provide direct evidence for the differential effect of clinical phenotype characteristics on processes involving tissue myelin and iron in mesial temporal lobe structures. This study offers a proof-of-concept for the investigation of novel imaging biomarkers in focal epilepsy.

Temporal trajectory of brain tissue property changes induced by electroconvulsive therapy

BackgroundAfter more than eight decades of electroconvulsive therapy (ECT) for pharmaco-resistant depression, the mechanisms governing its anti-depressant effects remain poorly understood. Computational anatomy studies using longitudinal T1-weighted magnetic resonance imaging (MRI) data have demonstrated ECT effects on hippocampus volume and cortical thickness, but they lack the interpretational specificity about underlying neurobiological processes. MethodsWe sought to fill in the gap of knowledge by acquiring quantitative MRI indicative for brain's myelin, iron and tissue water content at multiple time-points before, during and after ECT treatment. We adapted established tools for longitudinal spatial registration of MRI data to the relaxometry-based multi-parameter maps aiming to preserve the initial total signal amount and introduced a dedicated multivariate analytical framework. ResultsThe whole-brain voxel-based analysis based on a multivariate general linear model showed that there is no brain tissue oedema contributing to the predicted ECT-induced hippocampus volume increase neither in the short, nor in the long-term observations. Improvements in depression symptom severity over time were associated with changes in both volume estimates and brain tissue properties expanding beyond mesial temporal lobe structures to anterior cingulate cortex, precuneus and striatum. ConclusionThe obtained results stemming from multi-contrast MRI quantitative data provided a fingerprint of ECT-induced brain tissue changes over time that are contrasted against the background of established morphometry findings. The introduced data processing and statistical testing algorithms provided a reliable analytical framework for longitudinal multi-parameter brain maps. The results, particularly the evidence of lack of ECT impact on brain tissue water, should be considered preliminary considering the small sample size of the study.

VIPergic neuroprotection in epileptogenesis: challenges and opportunities

In mesial temporal lobe epilepsy (MTLE), seizures typically arise in the hippocampus or other mesial temporal lobe structures. The aetiology of MTLE epileptogenesis in still unknown, yet putative precipitating events such as trauma, complex febrile seizures, status epilepticus, inflammatory insults, or ischemia have been implicated. MTLE is commonly associated to a high degree of hippocampal sclerosis (HS) leading to frequent anti-epileptic drug refractoriness. Thus, the aim of recent therapeutic strategies has shifted from control of symptomatic seizures to putative prevention of epileptogenic processes. Vasoactive intestinal peptide (VIP) acts as a neurotransmitter, neurotrophic or neuroprotective factor in the central nervous system (CNS), also displaying anti-inflammatory and neurogenic actions. In the hippocampus, a brain area implicated in learning and memory, VIP released from basket cells and/or interneuron-selective interneurons controls GABAergic transmission and pyramidal cell activity influencing hippocampal-dependent synaptic plasticity (long-term potentiation and long-term depression) and cognition. VPAC1 receptor activation enhances hippocampal synaptic transmission by fostering disinhibition, while stimulation of VPAC2 receptors favours pyramidal cell excitability. Interestingly, VIP released from interneurons has potent anti-inflammatory actions, participates in the maintenance of the blood-brain barrier integrity, and strengthens neurogenesis. VPAC1 and VPAC2 receptors play differential roles in the regulation of the neuro-immune interactions. In this context, we gathered here the available information concerning the impact of VIP on neurotransmission and neuronal excitability in MTLE-HS and discuss the preventive use of selective VIP receptor ligands to abrogate epileptogenesis in MTLE-HS by controlling synaptic plasticity, neurogenesis and neuronal survival, neuroinflammation, and blood-brain barrier damage.

Multi-omics analysis suggests enhanced epileptogenesis in the Cornu Ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). We used a multi-omics approach to determine the profile of transcript and protein expression in the dorsal and ventral hippocampal dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of MTLE induced by pilocarpine. We performed label-free proteomics and RNAseq from laser-microdissected tissue isolated from pilocarpine-induced Wistar rats. We divided the DG and CA3 into dorsal and ventral areas and analyzed them separately. We performed a data integration analysis and evaluated enriched signaling pathways, as well as the integrated networks generated based on the gene ontology processes. Our results indicate differences in the transcriptomic and proteomic profiles among the DG and the CA3 subfields of the hippocampus. Moreover, our data suggest that epileptogenesis is enhanced in the CA3 region when compared to the DG, with most abnormalities in transcript and protein levels occurring in the CA3. Furthermore, our results show that the epileptogenesis in the pilocarpine model involves predominantly abnormal regulation of excitatory neuronal mechanisms mediated by N-methyl D-aspartate (NMDA) receptors, changes in the serotonin signaling, and neuronal activity controlled by calcium/calmodulin-dependent protein kinase (CaMK) regulation and leucine-rich repeat kinase 2 (LRRK2)/WNT signaling pathways.

Thalamic Lesions in a Toddler with Glutamic Acid Decarboxylase Autoimmune Encephalitis

AbstractWe present a child with glutamic acid decarboxylase (GAD) autoimmune encephalitis (AE) with bilateral thalamic lesions on magnetic resonance imaging (MRI) of the brain. A healthy 21-month-old girl, after superrefractory status epilepticus (SE) and fever developed dyskinesia and ataxia, which we subsequently diagnosed as GAD AE. She showed remarkable response to treatment with methylprednisolone and intravenous immunoglobulin (IVIg). Following an initial normal MRI of her brain, a further brain imaging showed bilateral thalamic lesions. This is an unusual finding since brain imaging abnormalities, when found in GAD AE, mostly involve the mesial temporal lobe structures. Thalamic lesions in GAD AE have not been reported previously.

The effects of insular and mesiotemporal lesions on affective information processing: Preliminary evidence from patients with epilepsy surgery

Depressive symptoms and anxiety are common complaints in patients who have had epilepsy surgery. Recent studies have reported disturbances in emotional memory, facial and vocal emotion recognition, and affective learning after temporal lobe and/or insular resection for drug-resistant seizures, suggesting that these regions may be involved in emotional processes underlying psychological symptoms. The insula is a core component of the salience network and is thought to be involved in processing emotions such as disgust, and the role of mesial temporal lobe structures in affective processing is well established. However, to our knowledge, no study has yet investigated whether attentional processing of affective information is altered when these structures are resected as part of an epilepsy surgery. The present study examined the interference control capacity and attentional biases for emotional information in adult patients with epilepsy who underwent temporal lobe resections including the amygdala and hippocampus (n = 15) and/or partial or complete insular resections (n = 16). Patients were tested on an Emotional Stroop test and on a Dot-Probe task using fearful and disgusting pictures and were compared with a healthy control group (n = 30) matched for age, gender, and education. Repeated-measures analyses of variances revealed a significant effect of emotional words on color naming speed in the Emotional Stroop task among insular patients, which was not observed in the other groups. By contrast, the groups did not differ on Dot-Probe task performance. These preliminary findings suggest that insular damage may alter emotional interference control.

Cerebrocerebellar structural covariance in temporal lobe epilepsy with hippocampal sclerosis

PurposeThe purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum. MethodsThe study cohort included 21 patients with intractable TLE-HS (14 left-sided, 7 right-sided) and 38 healthy controls (HC). All patients later underwent anteromedial temporal lobe resection. All subjects were examined using a 1.5-T magnetic resonance imaging (MRI). Volumes of distinct cerebral and cerebellar structures were measured using voxel-based morphometry. The structural covariance of temporal lobe structures, insula, and thalamus with cerebellar substructures was examined using partial least squares regression. ResultsMorphological changes were more significant in the group with left TLE-HS when comparing left-sided with right-sided structures as well as when comparing patients with controls. The gray matter volume (GMV) of the temporal lobe structures was smaller ipsilaterally to the seizure onset side in most cases. There was a significant amygdala enlargement contralateral to the side of hippocampal sclerosis in both patients with right and left TLE-HS as compared with controls. Selected vermian structures in patients with left but not right TLE-HS had significantly larger GMV than the identical substructures in controls. The structural covariance differed significantly between patients with left and right TLE-HS as compared with HC. The analysis revealed significant negative covariance between anterior vermis and mesial temporal structures in the group with left TLE-HS. No significance was observed for the group with right TLE-HS. ConclusionThere is significant asymmetry in the GMV of cerebral and cerebellar structures in patients with TLE-HS. Morphological changes are distinctly more pronounced in patients with left TLE-HS.The observed structural covariance between the cerebellum and supratentorial structures in TLE-HS suggests associations beyond the mesial temporal lobe structures and thalamus.

Differential Generation of Saccade, Fixation, and Image-Onset Event-Related Potentials in the Human Mesial Temporal Lobe

Event-related potentials (ERPs) are a commonly used electrophysiological signature for studying mesial temporal lobe (MTL) function during visual memory tasks. The ERPs associated with the onset of visual stimuli (image-onset) and eye movements (saccades and fixations) provide insights into the mechanisms of their generation. We hypothesized that since eye movements and image-onset provide MTL structures with salient visual information, perhaps they both engage similar neural mechanisms. To explore this question, we used intracranial electroencephalographic data from the MTLs of 11 patients with medically refractory epilepsy who participated in a visual search task. We characterized the electrophysiological responses of MTL structures to saccades, fixations, and image-onset. We demonstrated that the image-onset response is an evoked/additive response with a low-frequency power increase. In contrast, ERPs following eye movements appeared to arise from phase resetting of higher frequencies than the image-onset ERP. Intriguingly, this reset was associated with saccade onset and not termination (fixation), suggesting it is likely the MTL response to a corollary discharge, rather than a response to visual stimulation. We discuss the distinct mechanistic underpinnings of these responses which shed light on the underlying neural circuitry involved in visual memory processing.

Establishing a Developmentally Appropriate fMRI Paradigm Relevant to Presurgical Mapping of Memory in Children

Functional magnetic resonance imaging (fMRI) is an established eloquent cortex mapping technique that is now an integral part of the pre-operative work-up in candidates for epilepsy surgery. Emerging evidence in adults with epilepsy suggests that material-specific fMRI paradigms can predict postoperative memory outcomes, however these paradigms are not suitable for children. In pediatric age, the use of memory fMRI paradigms designed for adults is complicated by the effect of developmental stages in cognitive maturation, the impairment experienced by some people with temporal lobe epilepsy (TLE) and the normal representation of memory function during development, which may differ from adults. We present a memory fMRI paradigm designed to activate mesial temporal lobe structures that is brief, independent of reading ability, and therefore a novel candidate for use in children. Data from 33 adults and 19 children (all healthy controls) show that the paradigm captures the expected leftward asymmetry of mesial temporal activation in adults. A more symmetrical pattern was observed in children, consistent with the progressive emergence of hemispheric specialisation across childhood. These data have important implications for the interpretation of presurgical memory fMRI in the pediatric setting. They also highlight the need to carefully consider the impact of cognitive development on fMRI tools used in clinical practice.

Minimally Invasive Technique (Nummular Craniotomy) for Mesial Temporal Lobe Epilepsy: A Comparison of 2 Approaches

To describe our series of a minimally invasive technique using a small scalp incision and keyhole craniotomy for the removal of mesial temporal lobe structures through a transcortical approach in patients with medically intractable mesial temporal lobe epilepsy (MTLE). Studies that directly compare the clinical outcomes between minimally invasive and conventional techniques are scarce, and this information is lacking in the literature. The study enrolled 73 consecutive patients with refractory MTLE and unilateral hippocampal sclerosis; 30 patients were operated on with standard frontotemporal craniotomy between 2010 and 2013 and 43 patients were operated with a minimally invasive craniotomy (nummular craniotomy) between 2014 and 2016. The preoperative evaluation included clinical history, physical examination, video-electroencephalography, neuropsychologic assessment, and magnetic resonance imaging including thin-section coronal sequences. There were no deaths in either group. Postoperative complications in the standard frontotemporal craniotomy group included temporal muscle atrophy (n= 4; 13.3%), cerebrospinal fluid leakage (n= 1; 3.3%), and wound infection (n= 1; 3.3%). No complications were observed in the keyhole craniotomy group. There was no between-group difference in postoperative seizure control. The mean Engel class I seizure-free outcome was 90.4% in the standard frontotemporal craniotomy group and 90.7% in the nummular craniotomy group (P > 0.05). Lengths of hospitalization (2.81 vs. 4.37 days, P < 0.001) and operative time (85.79 vs. 142.73 minutes, P < 0.001) were lower in the keyhole than in the standard frontotemporal craniotomy group, respectively. The nummular technique was associated with faster recovery, early hospital discharge, and fewer complications than the standard technique. No differences were observed in postoperative seizure control. Keyhole craniotomy is a safe, easy, and effective treatment option for medically intractable MTLE.

Hippocampal pathology in amyotrophic lateral sclerosis: selective vulnerability of subfields and their associated projections

Although hippocampal involvement in amyotrophic lateral sclerosis (ALS) has been consistently highlighted by postmortem studies, memory impairment remains under-recognized and the involvement of specific hippocampal subfields and their connectivity patterns are poorly characterized in vivo. A prospective multimodal neuroimaging study has been undertaken with 50 well-characterized ALS patients, 18 patients with Alzheimer's disease, and 40 healthy controls to evaluate their mesial temporal lobe profile. Patients with ALS and Alzheimer's disease have divergent hippocampal signatures. The cornu ammonis 2/3 subfield and the hippocampus-amygdala transition area are the most affected regions in ALS in contrast to Alzheimer's disease, where the presubiculum and subiculum are the most vulnerable regions. Tractography reveals considerable fornix and perforant pathway pathology in both patient groups. Mesial temporal lobe structures in ALS have a selective and disease-specific vulnerability profiles, and their white matter projections exhibit concomitant degeneration. Our combined gray and white matter analyses indicate a connectivity-based, network-defined involvement of interconnected temporal lobe structures as opposed to contiguous involvement of adjacent structures. Our findings underline the importance of screening for memory deficits and personalized management strategies in ALS.