A new clinico-pathological classification system for mesial temporal sclerosis

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1–CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.     

Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).     

Correlations Between Granule Cell Dispersion, Mossy Fiber Sprouting, and Hippocampal Cell Loss in Temporal Lobe Epilepsy

PURPOSE: Correlations between granule cell dispersion (GCD), collateral mossy fiber (MF) sprouting, and hippocampal cell loss were studied to assess the relation between GCD and synaptic reorganization in the dentate gyrus of patients with epilepsy. METHODS: Twenty specimens from patients with medically intractable temporal lobe epilepsy (TLE) were studied along with two control specimens. GCD was considered to be present when the stratum granulosum was wider than 120 microm, the close apposition between the granule cell (GC) soma was lost, and GCs were scattered in the molecular layer (ML). Patterns of MF sprouting were differentiated as wide or narrow according to the area of neo-Timm's staining in the ML. GC loss and volumetric cell-density decreases in the different subfields were assessed. RESULTS: MF sprouting was observed in 16 (80%) and GCD in nine (45%) cases. A significant correlation was found between MF sprouting and cell loss in all the subfields except the cornu Ammonis field 2 (CA2). A wide band of MF sprouting was associated with severe cell loss. Cases with GCD had a wide band of MF sprouting and also a higher degree of cell loss than cases without GCD. CONCLUSION: GCD is associated with a specific pattern of MF sprouting, but cell loss was found to be a major determinant for MF reorganization.     

Etiology and site of temporal lobe epilepsy influence postictal cytokine release

Inflammatory mechanisms are involved in the pathogenesis of epilepsy. Vice versa, immune functions are regulated by the brain. We measured postictal changes in serum levels of the immuno-modulating cytokines IL-1β, IL-6 and TNFα in patients with well-defined temporal lobe epilepsy (TLE) and determined modifying factors. Serum levels of IL-1β, IL-6 and TNFα were quantified by ELISA at baseline as well as immediately, 1 h and 24 h after a complex partial (CPS) or secondary generalized tonic–clonic seizure (GTCS) during video-EEG monitoring in 25 patients suffering from temporal epilepsy. IL-6 increased by 51% immediately after the seizure (p < 0.01) and remained elevated for 24 h. This increase lacked in patients with hippocampal sclerosis (HS; n = 16, mean increase 28%, p > 0.5, vs. 112%, p < 0.01 in patients without HS). IL-6 levels were higher after right-sided seizures as compared to left-sided seizures 24 h after the seizure (8.7 pg/mL vs. 3.4 pg/mL, p < 0.05). In patients taking valproate (VPA, n = 9), the levels of IL-1β were higher as compared to patients not treated with VPA. The results suggest a relationship between the cytokine system and characteristics of TLE such as side and pathology.     

Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy

PurposeWe analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS).MethodHippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients’ neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed.ResultsGCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE.ConclusionGCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined.     

Circuit Mechanisms of Seizures in the Pilocarpine Model of Chronic Epilepsy: Cell Loss and Mossy Fiber Sprouting

We used the pilocarpine model of chronic spontaneous recurrent seizures to evaluate the time course of supragranular dentate sprouting and to assess the relation between several changes that occur in epilep tic tissue with different behavioral manifestations of this experimental model of temporal lobe epilepsy. Pilo carpine-induced status epilepticus (SE) invariably led to cell loss in the hilus of the dentate gyrus (DG) and to spontaneous recurrent seizures. Cell loss was often also noted in the DG and in hippocampal subfields CA1 and CA3. The seizures began to appear at a mean of 15 days after SE induction (silent period), recurred at variable frequencies for each animal, and lasted for as long as the animals were allowed to survive (325 days). The granule cell layer of the DG was dispersed in epileptic animals, and neo-Timm stains showed supra-and intragranular mossy fiber sprouting. Supragranular mossy fiber sprout ing and dentate granule cell dispersion began to appear early after SE (as early as 4 and 9 days, respectively) and reached a plateau by 100 days. Animals with a greater degree of cell loss in hippocampal field CAS showed later onset of chronic epilepsy (r= 0.83, p < 0.0005), suggest ing that CA3 represents one of the routes for seizure spread. These results demonstrate that the pilocarpine model of chronic seizures replicates several of the fea tures of human temporal lobe epilepsy (hippocampal cell loss, suprar and intragranular mossy fiber sprouting, den tate granule cell dispersion, spontaneous recurrent sei zures) and that it may be a useful model for studying this human condition. The results also suggest that even though a certain amount of cell loss in specific areas may be essential for chronic seizures to occur, excessive cell loss may hinder epileptogenesis.     

Increased leak conductance in dentate gyrus granule cells of temporal lobe epilepsy patients with Ammon's horn sclerosis

Purpose:   Temporal lobe epilepsy (TLE) is often associated with Ammon's horn sclerosis (AHS) characterized by hippocampal cell death and dentate gyrus granule cell dispersion (GCD). Granule cells survive AHS and have been proposed to be hyperexcitable in TLE. Here we studied whether the passive excitability of granule cells correlates with the severity of AHS.
Methods:   We analyzed the passive membrane properties of identified granule cells using patch-clamp recordings in acute tissue slices obtained from TLE surgery. Independent Wyler grading and GCD measurements were used to assess the severity of AHS.
Results:   The input resistances and membrane time constants of granule cells were reduced in high-grade versus low-grade AHS samples and negatively correlated with the degree of GCD. Granule cells possessed large Ba²⁺-sensitive, inwardly rectifying K⁺ conductances.
Discussion:   The increased leak conductance, likely mediated by K⁺ channels, does not argue for an increased excitability of granule cells but rather points to a neuroprotective mechanism in the sclerotic focus in TLE.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Exogenous reelin prevents granule cell dispersion in experimental epilepsy

Temporal lobe epilepsy (TLE) is often accompanied by granule cell dispersion (GCD), a migration defect of granule cells in the dentate gyrus. We have previously shown that a decrease in the expression of reelin, an extracellular matrix protein important for neuronal positioning, is associated with the development of GCD in TLE patients. Here, we used unilateral intrahippocampal injection of kainate (KA) in adult mice which is also associated with GCD formation and a decrease of reelin expression. In this mouse epilepsy model we aimed to prevent GCD development by the application of exogenous reelin. As a prerequisite we analyzed whether the reelin signaling transduction cascade was preserved in the KA-injected hippocampus. Using in situ hybridization and Western blot analysis we found that the expression of the reelin signaling components, apolipoprotein E receptor 2, the very-low-density lipoprotein receptor and the intracellular adaptor protein disabled 1, was maintained in dentate granule cells after KA injection. Next, recombinant reelin was infused into the KA-injected hippocampus by osmotic minipumps over a period of 2 weeks. Quantitative analysis of granule cell layer width revealed a significant reduction of GCD in reelin-treated, but not in saline-infused animals when compared to KA injection alone. Our findings highlight the crucial role of reelin for the maintenance of granule cell lamination in the dentate gyrus of adult mice and show that a reelin deficiency is causally involved in GCD development.     

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen–DR isotype (HLA-DR)-expressing CD4⁺ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14^lowCD16⁺ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR–expressing CD8⁺ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.     

Neuropathological spectrum of drug resistant epilepsy: 15-years-experience from a tertiary care centre

Neuropathology of drug resistant epilepsy (DRE) has direct bearing on the clinical outcome. Classification of the most common pathologies, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) have undergone several revisions and studies on the surgical pathology of DRE employing the updated ILAE classification are scarce. Here, we report the neuropathological spectrum of 482 surgically treated cases of DRE from a single institute using the latest ILAE classifications along with clinicoradiologic correlation. Majority of the cases (324, 67.2%) had temporal lobe epilepsy (TLE), with 158 (32.8%) having extratemporal seizure focus. Among TLE, HS was most common (n = 208, 64.2%), followed by neoplasms (42, 13%), FCD (26, 8%) and dual pathology (23, 7%). Less frequent were vascular malformations (cavernoma-3, arteriovenous malformation-1), mild malformation of cortical development (mMCD, 3), gliotic lesions (5), cysticercosis (2), double pathology (2) and polymicrogyria (1). Among extratemporal epilepsies, FCD was most common (46, 29.1%), followed by neoplasms (29, 18.3%), gliotic lesions (27, 17.1%), Rasmussen encephalitis (18, 11.4%), hypothalamic hamartoma (12, 7.6%), malformations of cortical development (10, 6.3%) and vascular malformations (6, 3.8%). Less frequent were double pathology (2, cysticercosis + FCD type IIb, DNET + FCD type IIb), mMCD (2), cysticercosis (1) and dual pathology (1). No underlying pathology was detected in 12 cases (2.5%). Radiopathological concordance was noted in 83%. In 36 cases (7.5%), histopathology detected an unsuspected second pathology that included FCD type III (n = 16) dual pathology (n = 18) and double pathology (n = 2). Further, in four MRI negative cases, histopathology was required for a conclusive diagnosis.     

Neuropathologische Befunde bei Fieberkrämpfen

Patients suffering from drug-resistant temporal lobe epilepsy (TLE) frequently reported about prolonged febrile seizures during their early childhood. Neuropathological evaluation of neurosurgical specimens obtained from TLE patients with prolonged febrile seizures before the age of 4 years compared with specimens from TLE patients without febrile seizures has revealed a few interesting differences: Segmental neuronal cell loss is usually more severe, the architecture of the granule cell layer is usually more disturbed, and postsurgical seizure control is usually more successful. On the other hand, hippocampal cell loss was not observed in a rat model of febrile seizures. In this model, young rats were submitted to hyperthermia and experienced prolonged febrile convulsions. One-third of the animals developed chronic limbic epilepsy. This animal model, by unraveling the effects of prolonged febrile seizures on neuronal function, thereby identified several molecular pathomechanisms and the potential contribution of such seizures to epilepsy.     

Involvement of the thalamocortical network in TLE with and without mesiotemporal sclerosis

Purpose: The thalamus plays an important role in seizure propagation in temporal lobe epilepsy (TLE). This study investigated how structural abnormalities in the focus, ipsilateral thalamus and extrafocal cortical structures relate to each other in TLE with mesiotemporal sclerosis (TLE‐MTS) and without hippocampal sclerosis (TLE‐no). Methods: T₁ and high‐resolution T₂ images were acquired on a 4T magnet in 29 controls, 15 TLE‐MTS cases, and 14 TLE‐no. Thalamus volumes were obtained by warping a labeled atlas onto each subject’s brain. Deformation‐based morphometry was used to identify regions of thalamic volume loss and FreeSurfer for cortical thickness measurements. CA1 volumes were obtained from high‐resolution T₂ images. Multiple regression analysis and correlation analyses for voxel‐ and vertex‐based analyses were performed in SPM2 and FreeSurfer. Results: TLE‐MTS had bilateral volume loss in the anterior thalamus, which was correlated with CA1 volume and cortical thinning in the mesiotemporal lobe. TLE‐no had less severe volume loss in the dorsal lateral nucleus, which was correlated with thinning in the mesiotemporal region but not with extratemporal thinning. Discussion: The findings suggest that seizure propagation from the presumed epileptogenic focus or regions close to it into the thalamus occurs in TLE‐MTS and TLE‐no and results in circumscribed neuronal loss in the thalamus. However, seizure spread beyond the thalamus seems not to be responsible for the extensive extratemporal cortical abnormalities in TLE.     

Neuropathologic and Clinical Features of Human Medial Temporal Lobe Epilepsy

Background and Purpose

There is recent evidence of various types of morphological changes in the hippocampus of a rodent model of medial temporal lobe epilepsy (mTLE). However, little is known about such changes in humans. We examined the histological changes [i.e., neuronal loss, cell genesis, and granule cell dispersion (GCD)] in surgical hippocampal specimens taken from patients with mTLE.

Methods

Nissl staining, and nestin and Prox1 immunohistochemistry were performed on human hippocampal specimens obtained from patients with medically intractable mTLE, thus allowing the analysis of neuronal loss, cell genesis, and GCD, respectively. We also assessed the correlations between clinical parameters and the histopathologic findings.

Results

The degree of cell genesis in the granule cell layer was significantly correlated with the severity of GCD, history of childhood febrile seizures, and frequent generalized seizures. Cell genesis was not correlated with cell death, age at seizure onset, duration of epilepsy, or the mean frequency of all seizures.

Conclusions

Our results indicate that cell genesis in the dentate gyrus of patients with mTLE is associated with GCD and is influenced by the presence of febrile seizures during childhood and the frequency of episodes of generalized seizures.     

Review: Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: Clinical,pathological and neuroimaging evidence

Cognitive decline is increasingly described as a co‐morbidity of temporal lobe epilepsy (TLE). Mechanisms underlying cognitive impairment are not fully understood despite examining clinical factors, such as seizure frequency, and cellular mechanisms of excitotoxicity. We review the neuropsychometry evidence for progressive cognitive decline and examine the pathology and neuroimaging evidence supporting a neurodegenerative process in hippocampal sclerosis (HS)‐related TLE. Accelerated cognitive decline is described in groups of adult HS‐related TLE patients. Large childhood studies show early onset of seizures result in poor development of verbal memory and a hindrance in achieving cognitive potential. We discuss HS classification according to different patterns of neuronal loss and correlation to post‐temporal lobectomy cognitive outcomes in refractory TLE patients. Factors such as lateralization of HS pathology, neuronal density and subtype have correlated to cognitive outcomes with varying significance between different studies. Furthermore, alterations in neuronal maturity, regenerative capacity and aberrant connectivity appear to affect cognitive performance post‐operatively suggesting a complex multifactorial process. More recent studies have identified tau pathology being present in HS‐related TLE and correlated to post‐operative cognitive decline in some patients. A traumatic head injury‐related or novel tauopathy has been hypothesized as an underlying process. We discuss the value of prospective and cross‐sectional imaging in assessing cognition and review volumetric magnetic resonance studies with progressive ipsilateral hippocampal atrophy identified to correlate with seizure frequency. Finally, we consider the use of positron emission tomography biomarkers, such as tau tracers, and connectivity studies that may examine in vivo pathways and further explore cognitive decline in TLE.     

International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods

Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.     

Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies

Ample evidence points to the dentate gyrus as anatomical region for persistent neurogenesis in the adult mammalian brain. This has been confirmed in a variety of animal models under physiological as well as pathophysiological conditions. Notwithstanding, similar experiments are difficult to perform in humans. Postmortem studies demonstrated persisting neurogenesis in the elderly human brain. In addition, neural precursor cells can be isolated from surgical specimens obtained from patients with intractable temporal lobe epilepsy (TLE) and propagated or differentiated into neuronal and glial lineages. It remains a controversial issue, whether epileptic seizures have an effect on or even increase hippocampal neurogenesis in humans. Recent data support the notion that seizures induce neurogenesis in young patients, whereas the capacity of neuronal recruitment and proliferation decreases with age. Animal models of TLE further indicate that these newly generated neurons integrate into epileptogenic networks and contribute to increased seizure susceptibility. However, pathomorphological disturbances within the epileptic hippocampus, such as granule cell dispersion (GCD), may not directly result from compromised neurogenesis. Still, the majority of adult TLE patients present with significant dentate granule cell loss at an end stage of the disease, which relates to severe memory and learning disabilities. In conclusion, surgical specimens obtained from TLE patients represent an important tool to study mechanisms of stem cell recruitment, proliferation and differentiation in the human brain. In addition, increasing availability of surgical specimens opens new avenues to systematically explore disease pathomechanisms in chronic epilepsies.     

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome

PurposeThe purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE.MethodsThirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5–6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5–8 min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately.ResultsDuration of epilepsy ranged between 5 and 55 years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p = 0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33 months, range 20–65 months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4 years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n = 12, p = 0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p = 0.0173).ConclusionsMultiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.     

Type of preoperative aura may predict postsurgical outcome in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeAs the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).MethodsIn this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or relapse. Outcome was compared between seven groups of patients according to their preoperative auras.ResultsTwo hundred thirty-seven patients were studied. The chance of becoming free of seizures after surgery in patients with abdominal aura was 65.1%, while in other patients, this was 43.3% (P = 0.01). In two-by-two comparisons, no other significant differences were observed.ConclusionPatients with medically refractory TLE–MTS who reported abdominal auras preceding their seizures fared better postoperatively with regard to seizure control compared with those who did not report auras, which may indicate bitemporal dysfunction, and to patients with other auras, which may indicate a widespread epileptogenic zone in the latter group of patients.