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Purpose: Limbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery. Methods: We investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events. Results: Histopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (β-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker. Conclusion: Our findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS. [ABSTRACT FROM AUTHOR]

Selective amygdalohippocampectomy is an effective treatment for patients with therapy-refractory temporal lobe epilepsy but may cause visual field defect (VFD). Here, we aimed to describe tissue-specific pre- and postoperative imaging correlates of the VFD severity using whole-brain analyses from voxel- to network-level. Twenty-eight patients with temporal lobe epilepsy underwent pre- and postoperative MRI (T1-MPRAGE and Diffusion Tensor Imaging) as well as kinetic perimetry according to Goldmann standard. We probed for whole-brain gray matter (GM) and white matter (WM) correlates of VFD using voxel-based morphometry and tract-based spatial statistics, respectively. We furthermore reconstructed individual structural connectomes and conducted local and global network analyses. Two clusters in the bihemispheric middle temporal gyri indicated a postsurgical GM volume decrease with increasing VFD severity (FWE-corrected p < 0.05). A single WM cluster showed a fractional anisotropy decrease with increasing severity of VFD in the ipsilesional optic radiation (FWE-corrected p < 0.05). Furthermore, patients with (vs. without) VFD showed a higher number of postoperative local connectivity changes. Neither in the GM, WM, nor in network metrics we found preoperative correlates of VFD severity. Still, in an explorative analysis, an artificial neural network meta-classifier could predict the occurrence of VFD based on presurgical connectomes above chance level. [ABSTRACT FROM AUTHOR]

Objective: Transsylvian selective amygdalo‐hippocampectomy (tsSAHE) represents a generally recognized surgical procedure for drug‐resistant mesial temporal lobe epilepsy (mTLE). Although postoperative seizure freedom can be achieved in about 70% of tsSAHE, there is a considerable amount of patients with persisting postoperative seizures. This might partly be explained by differing extents of resection of various tsSAHE target volumes. In this study we analyzed the resected proportions of hippocampus, amygdala as well as piriform cortex in regard of postoperative seizure outcome. Methods: Between 2012 and 2017, 82 of 103 patients with mTLE who underwent tsSAHE at the authors' institution were included in the analysis. Resected proportions of hippocampus, amygdala and temporal piriform cortex as target structures of tsSAHE were volumetrically assessed and stratified according to favorable (International League Against Epilepsy (ILAE) class 1) and unfavorable (ILAE class 2–6) seizure outcome. Results: Patients with favorable seizure outcome revealed a significantly larger proportion of resected temporal piriform cortex volumes compared to patients with unfavorable seizure outcome (median resected proportional volumes were 51% (IQR 42–61) versus (vs.) 13 (IQR 11–18), P = 0.0001). Resected proportions of hippocampus and amygdala did not significantly differ for these groups (hippocampus: 81% (IQR 73–88) vs. 80% (IQR 74–92) (P = 0.7); amygdala: 100% (IQR 100–100) vs. 100% (IQR 100–100) (P = 0.7)). Interpretation: These results strongly suggest temporal piriform cortex to constitute a key target resection volume to achieve seizure freedom following tsSAHE. [ABSTRACT FROM AUTHOR]

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 CD14lowCD16+ 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. [ABSTRACT FROM AUTHOR]

Limbic encephalitis (LE) forms a spectrum of autoimmune diseases involving temporal lobe epilepsy and memory impairment. Imaging features of LE are known to depend on the associated antibody and to occur on the brain network level. However, first studies investigating brain networks in LE have either focused on one distinct antibody subgroup or on distinct anatomical regions. In this study, brain graphs of 17 LE patients with autoantibodies against glutamic acid decarboxylase 65 (GAD‐LE), four LE patients with autoantibodies against leucine‐rich glioma‐inactivated 1, five LE patients with autoantibodies against contactin‐associated protein‐like 2, 26 age‐ and gender‐matched healthy control subjects, and 20 epilepsy control patients with hippocampal sclerosis were constructed based on T1‐weighted structural magnetic resonance imaging scans and diffusion tensor imaging. GAD‐LE showed significantly altered global network topology in terms of integration and segregation as compared to healthy controls and patients with hippocampal sclerosis (P <.01, analysis of variance with Tukey‐Kramer post hoc tests). Linear regression linked global network measures with amygdala volume and verbal memory performance (P <.05). Alterations of local network topology show serotype dependence in hippocampus, amygdala, insula, and various cortical regions. Our findings reveal serotype‐dependent patterns of structural connectivity and prove the relevance of in silico network measures on clinical grounds. [ABSTRACT FROM AUTHOR]

Supraspan list learning tests are sensitive measures used to assess temporal lobe dysfunction. Most frequently employed is the Rey Auditory Verbal Learning and Memory Test (RAVLT). The test's structure is determined by a short- and long-term memory component. During the first of five learning trials, the short-term memory component is the highest and steadily decreases over the following trials, while the long-term memory component concurrently increases and reaches its maximum at the delayed recall after a retention interval of 30 min. The study aimed to test the hypothesis that the functional relevance of left hippocampal integrity for conscious memory rises along with the increasing degree of the long-term memory component. Moreover, we investigated whether classical measures of short-term and working memory are also dependent on the hippocampus. The analysis was based on 37 adult patients who had undergone surgery for left mesial temporal lobe epilepsy. Neuronal cell densities of the resected left hippocampus were correlated with the presurgical memory performance across trials of the VLMT (the German RAVLT) and with digit span and working memory capacity (WMS-R). Whereas digit span and working memory capacity were not related to hippocampal cell counts, there was a significant correlation between left hippocampal integrity and VLMT memory performance, already regarding the first supraspan learning trial. Correlations steadily increased during the learning course. The highest correlation was seen regarding the delayed free recall. The results indicate an increasing correspondence between the integrity of the left hippocampus and verbal memory with an increasing long-term memory component. Immediate recall of verbal material became already dependent on left hippocampal integrity when the verbal memory load exceeded the memory span (supraspan list learning), while classical span measures that assess verbal short-term and working memory were not affected by left hippocampal pathology. [ABSTRACT FROM AUTHOR]

Objective Recent reports define temporal lobe epilepsy with amygdala enlargement ( TLE- AE) as a distinct electroclinical syndrome comparable to TLE with hippocampal sclerosis. In this retrospective observational study, we present the largest consecutive series of patients with new-onset TLE- AE to date and describe clinical characteristics and seizure outcome, and we aim to explore underlying autoimmune mechanisms within this syndrome. Methods We reviewed all consecutive patients between 2004 and 2014 at our tertiary epilepsy center at the University of Bonn, Germany, with new-onset (<5 years) TLE- AE, negative serum antibody (ab) test results, and with available follow-up data for at least 12 months. Results We identified 40 patients (23 male) with TLE- AE with a median age at epilepsy onset of 51 years (range 10-73) and a median disease duration of 11 months (range 0.5-55) at first presentation. At follow-up, 50% of the entire cohort achieved seizure freedom. Of interest, patients with remittent features of AE at follow-up (N = 24) had a superior outcome compared to those with stable magnetic resonance imaging ( MRI) features of AE (N = 16): 17 (71%) of 24 were seizure-free for at least 6 months compared to 3 (19%) of 16, respectively (p = 0.003). MRI volumetry confirmed significantly enlarged amygdalae in TLE- AE in relation to healthy controls, and additionally showed significantly greater volume reductions in patients with remittent AE compared to those with stable AE. Significance TLE- AE is a clinical syndrome beginning mostly in middle age, and in addition to its known association with ab-positive limbic encephalitis, it occurs in an ab-negative condition. Remission of AE in the course of the disease could be identified as a predictor for a favorable clinical outcome and is suspicious of an autoimmune etiology, although we could not confirm this hypothesis unequivocally with currently available noninvasive diagnostic tools. [ABSTRACT FROM AUTHOR]

Object: Resective surgery is a safe and effective treatment of drug-resistant epilepsy. If surgery has failed reoperation after careful re-evaluation may be a reasonable option. This study was to summarise the risks and benefits of reoperation in patients with epilepsy.Methods: This is a retrospective single centre study comprising clinical data, long-term seizure outcome, neuropsychological outcome and postoperative complications of patients, who had undergone a second resective epilepsy surgery from 1989 to 2009.Results: A total of 66 patients with median follow-up of 10.3 years were included into the study. Fifty-one patients (77%) had surgery for temporal lobe epilepsy, the remaining 15 cases for extra-temporal lobe epilepsies. The most frequent histological findings were tumours (n=33, 50%), followed by dysplasia, gliosis (n=11, each) and hippocampus sclerosis (n=9). The main reasons for seizure recurrence were incomplete resection (59.1%) of the putative epileptogenic lesion. After reoperation 46 patients (69.7%) were completely seizure-free International League Against Epilepsy 1 (ILAE 1) at the last available follow-up. The neuropsychological evaluation demonstrated that repeated losses in the same cognitive domain, that is, successive changes from better to worse performance categories, were rare and that those losses after first surgery were followed by improvement rather than decline. However, reoperations lead to an increased rate of permanent neurological deficits (9%), overall surgical complications (9%) and visual field deficits (67%).Conclusions: Reoperation after failed resective epilepsy surgery led to approximately 70% long-time seizure freedom and reasonable neuropsychological outcome. There is an increased risk of permanent postoperative neurological deficits, which should be taken into consideration when counselling for reoperation. [ABSTRACT FROM AUTHOR]

Objective: Limbic encephalitis (LE) is an autoimmune mediated disease leading to temporal lobe epilepsy, mnestic and psychiatric symptoms. In recent years, several LE subforms defined by serum antibody findings have been described. MRI usually shows volume changes of the amygdala and hippocampus. However, studies quantifying longitudinal volume changes in the acute disease stage are lacking. Methods: The aim of this retrospective observational study was to evaluate and quantify these volume changes by applying a fully automated volumetric approach to serial MRIs of 28 patients with antibody-associated LE. were compared with those of 28 age-matched and gender-matched healthy controls and analysed separately for the different antibody profiles and correlated with clinical parameters. Antibody profile analyses were exploratory due to the relatively small sample sizes. Results: We found distinct volumetric and clinical courses depending on the associated antibody. While LE associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) showed highly significant larger volumes of both the amygdala and the hippocampus within the first 12 months after disease onset, LE associated with glutamic acid decarboxylase antibodies (GAD-LE) only displayed greater amygdala volumes at this disease stage. Both subgroups showed a reduction of the amygdala and hippocampus volumes during follow-up with higher volume changes in VGKC-LE. Conclusions: These differences in the volumetric evolution corresponded to distinct clinical courses in terms of a more severe initial symptomatology regarding seizure, mnestic and psychiatric disturbances in VGKC-LE, which improved rapidly, corresponding to the evolution of the volumetric changes. In contrast to this, patients with GAD-LE were less severely affected at disease onset, showing a more unmodulated and chronic disease course during follow-up. [ABSTRACT FROM AUTHOR]

Objective Antibody-associated limbic encephalitis ( LE) is an increasingly recognized cause of mostly adult-onset temporal lobe epilepsy. Magnetic resonance imaging ( MRI) typically shows volume and signal changes of the mesiotemporal structures. However, recent studies indicate that imaging characteristics depend on the type of the associated antibody. The aim of the present study was to investigate early and chronic gray matter ( GM) volume changes in LE by means of voxel-based morphometry ( VBM). Methods Optimized VBM analysis was applied to altogether 73 MRI volumes of 55 patients with antibody-associated LE. Based on the time point of MRI acquisition, patients were split into two separate groups to enable the evaluation of early (≤2 years after LE onset) and chronic (>2 years after LE onset) GM volume changes. In addition, separate analyses for the two most common LE subtypes in our study cohort, that is, glutamic acid decarboxylase ( GAD)-associated LE and voltage-gated potassium channel ( VGKC)-complex-associated LE were performed. Age- and gender-matched healthy subjects served as controls. Results Referring to the entire LE group, VBM revealed bi-amygdalar GM volume increase in the early disease stage. In the chronic disease stage, amygdala enlargement had resolved and we found GM volume reduction in the right cerebellar hemisphere. In the subgroup analysis, VBM showed corresponding bi-amygdalar GM volume increase in VGKC-complex-associated LE on early MRI, whereas no changes were found in GAD-associated LE. In the chronic disease stage, VBM revealed left frontal GM volume increase in VGKC-complex-associated LE and right frontoparietal GM volume reduction in GAD-associated LE. Significance The present study provides further evidence of a predominant affection of the amygdala in the early disease stage of LE, which resolves during the later course of the disease. Furthermore, our results show that LE features distinct imaging characteristics depending on the associated antibody and thus may contribute to a better pathophysiologic understanding of this disease. [ABSTRACT FROM AUTHOR]

Objective: Chronic inflammatory processes are important promotors of temporal lobe epilepsy (TLE) development. Based on human herpesvirus 6 (HHV-6)DNAdetection in brain tissue from patients with TLE, an association of persistent viral infection with TLE has been discussed. Individual studies reported increased HHV-6 DNA in patients with clinical signs of previous inflammatory brain reaction, that is, febrile seizures or meningoencephalitis. However, detection rates vary considerably between different studies. Here we performed a large-scale analysis of viral DNA/RNA spectrum in high-quality TLE biopsies. In addition to all Herpesviridae, we addressed potentially relevant neurotropic RNA viruses. Methods: DNA and RNA were extracted from 346 fresh-frozen tissue samples removed by epilepsy surgery. Real-time polymerase chain reaction (PCR) and nested PCR were performed for Herpesviridae and RNA viruses, respectively. Clinical data were analyzed for earlier signs of inflammatory brain reactions. Fresh-frozen hippocampal tissue samples from patients without chronic central nervous system (CNS) disease served as controls (n = 62). Seven previous PCR studies with overall 178 TLE patients were additionally analyzed regarding a correlation of clinical parameters and HHV-6 detection. Methods: DNA and RNA were extracted from 346 fresh-frozen tissue samples removed by epilepsy surgery. Real-time polymerase chain reaction (PCR) and nested PCR were performed for Herpesviridae and RNA viruses, respectively. Clinical data were analyzed for earlier signs of inflammatory brain reactions. Fresh-frozen hippocampal tissue samples from patients without chronic central nervous system (CNS) disease served as controls (n = 62). Seven previous PCR studies with overall 178 TLE patients were additionally analyzed regarding a correlation of clinical parameters and HHV-6 detection. Results: PCR revealed HHV-6B DNA in 34 specimens (9.8%) from TLE patients. HHV-6B DNA was also present in eight control samples (12.9%; p > 0.05), but showed a lower virus concentration (p < 0.001). Other herpesviruses and RNA viruses were virtually absent. In patients with clinical signs of previous brain inflammation, HHV-6B DNA was observed in 15.0%, whereas only 6.3% of the samples from patients without febrile seizures or meningoencephalitis were positive for HHV-6B DNA (p < 0.05). A meta-analysis of the eight HHV-6 PCR studies revealed similar results. Significance: This biopsy-based study shows no differences in frequency of HHV-6B DNA detection between TLE patients and controls. These results do not support the hypothesis of a persistent HHV-6B infection as a major pathogenetic factor in TLE. However, the higher virus load in TLE patients and the increased detection rate of HHV-6B DNA in patients with previous inflammatory brain reactions require further investigations. [ABSTRACT FROM AUTHOR]

Episodes of transient loss of consciousness (TLOC) are commonly due to syncope or epileptic seizures. The distinction between both entities on clinical grounds and eyewitness accounts can be challenging and is often hampered by similar clinical features. We briefly summarize syncope-related symptoms and present the case of a female patient who suffered from TLOC episodes due to both reflex syncope and epileptic seizures. Seizure-induced syncope is a rare complication particularly of non-generalized temporal lobe seizures and may be suspected in people with epilepsy who report new semiological features with sudden onset of atonia, TLOC and seizure-related falls. We review epidemiological, clinical and electroencephalographic aspects of seizure-related asystole and syncope and discuss their clinical relevance. The implantation of a cardiac pacemaker appears to efficiently prevent seizure-related falls and consecutive injuries and is an important treatment option if full seizure-control cannot be achieved in these patients. We describe a second case of a patient with refractory temporal lobe epilepsy and seizure-related syncope which ceased after the implantation of a cardiac pacemaker. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Resection of the seizure focus leads to sustained seizure-freedom in intractable focal epilepsy in up to 80% of selected populations. However, surgery fails to help in a considerable proportion of patients. Reevaluation and reoperation may be considered in a selected group of patients with an unfavorable postsurgical outcome. Here, we reviewed 15 case series on reoperation after failed resective epilepsy surgery in adults in order to identify factors associated with a good chance of benefitting from a second operation. Methods: Literature review of case series describing the outcome of epilepsy surgical re-operations. Results: Overall, 3.8–14% of all patients who had resective epilepsy surgery underwent a second operation. A total of 402 reoperated patients were included. Reoperation was performed in average between 2 and 5.5 years after the first surgery. 36.6% of all patients were seizure-free with a minimal follow-up of 6 months to 4 years after the second operation. Postsurgical complications were observed in 13.5% and mainly consisted of visual field defects and, less frequently, of hemiparesis. The causes of failed first epilepsy surgery were heterogeneous and included incorrect localization or incomplete resection of the seizure focus, presence of additional seizure foci or progression of the underlying disease. Some features appear to indicate successful reoperation, such as concordance of postsurgical imaging and electroclinical findings as well as absence of brain trauma and cerebral infection prior to epilepsy onset. Conclusion: Reoperation after thorough assessment of all available clinical, imaging and EEG findings can be an efficacious and reasonably safe treatment option which can achieve sustained seizure control after failed resective epilepsy surgery. [Copyright &y& Elsevier]

Purpose Limbic encephalitis is an autoimmune-mediated disease leading to temporal lobe epilepsy, mnestic deficits, and affective disturbances. Magnetic resonance imaging ( MRI) usually shows signal and volume changes of the temporomesial structures. However, these abnormalities may be subtle, thereby hampering the diagnosis by conventional visual assessment. In the present study we evaluated the diagnostic value of a fully automated MRI postprocessing technique in limbic encephalitis and hippocampal sclerosis. Methods The MRI postprocessing was based largely on a recently described method allowing for an observer-independent quantification of the fluid-attenuated inversion recovery ( FLAIR) signal intensities of amygdala and hippocampus. A 95% confidence region was calculated from the FLAIR intensities of 100 healthy controls. We applied this analysis to the MRI data of 39 patients with antibody-associated limbic encephalitis and 63 patients with hippocampal sclerosis. Moreover, the results were compared to those of visual assessment by an experienced neuroradiologist. Key Findings The method detected limbic encephalitis and hippocampal sclerosis with a high sensitivity of 85% and 95%, respectively. The detection rate of the automated approach in limbic encephalitis was significantly superior to visual analysis (85% vs. 51%; p = 0.001), whereas no statistically significant difference for the detection rate in hippocampal sclerosis was found. Patients with limbic encephalitis had significantly higher absolute intensity values of the amygdala and a significantly higher percentage fell outside of the amygdalar confidence region compared to those with hippocampal sclerosis (79% vs. 27%; p < 0.001), whereas we found opposite results in the hippocampal analysis (38% vs. 95%; p < 0.001). Significance The FLAIR analysis applied in this study is a powerful tool to quantify signal changes of the amygdala and hippocampus in limbic encephalitis and hippocampal sclerosis. It significantly increases the diagnostic sensitivity in limbic encephalitis in comparison to conventional visual analysis. Furthermore, the method provides an interesting insight into the distinct properties of these two disease entities on MRI, indicating a predominant affection of the amygdala in limbic encephalitis, whereas the affection of the hippocampus is far less pronounced when compared to hippocampal sclerosis. [ABSTRACT FROM AUTHOR]

Abstract: Zero-lag phase synchronization of EEG activity has been reported to be a central mechanism accompanying long-term memory formation. In this pilot study, we examined the effects of synchronous low-amplitude stimulation of the rhinal cortex and the hippocampus in eleven temporal lobe epilepsy patients. The impact of in-phase stimulation (zero lag) on long-term memory encoding of words was contrasted with anti-phase (180° phase lag) and sham stimulation. We hypothesized more correctly remembered words for the in-phase compared to the sham condition and fewer correctly remembered words for the anti-phase vs. the sham condition. Indeed, we observed a trend for a linear condition effect for correctly remembered words, which is in accordance to our prediction (in-phase > sham > anti-phase). This finding suggests that even weak synchronous deep brain stimulation of rhinal cortex and hippocampus may modulate memory performance, while clear evidence for an enhancement of memory by this kind of deep brain simulation is still lacking. [Copyright &y& Elsevier]

Objectives: Human and animal studies provided controversial data on asymmetric cortical representation of cardiac function, which may partially be due to different study designs and inter-individual variability. Here, we investigated whether seizure-related changes in heart rate (HR) and cardiac repolarization depend on the side of seizure-activity in people with mesial temporal lobe epilepsy (mTLE). Methods: To account for inter-individual variability, EEG and ECG data were reviewed from patients with medically refractory mTLE undergoing pre-surgical video-EEG telemetry with at least 2 seizures arising from each hippocampus as assessed by bilateral hippocampal depths electrodes. RR and QT intervals were determined at different timepoints using a one-lead ECG. QT intervals were corrected for HR (QTc) using 4 established formulas. Results: Eighty-two seizures of 15 patients were analyzed. HR increased by ∼30% during hippocampal activity irrespective of the side (p = 0.411). QTc intervals were lengthened to a significantly greater extent during left hippocampal seizures (e.g. difference of QT intervals between preictal and ictal state using Bazett’s formula; left side 32.0±5.3 ms, right side 15.6±7.7 ms; p = 0.016). Abnormal QTc prolongation occurred in 7 of 41 left hippocampal seizures of 4 patients, and only in 2 of 37 right hippocampal seizures of 2 patients. Conclusions: Seizure-related modulation of cardiac repolarization, but not of HR, appears to depend on the side of ictal activity, strengthening the hypothesis of asymmetric cerebral representation of cardiac function. The clinical relevance of this is unclear, but may indicate an increased risk of abnormal ictal QT prolongation in people with left mTLE. [ABSTRACT FROM AUTHOR]

Several studies reported changes in white matter architecture following temporal lobe surgery in patients with temporal lobe epilepsy ( TLE) at short intervals after surgery. We investigated 20 patients with left-sided TLE using diffusion-imaging at two time points, that is, at 3-6 months and 12 months after surgery, to investigate postsurgical plasticity. We observed a loss of fiber tract integrity mainly in fiber tracts of the ipsilateral temporal lobe. Our data show that the remodeling of brain connectivity after surgical interventions continues for longer time periods. The functional implications of these plastic changes will have to be explored. [ABSTRACT FROM AUTHOR]

Background: Presurgical epilepsy diagnostics and surgical treatment have become standard procedures of neurology. Here, we report on presurgical patients grouped according to their underlying pathology by giving results of presurgical evaluation, surgical therapy and long-term follow-up between 1989-2009 and describe trends over this period. Patients and methods: Data of prospectively documented presurgical patients were retrospectively analysed. Trends were evaluated by a year-by-year analysis. Results: 2684 presurgical patients underwent presurgical work-up, 1721 of whom (64.1%) went on to resective surgery. The largest presurgical/surgical group was mediotemporal lobe epilepsy with hippocampal sclerosis (29.5%/35.4%). Of all operated patients, 1160 (67.4%) had a follow-up of =2 years. A total of 586 were continuously seizure-free without auras (50.5%; benign tumours: 61.0%; focal cortical dysplasia: 57.6%; mediotemporal lobe epilepsy with hippocampal sclerosis: 49.4%; non-lesional: 27.6%). Based on the number of the presurgically studied patients, we calculated as a novel measure of the effect of a presurgical/surgical programme an 'intention-to treat seizure-freedom' rate of 32.4%. Over time, the number of patients undergoing evaluation, but also of those not suitable or agreeable for invasive measures increased. Annual numbers of resective procedures remained stable. Average epilepsy duration of patients admitted for presurgical assessment increased. The proportion of patients with benign tumours declined. Intracranial studies and MRIhistopathology discrepancies decreased. Seizure-freedom rates remained constant. Conclusions: Epilepsy surgery is highly effective, especially in patients with clearly defined focal pathologies. At this specialised centre, there is a trend towards growing numbers of difficult patients and increasing epilepsy duration prior to referral for presurgical assessment. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to assess the localizing value of the initial semiological element in temporal lobe epilepsy (TLE). Video-EEG-documented seizures of 97 adult TLE patients were studied in relation to seizure origin (left versus right; mesial versus extra-mesial). Strikingly, seizures with mesial onset started with very few ictal phenomena, while seizures of extra-mesial origin began with a larger variety of ictal elements. Furthermore, following noticeable distributions were observed for the mesial group: (i) aura was the most common initial ictal phenomenon in the total patient collective, occurring significantly more frequently in mesial than in extra-mesial seizure onset. Aura appeared most often in seizures of left mesial origin. (ii) Vocalization presented a trend towards mesial left seizure origin. (iii) Oral automatisms showed a trend towards mesial seizure origin. Following noticeable distribution was observed for the extra-mesial group: In patients without aura, restlessness as initial ictal phenomenon appeared exclusively in seizures of extra-mesial right origin. Finally, behavioral arrest showed a trend towards left-sided seizure origin. In conclusion, the initial ictal element may add useful information concerning differentiation of seizure onset in TLE. [Copyright &y& Elsevier]

Summary: Analysis of ictal semiology is essential to presurgical evaluation of epilepsy patients providing information on seizure origin. To assess the significance of hypersalivation and postictal coughing for seizure origin in temporal lobe epilepsy (TLE), we analyzed video/EEG monitoring documented seizures of 107 adult patients for these seizure elements with respect to frequency and sequence of occurrence in relation to epileptogenic origin, comparing mesial versus extra-mesial and left versus right. Hypersalivation was rare, but occurred exclusively in seizures of mesial origin (9.4%). Comparison between left (11.4%) and right (6.9%) mesial origin was statistically insignificant. Postictal coughing also occurred exclusively in seizures of mesial onset (6.3%). Again, comparison between left (5.7%) and right (6.9%) mesial seizure onset was statistically insignificant. Thus, hypersalivation and postictal coughing are rare seizure phenomena in TLE, but their occurrence strongly support mesial seizure origin. [Copyright &y& Elsevier]

The dentate gyrus (DG) plays a pivotal role in the functional and anatomical organization of the hippocampus and is involved in learning and memory formation. However, the impact of structural DG abnormalities, i.e., granule cell dispersion (GCD), for hippocampal seizure susceptibility and its association with distinct lesion patterns in epileptic disorders, such as mesial temporal sclerosis (MTS) remains enigmatic and a large spectrum of pathological changes has been recognized. Here, we propose a clinico-pathological classification of DG pathology based on the examination of 96 surgically resected hippocampal specimens obtained from patients with chronic temporal lobe epilepsy (TLE). We observed three different histological patterns. (1) A normal granule cell layer was identified in 11 patients (no-GCP; 18.7%). (2) Substantial granule cell loss was evident in 36 patients (referred to as granule cell pathology (GCP) Type 1; 37.5%). (3) Architectural abnormalities were observed in 49 specimens, including one or more of the following features: granule cell dispersion, ectopic neurons or clusters of neurons in the molecular layer, or bi-lamination (GCP Type 2; 51%). Cell loss was always encountered in this latter cohort. Seventy-eight patients of our present series suffered from MTS (81.3%). Intriguingly, all MTS patients displayed a compromised DG, 31 (40%) with significant cell loss (Type 1) and 47 (60%) with GCD (Type 2). In 18 patients without MTS (18.7%), seven displayed focally restricted DG abnormalities, either cell loss ( n = 5) or GCD ( n = 2). Clinical histories revealed a significant association between DG pathology patterns and higher age at epilepsy surgery ( p = 0.008), longer epilepsy duration ( p = 0.004), but also with learning dysfunction ( p < 0.05). There was no correlation with the extent of pyramidal cell loss in adjacent hippocampal segments nor with postsurgical seizure relief. The association with long-term seizure histories and cognitive dysfunction is remarkable and may point to a compromised regenerative capacity of the DG in this cohort of TLE patients. [ABSTRACT FROM AUTHOR]

In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy (1H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction. To address this problem, we applied high-resolution 1H-MRS at 14.1 Tesla to measure metabolite concentrations in ex vivo tissue slices from three hippocampal subfields (CA1, CA3, dentate gyrus) as well as from the parahippocampal region of 12 patients with MTLE. In contrast to four patients with lesion-caused MTLE, we found a large variance of NAA concentrations in the individual hippocampal regions of patients with Ammon's horn sclerosis (AHS). Specifically, in subfield CA3 of AHS patients despite of a moderate preservation of neuronal cell densities the concentration of NAA was significantly lowered, while the concentrations of lactate, glucose, and succinate were elevated. We suggest that these subfield-specific alterations of metabolite concentrations in AHS are very likely caused by impairment of mitochondrial function and not related to neuronal cell loss. A subfield-specific impairment of energy metabolism is the probable cause for lowered NAA concentrations in sclerotic hippocampi of MTLE patients. [ABSTRACT FROM AUTHOR]

In temporal lobe epilepsy, long-term memory disturbance starts early in life mainly affecting declarative memory. Primary impairment of episodic memory often results in reduced semantic and autobiographic memory. Neuropsychological performance predicts academic achievement and everyday life functioning while subjective memory complaints are highly correlated with depression. Memory impairment is also influenced by initial brain damage, developmental retardation and dynamic factors (e.g., seizure frequency, medication). Damage of functional tissue, low mental reserve capacity, and poor seizure outcome increase the risk for postsurgical memory impairment whereas functional release due to seizure freedom counteracts negative impact. Preliminary findings indicate that postsurgical training improves memory deficits and encourage further research. [ABSTRACT FROM AUTHOR]

Abstract: Limbic encephalitis (LE) was described in the 1960s as a clinical–pathological syndrome in adults. Initially, the paraneoplastic form was the center of interest. An increasing number of diagnostically valuable autoantibodies in patients’ sera (and cerebrospinal fluid) have been identified. Lately, the impact of non-paraneoplastic LE cases has been acknowledged. In the serum of some of these patients, antibodies against voltage-dependent potassium channels (VGKC antibodies) have been detected. The characteristic MRI course of LE patients has recently been described in detail: hippocampal swelling and T2/FLAIR signal increase are early findings. After a few months, the swelling regresses, followed by hippocampal atrophy with continuous signal increase. A general consensus on formal diagnostic criteria for all LE subsyndromes has not yet been reached. This article proposes such diagnostic criteria and formulates suggestions for treatment. [Copyright &y& Elsevier]

Purpose: Surgical treatment of refractory temporal lobe epilepsy (TLE) is promising for selected patients, but only little experience has been acquired in operating on older patients, especially with limited resections. We intend to delineate clinical and surgical factors influencing outcome in patients older than 50 years at operation and to compare the results with those of a younger patient cohort. Methods: Fifty-two patients older than 50 years were operated on for intractable mesial or combined mesiolateral TLE between 1991 and 2002. The mean age at operation was 55 years, and the mean duration of epilepsy was 33 years. Forty selective amygdalohippocampectomies (33 for hippocampal sclerosis, seven for removal of a mesiotemporal lesion), five lateral temporal lesionectomies plus amygdalohippocampectomy, and seven anterior temporal lobectomies were performed. Eleven (21%) patients had undergone invasive presurgical video-EEG monitoring. The mean follow-up period was 33 months. We compared the results with those of a younger cohort operated on in the same time period. Results: Thirty-seven older patients attained complete seizure control (71% class I), and 10 patients had only rare postoperative seizures (19% class II). Four patients improved >75% (8% class III), and one patient did not improve (2% class IV). The same rate of seizure control was attained by 11 patients older than 60 years at surgery. These results were not significantly different from those in a younger patient group. A trend toward better seizure control was noted in 16 patients with an epilepsy duration of <30 years (all class I or II), and in 20 patients with a seizure frequency of fewer than five seizures per month (all class I or II). No mortality resulted from a total of 65 diagnostic and therapeutic procedures. A 3.8% permanent neurologic morbidity (dysphasia and hemiparesis) was noted. Hemianopia occurred in three (5.9%) patients. Neuropsychological testing revealed low preoperative performances and some gradual further deterioration after surgery. Conclusions: Results of surgery for TLE with mainly limited resections are promising in patients older than 50 years and older 60 years, despite the long seizure history. As expected, the risk of complications is somewhat higher compared with that in a younger control group. The impact of low neuropsychological performance is a concern. [ABSTRACT FROM AUTHOR]

Purpose: After pilocarpine-induced epilepsy in rats, volumetric magnetic resonance imaging (MRI) reveals significant morphologic changes in functionally relevant structures of the brain. To relate structural changes to functional alteration, we studied the correlation of regional brain atrophy (e.g., of the hippocampus) with lesion-induced learning deficits in the Morris water maze. Methods: MRI experiments were performed on an MR scanner at 4.7 Tesla. For volumetric analysis, various cerebral structures were segmented in horizontal and coronal T2-weighted MR images. Before the MRI investigations, animals were trained for 10 days in a Morris water maze. Results: Volumetric MRI revealed a significant loss in hippocampal size in both the dorsal and ventral parts, correlated with an increase in ventricular size. Furthermore, significant losses were found in the relative size of thalamus, putamen, cortex, and the combined areas of perirhinal, entorhinal, and piriform cortices adjacent to the hippocampus. A significant correlation of learning performance in the Morris water maze with the relative hippocampal area and not with other areas tested was observed in pilocarpine-treated animals. Conclusions: The data provide a quantitative analysis of functionally relevant structural alterations in rats with chronic epilepsy. Water maze performance of pilocarpine-treated animals correlates with the degree of hippocampal but not with the degree of cortical damage, demonstrating the potential of this method for the investigation of cognitive impairments in relation to cerebral changes. In addition, the data point to an important role of even the residual hippocampus in memory formation. [ABSTRACT FROM AUTHOR]

Purpose: Selective amygdalohippocampectomy (SAH) is a surgical treatment option for patients with medically intractable mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy, resection of unaffected tissue is limited, although it achieves equal seizure outcomes in selected patients. In SAH, the mesial structures can be approached by different routes, the transsylvian approach and the transcortical approach. Advantages or disadvantages with respect to postoperative cognitive outcome are still a matter of debate. Methods: Eighty randomized patients were included in the analyses. In 41 patients, the transsylvian approach, and in 39 patients, the transcortical approach was performed. All patients received comprehensive neuropsychological testing of verbal and nonverbal memory, attention, and executive functions before and 6 months or 1 year after SAH. Results: Seventy-five percent of patients became completely seizure free with no difference depending on the chosen approach. Repeated measures multivariate analysis of variance (MANOVA) showed that cognitive outcomes after both approaches were essentially the same. The only exception was phonemic fluency, which was significantly improved after transcortical but not after transsylvian SAH. Conclusions: The results indicate that either surgical approach can be chosen independent of cognitive outcome criteria. Improvement in phonemic fluency after transcortical SAH may reflect selective normalization of cognitive function after epilepsy surgery, whereas frontal lobe manipulation might have hindered recovery of this function after transsylvian SAH. [ABSTRACT FROM AUTHOR]

The epileptic seizures observed in a broad variety of diseases involving mitochondrial DNA (mtDNA) and central nervous system pathology strongly suggest the possible role of mitochondria in the pathomechanism of various forms of epilepsy. The mtDNA mutations in these diseases affect the functions of complexes of oxidative phosphorylation that have mitochondria-encoded subunits. Similar deficiencies of oxidative phosphorylation, in particular of Complexes I and IV, have been detected in the epileptogenic brain regions of therapy-resistant focal epilepsies, such as the hippocampal subfield CA3 in temporal lobe epilepsy with Ammon's horn sclerosis. This suggests that impaired mitochondrial function can affect the viability and excitability of hippocampal neurons because of (1) decreased production of adenosine 5′-triphosphate; (2) increased generation of reactive oxygen species; and (3) alteration of calcium homeostasis. [ABSTRACT FROM AUTHOR]

Epileptic activity evokes profound alterations of hippocampal organization and function. Genomic responses may reflect immediate consequences of excitatory stimulation as well as sustained molecular processes related to neuronal plasticity and structural remodeling. Using oligonucleotide microarrays with 8799 sequences, we determined subregional gene expression profiles in rats subjected to pilocarpine-induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA; P < 0.05, twofold change, n = 3 per stage). Patterns of gene expression corresponded to distinct stages of epilepsy development. The highest number of differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx. 700 genes) was observed 3 days after status epilepticus. The majority of up-regulated genes was associated with mechanisms of cellular stress and injury – 14 days after status epilepticus, numerous transcription factors and genes linked to cytoskeletal and synaptic reorganization were differentially expressed and, in the stage of chronic spontaneous seizures, distinct changes were observed in the transcription of genes involved in various neurotransmission pathways and between animals with low vs. high seizure frequency. A number of genes ( n = 18) differentially expressed during the chronic epileptic stage showed corresponding expression patterns in hippocampal subfields of patients with pharmacoresistant temporal lobe epilepsy ( n = 5 temporal lobe epilepsy patients; U133A microarrays, Affymetrix; covering 22 284 human sequences). These data provide novel insights into the molecular mechanisms of epileptogenesis and seizure-associated cellular and structural remodeling of the hippocampus. [ABSTRACT FROM AUTHOR]

For neuroprotective therapy of neurodegenerative diseases creatine treatment has gained special interest because creatine has been shown to cross the blood–brain barrier, accumulate in the human brain in vivo and cause delayed neuronal cell death in a large number of animal models. Here, we used the pilocarpine model of temporal lobe epilepsy to determine whether creatine administration is able to attenuate the epilepsy-associated decrease in hippocampal N -acetyl aspartate (NAA) concentrations, impairment of mitochondrial function and neuronal cell loss. In vivo1 H-NMR spectroscopy showed, in epileptic rats after creatine administration, higher hippocampal NAA concentrations, suggesting improved neuronal survival. However, in vitro observation of hippocampal slices from creatine-treated epileptic rats revealed a more pronounced loss of pyramidal neurons and decrease in activity of mitochondrial enzymes in hippocampal subfields. This indicates that NAA concentrations measured by in vivo1 H-NMR spectroscopy reflect alterations of metabolism rather than neuronal cell densities. Our data indicate an adverse effect of creatine on neuronal survival under conditions of enhanced neuronal activity. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Interictal [18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60–90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. Methods: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-μm-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. Results: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. Conclusions: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism. [ABSTRACT FROM AUTHOR]

Summary: Purpose: The technique of selective amygdalohippocampectomy (SAH) was originally developed in epilepsy surgery to spare unaffected brain tissue from surgery, thus minimizing the cognitive consequences of temporal lobe surgery. The results of previous studies, however, are equivocal in this regard. This study evaluated memory after SAH in a large sample of patients with mesial temporal lobe epilepsy. Methods: The 140 patients received material-specific memory tests before and 3 months after unilateral SAH. Results: Significant declines in all aspects of verbal learning and memory were found particularly for the left resected group. With reliability-of-change indices, a high number of patients showed postoperative verbal memory declines, ≤51% in left SAH and ≤32% in right SAH. For left SAH, a higher preoperative verbal memory performance, a lower preoperative nonverbal memory score, an older age at surgery, and a later onset of epilepsy predicted a stronger decline in verbal memory. After right SAH, the risk for a verbal memory decline was slightly increased when patients had surgical complications or a presurgical evaluation with bilateral intrahippocampal depth electrodes. Results concerning nonverbal memory were less clear. Conclusions: The results clearly indicate, that particularly left SAH can lead to a significant decline in memory functions. Predictors of postoperative verbal memory were similar to those reported for temporal lobectomy. Postoperative deteriorations were broader and stronger in our study than in previous studies. We discuss methodologic differences (sample size, retest interval, extent of resection) and other factors as possible reasons. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). Methods: Comparison of seizure outcome and AED us in operated-on TLE patients (n = 148) and nonsurgically treated TLE patients (n = 94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. Results: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure-free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. Conclusions: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup. [ABSTRACT FROM AUTHOR]

Abstract Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon’s horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE. During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE. [ABSTRACT FROM AUTHOR]

Brain electrical activity of 16 patients with temporal lobe epilepsy, recorded intracranially during seizure-free intervals as well as during transitions to the seizure state, was analysed using methods derived from the theory of non-linear dynamics. Long-lasting and marked changes towards low-dimensional system states were found to occur specifically up to 25 min prior to epileptic seizures and allow to predict the occurrence of individual seizures in time. These findings reflect a continuous increase in the degree of synchronicity, and thus open a window for the study of mechanisms generating seizures in humans. This offers new possibilities for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: In a previous study we reported clinically significant memory declines 3 months after selective amygdalohippocampectomy (SAH) in 140 patients with mesial temporal lobe epilepsy, particularly if the resection was left-sided. We supposed that the observed postoperative impairments might have reflected acute effects of surgery. Therefore we evaluated in the present study whether a recovery can be found 1 year after surgery. Methods: Verbal and nonverbal memory functions were assessed in 115 patients before and 3 and 12 months after unilateral SAH. Results: No recovery of postoperative verbal memory declines was found in the left-SAH group. Clinically meaningful losses were still evident in 33 to 50% of patients. In right-SAH patients, a recovery of verbal memory was indicated, and effects of surgical complications were no longer evident. One year after surgery, the corresponding preoperative performance was the only significant predictor of a postoperative change in the left-SAH group. Conclusions: Verbal memory decline observed 3 months after left SAH is persistent 1 year after surgery. Declines in verbal memory, which were observed in some right-SAH patients at the short-term follow-up, seem to be temporary. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Bilateral Stereotactic Radiofrequency Amygdalahippocampectomy for a Patient With Bilateral Temporal Lobe Epilepsy" by H. Luo, and colleagues in the 2013 issue.

Abstract: Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon''s horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca2+ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy. [Copyright &y& Elsevier]

Abstract: The medial temporal lobes (MTLs) are essential for both encoding and retrieval processes in declarative memory. In addition, they are a frequent seizure focus for medically refractory epilepsy. One of the major side effects of MTL resection is a decline in memory functions. Most functional imaging paradigms have been developed to find preoperative measures that, to obtain a prognosis of postoperative memory performance, employ explicit memory encoding strategies to elicit MTL activation, and require a great amount of cognitive effort. We applied three different implicit encoding tasks, which require less effort and time, to a group of healthy subjects. We found left-lateralized activation for verbal stimuli, bilateral activation for pictures, and right-lateralized activation for faces. The present study shows that even with an implicit memory-encoding paradigm, a lateralized activation of MTL structures can be achieved. This may lead to paradigms for routine clinical application that require less cognitive effort and time on the part of patients. [Copyright &y& Elsevier]

Summary: Temporal lobe epilepsy is characterized by a progressive loss of memory capacities, due to sclerosis and functional impairment of mesiotemporal brain areas. We have shown recently that topiramate (TPM) dose-dependently protects hippocampal CA1 and CA3 neurons during initial status epilepticus in the rat pilocarpine model of temporal lobe epilepsy by inhibition of mitochondrial transition pore opening. In the present study, in order to evaluate possible positive effects of the treatment on learning and memory, we investigated water maze performance of rats receiving different dosages of TPM (20 and 100mg/kg) after 40min and 4mg/kg diazepam after 160min of pilocarpine-induced status epilepticus in relation to performance of animals receiving 4mg/kg diazepam after 40min of SE, and to performance of sham-treated control animals. Unexpectedly, 20 but not 100mg/kg TPM significantly extenuated short-term memory deficits. While neuroprotective effects of TPM were observed in hippocampal CA subfields of animals treated with 100mg/kg TPM, cell loss in rats treated with 20mg/kg TPM was indistinguishable from animals receiving diazepam only. The present results indicate a negative dose-dependency of memory-saving effects of TPM applied during status epilepticus apparently dissociated from hippocampal neuroprotection. [Copyright &y& Elsevier]

Right temporal lobe structures are involved in face and facial expression processing and in mnestic functions. Face and facial expression memory was investigated in 15 patients with left (LTLE) and 18 patients with right (RTLE) temporal lobe epilepsy as well as 13 healthy controls. Pairs of pictures combining four faces and four emotions had to be matched according to face identity or facial expression. In the memory tasks, the two pictures of a pair were divided by a memory interval of 2000 milliseconds, whereas in the perception tasks (control condition) both pictures were presented simultaneously. RTLE patients had significantly lower scores than healthy controls in face memory. LTLE patients had significantly lower scores than healthy controls in face and facial expression memory. The data confirm impaired face memory in RTLE patients and show that LTLE patients display deficits in face as well as in facial expression memory. Results are discussed according to functional reorganization, memory strategies, perception performance, naming problems, and group characteristics. [Copyright &y& Elsevier]

Abstract Objective Paraneoplastic limbic encephalitis (LE) occurs frequently with considerable variability according to literature reports. We thus determined the cancer frequency in mixed LE subtypes sharing the diagnosis of temporal lobe epilepsy (TLE). Methods All patients underwent magnetic resonance imaging (MRI) of the brain, electroencephalography (EEG) recordings, neuropsychological testing, immunohistochemistry, and clinical examination together with whole body 2-fluor-2-desoxy- d -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) to detect cancer in this observatory study. Results Ninety-three patients (median: 52 years) with TLE due to autoimmune LE were investigated. Cancer was detected in the FDG-PET/CTs of 3 out of 93 (3.2%) patients with LE. Cancer was diagnosed upon, 5 years earlier and 5 years after FDG-PET/CT in 7 of 93 (7.5%) of all patients with LE. The cancer frequency in those patients was significantly lower than that reported in the largest series of patients with LE associated with and without different antibodies (7.5% vs. 23.5%, Bootstrap test, p < 0.05), but was indistinguishable from the estimated age-dependent cancer frequency in the German regional North-Rhine-Westfalian population without LE in 2014 (Chi-square test: p = 0.2). Conclusions Our findings reveal that the cancer frequency in patients with TLE with LE detected by FDG-PET/CT is low and not different from the age-dependent natural cancer occurrence in a regional population. Highlights • Cancer frequency in limbic encephalitis detected via FDG-PET/CT is low. • Low cancer frequency evidenced when compared to a large limbic encephalitis cohort. • Cancer in pooled limbic encephalitis subtypes occurs as in a regional population. [ABSTRACT FROM AUTHOR]