Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

Download Full-text

Multiple hippocampal transections for refractory pediatric mesial temporal lobe epilepsy: seizure and neuropsychological outcomes

Journal of Neurosurgery Pediatrics ◽

10.3171/2020.4.peds19760 ◽

2020 ◽

Vol 26 (4) ◽

pp. 379-388

Author(s):

Ahmad Marashly ◽

Jennifer Koop ◽

Michelle Loman ◽

Irene Kim ◽

Mohit Maheshwari ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Verbal Memory ◽

Focal Epilepsy ◽

Hippocampal Sclerosis ◽

Neuropsychological Functioning ◽

Memory Function ◽

Seizure Outcome ◽

Epileptogenic Zone ◽

Seizure Propagation

OBJECTIVETemporal lobe epilepsy (TLE) is the most common focal epilepsy across adult and pediatric age groups. It is also the most amenable to surgery, with excellent long-term seizure outcome. Most TLE cases have an epileptogenic zone in the mesial temporal structures, namely the hippocampus. Resecting the dominant hippocampus has been shown to be associated with significant verbal memory deficits, especially in patients with intact verbal memory scores presurgically. Multiple hippocampal transection (MHT) is a relatively new surgical technique designed to interrupt the longitudinal hippocampal circuitry involved in seizure propagation yet preserve the circular fibers involved in memory function. This technique has been used to treat mesial TLE in both dominant- and nondominant-hemisphere cases, almost exclusively in adults. It has been applied to normal and sclerotic hippocampi.METHODSIn this study, information on 3 pediatric patients who underwent MHT for mesial TLE at Children’s Wisconsin between 2017 and 2018 is included. Clinical, electroencephalographic, and neuropsychological features and outcomes are described in detail.RESULTSMRI revealed a tumor in the amygdala with a normal hippocampus in 1 patient and hippocampal sclerosis in 2 patients. All patients underwent stereoelectroencephalography confirming the involvement of the hippocampus in seizure onset. MHTs were completed under intraoperative monitoring, with amygdala and temporal tip resection in all patients due to early spread to these regions. All patients had excellent seizure outcomes at 1 year, and 2 of the 3 patients remain seizure free at last follow-up (range 20–36 months), all with stable or improved neuropsychological profiles, including verbal memory.CONCLUSIONSMHT is a relatively new surgical procedure designed to preserve essential memory circuitry while disrupting seizure propagation pathways in the hippocampus. A growing body of literature shows good seizure and neuropsychological results, but mainly in adults. This is the first series of MHTs used exclusively in children at one medical center, showcasing excellent seizure control and preservation of neuropsychological functioning. One of the patients is also the first described to have MHT in the setting of an amygdalar tumor abutting the hippocampus, further expanding the pathological setting in which MHT can be used effectively.

Download Full-text

Parameters of autonomic regulation in patients with focal frontal and temporal epilepsy

I P Pavlov Russian Medical Biological Herald ◽

10.23888/pavlovj202129145-53 ◽

2021 ◽

Vol 29 (1) ◽

pp. 45-53

Author(s):

Julia I. Medvedeva ◽

Roman A. Zorin ◽

Vladimir A. Zhadnov ◽

Michael M. Lapkin

Keyword(s):

Regression Analysis ◽

Temporal Lobe Epilepsy ◽

Evoked Potentials ◽

Temporal Lobe ◽

Focal Epilepsy ◽

Autonomic Regulation ◽

Control Group ◽

Temporal Epilepsy ◽

Logit Regression ◽

Autonomic Support

Aim. This study aimed to investigate the mechanisms of autonomic regulation and autonomic support in focal frontal and temporal lobe epilepsy. Materials and Methods. Thirty-six individuals were examined (19 men and 17 women; mean age 33.71.4 years) in the control group (without history of epileptic seizures) and 68 patients (32 men and 36 women, 34.11.5 years) with focal epilepsy (36 patients with frontal lobe epilepsy, of which 32 had temporal lobe epilepsy). Physiological parameters of heart rate variability and of skin sympathetic evoked potentials were evaluated. Results. Predomination of sympathetic influences in both groups of patients was found. According to the analysis of skin sympathetic evoked potentials, a high activity of the suprasegmental autonomic centers was determined in patients with epilepsy. Based on the results of the correlation analysis, the initial state in patients with temporal lobe epilepsy was characterized by greater intrasystemic tension that reflects the high level of physiological costs. The logit regression analysis model makes it possible to distribute patients with focal epilepsy into groups with different disease courses on the basis of the parameters of the autonomic support of the activity. Conclusion. In patients with focal epilepsy, predomination of sympathetic influences was observed, as well as greater activity of the suprasegmental centers of the autonomic regulation. Intrasystemic ratios of autonomic regulation parameters demonstrate an increase in the intrasystemic tension and a limitation of functional reserves in patients with temporal lobe epilepsy. A complex of parameters of autonomic support allows, based on the logit regression analysis, to distribute patients into groups with different courses of focal epilepsy.

Download Full-text

Temporal Lobe Epilepsy

10.1093/med/9780199937837.003.0038 ◽

2017 ◽

Author(s):

Edward H. Bertram

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Entorhinal Cortex ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Focal Epilepsy ◽

Neural Circuitry ◽

Human Condition ◽

Physiological Changes ◽

Limbic Structures

Temporal lobe epilepsy, as discussed in this chapter, is a focal epilepsy that involves primarily the limbic structures of the medial temporal lobe (amygdala, hippocampus, and entorhinal cortex). In recent years animal models have been developed that mirror the pathology and pathophysiology of this disease. This chapter reviews the human condition, the structural and physiological changes that support the development of seizures. The neural circuitry of seizure initiation will be reviewed with a goal of creating a framework for developing more effective treatments for this disease.

Download Full-text

Periodic epileptiform discharges in mesial temporal lobe epilepsy with hippocampal sclerosis

Seizure ◽

10.1016/j.seizure.2013.05.013 ◽

2013 ◽

Vol 22 (9) ◽

pp. 735-742 ◽

Cited By ~ 2

Author(s):

Daniel San-Juan ◽

Adriana Patricia M. Mayorga ◽

Juan de Dios Del Castillo Calcáneo ◽

Maricarmen Fernández González-Aragón ◽

Mario Alonso-Vanegas ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Epileptiform Discharges ◽

Mesial Temporal Lobe

Download Full-text

Interictal Epileptiform Discharges in Temporal Lobe Epilepsy Due to Hippocampal Sclerosis Versus Medial Temporal Lobe Tumors

Epilepsia ◽

10.1111/j.1528-1157.1999.tb00856.x ◽

1999 ◽

Vol 40 (9) ◽

pp. 1261-1268 ◽

Cited By ~ 46

Author(s):

H. M. Hamer ◽

I. Najm ◽

A. Mohamed ◽

E. Wyllie

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Hippocampal Sclerosis ◽

Epileptiform Discharges ◽

Interictal Epileptiform Discharges

Download Full-text

Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis

Mediators of Inflammation ◽

10.1155/2016/8290562 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 12

Author(s):

Marcelo Ananias Teocchi ◽

Lília D’Souza-Li

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Death Receptor ◽

Death Receptors ◽

Control Group ◽

Extrinsic Pathway ◽

Seizure Models ◽

Pharmacological Studies ◽

Encoding Genes

Seizure models have demonstrated that neuroinflammation and neurodegeneration are preponderant characteristics of epilepsy. Considering the lack of clinical studies, our aim is to investigate the extrinsic pathway of apoptosis in pharmacoresistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients, TLE(HS). By a specific death receptor-mediated apoptosis array plate, 31 upregulated targets were revealed in the sclerotic hippocampus from TLE(HS) patients. Amongst them are the encoding genes for ligands (FASLG,TNF,andTNFSF10) and death receptors (FAS,TNFRSF1A,TNFRSF10A,andTNFRSF10B). In addition, we evaluated the hippocampal relative mRNA expression of the two TNF receptors,TNFRSF1AandTNFRSF1B, in patients, being both upregulated (n=14;P<0.01andP<0.04, resp.) when compared to thepost mortemcontrol group (n=4). Our results have clearly suggested that three different death receptor apoptotic systems may be associated with the maintenance and progression of TLE-associated HS: (1) TNF-TNFRSF1A, (2) FASLG-FAS, and (3) TNFSF10-TNFRSF10A/B. Their effects on epilepsy are still scarcely comprehended. Our study points out to TNF and TNF receptor superfamily pathways as important targets for pharmacological studies regarding the benefits of an anti-inflammatory therapy in these patients.

Download Full-text

Temporal plus epilepsy is a major determinant of temporal lobe surgery failures

Brain ◽

10.1093/brain/awv372 ◽

2015 ◽

Vol 139 (2) ◽

pp. 444-451 ◽

Cited By ~ 86

Author(s):

Carmen Barba ◽

Sylvain Rheims ◽

Lorella Minotti ◽

Marc Guénot ◽

Dominique Hoffmann ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Epilepsy Surgery ◽

Hippocampal Sclerosis ◽

Cox Proportional Hazards Model ◽

Temporal Lobectomy ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Anterior Temporal Lobectomy

Abstract See Engel (doi:10.1093/awv374) for a scientific commentary on this article. Reasons for failed temporal lobe epilepsy surgery remain unclear. Temporal plus epilepsy, characterized by a primary temporal lobe epileptogenic zone extending to neighboured regions, might account for a yet unknown proportion of these failures. In this study all patients from two epilepsy surgery programmes who fulfilled the following criteria were included: (i) operated from an anterior temporal lobectomy or disconnection between January 1990 and December 2001; (ii) magnetic resonance imaging normal or showing signs of hippocampal sclerosis; and (iii) postoperative follow-up ≥ 24 months for seizure-free patients. Patients were classified as suffering from unilateral temporal lobe epilepsy, bitemporal epilepsy or temporal plus epilepsy based on available presurgical data. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom over time. Predictors of seizure recurrence were investigated using Cox proportional hazards model. Of 168 patients included, 108 (63.7%) underwent stereoelectroencephalography, 131 (78%) had hippocampal sclerosis, 149 suffered from unilateral temporal lobe epilepsy (88.7%), one from bitemporal epilepsy (0.6%) and 18 (10.7%) from temporal plus epilepsy. The probability of Engel class I outcome at 10 years of follow-up was 67.3% (95% CI: 63.4–71.2) for the entire cohort, 74.5% (95% CI: 70.6–78.4) for unilateral temporal lobe epilepsy, and 14.8% (95% CI: 5.9–23.7) for temporal plus epilepsy. Multivariate analyses demonstrated four predictors of seizure relapse: temporal plus epilepsy (P < 0.001), postoperative hippocampal remnant (P = 0.001), past history of traumatic or infectious brain insult (P = 0.022), and secondary generalized tonic-clonic seizures (P = 0.023). Risk of temporal lobe surgery failure was 5.06 (95% CI: 2.36–10.382) greater in patients with temporal plus epilepsy than in those with unilateral temporal lobe epilepsy. Temporal plus epilepsy represents a hitherto unrecognized prominent cause of temporal lobe surgery failures. In patients with temporal plus epilepsy, anterior temporal lobectomy appears very unlikely to control seizures and should not be advised. Whether larger resection of temporal plus epileptogenic zones offers greater chance of seizure freedom remains to be investigated.

Download Full-text

18F-FDG-PET patterns of surgical success and failure in mesial temporal lobe epilepsy

Neurology ◽

10.1212/wnl.0000000000003714 ◽

2017 ◽

Vol 88 (11) ◽

pp. 1045-1053 ◽

Cited By ~ 28

Author(s):

Francine Chassoux ◽

Eric Artiges ◽

Franck Semah ◽

Agathe Laurent ◽

Elisabeth Landré ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Fdg Pet ◽

Hippocampal Sclerosis ◽

Statistical Parametric Mapping ◽

Mesial Temporal Lobe Epilepsy ◽

Epileptogenic Zone ◽

Metabolic Pattern ◽

Suboptimal Outcome ◽

Mesial Temporal Lobe

Objective:To search for [18F]-fluorodeoxyglucose (FDG)-PET patterns predictive of long-term prognosis in surgery for drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS).Methods:We analyzed metabolic data with [18F]-FDG-PET in 97 patients with MTLE (53 female participants; age range 15–56 years) with unilateral HS (50 left) and compared the metabolic patterns, electroclinical features, and structural atrophy on MRI in patients with the best outcome after anteromesial temporal resection (Engel class IA, completely seizure-free) to those with a non-IA outcome, including suboptimal outcome and failure. Imaging processing was performed with statistical parametric mapping (SPM5).Results:With a mean follow-up of >6 years (range 2–14 years), 85% of patients achieved a class I outcome, including 45% in class IA. Class IA outcome was associated with a focal anteromesial temporal hypometabolism, whereas non-IA outcome correlated with extratemporal metabolic changes that differed according to the lateralization: ipsilateral mesial frontal and perisylvian hypometabolism in right HS and contralateral fronto-insular hypometabolism and posterior white matter hypermetabolism in left HS. Suboptimal outcome presented a metabolic pattern similar to the best outcome but with a larger involvement of extratemporal areas, including the contralateral side in left HS. Failure was characterized by a mild temporal involvement sparing the hippocampus and relatively high extratemporal hypometabolism on both sides. These findings were concordant with electroclinical features reflecting the organization of the epileptogenic zone but were independent of the structural abnormalities detected on MRI.Conclusions:[18F]-FDG-PET patterns help refine the prognostic factors in MTLE and should be implemented in predictive models for epilepsy surgery.

Download Full-text

Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

Molecular Brain ◽

10.1186/s13041-021-00824-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Hao Wu ◽

Yong Liu ◽

Lishuo Liu ◽

Qiang Meng ◽

Changwang Du ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Clock Gene ◽

High Throughput Sequencing ◽

Clock Genes ◽

Hippocampal Sclerosis ◽

Control Group ◽

Type I ◽

Sequencing Analysis ◽

Clock Proteins

AbstractClock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have documented the abnormal expression of clock genes in epilepsy. However, the molecular mechanism of brain and muscle Arnt-like protein 1 (Bmal1), one of the core clock genes, in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) remain unclear. We first investigated the levels of Bmal1 and other clock proteins in the hippocampus of subjects with epilepsy to define the function of Bmal1. The levels of Bmal1 were decreased during the latent and chronic phases in the experimental group compared with those in the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High-throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. PCDH19 expression was also decreased in the hippocampus of epileptic mice. Furthermore, the higher levels of Bmal1 and PCDH19 were detected in patients with no hippocampal sclerosis (no HS) than in patients with HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in epileptogenesis and seizures via PCDH19 in TLE.

Download Full-text