Pathological Targets for Treating Temporal Lobe Epilepsy: Discoveries From Microscale to Macroscale

Temporal lobe epilepsy (TLE) is one of the most common and severe types of epilepsy, characterized by intractable, recurrent, and pharmacoresistant seizures. Histopathology of TLE is mostly investigated through observing hippocampal sclerosis (HS) in adults, which provides a robust means to analyze the related histopathological lesions. However, most pathological processes underlying the formation of these lesions remain elusive, as they are difficult to detect and observe. In recent years, significant efforts have been put in elucidating the pathophysiological pathways contributing to TLE epileptogenesis. In this review, we aimed to address the new and unrecognized neuropathological discoveries within the last 5 years, focusing on gene expression (miRNA and DNA methylation), neuronal peptides (neuropeptide Y), cellular metabolism (mitochondria and ion transport), cellular structure (microtubule and extracellular matrix), and tissue-level abnormalities (enlarged amygdala). Herein, we describe a range of biochemical mechanisms and their implication for epileptogenesis. Furthermore, we discuss their potential role as a target for TLE prevention and treatment. This review article summarizes the latest neuropathological discoveries at the molecular, cellular, and tissue levels involving both animal and patient studies, aiming to explore epileptogenesis and highlight new potential targets in the diagnosis and treatment of TLE.

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Faculty Opinions recommendation of Optimized SEEG-guided radiofrequency thermocoagulation for mesial temporal lobe epilepsy with hippocampal sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736604573.793566615 ◽

2019 ◽

Author(s):

John Paul Leach

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Radiofrequency Thermocoagulation ◽

Mesial Temporal Lobe

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Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22083860 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3860

Author(s):

Elisa Ren ◽

Giulia Curia

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Knowledge ◽

Focal Epilepsy ◽

Ex Vivo ◽

Hippocampal Sclerosis ◽

Control Group ◽

Epileptogenic Zone ◽

Epileptiform Discharges

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.

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Stereotactic EEG-guided radiofrequency thermocoagulation versus anterior temporal lobectomy for mesial temporal lobe epilepsy with hippocampal sclerosis: study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05378-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yi-He Wang ◽

Si-Chang Chen ◽

Peng-Hu Wei ◽

Kun Yang ◽

Xiao-Tong Fan ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Controlled Trial ◽

Mesial Temporal Lobe Epilepsy ◽

Temporal Lobectomy ◽

Anterior Temporal Lobectomy ◽

Radiofrequency Thermocoagulation ◽

Mesial Temporal Lobe ◽

Randomised Controlled

Abstract Introduction In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE. Methods and analysis STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes. Discussion SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE. Trial registration ClinicalTrials.gov NCT03941613. Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

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A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2021.111281 ◽

2021 ◽

pp. 111281

Author(s):

Nathália Stela Visoná de Figueiredo ◽

Larissa Botelho Gaça ◽

Idaiane Batista Assunção-Leme ◽

Lenon Mazetto ◽

Maria Teresa Fernandes Castilho Garcia ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Comorbid Depression ◽

Volumetric Study ◽

Mesial Temporal Lobe

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Mapping of the progressive metabolic changes occurring during the development of hippocampal sclerosis in a model of mesial temporal lobe epilepsy

Brain Research ◽

10.1016/s0006-8993(99)02092-2 ◽

2000 ◽

Vol 852 (2) ◽

pp. 255-262 ◽

Cited By ~ 24

Author(s):

Viviane Bouilleret ◽

Sylvette Boyet ◽

Christian Marescaux ◽

Astrid Nehlig

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Metabolic Changes ◽

Mesial Temporal Lobe

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Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery

Seizure ◽

10.1016/j.seizure.2017.04.006 ◽

2017 ◽

Vol 48 ◽

pp. 74-78 ◽

Cited By ~ 4

Author(s):

Sara Casciato ◽

Angelo Picardi ◽

Alfredo D’Aniello ◽

Marco De Risi ◽

Giovanni Grillea ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Seizure Outcome ◽

Temporal Pole

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Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy

Journal of Neurosurgery ◽

10.3171/2008.11.jns08779 ◽

2009 ◽

Vol 111 (6) ◽

pp. 1237-1247 ◽

Cited By ~ 17

Author(s):

László Seress ◽

Hajnalka Ábrahám ◽

Zsolt Horváth ◽

Tamás Dóczi ◽

József Janszky ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Pyramidal Neurons ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Drug Resistant ◽

Hippocampal Dentate Gyrus ◽

Mossy Cells ◽

Mesial Temporal Lobe

Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

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