The Genetics of Temporal Lobe Epilepsy and Implications for Treatment

Temporal Lobe Epilepsy and GEFS+ Phenotypes Associated with SCN1B Mutations. Scheffer IE, Harkin LA, Grinton BE, Dibbens LM, Turner SJ, Zielinski MA, Xu R, Jackson G, Adams J, Connellan M, Petrou S, Wellard RM, Briellmann RS, Wallace RH, Mulley JC, Berkovic SF. Brain 2007;130(Pt 1):100–109. SCN1B, the gene encoding the sodium channel β1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery.

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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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PHARMACORESISTENT TEMPORAL LOBE & EXTRA TEMPORAL EPILEPSY: OUTCOMES AFTER SURGERY.

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i6.1952 ◽

2021 ◽

Vol 5 (6) ◽

Author(s):

Govind Mangal ◽

Uday Bhaumik ◽

Giriraj Prajapati ◽

Poojan Thakor

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Age Of Onset ◽

Hippocampal Sclerosis ◽

Temporal Lobectomy ◽

Temporal Epilepsy ◽

Post Surgery ◽

Study Population ◽

The Mean

Background: Our aim was to follow up patients postoperatively to identify seizure remission and relapse after surgery, to enable individuals considering surgery to make informed choices. Methods: Ninteen consecutive patients operated for drug resistant Temporal lobe & extra temporal lobe epilepsy between 2019 and 2020, at our centre. All the patients had at least one year post surgery follow-up. Results: The mean age of study population was 20.87 ± 10.08 years. The mean age of onset of epilepsy in study population was 14.9 ± 8 years. There were no acute post operative seizures. The most common histpathological finding was hippocampal sclerosis in 15 patients. The patients were followed up and 15 were in the class 1 of engel classification. 2 in class 2, rest had one each Conclusion: Following surgery approx half of patients were seizure free and Engel's favourable outcome was noted. The predictors of unfavourable outcome were younger age of onset and pronged duration and of epilepsy Keywords: Temporal lobe epilepsy, temporal lobectomy, amygdalohippocampectomy, outcome, extra temporal lobe epilepsy, extra temporal lobectomy

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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 randomized controlled trial

10.21203/rs.3.rs-56665/v1 ◽

2021 ◽

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

Abstract Introduction: In this report, we aim to describe the design for the randomized 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 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. Disscussion: SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual filed 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 a higher levels of clinical evidence for the treatment for mTLE. Trial registration: The STARTS protocol has been registered on the US National Institutes of Health (ClinicalTrials.gov): NCT03941613. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

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Effects of febrile seizures in mesial temporal lobe epilepsy with hippocampal sclerosis on gene expression using bioinformatical analysis

Acta Epileptologica ◽

10.1186/s42494-020-00027-9 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Yinchao Li ◽

Chengzhe Wang ◽

Peiling Wang ◽

Xi Li ◽

Liemin Zhou

Keyword(s):

Gene Expression ◽

Temporal Lobe Epilepsy ◽

Ion Channel ◽

Temporal Lobe ◽

Febrile Seizure ◽

Hippocampal Sclerosis ◽

Febrile Seizures ◽

Mesial Temporal Lobe Epilepsy ◽

Channel Activity ◽

Mesial Temporal Lobe

Abstract Background To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and explore the molecular mechanism of MTLE-HS. Methods Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between MTLE-HS with and without febrile seizure history were screened by the GEO2R software. Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software. Protein–protein interaction (PPI) networks among DEGs were constructed using the STRING database and analyzed by Cytoscape. Results A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLE-HS samples without febrile seizure, including 25 down-regulated and 490 up-regulated genes. These DEGs were expressed mostly in plasma membrane and synaptic vesicles. The major molecular functions of those genes were voltage-gated ion channel activity, extracellular ligand-gated ion channel activity and calcium ion binding. The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport. Five genes (SNAP25, SLC32A1, SYN1, GRIN1, and GRIA1) were significantly expressed in the MTLE-HS with prolonged febrile seizures. Conclusion The pathogenesis of MTLE-HS involves multiple genes, and prolonged febrile seizures could cause differential expression of genes. Thus, investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.

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Detection of temporal lobe epilepsy using support vector machines in multi-parametric quantitative MR imaging

Computerized Medical Imaging and Graphics ◽

10.1016/j.compmedimag.2014.07.002 ◽

2015 ◽

Vol 41 ◽

pp. 14-28 ◽

Cited By ~ 25

Author(s):

Diego Cantor-Rivera ◽

Ali R. Khan ◽

Maged Goubran ◽

Seyed M. Mirsattari ◽

Terry M. Peters

Keyword(s):

Support Vector Machines ◽

Mr Imaging ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Support Vector ◽

Quantitative Mr Imaging ◽

Quantitative Mr ◽

Vector Machines

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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.

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Reduced Sensitivity of the N400 and Late Positive Component to Semantic Congruity and Word Repetition in Left Temporal Lobe Epilepsy

Clinical Electroencephalography ◽

10.1177/155005940203300307 ◽

2002 ◽

Vol 33 (3) ◽

pp. 111-118 ◽

Cited By ~ 16

Author(s):

John M. Olichney ◽

Brock R. Riggins ◽

Dieter G. Hillert ◽

Ralph Nowacki ◽

Evelyn Tecoma ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Temporal Lobectomy ◽

Positive Component ◽

Left Temporal Lobe ◽

Late Positive Component ◽

Semantic Categorization ◽

Word Repetition ◽

Category Exemplars

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% “congruous” (category exemplars) and 50% “incongruous” (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from ∼10–140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

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Failure to find association between febrile seizures and SCN1A rs3812718 polymorphism in south Indian patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Epilepsy Research ◽

10.1016/j.eplepsyres.2012.04.009 ◽

2012 ◽

Vol 101 (3) ◽

pp. 288-292 ◽

Cited By ~ 6

Author(s):

Shabeesh Balan ◽

Neetha Nanoth Vellichirammal ◽

Moinak Banerjee ◽

Kurupath Radhakrishnan

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Febrile Seizures ◽

Mesial Temporal Lobe Epilepsy ◽

Indian Patients ◽

South Indian ◽

Mesial Temporal Lobe

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Febrile Status Epilepticus

Journal of Pediatric Epilepsy ◽

10.1055/s-0039-1701034 ◽

2019 ◽

Vol 08 (03) ◽

pp. 079-082

Author(s):

Isaac Molinero ◽

Shlomo Shinnar

Keyword(s):

Risk Factors ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Early Treatment ◽

Febrile Seizure ◽

Hippocampal Sclerosis ◽

Febrile Seizures ◽

Medical Emergency ◽

Febrile Status Epilepticus

AbstractFebrile status epilepticus (FSE) is defined as a febrile seizure lasting 30 minutes or more and is considered the extreme end of the complex febrile seizure spectrum. It remains unclear why some children are predisposed to the development of FSE compared with others. FSE is considered as medical emergency and as such, early treatment is crucial. The consequences of FSE have been a topic of interest for many years, specially its association with temporal lobe epilepsy and hippocampal sclerosis. In this article, we review the epidemiology, risk factors, pathophysiology, treatment, and prognosis including findings from the “Consequences of Prolonged Febrile Seizures in Childhood” (FEBSTAT) study.

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