scholarly journals A PIK3R2 Mutation in Familial Temporal Lobe Epilepsy as a Possible Pathogenic Variant

2021 ◽  
Vol 12 ◽  
Author(s):  
Yishu Wang ◽  
Jing Peng ◽  
Shuwei Bai ◽  
Haojun Yu ◽  
Hong He ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mononuclear Cells ◽  
Focal Epilepsy ◽  
Mesial Temporal Lobe Epilepsy ◽  
Pathogenic Variant ◽  
Regulatory Subunit ◽  
Control Group ◽  
Functional Assay ◽  
Peripheral Blood Mononuclear

Temporal lobe epilepsy (TLE), the most common form of medically refractory focal epilepsy in adults, often requires surgery to alleviate seizures. By using next-generation sequencing, we identified a PIK3R2 mutation (NM_005027.4: c.265C > T; NP_005018.2: p.Arg89Cys) in a family with mesial temporal lobe epilepsy. PIK3R2 encodes p85β, the regulatory subunit of Class IA phosphoinositide 3-kinase (PI3K) and the mutation we identified in PIK3R2 seems to function unexpectedly as a possible pathogenic variant. The mutation is predicted to be potentially pathogenic by multiple bioinformatics tools. Through a functional assay, we verified that the mutation enhances the function of PI3K in induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of the proband. Finally, pathological testing of the resected temporal lobe cortex showed that the expression of PIK3R2 was significantly higher in patients with refractory temporal lobe epilepsy than in those of non-epileptic diseases as a control group. It can be inferred that PIK3R2 might play an important role in the development of TLE.

scholarly journals Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

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.

Accuracy and Efficacy for Robotic Assistance in Implanting Responsive Neurostimulation Device Electrodes in Bilateral Mesial Temporal Lobe Epilepsy

2017 ◽  
Vol 14 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Alvin Y Chan ◽  
Lilit Mnatsakanyan ◽  
Mona Sazgar ◽  
Indranil Sen-Gupta ◽  
Jack J Lin ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Focal Epilepsy ◽  
Mesial Temporal Lobe Epilepsy ◽  
Advanced Technology ◽  
Robotic Assistance ◽  
Mesial Temporal Lobe ◽  
Robotic Devices ◽  
New Treatment

Abstract BACKGROUND Responsive neurostimulation (RNS) is a relatively new treatment option that has been shown to be effective for patients with medically refractory focal epilepsy when resection is not possible, especially in bilateral mesial temporal onset. Robotic devices are becoming increasingly popular for use in stereotactic procedures such as stereoelectroencephalography, but have yet to be used when implanting RNS devices. OBJECTIVE To show that these 2 forms of advanced technology were compatible and could be used effectively in patient care. METHODS We implanted RNS devices in 3 patients with bilateral mesial temporal lobe epilepsy. Each patient was placed in the prone position, and electrode trajectories were planned via the robotic navigation system via a transoccipital approach. One lead was placed along each amygdalohippocampal complex. A small craniectomy was then created in the parietal region for RNS generator implantation. Actual and expected target locations and distance were calculated for each depth. There were no complications in this group. RESULTS RNS devices with bilateral leads were successfully implanted in all 3 patients, with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and there were no complications in this group. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm. CONCLUSION We show that implanting RNS devices with robotic assistance is feasible with excellent precision and accuracy. The advantages of using robotic assistance include higher flexibility, accuracy, precision, and consistency.

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

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.

Lateralising value of experiential hallucinations in temporal lobe epilepsy

2015 ◽  
Vol 86 (11) ◽  
pp. 1273-1276 ◽  
Author(s):  
Lukas Heydrich ◽  
Guillaume Marillier ◽  
Nathan Evans ◽  
Olaf Blanke ◽  
Margitta Seeck
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Single Photon ◽  
Focal Epilepsy ◽  
Photon Emission ◽  
Mesial Temporal Lobe Epilepsy ◽  
Positron Emission ◽  
Mesial Temporal Lobe ◽  
Deja Vu ◽  
Déjà Vu

ObjectivesEver since John Hughlings Jackson first described the so-called ‘dreamy state’ during temporal lobe epilepsy, that is, the sense of an abnormal familiarity (déjà vu) or vivid memory-like hallucinations from the past (experiential hallucinations), these phenomena have been studied and repeatedly linked to mesial temporal lobe structures. However, little is known about the lateralising value of either déjà vu or experiential hallucinations.MethodsWe analysed a sample of 28 patients with intractable focal epilepsy suffering from either déjà vu or experiential hallucinations. All the patients underwent thorough presurgical examination, including MRI, positron emission tomography, single-photon emission CT, EEG and neuropsychological examination.ResultsWhile déjà vu was due to right or left mesial temporal lobe epilepsy, experiential hallucinations were strongly lateralised to the left mesial temporal lobe. Moreover, there was a significant effect for interictal language deficits being more frequent in patients suffering from experiential hallucinations.ConclusionsThese results suggest a lateralising value for experiential hallucinations to the left temporal lobe.

scholarly journals Interleukin-1β secretion in hippocampal sclerosis patients with mesial temporal lobe epilepsy

2013 ◽  
Vol 5 (3) ◽  
pp. 17 ◽  
Author(s):  
Nihal Olgac Dundar ◽  
Berrin Aktekin ◽  
Nilufer Cicek Ekinci ◽  
Duygu Sahinturk ◽  
Ugur Yavuzer ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Promoter Region ◽  
Mononuclear Cells ◽  
Hippocampal Sclerosis ◽  
Intractable Epilepsy ◽  
Mesial Temporal Lobe Epilepsy ◽  
Epilepsy Syndrome ◽  
Significant Difference ◽  
Mesial Temporal Lobe

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common medically intractable epilepsy syndrome. Although pathogenesis of HS still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population revealed that the homozygotes for allele T at position −511 of the interleukin (IL)-1β gene promoter region (IL-1β-511 T/T) confers susceptibility to the development of HS. However, whether this polymorphism has an effect on IL-1β levels in MTLE-HS patients was not demonstrated. This study aimed to analyze the distribution of this particular polymorphism in a group of Turkish HS patients and correlate the polymorphism with IL-1β secretion from the lymphocytes, thus revealing a functional role for IL-1β in the etiopathogenesis of HS. A single base pair polymorphism at position −511 in the promoter region of the IL-1β gene was analyzed. The spontaneous and 1 ng/mL lipopolysaccharide-stimulated production of IL-1β by peripheral blood mononuclear cells after 4 and 24 h of incubation were measured by ELISA method. The heterozygous type (−511 C/T) was the most common genotype. There was no difference in frequency of allele −511 T between patients and controls. Analysis of IL-1β levels, genotype and allele distributions showed no significant difference among the groups (P>0.05). Nevertheless, it was seen that patients who carry a T allele at position -511 of the IL-1β gene had increased IL-1β levels. T-allele carriage may be important. Only IL-1β secretion from the lymphocytes has been assessed in this study. Considering the importance of IL-1β in the etiopathogenesis of HS, further studies are needed to evaluate locally produced IL-1β levels.

scholarly journals Menstrual cycle worsening of epileptic seizures in women with symptomatic focal epilepsy

2005 ◽  
Vol 63 (3b) ◽  
pp. 751-756 ◽  
Author(s):  
Ana Carolina Belini Bazán ◽  
Maria Augusta Montenegro ◽  
Fernando Cendes ◽  
Li Li Min ◽  
Carlos A.M. Guerreiro
Keyword(s):  
Menstrual Cycle ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Epileptic Seizures ◽  
Mesial Temporal Lobe Epilepsy ◽  
Menstrual Cycles ◽  
Medical Appointment ◽  
Mesial Temporal Lobe

INTRODUCTION: Hormonal fluctuation is responsible for worsening of epileptic seizures during the menstrual cycle. OBJETIVE: To identify irregularities in the menstrual cycles of women with mesial temporal lobe epilepsy (MTLE) and extratemporal focal epilepsy (ETFE) and correlate the frequency of seizures during the menstrual cycles. METHOD: We evaluated prospectively women in the menacme with MTLE and ETFE. Calendars were provided for these patients, and they were asked to mark their seizure frequency according to the menses. Calendars were reviewed in each routine medical appointment. RESULTS: Thirty-nine patients with MTLE and 14 with ETFE were evaluated. We registered 211 cycles in the patients with MTLE and 49 in those with ETFE. Irregular menstrual cycles were found in 28 (28/39, 71.7%) patients with MTLE and 6 (6/14, 42.8%) with ETFE (p=0.052). Premenstrual seizure worsening was observed in 46 (21.8%) patients with MTLE and 9 (18.3%) with ETFE (p=0.596). Menstrual worsening was observed in 47 (22.2%) patients with MTLE and 15 (30.6%) with ETFE (p=0. 217). Ovulatory worsening was observed in 36 (17%) patients with MTLE and 13 (26.5%) with ETFE (p=0,126). Catamenial worsening was observed in 58 (27.4%) of the patients with MTLE and in 17 (34.7%) of the patients with ETFE (p=0.315). CONCLUSION: There was no difference between the group of patients with MTLE and ETFE regarding the frequency of irregular cycles and seizure worsening during the premenstrual, menstrual, catamenial or ovulatory periods.

scholarly journals Structural Abnormalities are Similar in Familial and Nonfamilial Mesial Temporal Lobe Epilepsy

2004 ◽  
Vol 31 (3) ◽  
pp. 368-372 ◽  
Author(s):  
Fabio Thadeu Ferreira ◽  
Eliane Kobayashi ◽  
Iscia Lopes-Cendes ◽  
Fernando Cendes
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Visual Analysis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Control Group ◽  
Hippocampal Atrophy ◽  
Anterior Temporal Lobe ◽  
Temporal Lobes ◽  
Mesial Temporal Lobe ◽  
Lobe Atrophy

Background/Objective:Diffuse temporal lobe abnormalities can be observed on MRI of patients with mesial temporal lobe epilepsy (MTLE). Our objective was to perform qualitative and quantitative analyses of temporal lobe structures in patients with familial MTLE (FMTLE) and nonfamilial MTLE.Methods:Two groups of patients were ascertained: 67 FMTLE patients (14 with refractory seizures) and 30 patients with nonfamilial refractory MTLE. We performed qualitative analyses of MRI (with multiplanar reconstruction) and volumes of hippocampi and anterior temporal lobes in all patients, and in a normal control group of 23 individuals. We used the Chi-square test and ANOVA for statistical analyses.Results:We identified anterior temporal lobe abnormalities by visual analysis in only 4% of FMTLE patients and atrophy of the anterior temporal lobe by volumetric analysis in 19%. In the group of nonfamilial MTLE patients we found anterior temporal lobe abnormalities by visual analysis in 17% of patients and anterior temporal lobe atrophy in 13%. Hippocampal atrophy was present in 90% of FMTLE and in 83% of nonfamilial MTLE. No signs of cortical dysplasia were observed.Conclusion:Anterior temporal lobe atrophy and other abnormalities outside the mesial portion of temporal lobes were infrequent in both familial and nonfamilial MTLE patients. Despite the genetic basis, hippocampal atrophy in FMTLE is not associated with other abnormalities outside the mesial temporal regions.

scholarly journals Brain SPECT in mesial temporal lobe epilepsy: comparison between visual analysis and SPM

2010 ◽  
Vol 68 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Bárbara Juarez Amorim ◽  
Celso Darío Ramos ◽  
Allan Oliveira dos Santos ◽  
Mariana da Cunha Lopes de Lima ◽  
Li Li Min ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Visual Analysis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Brain Spect ◽  
Control Group ◽  
Epileptogenic Focus ◽  
Helpful Tool ◽  
Temporal Lobes ◽  
Mesial Temporal Lobe

OBJECTIVE: To compare the accuracy of SPM and visual analysis of brain SPECT in patients with mesial temporal lobe epilepsy (MTLE). METHOD: Interictal and ictal SPECTs of 22 patients with MTLE were performed. Visual analysis were performed in interictal (VISUAL(inter)) and ictal (VISUAL(ictal/inter)) studies. SPM analysis consisted of comparing interictal (SPM(inter)) and ictal SPECTs (SPM(ictal)) of each patient to control group and by comparing perfusion of temporal lobes in ictal and interictal studies among themselves (SPM(ictal/inter)). RESULTS: For detection of the epileptogenic focus, the sensitivities were as follows: VISUAL(inter)=68%; VISUAL(ictal/inter)=100%; SPM(inter)=45%; SPM(ictal)=64% and SPM(ictal/inter)=77%. SPM was able to detect more areas of hyperperfusion and hypoperfusion. CONCLUSION: SPM did not improve the sensitivity to detect epileptogenic focus. However, SPM detected different regions of hypoperfusion and hyperperfusion and is therefore a helpful tool for better understand pathophysiology of seizures in MTLE.

scholarly journals MRI network progression in mesial temporal lobe epilepsy related to healthy brain architecture

2021 ◽  
pp. 1-17
Author(s):  
Victoria L. Morgan ◽  
Graham W. Johnson ◽  
Leon Y. Cai ◽  
Bennett A. Landman ◽  
Kurt G. Schilling ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Focal Epilepsy ◽  
Structural Connectivity ◽  
Mesial Temporal Lobe Epilepsy ◽  
Seizure Focus ◽  
Functional Gradient ◽  
Mesial Temporal Lobe ◽  
Brain Architecture ◽  
The Brain

We measured MRI network progression in mesial temporal lobe epilepsy (mTLE) patients as a function of healthy brain architecture. Resting-state functional MRI and diffusion-weighted MRI were acquired in 40 unilateral mTLE patients and 70 healthy controls. Data were used to construct region-to-region functional connectivity, structural connectivity, and streamline length connectomes per subject. Three models of distance from the presumed seizure focus in the anterior hippocampus in the healthy brain were computed using the average connectome across controls. A fourth model was defined using regions of transmodal (higher cognitive function) to unimodal (perceptual) networks across a published functional gradient in the healthy brain. These models were used to test whether network progression in patients increased when distance from the anterior hippocampus or along a functional gradient in the healthy brain decreases. Results showed that alterations of structural and functional networks in mTLE occur in greater magnitude in regions of the brain closer to the seizure focus based on healthy brain topology, and decrease as distance from the focus increases over duration of disease. Overall, this work provides evidence that changes across the brain in focal epilepsy occur along healthy brain architecture.

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