Human and Rodent Temporal Lobe Epilepsy is Characterized by Changes in O-GLCNAC Homeostasis that can be Reversed to Dampen Epileptiform Activity

AbstractTemporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that integrate energy supply with demand. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to determine whether changes in OGT/OGA cycling and disruptions in protein O-GlcNAcylation occur in the epileptic hippocampus. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.

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Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery

Journal of Neurosurgery ◽

10.3171/jns.2000.93.1.0044 ◽

2000 ◽

Vol 93 (1) ◽

pp. 44-52 ◽

Cited By ~ 108

Author(s):

Guy M. McKhann ◽

Julie Schoenfeld-McNeill ◽

Donald E. Born ◽

Michael M. Haglund ◽

George A. Ojemann

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Seizure Control ◽

Epileptiform Activity ◽

Neuronal Loss ◽

Mesial Temporal Lobe Epilepsy ◽

Mesial Temporal Sclerosis ◽

Content Type ◽

Pathological Subtype ◽

Fine Print

Object. Among the variety of surgical procedures that are performed for the treatment of medically refractory mesial temporal lobe epilepsy (TLE), no consensus exists as to how much of the hippocampus should be removed. Whether all patients require a maximal hippocampal resection has not yet been determined.Methods. At the University of Washington, all TLE operations are performed in a tailored fashion, guided by electrocorticography (ECoG). The amount of hippocampal resection is determined intraoperatively by the extent of interictal epileptiform abnormalities on ECoG recorded from that structure, resulting in a hippocampal resection that is individualized for each patient. Using this approach, the authors prospectively observed 140 consecutive patients who underwent surgery for mesial TLE with pathological diagnoses of either mesial temporal sclerosis with neuronal loss (MTS group) or mild gliosis without neuronal loss (non-MTS group) to determine whether the extent of hippocampal resection correlates with outcome when a tailored approach is used. Additionally, the authors analyzed whether the presence of residual interictal epileptiform activity on ECoG following mesial temporal resection predicts poorer seizure control.With at least 18 months of clinical follow up, 67% of the 140 patients were seizure free or had only a single postoperative seizure. There was no correlation between the size of the hippocampal resection and seizure control in the group as a whole or when stratified by pathological subtype. Using an intraoperatively tailored strategy, individuals with a larger hippocampal resection (> 2.5 cm) were not more likely to have seizure-free outcomes than patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS patients, in whom postoperative ECoG detected residual epileptiform hippocampal (but not cortical or parahippocampal) interictal activity following surgical resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p = 0.002 in the non-MTS group).Conclusions. Intraoperative hippocampal ECoG can predict how much hippocampus should be removed to maximize seizure-free outcome, allowing for sparing of possibly functionally important hippocampus.

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Interictal epileptiform activity in temporal lobe epilepsy studied by cortical current density reconstruction

NeuroImage ◽

10.1016/s1053-8119(01)91496-x ◽

2001 ◽

Vol 13 (6) ◽

pp. 153

Author(s):

Sven Hoegg ◽

Hans-Jürgen Huppertz ◽

Christian Sick ◽

Josef Zentner ◽

Andreas Schulze-Bonhage ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Density ◽

Epileptiform Activity

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Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽

10.3390/antiox10111702 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1702

Author(s):

Sereen Sandouka ◽

Tawfeeq Shekh-Ahmad

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Antioxidant Capacity ◽

Temporal Lobe ◽

Epileptiform Activity ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

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P458: HMGA2 gene allele variants are associated with EEG interictal epileptiform activity in temporal lobe epilepsy

Clinical Neurophysiology ◽

10.1016/s1388-2457(14)50558-5 ◽

2014 ◽

Vol 125 ◽

pp. S170-S171

Author(s):

J.A. Bragatti ◽

I.C. Bandeira ◽

A.M. Carvalho ◽

P.A. Cherubini ◽

C.M. Torres ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Epileptiform Activity

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Efficacy of limited hippocampal radiofrequency thermocoagulation for mesial temporal lobe epilepsy

Journal of Neurosurgery ◽

10.3171/2018.4.jns184 ◽

2019 ◽

Vol 131 (3) ◽

pp. 781-789 ◽

Cited By ~ 1

Author(s):

Ching-Yi Lee ◽

Han-Tao Li ◽

Tony Wu ◽

Mei-Yun Cheng ◽

Siew-Na Lim ◽

...

Keyword(s):

Adverse Effects ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Seizure Frequency ◽

Seizure Control ◽

Mesial Temporal Lobe Epilepsy ◽

Temporary Increase ◽

Drug Resistant ◽

Radiofrequency Thermocoagulation ◽

Mesial Temporal Lobe

OBJECTIVERadiofrequency thermocoagulation (RFTC), which has been developed for drug-resistant epilepsy patients, involves less brain tissue loss due to surgery, fewer surgical adverse effects, and generally good seizure control. This study demonstrates the effectiveness of RFTC performed at limited hippocampal locations.METHODSDaily seizure diaries were prospectively maintained for at least 6 months by 9 patients (ages 30–59 years) with drug-resistant mesial temporal lobe epilepsy (MTLE) before treatment with RFTC. The limited target for stereotactic RFTC was chosen based on intraoperative electroencephalography (EEG) recording and was initially tested with a Radionics electrode at a low temperature, 45°C, for 60 seconds. The therapeutic RFTC heating parameters were 78°C–80°C for 90 seconds. All patients who received the RFTC treatment underwent both MRI and EEG recording immediately postoperatively and at the 3-month follow-up. Monthly outpatient clinic visits were arranged over 6 months to document seizure frequency and severity to clarify the changes noted in imaging studies and EEG patterns.RESULTSTwo patients were excluded from our analysis because one had undergone multiple seizure surgeries and the other had a poor recording of seizure frequency, before the RFTC surgery. Five and two patients underwent left-sided and right-sided RFTC, respectively. None of the patients had generalized tonic-clonic attacks postoperatively, and no adverse effects or complications occurred. According to MRI data, the effect of coagulation was limited to less than 1.0 cm in diameter and perifocal edema was also in limited range. The seizure frequency within 6 months decreased postoperatively with a mean reduction in seizures of 78% (range 36%–100%). Only two patients had a temporary increase in seizure frequency within 2 weeks of the surgery, and over 50% of all patients showed a decrease in average seizure frequency.CONCLUSIONSThe study results confirm that limited RFTC provides a more effective surgery with similar seizure control but fewer complications than resective surgery for drug-resistant MTLE patients.

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Seizure Control of Current Shunt on Rats with Temporal Lobe Epilepsy and Neocortical Epilepsy

PLoS ONE ◽

10.1371/journal.pone.0086477 ◽

2014 ◽

Vol 9 (1) ◽

pp. e86477 ◽

Cited By ~ 1

Author(s):

Limin Zhang ◽

Shuli Liang ◽

Guojun Zhang ◽

Zhizhong Liu ◽

Hong Lv ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Seizure Control ◽

Neocortical Epilepsy ◽

Current Shunt

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Patterns of seizure control in patients with mesial temporal lobe epilepsy with and without hippocampus sclerosis

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20140199 ◽

2015 ◽

Vol 73 (2) ◽

pp. 79-82 ◽

Cited By ~ 10

Author(s):

Ana Carolina Coan ◽

Brunno M. Campos ◽

Felipe P.G Bergo ◽

Bruno Y. Kubota ◽

Clarissa L. Yasuda ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Seizure Control ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Similar Proportion ◽

Seizure Freedom ◽

Seizure Recurrence ◽

Prolonged Seizure ◽

Mesial Temporal Lobe

Objective Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. “Infrequent seizures” was considered as up to three seizures per year and “frequent seizures” as any period of seizures higher than that. Results Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). Conclusion Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures.

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