Evaluation of GABA System and Cell Damage in Parahippocampus of Patients with Temporal Lobe Epilepsy Showing Antiepileptic Effects after Subacute Electrical Stimulation

Cuéllar-Herrera, Manola; Velasco, Marcos; Velasco, Francisco; Velasco, Ana Luisa; Jiménez, Fiacro; Orozco, Sandra; Briones, Magdalena; Rocha, Luísa

doi:10.1111/j.0013-9580.2004.43503.x

Cited by 46 publications

(30 citation statements)

References 48 publications

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“…The severe neuronal reduction that accompanies mesial temporal sclerosis may represent a less satisfactory tissue for modulation with stimulation. This is supported by a previous report (Cuellar‐Herrera, 2004) that associates response to subacute electrical stimulation with high GABA levels in the stimulated tissue, which was significantly higher in specimens with higher cell counts, these corresponding to patients with minimal or no mesial temporal sclerosis. Another possibility is that sclerotic tissue has high impedance and requires higher density charge to be stimulated, although we required approximately the same intensity to induce electrocortical potentials in cases with and without hippocampal sclerosis.…”

Section: Discussionsupporting

confidence: 88%

“…Patients had antiepileptic drug therapy stopped and initiated neuromodulation trial; in seven of these, seizures stopped on day 6 and interictal spikes showed a significant reduction after day 13 of subacute stimulation. In these preliminary and subsequent studies, some basic mechanisms underlying the beneficial therapeutic effect on seizures due to hippocampal stimulation were also investigated (Gordon et al, 1990; Velasco et al, 2001a, 2001b; Cuellar‐Herrera, 2004; Velasco et al, 2006). Data obtained suggested that the antiepileptic effect of hippocampal stimulation is due to an inhibitory mechanism.…”

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confidence: 99%

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Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double‐Blind, Long‐Term Follow‐Up Study

et al. 2007

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Summary: Purpose: Our aim was to evaluate the safety and efficacy of electrical stimulation of the hippocampus in a long‐term follow‐up study, as well as its impact on memory performance in the treatment of patients with refractory mesial temporal lobe epilepsy. Methods: Nine patients were included. All had refractory partial complex seizures, some with secondary generalizations. All patients had a 3‐month‐baseline‐seizure count, after which they underwent bilateral hippocampal diagnostic electrode implantation to establish focus laterality and location. Three patients had bilateral, and six, unilateral foci. Diagnostic electrodes were explanted and definitive Medtronic electrodes were implanted directed into the hippocampal foci. Position was confirmed with MRI and afterwards, the deep brain stimulation system internalized. Patients signed the informed consent approved by the Hospital's Ethics Committee and began a double‐blind stimulation protocol. Patients attended a medical appointment every 3 months for seizure diary collection, deep brain stimulation system checkup, and neuropsychological testing. Results: Follow‐up ranged from 18 months to 7 years. Patients were divided in two groups: five had normal MRIs and seizure reduction of >95%, while four had hippocampal sclerosis and seizure reduction of 50–70%. No patient had neuropsychological deterioration, nor did any patient show side effects. Three patients were explanted after 2 years due to skin erosion in the trajectory of the system. Conclusions: Electrical stimulation of the hippocampus provides a nonlesional method that improves seizure outcome without memory deterioration in patients with hippocampal epileptic foci.

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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double‐Blind, Long‐Term Follow‐Up Study

et al. 2007

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“…In the PRS group, however, they increased largely compared with the PRC group (Figure 5a and Figure 5b) [41]. Previously published studies suggested that the GABA A receptor might be involved in the effects of Hip-LFS [18][19][20][21]. The GABA A receptors increased significantly following two weeks of Hip-LFS [23], and the gene that encodes them is a target of cAMP response element-binding protein (CREB) modulation [3,28].…”

Section: Discussionmentioning

confidence: 99%

“…Studies suggested that the GABA A receptor might be involved in the effect of hippocampal stimulation [18][19][20][21]. Recent publications have considered that the mechanism of hippocampal stimulation may be related to the extrasynaptic expression level of the GABA A receptor α5 subunit [22].…”

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Hippocampal Low-Frequency Stimulation Decreased cAMP Response Element-Binding Protein and Increased GABAA Receptor Subunit α1 in Amygdala-Kindled Pharmacoresistant Epileptic Rats

Wu¹,

Wang²,

Zhou³

et al. 2017

Neuropsychiatry

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Aim: To observe the changes in cAMP response element-binding protein (CREB) and GABA A receptor subunit α1 in amygdala-kindled pharmacoresistant epileptic rats subjected to hippocampal low-frequency stimulation (Hip-LFS). Methods:A total of sixteen pharmacoresistant epileptic rats were selected from fifty rats with amygdalakindled epilepsy by testing their seizure response to phenytoin (PHT) and phenobarbital (PB). The pharmacoresistant epileptic rats were assigned to a pharmacoresistant control group (PRC group) or a pharmacoresistant stimulation group (PRS group), each of which included 8 rats. The same number of pharmacosensitive epileptic rats was assigned to a pharmacosensitive control group (PSC group, 8 rats). A normal rat control (NRC) group of 8 rats was also used in the study. A stimulation electrode was implanted in the hippocampus of each rat from each of the four groups. Hip-LFS was administered to the PRS group twice per day for 2 weeks. The other three groups only received hippocampal sham stimulation. Following 2 weeks of Hip-LFS, seizure degree and amygdala EEG were recorded. The levels of CREB protein and GABA A receptor subunit α1 in the hippocampal tissues were measured by a Western blot. Results:The CREB level increased remarkably and the GABA A receptor subunit α1 level decreased in the pharmacoresistant epileptic rats compared with the control. Following two weeks of Hip-LFS, stimulation-induced seizures and amygdala EEG were inhibited significantly. The CREB and p-CREB level decreased significantly in the PRS group compared with the PRC group. However, the GABA A α1 subunit level in the PRS group increased dramatically compared with that in the PRC group. Conclusions:Hip-LFS might increase the expression of the GABA A α1 subunit and decrease the level of CREB. The Hip-LFS-induced increase in the level of the GABA A receptor α1 subunit might be associated with the decreases in CREB and p-CREB in the treatment of amygdala-kindled pharmacoresistant epileptic rats.

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“…Another variable is tissue pathology: if electric stimulation works through GABAergic systems, as previously suggested 10,11 , then patients with hippocampal sclerosis should have a poorer response, since they have less of this neuronal population. This may be at least partially true, as it has been observed that patients without MTS have a better response to HS.…”

Section: Patient-dependent Variablesmentioning

confidence: 99%

Temporal Lobe Epilepsy and Hippocampal Stimulation

Mandzia

Andrade

Burneo

et al. 2012

Can. J. Neurol. Sci.

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Hippocampal stimulation in medically intractable mesial temporal lobe epilepsy may be effective in reducing seizure frequency in patients for a period of up to 18 months Clinical Scenario: A 55-year-old man has had temporal lobe epilepsy for 20 years and has failed treatment with multiple antiepileptic medications. He has on average 20 complex partial seizures per month. He does not have mesial temporal sclerosis on magnetic resonance imaging (MRI). He is not considering surgery. Video electroencephalogram (EEG) and electrode depth recording has confirmed a left mesial temporal lobe (MTL) focus.Clinical Question: What is the safety, efficacy, and long term seizure control in patients with MTL epilepsy treated with hippocampal stimulation? Search Strategy: Medline was used to search for articles by combining "epilepsy, Temporal lobe/th [therapy]" with hippocampal stimulation which mapped to "electric stimulation/ or hippocampus". This yielded 51 articles; when English language and humans were used as limits yielded 35 articles. Three articles were relevant. The first article by Boon et al (2007) was an open pilot study and two of the 12 consecutive patients with refractory MTL seizures underwent resective surgery. The other study by Tellez-Zenteno et al (2006) used an individual patient randomized-controlled trial design (N of 1), but only included 4 patients. It was felt that the study by Velasco et al (2007) was the best evidence having the largest published study using a doubleblinded protocol. Clinical Bottom Lines:1. A seizure reduction of 79% (p<0.0005) occurred in all patients with electrical stimulation of the hippocampus. In patients without mesial temporal sclerosis (MTS) compared to those with MTS, seizure reduction appeared earlier (at 1 mo vs. 8 mo) and to a greater extent (95%, p<0.0005 vs. 69%, p<0.05 at 18 months).2. There was a significant rate of complication consisting of skin erosion resulting in infection requiring removal of the stimulation device in three out of nine participants (33%).The evidence: Velasco et al (2007) evaluated the safety, efficacy of hippocampal electrical stimulation and long-term follow-up in nine non-consecutive patients with medically refractory mesial temporal lobe epilepsy. All patients had complex partial seizures with 7/9 also having secondary generalized tonic-clonic seizures. Patients were selected from a larger group of patients who underwent bilateral hippocampal electrode implantation for diagnostic purposes. The study group consisted of nine patients (six male, three female) between the ages of 14-43 years. Average number of seizures per month was 28 (15-70) measured within a three month period. Five had normal MRIs and the remaining four had mesial temporal sclerosis. Three patients had bilateral foci and six had a unilateral focus of MTL seizure activity. Patients were randomized to a double blind stimulation protocol: five of the patients had an initial one month "off" period and the remaining four initiated stimulation immediately after implantation. P...

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Evaluation of GABA System and Cell Damage in Parahippocampus of Patients with Temporal Lobe Epilepsy Showing Antiepileptic Effects after Subacute Electrical Stimulation

Cited by 46 publications

References 48 publications

Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double‐Blind, Long‐Term Follow‐Up Study

Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double‐Blind, Long‐Term Follow‐Up Study

Hippocampal Low-Frequency Stimulation Decreased cAMP Response Element-Binding Protein and Increased GABAA Receptor Subunit α1 in Amygdala-Kindled Pharmacoresistant Epileptic Rats

Temporal Lobe Epilepsy and Hippocampal Stimulation

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