Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects. Therefore, we compared here these results with those obtained by optogenetic stimulation of medial septum PV-positive neurons at 8 Hz in male PV-ChR2 mice (P60-P100) undergoing an initial, pilocarpine-induced status epilepticus (SE). Optogenetic stimulation (5 min ON, 10 min OFF) was performed from day 8 to day 12 after SE at a frequency of 8 Hz (n = 6 animals) or 0.5 Hz (n = 8 animals). Surprisingly, in both groups, no effects were observed on the occurrence of interictal spikes and interictal high frequency oscillations (HFOs). However, 0.5 Hz stimulation induced a significant decrease of seizure occurrence (p < 0.05). Such anti-ictogenic effect was not observed in the 8 Hz protocol that instead triggered seizures (p < 0.05); these seizures were significantly longer under optogenetic stimulation compared to when optogenetic stimulation was not implemented (p < 0.05). Analysis of ictal HFOs revealed that in the 0.5 Hz group, but not in the 8 Hz group, seizures occurring under optogenetic stimulation were associated with significantly lower rates of fast ripples compared to when optogenetic stimulation was not performed (p < 0.05). Our results indicate that activation of GABAergic PV-positive neurons in the medial septum exerts seizure-suppressing effects that are frequency-dependent and associated with low rates of fast ripples. Optogenetic activation of medial septum PV-positive neurons at 0.5 Hz is efficient in blocking seizures in the pilocarpine model of MTLE, an effect that did not occur with 8 Hz stimulation.

Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model-A preliminary study.

OBJECTIVE: Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures. METHODS: A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures. RESULTS: Hippocampal seizures were observed 40-120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures. SIGNIFICANCE: In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Dynamical modulation of hypersynchronous seizure onset with transcranial magneto-acoustic stimulation in a hippocampal computational model.

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.

Neuromodulatory Focused Ultrasound for Epilepsy: Are Animal Models Useful?

Ultrasound neuromodulation is a potential alternative therapy for suppressing epileptic discharges. Recently, several human clinical trials have reported promising results from repeated focused ultrasound (FUS) treatments for temporal lobe epilepsy. In this Viewpoint, we highlight the valuable guidance of preclinical validation methods for choosing the optimal FUS parameters, thus ensuring consistency with the outcomes of clinical trials and leading human trials to the safest and most effective approaches.

Long-term outcome of treatment-naïve patients with mesial temporal lobe epilepsy with hippocampal sclerosis: A retrospective study in a single center.

PURPOSE: This study aimed to describe long-term treatment outcomes of treatment-naïve patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: A retrospective review was conducted of treatment-naïve patients with MTLE-HS who visited the Yonsei Epilepsy Clinic from April 2000 to April 2022 and were followed up for at least 2 years. Seizure freedom (SF) was defined as no seizures or auras only for >1 year, and complete SF was defined as no seizures including auras for >1 year. RESULTS: Eighty-four treatment-naïve patients with MTLE-HS with a median follow-up of 122 months were included. Except for one patient who underwent early surgical treatment, of the remaining 83 patients, 31 (37.3 %) achieved SF and remained in remission, 38 (45.8 %) had fluctuations in seizure control, and 14 (16.9 %) never achieved SF. Additionally, 18 (21.7 %) patients achieved complete SF and remained in remission, 42 (50.6 %) showed fluctuations, and 23 (27.7 %) never achieved complete SF. Fifty-three (63.9 %) patients achieved SF and 34 (41.0 %) achieved complete SF at their last visit. Older age at epilepsy onset, male sex, low pretreatment seizure density, history of central nervous system infection before age 5, absence of aura, and fewer antiseizure medications in the final regimen were associated with favorable outcome. Of the 84 patients, 11 (13.1 %) underwent temporal lobectomy. CONCLUSIONS: Medical treatment outcomes in treatment-naïve MTLE-HS were relatively better than previously reported outcomes in MTLE-HS, although frequent fluctuations in seizure control were observed.

Adenosine kinase gene modified mesenchymal stem cell transplantation retards seizure severity and associated cognitive impairment in a temporal lobe epilepsy rat model.

PURPOSE: Temporal lobe epilepsy (TLE) has a high risk of developing drug resistant and cognitive comorbidities. Adenosine has potential anticonvulsant effects as an inhibitory neurotransmitter, but drugs targeting its receptors and metabolic enzyme has inevitable side effects. Therefore, we investigated adenosine augmentation therapy for seizure control and cognitive comorbidities in TLE animals. METHODS: Using lentiviral vectors coexpressing miRNA inhibiting the expression of adenosine kinase (ADK), we produced ADK--rMSC (ADK knockdown rat mesenchymal stem cell). ADK--rMSC and LV-con-rMSC (rMSC transduced by randomized scrambled control sequence) were transplanted into the hippocampus of TLE rat respectively. ADK-+DPCPX group was transplanted with ADK--rMSC and intraperitoneally injected with DPCPX (adenosine A1 receptor antagonist). Seizure behavior, EEG, CA1 pyramidal neuron apoptosis, and behavior in Morris water maze and novel object recognition test were studied RESULTS: Adenosine concentration in the supernatants of 105 ADK--rMSCs was 13.8 ng/ml but not detectable in LV-con-rMSCs. ADK--rMSC (n = 11) transplantation decreased spontaneous recurrent seizure (SRS) duration compared to LV-con-rMSC (n = 11, P < 0.05). CA1 neuron apoptosis was decreased in ADK--rMSC (n = 3, P < 0.05). ADK--rMSC (n = 11) improved the Morris water maze performance of TLE rats compared to LV-con-rMSC (n = 11, escape latency, P < 0.01; entries in target quadrant, P < 0.05). The effect of ADK--rMSC on neuron apoptosis and spatial memory were counteracted by DPCPX. However, ADK--rMSC didn't improve the performance in novel object recognition test. CONCLUSION: Adenosine augmentation-based ADK--rMSC transplantation is a promising therapeutic candidate for TLE and related cognitive comorbidities.

Low frequency stimulation for seizure suppression: Identification of optimal targets in the entorhinal-hippocampal circuit.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is a common form of drug-resistant focal epilepsy in adults. Treatment for pharmacoresistant patients remains a challenge, with deep brain stimulation (DBS) showing promise for alleviating intractable seizures. This study explores the efficacy of low frequency stimulation (LFS) on specific neuronal targets within the entorhinal-hippocampal circuit in a mouse model of MTLE. OBJECTIVE: Our previous research demonstrated that LFS of the medial perforant path (MPP) fibers in the sclerotic hippocampus reduced seizures in epileptic mice. Here, we aimed to identify the critical neuronal population responsible for this antiepileptic effect by optogenetically stimulating presynaptic and postsynaptic compartments of the MPP-dentate granule cell (DGC) synapse at 1 Hz. We hypothesize that specific targets for LFS can differentially influence seizure activity depending on the cellular identity and location within or outside the seizure focus. METHODS: We utilized the intrahippocampal kainate (ihKA) mouse model of MTLE and targeted specific neural populations using optogenetic stimulation. We recorded intracranial neuronal activity from freely moving chronically epileptic mice with and without optogenetic LFS up to 3 h. RESULTS: We found that LFS of MPP fibers in the sclerotic hippocampus effectively suppressed epileptiform activity while stimulating principal cells in the MEC had no impact. Targeting DGCs in the sclerotic septal or non-sclerotic temporal hippocampus with LFS did not reduce seizure numbers but shortened the epileptiform bursts. CONCLUSION: Presynaptic stimulation of the MPP-DGC synapse within the sclerotic hippocampus is critical for seizure suppression via LFS.

Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy.

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus. It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy, but still lacks effective treatments. Here, we aimed to test the effects of low-frequency stimulation (LFS) at the subiculum for secondary epileptogenesis in a mouse model. Here, secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli. Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice. LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex, characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci. Only application along with the primary epileptogenesis was effective. Notably, the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci. These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.

Effect of low­frequency repetitive transcranial magnetic stimulation on cognitive function in rats with medial temporal lobe epilepsy.

Epilepsy, especially the medial temporal lobe epilepsy (TLE), can result in cognitive impairment. Low­frequency repetitive magnetic stimulation (rTMS) has been verified to suppress neural excitability and reduce seizures. Given its potential in modifying cortical activity, we aimed to investigate its impact on cognitive function in the context of epilepsy, a condition where the use of rTMS has not been extensively explored. However, the influence on cognitive function has not yet been investigated. Therefore, this study aimed to investigate the effects of low­frequency rTMS on cognitive improvement in epileptic rats. Rats used in this study were randomly divided into five groups: the sham group, the epilepsy group, and three epilepsy groups treated with rTMS at different frequencies. Each group underwent the Morris water maze test to investigate hippocampus­dependent episodic memory, to evaluate their cognitive performance. Further assessments included patch clamp and western blot techniques to estimate the synaptic function in the hippocampus. Comparison between groups showed that low­frequency rTMS significantly reduced spontaneous recurrent seizures and improved spatial learning and memory impairment in epileptic rats. Additionally, rTMS remodeled the synaptic plasticity affected by seizures and notably enhanced the expression of AMPAR and synaptophysin. Low­frequency rTMS can antagonize the cognitive impairment caused by TLE, and promote synaptic connections.

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy / 中华医学杂志(英文版)

BACKGROUND@#Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.@*METHODS@#We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.@*RESULTS@#The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.@*CONCLUSION@#Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Cuerpos amiláceos en la neocorteza de pacientes con epilepsia del lóbulo temporal y displasia cortical focal / Corpora amylacea in the neocortex in patients with temporal lobe epilepsy and focal cortical dysplasia

Introducción: Los cuerpos amiláceos (CoA) se presentan en aproximadamente el 60% de los hipocampos atróficos resecados de pacientes con epilepsia del lóbulo temporal farmacorresistente (ELTFR). Su presencia en la neocorteza temporal lateral ha sido observada con menor frecuencia. Objetivo: El objetivo es evaluar la presencia, la distribución y la densidad de CoA en el lóbulo temporal lateral de pacientes con ELTFR y displasia cortical focal (DCF) y la relación de su densidad con variables demográficas y clínicas. Métodos: Analizamos histológicamente el tejido resecado de 35 pacientes con ELTFR. La densidad de los CoA fue evaluada con una escala semicuantitativa según los criterios de Cherian et al. Resultados: La presencia de CoA en la neocorteza de 9 pacientes estuvo asociada a esclerosis hipocampal (DCF tipo IIIa, 7 casos), tumor neuroepitelial disembrioplásico (DCF tipo IIIb, un caso) y angioma cavernoso (DCF tipo IIIc, un caso). Todos los pacientes tuvieron afectación de la superficie meníngea (SM) y en 8 casos se localizaron en el parénquima cerebral (sustancia blanca) y alrededor de los vasos sanguíneos. La densidad de los CoA en SM tuvo una correlación negativa con la edad de inicio de las crisis (r = -0,828, p < 0,05) y positiva con la duración de la enfermedad (r = 0,678, p < 0,05) pero no con la evolución clínica postquirúrgica. Conclusiones: En pacientes con ELTFR con lesión principal (EH, tumor, malformación vascular) asociada a DCF ligeras se constata la acumulación de CoA en la neocorteza. No se encontró una asociación entre la presencia de CoA y la evolución clínica al año de la cirugía

Introduction: Corpora amylacea (CoA) are present in about 60% of atrophic hippocampi resected from patients with drug resistant temporal lobe epilepsy (DRTLE). They have also been described in the lateral temporal neocortex, although less frequently. Objective: The objective is to measure the presence, distribution and density of CoA in the lateral temporal lobes of patients with DRTLE and focal cortical dysplasia (FCD), also examining how CoA density may be linked to demographic and clinical traits. Methods: Resected tissue from 35 patients was analysed. CoA density was assessed with a semi-quantitative scale according to the criteria established by Cherian et al. Results: Presence of CoA in the neocortex of 9 patients was associated with hippocampal sclerosis (FCD type IIIa, 7 cases), disembryoplastic neuroepithelial tumour (FCD type IIIb, 1 case), and cavernous angioma (FCD type IIIc, 1 case). The meningeal surface (MS) was involved in all cases, and 8 cases displayed CoA in the cerebral parenchyma (white matter) and around blood vessels. CoA density on the MS showed a negative correlation with age at seizure onset (r = -0.828, P < .05) and a positive correlation with disease duration (r = 0.678, P < .05) but not with postoperative clinical outcome. Conclusions: Patients with DRTLE and a primary lesion (hippocampal sclerosis, tumour, vascular malformation) associated with mild FCD were shown to have CoA deposits in the neocortex. No association was found between presence of CoA and clinical outcome one year after surgery

Evaluación videoelectroencefalográfica complementada con análisis espectral y de las fuentes generadoras del electroencefalograma en pacientes con epilepsia del lóbulo temporal medial resistente a los fármacos / Video-EEG evaluation complemented by spectral and EEG source analysis in patients with medication-resistant medial temporal lobe epilepsy

Objetivo. Evaluar la contribución de la monitorización prolongada videoelectroencefalográfica (video EEG) complementada con análisis espectral y de las fuentes generadoras del electroencefalograma (EEG) en la identificación de la zona epileptogénica de pacientes con epilepsia del lóbulo temporal medial candidatos a cirugía resectiva no lesional. Pacientesy métodos. Se evaluaron los patrones electrográficos del inicio ictal en más de 667 crisis correspondientes a 41 pacientes con diagnóstico clínico de epilepsia parcial resistente a fármacos. Para el análisis se utilizaron el software Harmonie y la tomografía eléctrica de resolución variable (VARETA). Resultados. Mediante video-EEG se determinó que el 53,6por ciento de lospacientes evaluados presentaba crisis parciales complejas de origen temporal; éstas se caracterizaron por una frecuencia media de 5,56 ± 1,56 Hz, mientras que las no temporales presentaron una frecuencia en el rango de 9,17 ± 3,32 Hz. La localizacióntopográfica de la frecuencia ictal dominante durante el período de energía espectral máxima en los pacientes conepilepsia del lóbulo temporal permitió distinguir a un grupo de pacientes con crisis mesiales y otros no mesiales que superaron el número determinado por la inspección visual del EEG: un 78,9 frente a un 47,3por ciento, respectivamente. Se evidenció unacoincidencia del 100por ciento entre la zona de inicio ictal definida por EEG de superficie complementada con análisis espectral, el generador de esta actividad definido por VARETA y la zona epileptogénica. Conclusiones. La información localizadora aportadapor el video-EEG complementada con el análisis espectral y de las fuentes del EEG permite localizar de forma no invasiva la zona epileptogénica en pacientes con epilepsia del lóbulo temporal medial aun cuando los estudios imaginológicos estructurales evidencian ausencia o bilateralidad de anomalías(AU)

Summary. Aim. To evaluate the value of prolonged video electroencephalographic (video-EEG) monitoring complemented with spectral and EEG source analysis in identifying the epileptogenic area in patients with medial temporal lobe epilepsy who are candidates for non-lesional resective surgery. Patients and methods. The electrographic patterns during the onset of seizures were evaluated in over 667 seizures from 41 patients with a clinical diagnosis of medication-resistant partial epilepsy. Analyses were performed using Harmonie software and variable resolution electrical tomography (VARETA). Results. Video- EEG was used to determine that 53.6percent of the patients evaluated suffered complex partial seizures of a temporal origin; these were characterised by having an average frequency of 5.56 ± 1.56 Hz, while the non-temporal seizures displayed a frequency within the range 9.17 ± 3.32 Hz. The topographic location of the dominant ictal frequency during the period of maximum spectral energy in patients with temporal lobe epilepsy enabled us to draw a distinction between a group of patients withmesial seizures and those with non-mesial seizures that exceeded the number that was determined by visual inspection of the EEG, that is, 78.9 versus 47.3percent, respectively. There was a 100percent coincidence between the area where the seizures began asdefined by surface EEG complemented with spectral analysis, the generator of this activity as defined by VARETA and the epileptogenic region. Conclusions. The localising information provided by video-EEG complemented with spectral and EEG source analysis allows for non-invasive location of the epileptogenic region in patients with medial temporal lobe epilepsy even when structural imaging studies show an absence or bilaterality of abnormalities(AU)

Evaluación videoelectroencefalográfica complementada con análisis espectral y de las fuentes generadoras del electroencefalograma en pacientes con epilepsia del lóbulo temporal medial resistente a los fármacos / Video-EEG evaluation complemented by spectral and EEG source analysis in patients with medication-resistant medal temporal lobe epilepsy

Objetivo. Evaluar la contribución de la monitorización prolongada videoelectroencefalográfica (video-EEG) complementada con análisis espectral y de las fuentes generadoras del electroencefalograma (EEG) en la identificación de la zona epileptogénica de pacientes con epilepsia del lóbulo temporal medial candidatos a cirugía resectiva no lesional. Pacientes y métodos. Se evaluaron los patrones electrográficos del inicio ictal en más de 667 crisis correspondientes a 41 pacientes con diagnóstico clínico de epilepsia parcial resistente a fármacos. Para el análisis se utilizaron el software Harmonie y la tomografía eléctrica de resolución variable (VARETA). Resultados. Mediante video-EEG se determinó que el 53,6% de los pacientes evaluados presentaba crisis parciales complejas de origen temporal; éstas se caracterizaron por una frecuencia media de 5,56 ± 1,56 Hz, mientras que las no temporales presentaron una frecuencia en el rango de 9,17 ± 3,32 Hz. La localización topográfica de la frecuencia ictal dominante durante el período de energía espectral máxima en los pacientes con epilepsia del lóbulo temporal permitió distinguir a un grupo de pacientes con crisis mesiales y otros no mesiales que superaron el número determinado por la inspección visual del EEG: un 78,9 frente a un 47,3%, respectivamente. Se evidenció una coincidencia del 100% entre la zona de inicio ictal definida por EEG de superficie complementada con análisis espectral, el generador de esta actividad definido por VARETA y la zona epileptogénica. Conclusiones. La información localizadora aportada por el video-EEG complementada con el análisis espectral y de las fuentes del EEG permite localizar de forma no invasiva la zona epileptogénica en pacientes con epilepsia del lóbulo temporal medial aun cuando los estudios imaginológicos estructurales evidencian ausencia o bilateralidad de anomalías

Aim. To evaluate the value of prolonged video-electroencephalographic (video-EEG) monitoring complemented with spectral and EEG source analysis in identifying the epileptogenic area in patients with medial temporal lobe epilepsy who are candidates for non-lesional resective surgery. Patients and methods. The electrographic patterns during the onset of seizures were evaluated in over 667 seizures from 41 patients with a clinical diagnosis of medication-resistant partial epilepsy. Analyses were performed using Harmonie software and variable resolution electrical tomography (VARETA). Results. Video- EEG was used to determine that 53.6% of the patients evaluated suffered complex partial seizures of a temporal origin; these were characterised by having an average frequency of 5.56 ± 1.56 Hz, while the non-temporal seizures displayed a frequency within the range 9.17 ± 3.32 Hz. The topographic location of the dominant ictal frequency during the period of maximum spectral energy in patients with temporal lobe epilepsy enabled us to draw a distinction between a group of patients with mesial seizures and those with non-mesial seizures that exceeded the number that was determined by visual inspection of the EEG, that is, 78.9 versus 47.3%, respectively. There was a 100% coincidence between the area where the seizures began as defined by surface EEG complemented with spectral analysis, the generator of this activity as defined by VARETA and the epileptogenic region. Conclusions. The localising information provided by video-EEG complemented with spectral and EEG source analysis allows for non-invasive location of the epileptogenic region in patients with medial temporal lobe epilepsy even when structural imaging studies show an absence or bilaterality of abnormalities

La experiencia en la práctica médica / Experience in medical practice

No disponible

No disponible

La experiencia en la práctica médica. Réplica / Experience in medical practice. Reply

No disponible

No disponible

O Methohexital Sódico (Brevital) no Teste de Wada: relato de dois casos / The sodium methohexital (Brevital) in Wada's test: report of two cases

O Teste de Wada continua sendo um exame frequentemente utilizado, para a avaliação qualitativa e quantitativa da lateralidade das funções de linguagem e das funções de memória verbal, e do possível déficit residual, uma vez que simula o efeito da cirurgia na investigação pré-operatória de candidatos a lobectomia temporal. No Brasil, há consideráveis dificuldades impostas pelas autoridades sanitárias para obtenção do Amytal (amobarbital sódico). Descreve o protocolo do Teste de Wada realizado com Brevital (methoexital sódico) em dois candidatos a lobectomia temporal, comentar sua eficácia e suas diferenças em relação ao realizado com o Amytal. Relatou-se o uso do Brevital em dois pacientes submetidos a determinação da lateralidade da linguagem e da memória através de protocolo adaptado pata tal. O Brevital, um anestésico de ação curta, mostrou-se eficiente em ambos os casos como substituto ao Amytal. O Brevital pode ser utilizado no Brasil para a realização do Teste de Wada, com a vantagem de possibilitar um exame mais breve, assim como uma investigação abrangente das funções de memória

Epilepsia temporal: hepar sulphur, un caso clínico, dosis única / Temporal epilepsy: hepar sulphur, clinical case, single dose

En este trabajo se relata el caso de un paciente adolescente con antecedentes de epilepsia temporal desde la infancia, corroborada por electroencefalograma, y trastornos de la conducta grave que requieren intervención policial. Medicado con Hepar sulphur en dosis única, mejora su conducta y normaliza el electroencefalograma. Se trata de un caso con 4¢ años de control (AU)

Epilepsia temporal: hepar sulphur, un caso clínico, dosis única / Temporal epilepsy: hepar sulphur, clinical case, single dose

En este trabajo se relata el caso de un paciente adolescente con antecedentes de epilepsia temporal desde la infancia, corroborada por electroencefalograma, y trastornos de la conducta grave que requieren intervención policial. Medicado con Hepar sulphur en dosis única, mejora su conducta y normaliza el electroencefalograma. Se trata de un caso con 4½ años de control