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1.
Int J Mol Sci ; 25(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39273262

RESUMEN

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.


Asunto(s)
Antioxidantes , Catalasa , Epilepsia del Lóbulo Temporal , Glutatión Peroxidasa , Levetiracetam , Estrés Oxidativo , Superóxido Dismutasa , Animales , Levetiracetam/farmacología , Levetiracetam/uso terapéutico , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/metabolismo , Masculino , Superóxido Dismutasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Catalasa/metabolismo , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Oxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Modelos Animales de Enfermedad , Peróxido de Hidrógeno/metabolismo , Ratas Wistar
2.
Toxins (Basel) ; 16(8)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39195752

RESUMEN

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202's ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.


Asunto(s)
Anticonvulsivantes , Modelos Animales de Enfermedad , Convulsiones , Animales , Masculino , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Ratones , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Pilocarpina , Ácido Kaínico/análogos & derivados , Péptidos/farmacología , Péptidos/uso terapéutico , Péptidos/administración & dosificación , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/inducido químicamente
3.
Int J Mol Sci ; 25(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38892194

RESUMEN

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.


Asunto(s)
Epilepsia del Lóbulo Temporal , MicroARNs , Canal de Sodio Activado por Voltaje NAV1.1 , Polimorfismo de Nucleótido Simple , Humanos , Canal de Sodio Activado por Voltaje NAV1.1/genética , MicroARNs/genética , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Femenino , Masculino , Brasil , Adulto , Predisposición Genética a la Enfermedad , Epilepsia Refractaria/genética , Epilepsia Refractaria/tratamiento farmacológico , Persona de Mediana Edad , Adulto Joven , Genotipo , Estudios de Cohortes , Alelos , Frecuencia de los Genes , Adolescente , Estudios de Casos y Controles
4.
Rev Neurol ; 78(11): 295-305, 2024 Jun 01.
Artículo en Español, Inglés | MEDLINE | ID: mdl-38813787

RESUMEN

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.


TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.


Asunto(s)
Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Medición de Riesgo , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia Refractaria/cirugía , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/etiología , Adulto Joven , Adolescente , Niño , Lenguaje
5.
Chaos ; 34(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717398

RESUMEN

We use a multiscale symbolic approach to study the complex dynamics of temporal lobe refractory epilepsy employing high-resolution intracranial electroencephalogram (iEEG). We consider the basal and preictal phases and meticulously analyze the dynamics across frequency bands, focusing on high-frequency oscillations up to 240 Hz. Our results reveal significant periodicities and critical time scales within neural dynamics across frequency bands. By bandpass filtering neural signals into delta, theta, alpha, beta, gamma, and ripple high-frequency bands (HFO), each associated with specific neural processes, we examine the distinct nonlinear dynamics. Our method introduces a reliable approach to pinpoint intrinsic time lag scales τ within frequency bands of the basal and preictal signals, which are crucial for the study of refractory epilepsy. Using metrics such as permutation entropy (H), Fisher information (F), and complexity (C), we explore nonlinear patterns within iEEG signals. We reveal the intrinsic τmax that maximize complexity within each frequency band, unveiling the nonlinear subtle patterns of the temporal structures within the basal and preictal signal. Examining the H×F and C×F values allows us to identify differences in the delta band and a band between 200 and 220 Hz (HFO 6) when comparing basal and preictal signals. Differences in Fisher information in the delta and HFO 6 bands before seizures highlight their role in capturing important system dynamics. This offers new perspectives on the intricate relationship between delta oscillations and HFO waves in patients with focal epilepsy, highlighting the importance of these patterns and their potential as biomarkers.


Asunto(s)
Biomarcadores , Ritmo Delta , Humanos , Biomarcadores/metabolismo , Ritmo Delta/fisiología , Electroencefalografía/métodos , Epilepsia/fisiopatología , Procesamiento de Señales Asistido por Computador , Masculino , Dinámicas no Lineales , Femenino , Adulto , Epilepsia del Lóbulo Temporal/fisiopatología
6.
Acta Neurobiol Exp (Wars) ; 84(1): 51-58, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38587324

RESUMEN

Levetiracetam (LEV) is a drug commonly used as an anticonvulsant. However, recent evidence points to a possible role as an antioxidant. We previously demonstrated the antioxidant properties of LEV by significantly increasing catalase and superoxide dismutase activities and decreasing the hydrogen peroxide (H2O2) levels in the hippocampus of rats with temporal lobe epilepsy (TLE) showing scavenging properties against the hydroxyl radical. The aim of the present work was to evaluate, the effect of LEV on DNA oxidation, by determining 8­hydroxy­2­deoxyguanosine (8­OHdG) levels, and glutathione content, through reduced (GSH) and oxidized (GSSG) glutathione levels, in the hippocampus of rats with TLE. Male Wistar rats were assigned to the control (CTRL), CTRL+LEV, epileptic (EPI) and EPI+LEV groups. TLE was induced using the lithium­pilocarpine model. Thirteen weeks after TLE induction, LEV was administered for one week through osmotic pumps implanted subcutaneously. The determination of 8­OHdG, GSH and GSSG levels were measured using spectrophotometric methods. We showed that LEV alone significantly increased 8­OHdG and GSSG levels in the hippocampus of control rats compared to those in epileptic condition. No significant differences in GSH levels were observed. LEV could induce changes in the hippocampus increasing DNA oxidation and GSSG levels under nonepileptic condition but not protecting against the mitochondrial dysfunction observed in TLE probably by mechanisms related to changes in chromatin structure, neuroinflammation and alterations in redox components.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Piracetam , Masculino , Ratas , Animales , Levetiracetam/efectos adversos , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Piracetam/efectos adversos , Antioxidantes/uso terapéutico , Disulfuro de Glutatión/efectos adversos , Peróxido de Hidrógeno/efectos adversos , Ratas Wistar , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Glutatión/metabolismo , Oxidación-Reducción
7.
Epileptic Disord ; 26(3): 382-391, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38588048

RESUMEN

The presence of dysmorphic neurons with strong cytoplasmatic accumulation of heavy non-phosphorylated neurofilament is crucial for the diagnostics of focal cortical dysplasia type II (FCDII). While ILAE's classification describes neocortical dysplasias, some groups have reported patients with mesial t abnormal neurons in the hippocampus of mesial temporal lobe epilepsy. Here we report a patient with such abnormal neurons in the hippocampus and compared it with previous reports of hippocampal dysplasia. Finally, we discuss the need for diagnostic criteria of hippocampal dysplasia.


Asunto(s)
Epilepsia del Lóbulo Temporal , Hipocampo , Adulto , Humanos , Epilepsia , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Imagen por Resonancia Magnética , Malformaciones del Desarrollo Cortical/diagnóstico , Malformaciones del Desarrollo Cortical/patología , Malformaciones del Desarrollo Cortical de Grupo I/diagnóstico , Malformaciones del Desarrollo Cortical de Grupo I/patología
8.
Am J Trop Med Hyg ; 110(4): 700-705, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38442416

RESUMEN

The aim of this study was to analyze postsurgical outcomes for individuals with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who underwent anterior temporal lobectomy, based on the presence of calcified neurocysticercosis (cNCC). A retrospective cross-sectional study was conducted on 89 patients with MTLE-HS who underwent anterior temporal lobectomy between January 2012 and December 2020 at a basic epilepsy surgery center located in Lima, Peru. We collected sociodemographic, clinical, and diagnostic information. The postsurgical results were analyzed using bivariate analysis according to the Engel classification. We included 89 individuals with a median age of 28 years (interquartile range [IQR]: 24-37), and more than half (55.1%) were male. Seventeen (19.1%) were diagnosed with cNCC. A greater number of patients with cNCC had lived in rural areas of Peru during their early life compared with those without cNCC (12 [70.6%] versus 26 [36.1%]; P = 0.010). Patients with cNCC exhibited a greater median frequency of focal to bilateral tonic-clonic seizures per month (1 [IQR: 0-2] versus 0 [0-0.5]; P = 0.009). Conversely, a lower proportion of patients with cNCC reported a history of an initial precipitating injury in comparison to the group without cNCC (4 [23.5%] versus 42 [58.3%]; P = 0.014). At the 1-year follow-up, most patients (82.4%) with cNCC were categorized as Engel IA. Similarly, at the 2-year follow-up, nine (75.0%) were classified as Engel IA. Our findings suggest that most patients diagnosed with cNCC exhibit favorable postsurgical outcomes, comparable to those without cNCC. Additionally, it can be postulated that cNCC may play a role as an initial precipitating injury.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Esclerosis del Hipocampo , Neurocisticercosis , Compuestos de Nitrosourea , Humanos , Masculino , Adulto , Femenino , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/cirugía , Neurocisticercosis/complicaciones , Neurocisticercosis/cirugía , Estudios Retrospectivos , Estudios Transversales , Resultado del Tratamiento , Epilepsia/complicaciones , Hipocampo
9.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38338984

RESUMEN

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Piracetam , Humanos , Ratas , Animales , Levetiracetam/farmacología , Levetiracetam/uso terapéutico , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/genética , Transcriptoma , Piracetam/farmacología , Piracetam/uso terapéutico , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Giro Dentado
10.
Epilepsia Open ; 9(2): 626-634, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38217377

RESUMEN

OBJECTIVE: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS). METHODS: Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring. RESULTS: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05). SIGNIFICANCE: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population. PLAIN LANGUAGE SUMMARY: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Esclerosis del Hipocampo , Humanos , Encéfalo , Lenguaje
11.
Biomed Chromatogr ; 38(4): e5820, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38154955

RESUMEN

Temporal lobe epilepsy (TLE) is a common form of refractory epilepsy in adulthood. The metabolic profile of epileptogenesis is still poorly investigated. Elucidation of such a metabolic profile using animal models of epilepsy could help identify new metabolites and pathways involved in the mechanisms of epileptogenesis process. In this study, we evaluated the metabolic profile during the epileptogenesis periods. Using a pilocarpine model of epilepsy, we analyzed the global metabolic profile of hippocampal extracts by untargeted metabolomics based on ultra-performance liquid chromatography-high-resolution mass spectrometry, at three time points (3 h, 1 week, and 2 weeks) after status epilepticus (SE) induction. We demonstrated that epileptogenesis periods presented different hippocampal metabolic profiles, including alterations of metabolic pathways of amino acids and lipid metabolism. Six putative metabolites (tryptophan, N-acetylornithine, N-acetyl-L-aspartate, glutamine, adenosine, and cholesterol) showed significant different levels during epileptogenesis compared to their respective controls. These putative metabolites could be associated with the imbalance of neurotransmitters, mitochondrial dysfunction, and cell loss observed during both epileptogenesis and epilepsy. With these findings, we provided an overview of hippocampal metabolic profiles during different stages of epileptogenesis that could help investigate pathways and respective metabolites as predictive tools in epilepsy.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Animales , Epilepsia/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Metaboloma , Pilocarpina/metabolismo
12.
REVISA (Online) ; 13(1): 102-113, 2024.
Artículo en Portugués | LILACS | ID: biblio-1531982

RESUMEN

Objetivo:Compreender o cenário atual da ELT-HS, caracterizado por sua fisiopatologia, manifestações clínicas, métodos diagnósticos e tratamentos. Método:Trata-se de uma revisão integrativa da literatura, com caráter descritivo, de artigos indexados no Sistema de Análise e Recuperação da Literatura Médica Online MEDLINE/Pubmed, Literatura Latino-Americana e do Caribe em Ciências da Saúde LILACS, e nas bases de dados Científicas Electronic Library Online (SciELO), pesquisados na período compreendido entre outubro de 2022 e março de 2023. Foram incluídos artigos em português e inglês que contemplassem os objetivos da revisão, publicados nos últimos dez anos (2011-2021).Resultados: Inicialmente foram encontrados 144 artigos nas bases de dados, que após a leitura, foramselecionados na pesquisa 40 artigos que correspondiam ao objetivo proposto. Os artigos analisados correspondem aos anos de 2011 a 2021. Conclusão:O tratamento cirúrgico da ELT-HS tem se mostrado eficaz para resolução completa das crises na maioria dos pacientes. O conhecimento sobre sua fisiopatologia, manifestações clínicas, diagnóstico e tratamentos são de fundamental importância para os médicos que atendem pacientes com epilepsia.


Objective: To understand the current scenario of TLE-HS, characterized by its pathophysiology, clinical manifestations, diagnostic methods and treatments. Method:This is an integrative literature review with descriptive character, of articles indexed in the Medical Literature Analysis And Retrieval System Online MEDLINE/Pubmed, Latin American and Caribbean Literature in Health Sciences LILACS, and Scientic databases Electronic Library Online (SciELO), researched in the period between october 2022 and march 2023. Articles in Portuguese and English that contemplated the objectives of the review, published in the last ten years (2011-2021), were included. Results:Initially, 144 articles were found in the databases, which after reading, 40 articles were selected in the research that corresponded to the proposed objective. The articles analyzed are equivalent to the years 2011 to 2021. Conclusion:The surgical treatment of TLE-HS has been shown to be effective for the complete resolution of crises in most patients. Knowledge about its pathophysiology, clinical manifestations, diagnosis and treatments are of fundamental importance for physicians who treat patients with epilepsy


Objetivo: Comprender el escenario actual de la TLE-HS, caracterizado por su fisiopatología, manifestaciones clínicas, métodos diagnósticos y tratamientos. Método: Se trata de una revisión bibliográfica integradora con carácter descriptivo, de artículos indexados en el Sistema de Análisis y Recuperación de Literatura Médica en Línea MEDLINE/Pubmed, Literatura Latinoamericana y del Caribe en Ciencias de la Salud LILACS, y bases de datos Scientic Electronic Library Online (SciELO), investigados en el período comprendido entre octubre de 2022 y marzo de 2023. Se incluyeron artículos en portugués e inglés que contemplaran los objetivos de la revisión, publicados en los últimos diez años (2011-2021). Resultados:Inicialmente se encontraron 144 artículos en las bases de datos, de los cuales luego de la lectura se seleccionaron 40 artículos en la investigación que correspondía al objetivo propuesto. Los artículos analizadoscorresponden a los años 2011 a 2021. Conclusión:El tratamiento quirúrgico del ELT-HS se ha mostrado eficaz para la resolución completa de las crisis en la mayoría de los pacientes. El conocimiento sobre su fisiopatología, manifestaciones clínicas, diagnóstico y tratamientos es de fundamental importancia para los médicos que tratan pacientes con epilepsia


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Esclerosis del Hipocampo
13.
Epilepsia Open ; 8(4): 1532-1540, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37750472

RESUMEN

OBJECTIVE: To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement. METHODS: We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups. RESULTS: We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012). SIGNIFICANCE: Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.


Asunto(s)
Epilepsia del Lóbulo Temporal , Esclerosis del Hipocampo , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Lóbulo Temporal/patología , Lóbulo Temporal/cirugía , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Electroencefalografía , Esclerosis/complicaciones , Esclerosis/patología
14.
Acta neurol. colomb ; 39(3)sept. 2023.
Artículo en Español | LILACS | ID: biblio-1533498

RESUMEN

Introducción: La epilepsia del lóbulo temporal mesial se considera la más frecuente de las epilepsias focales, con signos y síntomas característicos que ayudan a definir su diagnóstico. Contenidos: Dentro de su historia natural, las crisis pueden iniciar en los primeros años de vida, usualmente como episodios febriles con un periodo de remisión, para reaparecer en la adolescencia o en el adulto joven. La presentación electroencefalográfica tiene un patrón característico, con aparición de puntas y ondas agudas interictales en la región temporal anterior, por lo general unilaterales, y con actividad ictal generalmente theta en la misma localización. La causa más frecuente es la esclerosis del hipocampo. El tratamiento con medicamentos anticrisis puede controlar la epilepsia, aunque algunos casos pueden evolucionar a la farmacorresistencia, en la cual la cirugía de epilepsia está indicada, y tiene buenos resultados. Conclusiones: Esta revisión se centra en la descripción de las características electroclínicas de la epilepsia temporal mesial, para hacer un diagnóstico temprano e iniciar un tratamiento adecuado, a efectos de lograr un mejor pronóstico y una mejor calidad de vida para los pacientes con epilepsia y sus familiares.


Introduction: Mesial temporal lobe epilepsy is considered the most common of the focal epilepsies, with characteristic signs and symptoms that help define its diagnosis. Contents: In the natural history of the disease, seizures can begin in the first years of life, usually as febrile seizures with a period of remission, to reappear in adolescence or in the young adult. The electroencephalographic presentation has a characteristic pattern with the appearance of interictal sharp waves and spikes in the anterior temporal region, usually unilateral, and with generally theta ictal activity in the same location. The most common cause is hippocampal sclerosis. Treatment with antiseizure medication can control epilepsy. However, in some cases evolution of drug resistance can occur, leading to epilepsy surgery as the most appropriate treatment, based on its good results. Conclusions: This review focuses on the description of the electroclinical characteristics of temporal mesial epilepsy, in order to make an early diagnosis and adequate treatment, thus providing a better prognosis and quality of life for patients with epilepsy and their families.


Asunto(s)
Calidad de Vida , Convulsiones Febriles , Diagnóstico , Epilepsia del Lóbulo Temporal , Pacientes , Pronóstico , Esclerosis , Revisión , Historia Natural
15.
Acta neurol. colomb ; 39(3)sept. 2023.
Artículo en Español | LILACS | ID: biblio-1533500

RESUMEN

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.


Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life


Asunto(s)
Núcleos Talámicos Anteriores , Núcleos Talámicos Intralaminares , Epilepsia del Lóbulo Temporal , Estimulación del Nervio Vago , Estimulación Eléctrica , Hipocampo
16.
Epilepsia Open ; 8(3): 1175-1181, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37394997

RESUMEN

Mesial temporal lobe epilepsy, one of the most common forms of epilepsy, is often linked with drug resistance. Surgical intervention is a reliable and safe treatment option, though research into postsurgical outcomes in our locality remains limited. We performed a retrospective observational study included 91 patients with mesial temporal lobe epilepsy and hippocampal sclerosis who had undergone anterior temporal lobectomy between 2012 and 2020 at a surgical epilepsy center located in Lima, Peru. Postoperative outcomes were analyzed using bivariate and multivariate analysis based on the Engel classification. We found that after 12 months of follow-up, 78.65% of the 91 patients achieved an Engel IA classification, while 9.09% attained Engel IB classification and 11.24% were designated as Engel II, with only 1.12% classified as Engel IVA. The median QOLIE31 score was 84 (IQR: 75-90), with 74.16% of the participants successfully reintegrating into academic or employment activities. After 24 months, only 68 patients completed the follow-up, with 69.12% achieving an Engel IA classification. Individuals with a secondary education or higher were more likely to achieve an Engel IA classification at 12 months (OR: 5.11; P = 0.005; CI: 1.63-16.01), after adjusting for sex and age. We concluded that most patients exhibited favorable outcomes after 1 year of follow-up. However, lower educational attainment was linked to worse postsurgical outcomes.


Asunto(s)
Epilepsia del Lóbulo Temporal , Esclerosis del Hipocampo , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Resultado del Tratamiento , Perú , Hipocampo/cirugía
18.
Arq Neuropsiquiatr ; 81(7): 647-655, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37494949

RESUMEN

BACKGROUND: Temporal lobe epilepsy (TLE) is a high prevalence neurological disorder. Surgery has emerged as a promising treatment. OBJECTIVE: The objective of this work is to compare the surgical results of anterior temporal lobectomy (ATL) versus selective amygdalohippocampectomy (SAH) in a cohort of 132 patients. METHODS: We performed a retrospective study of 146 patients operated for TLE from 2008 to 2019. Initially, 13 patients were excluded from the study due to insufficient medical record data or follow-up loss. One patient was excluded from the analysis of the results due to death in the first postoperative week. We used the ILAE scale to classify seizure control after surgery. In patients with left hippocampal sclerosis, SAH was performed and in right temporal lobe epilepsy, ATL was the approach of choice. RESULTS: The mean follow-up time after surgery was 57.2 months (12-137). In our data analysis, we found that the group of patients undergoing ATL had a higher prevalence of being completely seizure-free (ILAE I) (57.1% versus 31%) and a higher rate of satisfactory seizure control (88.6% versus 69.3%) p = 0,006, when compared with patients undergoing SAH. CONCLUSION: The literature is still controversial about seizure control concerning the technique used due to the lack of a robust methodology. Our data analysis identified the superiority of ATL over SAH in seizure outcomes. ATL may be the best option for adequately controlling seizures with minimal additional morbidity in countries with a cost limitation for extended propaedeutics.


ANTECEDENTES: A epilepsia do lobo temporal (TLE) é uma desordem neurológica de alta prevalência. A cirurgia surgiu como um tratamento promissor. OBJETIVO: O objetivo deste trabalho é comparar os resultados da lobectomia temporal anterior (ATL) versus amigdalohipocampectomia seletiva (SAH) em uma coorte de 132 pacientes. MéTODOS: Realizamos um estudo retrospectivo de 146 pacientes operados por TLE de 2008 a 2019. Inicialmente, 13 pacientes foram excluídos por insuficiência de dados em prontuário ou perda de seguimento. Um paciente foi excluído da análise por óbito na primeira semana de pós-operatório. Usamos a escala ILAE para classificar o controle das crises após a cirurgia. Em pacientes com esclerose hipocampal à esquerda, foi realizada a SAH, e na epilepsia do lobo temporal à direita, a ATL foi a abordagem de escolha. RESULTADOS: O tempo médio de seguimento após a cirurgia foi de 57,2 meses (12­137). Em nossa avaliação, encontramos que o grupo de pacientes submetidos à ATL apresentou maior prevalência de ausência total de crises (ILAE I) (57,1% versus 31%) e maior taxa de controle satisfatório da epilepsia (88,6% versus 69,3%) p = 0,006, quando comparado ao grupo submetido à SAH. CONCLUSãO: A literatura ainda é controversa em relação à redução das crises de acordo com a técnica utilizada devido a falta de uma metodologia robusta. Nosso estudo identificou superioridade da ATL sobre a SAH nos desfechos convulsivos. ATL pode ser a melhor opção para controlar adequadamente as convulsões com morbidade adicional mínima em países com limitação de custo para propedêutica estendida.


Asunto(s)
Epilepsia del Lóbulo Temporal , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Lobectomía Temporal Anterior/métodos , Estudios Retrospectivos , Brasil/epidemiología , Resultado del Tratamiento , Convulsiones/cirugía , Hipocampo/cirugía
19.
Ann Clin Transl Neurol ; 10(7): 1106-1118, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37208853

RESUMEN

OBJECTIVE: Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. METHODS: 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. RESULTS: There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. INTERPRETATION: These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.


Asunto(s)
Epilepsia del Lóbulo Temporal , Sustancia Blanca , Adulto , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Longevidad , Imagen de Difusión Tensora/métodos , Encéfalo/diagnóstico por imagen
20.
Arq Neuropsiquiatr ; 81(5): 492-501, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37257470

RESUMEN

BACKGROUND: Cognitive event-related potentials (ERPs) allow for lateralization of the epileptogenic zone (EZ) to estimate the reserve of memory in the contralateral non-epileptogenic hemisphere, and to investigate the prognosis of temporal lobe seizure control in unilateral temporal lobe epilepsy (TLE). OBJECTIVE: To define the accuracy of cognitive evoked anterior mesial temporal lobe (AMTL-N400) and P600 potentials in detecting the epileptogenic zone in temporal lobe epilepsy (TLE), and second, to evaluate the possibility of using them as markers of cognitive outcome. METHODS: The systematic review using Medline/PubMed, Embase, and Lilacs database was conducted in September 2021. Only articles published in English from 1985 to June 2021 were included. We searched for studies with: (1) depth intracranial electroencephalography (iEEG) recordings analysis of rhinal and hippocampal activity (2) correlations between ERP results obtained in the mesial temporal regions (AMTL-N400 and P600) and the epileptogenic zone. RESULTS: Six out of the seven studies included in this review defined the laterality of the epileptogenic zone (EZ) during presurgical investigation using ERPs. One study showed that the contralateral AMTL-N400 predicts seizure control. Another study found correlation between the amplitudes of the right AMTL-N400 and postoperative memory performance. CONCLUSIONS: There is evidence that the reduced amplitude of the AMTL-N400 has high accuracy in identifying the epileptogenic zone, as it does in estimating the extent of seizure control and memory impairment in postoperative patients.


ANTECEDENTES: Potenciais relacionados a eventos (PREs) cognitivos permitem a lateralização da zona epileptogênica (ZE), estimar a reserva de memória no hemisfério contralateral não-epileptogênico, e estimar o prognóstico pós-operatório em pacientes com epilepsia do lobo temporal (ELT) unilateral quanto ao controle de crises. OBJETIVO: Definir a acurácia dos potenciais evocados cognitivos do lobo temporal mesial anterior (LTMA-N400) e P600 na detecção da zona epileptogênica na epilepsia do lobo temporal (ELT), além de avaliar a possibilidade de usá-los como marcadores de desfecho cognitivo. MéTODOS: A revisão sistemática foi realizada em setembro de 2021 usando as bases de dados Medline/PubMed, Embase e Lilacs. Apenas artigos publicados em inglês no período entre 1985 e junho de 2021 foram incluídos. Buscamos estudos com: (1) análises dos registros de electroencefalografia intracraniana (EEGi) da atividade rinal e hipocampal (2) correlações entre os resultados de PREs obtidos nas regiões temporais mesiais (AMTL-N400 e P600) e a zona epileptogênica. RESULTADOS: Seis dos sete estudos incluídos nesta revisão definiram a lateralidade da zona epileptogênica (ZE) durante a investigação pré-cirúrgica usando PREs. Um estudo mostrou que o AMTL-N400 contralateral prediz o controle das crises. Outro estudo encontrou correlação entre as amplitudes do AMTL-N400 direito e o desempenho da memória pós-operatória. CONCLUSõES: Há evidências de que a amplitude reduzida do AMTL-N400 tem alta precisão na identificação da zona epileptogênica, assim como na estimativa do prognóstico quanto ao controle de crises a longo prazo e prejuízo da memória em pacientes submetidos à cirurgia ressectiva.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Humanos , Masculino , Femenino , Potenciales Evocados/fisiología , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/psicología , Electroencefalografía , Hipocampo/cirugía , Convulsiones
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