RESUMEN
OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. RESULTS: Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. SIGNIFICANCE: This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.
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Trastornos del Movimiento , ATPasa Intercambiadora de Sodio-Potasio , Humanos , Femenino , ATPasa Intercambiadora de Sodio-Potasio/genética , Lactante , Trastornos del Movimiento/genética , Trastornos del Movimiento/fisiopatología , Trastornos del Movimiento/tratamiento farmacológico , Trastornos del Movimiento/etiología , Niño , Espasmos Infantiles/genética , Espasmos Infantiles/fisiopatología , Espasmos Infantiles/tratamiento farmacológico , Preescolar , Epilepsia Refractaria/genética , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Discapacidad Intelectual/genética , Discapacidad Intelectual/fisiopatología , Estudios Retrospectivos , Memantina/uso terapéuticoRESUMEN
In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules' main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
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Región CA1 Hipocampal/patología , Epilepsia Refractaria/genética , Epilepsia Refractaria/fisiopatología , Adolescente , Adulto , Encéfalo/patología , Región CA1 Hipocampal/metabolismo , Disfunción Cognitiva/fisiopatología , Giro Dentado/patología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Expresión Génica/genética , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Neuronas/patología , Convulsiones/fisiopatología , Transcriptoma/genéticaRESUMEN
OBJECTIVE: We present the findings related to seizure outcome during hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporal lobe epilepsy. METHODS: Twenty-five patients submitted to Hip-DBS were studied. All patients were evaluated with interictal and ictal electroencephalography (EEG) and high-resolution 1.5 T magnetic resonance imaging (MRI). The hippocampus was targeted directly on MRI using a posterior occipital burr hole approach. Bipolar continuous stimulation was ramped up until 3.0 V (300 µs, 130 Hz). Patients were considered responders if at least 50% seizure frequency reduction was obtained. RESULTS: Median age was 39 years; median follow-up time was 57 months (16 women). All patients had focal with impaired awareness seizure (FIAS) and 23 patients had focal aware seizure (FAS). Baseline median FAS and FIAS frequency was 8. Ictal EEG showed unilateral (n = 10) or bilateral (n = 15) seizure onset. MRI showed unilateral (n = 11) or bilateral (n = 8) mesial temporal sclerosis (MTS) and was normal in six6 patients. Fifteen patients were submitted to bilateral and 10 patients to unilateral Hip-DBS. Median reduction in FAS frequency was 66%. Eighteen patients with FAS were considered responders and five (21%) were free of FAS. Median FIAS frequency (n = 25) reduction was 91%. Twenty-two patients were considered responders and eight (32%) were free of FIAS. FIAS were significantly more reduced then FAS (P = .017). There was no relation between any contact's position within the hippocampus and outcome for either FAS (P = .727) or FIAS (P = .410). There was no difference in outcome in patients submitted to either unilateral or bilateral Hip-DBS regarding FAS (P = .978) or FIAS (P = .693). SIGNIFICANCE: Hip-DBS significantly reduced the frequency of both FAS and FIAS in this cohort of patients with refractory temporal lobe epilepsy. Hip-DBS might represent a good therapeutic option in such patients not amenable to resective surgery.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Epilepsia Refractaria/terapia , Epilepsia del Lóbulo Temporal/terapia , Hipocampo , Adolescente , Adulto , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis , Resultado del Tratamiento , Adulto JovenRESUMEN
The Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though rarely getting sick. Previous studies on male Proechimys have revealed an endogenous resistance to epilepsy. Here, we assess in female Proechimys, whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX) Proechimys were compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE in Proechimys was higher (25- to 50-folds more). Despite a higher dose, Proechimys did not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that female Proechimys are resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance in Proechimys against SE induction.
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Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/fisiopatología , Pilocarpina/uso terapéutico , Roedores/fisiología , Estado Epiléptico/tratamiento farmacológico , Animales , Glucemia/análisis , Modelos Animales de Enfermedad , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/metabolismo , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatología , Ovariectomía , Progesterona/sangre , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Roedores/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/fisiopatologíaRESUMEN
Congenital Zika virus syndrome (CZVS) is associated with severe neurological deficits. Clinical characteristics of epilepsy and the electroencephalographic (EEG) pattern in CZVS were documented in infancy. In this study, we aimed to describe the EEG findings observed during the follow-up of children with CZVS. Seventy-six EEGs of 55 children (60% female; mean age = 50 months) with confirmed CZVS were analyzed, considering the background, interictal, and ictal epileptiform discharges. Continuous (or almost continuous) epileptiform discharges during non-rapid eye movement sleep were identified in 22 (40%) patients. In 20 (90.1%) patients, the pattern was symmetrical, with an anterior predominance of the epileptiform activity. All patients with this pattern had epilepsy, which was severe in 15 (68.2%) and demanded polytherapy in 19 (86.4%). Subcortical calcifications (77.3%) and multifocal EEGs (72.8%) in earlier ages occurred more often in patients with this pattern. Other unspecific interictal EEG patterns were focal epileptiform discharges in 23 (41.8%) and multifocal activity in six (10.9%). In CZVS, continuous (or almost continuous) epileptiform discharges during sleep emerge as a pattern after the second year of life. This was associated with severe and drug-resistant epilepsy, but not necessarily with an apparent regression. Subcortical calcifications and multifocal epileptiform discharges in infancy are associated with this pattern.
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Encéfalo/fisiopatología , Epilepsia/fisiopatología , Malformaciones del Desarrollo Cortical/fisiopatología , Sueño , Infección por el Virus Zika/congénito , Infección por el Virus Zika/fisiopatología , Anticonvulsivantes/uso terapéutico , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/fisiopatología , Encéfalo/diagnóstico por imagen , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Calcinosis/diagnóstico por imagen , Calcinosis/fisiopatología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Preescolar , Progresión de la Enfermedad , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Epilepsias Parciales/diagnóstico por imagen , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/fisiopatología , Epilepsia/diagnóstico por imagen , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Masculino , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Tamaño de los Órganos , Polimicrogiria/diagnóstico por imagen , Polimicrogiria/fisiopatología , Índice de Severidad de la Enfermedad , Síndrome , Enfermedades Talámicas/diagnóstico por imagen , Enfermedades Talámicas/fisiopatología , Infección por el Virus Zika/diagnóstico por imagenRESUMEN
Paciente de 4 años de edad, con epilepsia de difícil manejo, cuya etiología se atribuye a patología autoinmune y que finalmente se diagnostica una mutación de protocadherina (PCDH19). Se discute la fisiopatología, características clínicas, exámenes y los posibles tratamientos.
Four-year-old patient with intractable epilepsy, whose etiology is attributed to autoimmune pathology and who is eventually diagnosed with a protocadherin mutation (PCDH19). Pathophysiology, clinical characteristics, examinations and possible treatments are discussed.
Asunto(s)
Humanos , Femenino , Preescolar , Epilepsia Refractaria/genética , Protocadherinas/genética , Pregnanolona , Cromosomas Humanos X , Genes Ligados a X , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/terapia , MutaciónRESUMEN
OBJECTIVE: Drug-resistant focal epilepsy is widely recognized as a network disease in which epileptic seizure propagation is likely coordinated by different neuronal oscillations such as low-frequency activity (LFA), high-frequency activity (HFA), or low-to-high cross-frequency coupling. However, the mechanism by which different oscillatory networks constrain the propagation of focal seizures remains unclear. METHODS: We studied focal epilepsy patients with invasive electrocorticography (ECoG) recordings and compared multilayer directional network interactions between focal seizures either with or without secondary generalization. Within-frequency and cross-frequency directional connectivity were estimated by an adaptive directed transfer function and cross-frequency directionality, respectively. RESULTS: In the within-frequency epileptic network, we found that the seizure onset zone (SOZ) always sent stronger information flow to the surrounding regions, and secondary generalization was accompanied by weaker information flow in the LFA from the surrounding regions to SOZ. In the cross-frequency epileptic network, secondary generalization was associated with either decreased information flow from surrounding regions' HFA to SOZ's LFA or increased information flow from SOZ's LFA to surrounding regions' HFA. INTERPRETATION: Our results suggest that the secondary generalization of focal seizures is regulated by numerous within- and cross-frequency push-pull dynamics, potentially reflecting impaired excitation-inhibition interactions of the epileptic network. ANN NEUROL 2019;86:683-694.
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Epilepsia Refractaria/fisiopatología , Epilepsias Parciales/fisiopatología , Convulsiones/fisiopatología , Adolescente , Adulto , Niño , Electrocorticografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Focal epilepsy secondary to mesial temporal sclerosis (MTS) is one of the main causes of refractory epilepsy. It is typically associated with frontotemporal discharges in the electroencephalogram (EEG), a characteristic image in the magnetic resonance scan and a probability of post-operative remission above 70%. AIMS: To identify different patterns of ictal propagation in surface EEG recordings in patients with refractory epilepsy and MTS, and to analyse their relation with the post-operative outcome. PATIENTS AND METHODS: We conducted a retrospective review of the medical records of patients with refractory epilepsy secondary to MTS evaluated in the Epilepsy Surgery Programme of the Hospital de Clinicas, Montevideo (n = 30). The propagation of ictal rhythms was analysed in time windows of three seconds, and propagation maps were produced for each seizure. RESULTS: Six patterns were identified: ipsilateral temporal (type 1; 37%), bilateral frontotemporal with (type 2A; 22%) or without (type 2B; 17%) extension to suprasylvian regions, alternating temporal (type 3; 13%), unilateral suprasylvian (type 4; 7%) and bilateral at onset (type 5; 3%). The type 1 pattern was associated with classic clinical features and a favourable post-operative outcome. The clinical variants were associated with extratemporal EEG propagation. Patients with reflex seizures continued with post-operative seizures. Overall, no unambiguous relation was found between the ictal EEG pattern and the post-operative outcome. CONCLUSIONS: The ictal EEG pattern does not allow for a surgical prognosis in patients with epilepsy secondary to MTS. The history of reflex seizures in these patients may be a red flag suggesting a less favourable surgical outcome.
TITLE: Variantes clinicoelectroencefalograficas en la epilepsia del lobulo temporal mesial farmacorresistente.Introduccion. La epilepsia focal secundaria a esclerosis temporal mesial (ETM) constituye una de las principales causas de epilepsia refractaria al tratamiento farmacologico. Tipicamente asocia descargas frontotemporales en el electroencefalograma (EEG), imagen caracteristica en la resonancia magnetica y probabilidad de remision posquirurgica mayor del 70%. Objetivos. Identificar diferentes patrones de propagacion ictal en los registros electroencefalograficos de superficie en pacientes con epilepsia farmacorresistente y ETM, y analizar su relacion con la evolucion postoperatoria. Pacientes y metodos. Se revisaron retrospectivamente los registros de pacientes con epilepsia refractaria secundaria a ETM evaluados en el Programa de Cirugia de Epilepsia del Hospital de Clinicas, Montevideo (n = 30). La propagacion de ritmos ictales se analizo en ventanas temporales de tres segundos, y se elaboraron mapas de propagacion para cada crisis. Resultados. Se identificaron seis patrones: temporal ipsilateral (tipo 1; 37%), frontotemporal bilateral con (tipo 2A; 22%) o sin (tipo 2B; 17%) extension a regiones suprasilvianas, temporal alternante (tipo 3; 13%), suprasilviano unilateral (tipo 4; 7%) y bilateral de inicio (tipo 5; 3%). El patron de tipo 1 asocio un cuadro clinico clasico y buena evolucion posquirurgica. Las variantes clinicas se asociaron a propagacion EEG extratemporal. Los pacientes con crisis reflejas persistieron con crisis postoperatorias. En su conjunto, no se hallo una relacion univoca entre el patron EEG ictal y la evolucion postoperatoria. Conclusiones. El patron EEG ictal no permite predecir el pronostico quirurgico en pacientes con epilepsia secundaria a ETM. La historia de crisis reflejas en estos pacientes puede constituir una 'bandera roja' y sugerir un peor pronostico quirurgico.
Asunto(s)
Epilepsia Refractaria/fisiopatología , Electroencefalografía , Epilepsia del Lóbulo Temporal/fisiopatología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. CONCLUSION: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.
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Cognición/fisiología , Epilepsia del Lóbulo Temporal/psicología , Pruebas Neuropsicológicas , Autoinforme , Somnolencia , Adulto , Anticonvulsivantes/uso terapéutico , Estudios de Casos y Controles , Demografía , Epilepsia Refractaria/fisiopatología , Escolaridad , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis/complicacionesRESUMEN
ABSTRACT Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. Conclusion: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.
RESUMO A sonolência e o comprometimento cognitivo são queixas comuns na epilepsia. Investigamos se a sonolência relatada pelo paciente está associada ao desempenho cognitivo na epilepsia do lobo temporal mesial refratária com esclerose do hipocampo (ELTM-EH). 71 pacientes com ELTM-EH foram avaliados pela Escala de Sonolência de Stanford (ESS) antes da avaliação neuropsicológica. A média na ESS foi comparada com a de controles. Cada teste foi comparado entre os pacientes com sonolência (ESS ≥ 3) ou sem sonolência (ESS <3). Diferenças foram controladas por regressão logística múltipla. Os pacientes relataram uma sonolência maior do que os controles (p <0,0001). Após a regressão, a sonolência relatada pelos pacientes mostrou-se associada a apenas um teste (RAVLT total). Os pacientes com ELTM-EH referem mais sonolência do que os controles, mas esta não foi associada com a cognição. Se confirmado em outras populações, nossos resultados implicarão na tomada de decisão sobre o impacto da sonolência no contexto neuropsicológico.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Cognición/fisiología , Epilepsia del Lóbulo Temporal/psicología , Autoinforme , Somnolencia , Pruebas Neuropsicológicas , Esclerosis/complicaciones , Estudios de Casos y Controles , Demografía , Escolaridad , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Hipocampo/patología , Anticonvulsivantes/uso terapéuticoRESUMEN
A promising alternative for the treatment of refractory epilepsy is electrical stimulation (ES) of the central nervous system. Based on the premise that epilepsy is a result of neural hypersynchronization, we have previously demonstrated that a novel non-standard form of electrical stimulation with randomized inter-pulse intervals, termed non-periodic stimulation (NPS), applied to the amygdala is robustly anticonvulsant. This investigation also suggested that NPS attains its therapeutic effect by desynchronization of epileptiform activity. Here, we further explored the desynchronization hypothesis by testing how the efficacy of NPS in the suppression of convulsive behaviors depends on morphological, spatial, and temporal parameters of stimulus. For this purpose, we varied the number of pulse phases (monopolar versus bipolar square pulses), side of stimulation (right versus left), number of application hemispheres (unilateral versus bilateral), and interhemispheric temporal synchronicity (synchronous versus asynchronous), while measuring the impact on the anticonvulsant action of NPS. Wistar rats received a controlled infusion of the convulsant agent pentylenetetrazole (PTZ, 10 mg/min), together with one of six variations of NPS applied to the amygdala. A stimulated PTZ-free group of animals was also performed as a positive control. Latency to convulsive behavior was used to measure seizure threshold. Animals receiving NPS displayed significant higher threshold for forelimb clonus and generalized tonic-clonic seizures for all patterns. Thresholds seemed to increase gradually from mono to biphasic, unilateral to bilateral, and synchronous to asynchronous stimuli. Thus, combined biphasic, bilateral, and asynchronous stimulation resulted in the greatest seizure threshold. PTZ free animals did not develop any observable convulsive behavior or other uncommon motor activity. These results confirm that NPS has anticonvulsant properties and that biphasic, bilateral, and asynchronous stimulation enhances its efficacy. The fact that lack of synchronism between stimuli of each hemisphere maximizes NPS anticonvulsant power is evidence to desynchronization as tool for suppression of seizures.
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Amígdala del Cerebelo/fisiopatología , Estimulación Encefálica Profunda/métodos , Convulsiones/fisiopatología , Convulsiones/terapia , Animales , Sincronización Cortical , Modelos Animales de Enfermedad , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/terapia , Estimulación Eléctrica/métodos , Epilepsia Tónico-Clónica/fisiopatología , Epilepsia Tónico-Clónica/terapia , Miembro Anterior/fisiopatología , Masculino , Pentilenotetrazol , Distribución Aleatoria , Ratas Wistar , Factores de TiempoRESUMEN
Human hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions as cornu Ammonis (CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.
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Epilepsia Refractaria/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Hipocampo/fisiopatología , Convulsiones/fisiopatología , Adulto , Región CA1 Hipocampal/fisiopatología , Región CA2 Hipocampal/fisiopatología , Región CA3 Hipocampal/fisiopatología , Giro Dentado/fisiopatología , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Femenino , Humanos , Masculino , Potasio/metabolismo , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológicoRESUMEN
Objectives To assess depressive disorders in patients with mesial temporal lobe epilepsy (MTLE) refractory to medical treatment. Methods Adult patients with refractory MTLE completed two questionnaires (Mini International Neuropsychiatric Interview (MINI) and the Beck Depression Inventory (BDI) had a semi-structured psychiatric interview and a high resolution MRI scan. For complete neuropsychiatric diagnosis, as per International Classification of Diseases (ICD-10), the results were combined with clinical history and additional information from the patients' family. Results Of the 40 patients identified for this case series study which took place from 2008-2012, 31 (77.5%) had a depressive disorder: 14 had dysthymia, 11 had recurrent depressive disorder and 6 had bipolar disorder. Of the nine patients without a firm diagnosis of mood disorder, seven had isolated symptoms of depression or anxiety and two presented with mixed depression/anxiety symptoms. Only 8/31 (25.8%) patients were receiving antidepressant treatment. There was no association between BDI scores and seizure frequency. No significant difference was found between patients with and without depression and the presence or laterality of HA. Conclusions Depressive disorders are common, underdiagnosed and undertreated in patients with refractory MTLE.
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Anticonvulsivantes/uso terapéutico , Antidepresivos/uso terapéutico , Trastorno Depresivo/fisiopatología , Epilepsia Refractaria/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Calidad de Vida/psicología , Adulto , Benzodiazepinas/uso terapéutico , Carbamazepina/uso terapéutico , Clobazam , Trastorno Depresivo/complicaciones , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/tratamiento farmacológico , Epilepsia Refractaria/complicaciones , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Escalas de Valoración Psiquiátrica , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. METHODS: This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. RESULTS: The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. CONCLUSIONS: KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients.
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Fenómenos Fisiológicos Nutricionales de los Adolescentes , Fenómenos Fisiológicos Nutricionales Infantiles , Dieta Cetogénica/efectos adversos , Epilepsia Refractaria/dietoterapia , Dislipidemias/etiología , Adolescente , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Biomarcadores/sangre , Brasil/epidemiología , Niño , Dieta Aterogénica/efectos adversos , Progresión de la Enfermedad , Epilepsia Refractaria/sangre , Epilepsia Refractaria/fisiopatología , Dislipidemias/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Estudios Prospectivos , RiesgoRESUMEN
Doose and Lennox-Gastaut (syndromes) are rare generalized electroclinical affections of early infancy of variable prognosis which manifest with very diverse kinds of seizures. Very frequently, these types of epilepsy become drug resistant and finding reliable treatment results is very difficult. As a result of this, fighting against these syndromes becomes a long term (or endless) event for the little patient, the neurologist and the parents. A lot of Electroencephalographic (EEG) records are so accumulated during the child's life in order to monitor evolution and correlate it with medications. So, given a bunch of EEG, three questions arise: (a) On which year was the child healthier (less affected by seizures)? (b) Which area of the brain has been the most affected? (c) What is the status of the child with respect to others (which also have a bunch of EEG, each)? Answering these interrogations by traditional scrutinizing of the whole database becomes subjective, if not impossible. We propose to answer these questions objectively by means of time series entropies. We start with our modified version of the Multiscale Entropy (MSE) in order to generalize it as a Bivariate MSE (BMSE) and from them, we compute two indices. All were tested in a series of patients and coincide with medical conclusions. As far as we are concerned, our contribution is new.
Asunto(s)
Encéfalo/fisiopatología , Epilepsia Refractaria/fisiopatología , Electroencefalografía/métodos , Epilepsias Mioclónicas/fisiopatología , Síndrome de Lennox-Gastaut/fisiopatología , Modelos Neurológicos , Adolescente , Algoritmos , Bases de Datos Factuales , Progresión de la Enfermedad , Entropía , Humanos , Procesamiento de Señales Asistido por ComputadorRESUMEN
PURPOSE: Temporal lobe epilepsy (TLE) is the most common variety of focal epilepsy among adults. The neuroinflammatory mechanisms of epilepsies may be involved in the genesis of seizures and refractory epilepsies, particularly in the case of progressive syndromes such as TLE associated with mesial hippocampal sclerosis (TLE-HS). The goal of the present study is investigate the genetic profile of susceptibility of individuals with TLE-HS by analyzing the possible association of TLE-HS with human leukocyte antigen (HLA) DRB1, DQA1 and DQB1 alleles. METHODS: Peripheral blood samples were collected from 42 individuals with pharmacoresistant TLE-HS and 89 healthy controls. The typing of the HLA class II alleles from DRB1, DQB1, and DQA1 loci were analyzed using sequence-specific primer-polymerase chain reaction (SSP-PCR) and identified through sequencing. Statistical analysis of relative allele frequencies was performed using an Excel spreadsheet; p-value, relative risk (RR), and odds ratio (OR) were calculated using the software Epi Info 6.0. p-values <0.05 following Bonferroni's method correction were considered statistically significant. RESULTS: HLA-DRB1*13:02 was the only allele with a statistically significant difference (p=0.01) in frequency between patients and controls. However, the significance was lost following Bonferroni's method correction (p=0.44). The remainder of the alleles in the HLA-DRB1, HLA-DQB1 and HLA-DQA1 regions did not exhibit any significant association. CONCLUSION: The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS.