RESUMEN
OBJECTIVE: We aimed to study the correlation between seizure outcomes in patients with drug-resistant epilepsy (DRE) who underwent laser interstitial thermal therapy (LITT) and stereoelectroencephalographic electrophysiologic patterns with respect to the extent of laser ablation. METHODS: We retrospectively analyzed 16 consecutive DRE patients who underwent LITT. A seizure onset zone (SOZ) was obtained from multidisciplinary patient management conferences and again was confirmed independently by two epileptologists based on conventional analysis. SOZs were retrospectively divided into localized, lobar and multilobar, and nonlocalized onset types. A posteriori-predicted epileptogenic zone (PEZ) was identified using the previously developed "EZ fingerprint" pipeline. The completeness of the SOZ and PEZ ablation was compared and correlated with the duration of seizure freedom (SF). RESULTS: Of 16 patients, 11 had an a posteriori-identified PEZ. Three patients underwent complete ablation of SOZ with curative intent, and the other 13 with palliative intent. Of three patients with complete ablation of the SOZ, two had concordant PEZ and SOZ and achieved 40- and 46-month SF without seizure recurrence. The remaining patient, without any PEZ identified, had seizure recurrence within 1 month. Six of 13 patients with partial ablation of the SOZ and PEZ achieved mean seizure freedom of 19.8 months (range = 1-44) with subsequent seizure recurrence. The remaining seven patients had partial ablation of the SOZ without the PEZ identified or ablation outside the PEZ with seizure recurrence within 1-2 months, except one patient who had 40-month seizure freedom after ablation of periventricular heterotopia. SIGNIFICANCE: Only complete ablation of the well-restricted SOZ concordant with the PEZ was associated with long-term SF, whereas partial ablation of the PEZ might lead to SF with eventual seizure recurrence. Failure to identify PEZ and ablation limited to the SOZ often led to 1-2 months of SF.
Asunto(s)
Epilepsia Refractaria , Epilepsia , Terapia por Láser , Neocórtex , Humanos , Neocórtex/cirugía , Estudios Retrospectivos , Epilepsia/cirugía , Convulsiones , Epilepsia Refractaria/cirugía , Electroencefalografía/métodos , Resultado del Tratamiento , Imagen por Resonancia MagnéticaRESUMEN
AIMS: Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. METHODS: A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. RESULTS: The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). CONCLUSIONS: The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.
Asunto(s)
Epilepsia del Lóbulo Temporal , Neocórtex , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/metabolismo , Neocórtex/diagnóstico por imagen , Neocórtex/cirugía , Fluorodesoxiglucosa F18 , Resultado del Tratamiento , Metaboloma , Tomografía de Emisión de Positrones , Hipocampo/metabolismoRESUMEN
Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.
Asunto(s)
Epilepsia Refractaria/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Neocórtex/fisiopatología , Red Nerviosa/fisiopatología , Neuronas/fisiología , Sinapsis/fisiología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Humanos , Neocórtex/cirugía , Sinaptofisina/metabolismo , Aprendizaje Verbal/fisiología , Sustancia BlancaRESUMEN
We describe a patient with focal epilepsy characterized by ictal asystole episodes and low-grade tumour over the left temporal neocortex. Non-invasive pre-surgical evaluation showed an epileptogenic zone extended beyond the low-grade tumour. This extension was confirmed by intraoperative electrocorticography. One-stage surgery with anterior temporal lobe resection was performed. The patient was seizure-free after one year of follow-up. Detailed electroclinical and therapeutic reasoning with hypotheses defining epileptogenic and symptomatogenic networks are discussed.
Asunto(s)
Paro Cardíaco , Neocórtex , Neoplasias , Electroencefalografía , Epilepsias Parciales , Epilepsia del Lóbulo Temporal/cirugía , Paro Cardíaco/etiología , Humanos , Neocórtex/cirugía , Neoplasias/complicacionesRESUMEN
End folium sclerosis or hippocampal sclerosis (HS) type 3 is often associated with another coexisting epileptogenic lesion (dual pathology); however, the pathogenesis of HS type 3 remains elusive. A 46-year-old man presented with medically intractable focal aware seizures and focal impaired awareness seizures (FIAS) with occasional focal to bilateral tonic-clonic seizures (FBTCS) two years after surgical treatment with extensive cranial reconstruction for a brain abscess in the right temporal lobe associated with intracranial extension of ipsilateral cholesteatoma. Head magnetic resonance imaging (MRI) at age 49 revealed atrophy of the right cerebral hemisphere including the hippocampus and amygdala. The patient's first epilepsy surgery was a lateral temporal lobectomy, in which the mesial temporal structures were preserved because no epileptiform discharge was detected on the intraoperative electrocorticogram. However, FIAS with FBTCS started 15 months after the operation. The second surgery, amygdalohippocampectomy, at age 52, resulted in the patient being seizure-free again for one year before seizures of the right lateral temporal origin recurred. He underwent a third surgery, resection of the Heschl's and supramarginal gyri, at age 53, but he continued to have drug-resistant epilepsy over two years after that. Histopathological examination revealed dual pathology consisting of glial scar in the lateral temporal lobe and ipsilateral HS type 3 with an unusually severe lesion in the subiculum. No significant inflammatory change was observed. The clinicopathological features in the present case indicate that HS developed secondarily in the context of neocortical epilepsy due to glial scar, suggesting a role of repetitive abnormal electrical input from neocortical epileptogenic lesions into the hippocampus finally via the perforant pathway in the pathogenesis of HS type 3. Severe hippocampal atrophy on preoperative MRI together with its silent electrocorticogram recording at initial epilepsy surgery may represent clinically pre-epileptogenic HS in a seizure-free "silent or latent period" before completion of hippocampal epileptogenesis to the extent that clinical epileptic seizures occur.
Asunto(s)
Absceso Encefálico/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Gliosis/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Neocórtex/diagnóstico por imagen , Absceso Encefálico/complicaciones , Absceso Encefálico/cirugía , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/cirugía , Gliosis/etiología , Gliosis/cirugía , Hipocampo/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neocórtex/cirugía , EsclerosisAsunto(s)
Citocinas/metabolismo , Epilepsia del Lóbulo Temporal/inmunología , Microvasos/patología , Neocórtex/irrigación sanguínea , Óxido Nítrico Sintasa de Tipo II/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Citocinas/análisis , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Humanos , Masculino , Microvasos/inmunología , Persona de Mediana Edad , Neocórtex/inmunología , Neocórtex/patología , Neocórtex/cirugía , Óxido Nítrico Sintasa de Tipo II/análisis , Adulto JovenRESUMEN
We examined the clinical, semiological, scalp EEG, and neuropsychological features of patients with "pure" neocortical temporal lobe epilepsy (NTLE) who were successfully treated by neocortical temporal resection sparing the mesial temporal structures. This retrospective study included 17 patients with lesional NTLE who satisfied the following criteria: presence of a discrete structural lesion in the lateral temporal lobe on preoperative MRI; lateral temporal resection sparing the mesial temporal structures; follow-up for at least two years after surgery; and favourable postoperative seizure outcome (Engel Class I). The study included 10 females and seven males, and the age at surgery ranged from 15 to 48 years (mean: 30.7 years). Auras, video-recorded seizure semiology, interictal and ictal EEG, and pre- and post-operative neuropsychological data were reviewed. Twenty patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, who had a favourable postoperative seizure outcome (Engel Class I), were selected as a control group. Age at seizure onset was significantly greater in patients with NTLE than in controls. A history of febrile convulsion was significantly less frequent in NTLE patients. Epigastric ascending sensation (6% versus 40%; p=0.017), oral automatisms (29% versus 80%; p=0.003), gestural automatisms (47% versus 80%; p=0.047), and dystonic posturing (0% versus 40%; p=0.003) were significantly less frequent in NTLE than controls. Ictal unitemporal rhythmic theta activity was also significantly less frequent in NTLE than controls (35.3% versus 75%; p=0.015). Preoperative IQ score (range: 68 to 114; mean: 88.9) and preoperative memory quotient score (range: 56-122; mean: 98.1) were significantly higher in NTLE (p=0.003 and p=0.048, respectively). There were notable differences in clinical, semiological, EEG, and neuropsychological features between "pure" NTLE and MTLE. These findings may be useful to identify the epileptogenic zone.
Asunto(s)
Ondas Encefálicas/fisiología , Disfunción Cognitiva/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Hipocampo/patología , Inteligencia/fisiología , Neocórtex/fisiopatología , Adolescente , Adulto , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Disfunción Cognitiva/cirugía , Electroencefalografía , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neocórtex/patología , Neocórtex/cirugía , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
OBJECTIVES: Neuroinflammation, implicated in epilepsy, can be imaged in humans with positron emission tomography (PET) ligands for translocator protein 18 kDa (TSPO). Previous studies in patients with temporal lobe epilepsy and mesial temporal sclerosis found increased [11C]PBR28 uptake ipsilateral to seizure foci. Neocortical foci present more difficult localization problems and more variable underlying pathology. METHODS: We studied 11 patients with neocortical seizure foci using [11C]PBR28 or [11C] N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA) 713, and 31 healthy volunteers. Seizure foci were identified with structural magnetic resonance imaging (MRI) and ictal video-electroencephalography (EEG) monitoring. Six patients had surgical resections; five had focal cortical dysplasia type 2A or B and one microdysgenesis. Brain regions were delineated using FreeSurfer and T1-weighted MRI. We measured brain radioligand uptake (standardized uptake values [SUVs]) in ipsilateral and contralateral regions, to compare calculated asymmetry indices [AIs; 200% *(ipsilateral - contralateral)/(ipsilateral + contralateral)] between epilepsy patients and controls, as well as absolute [11C]PBR28 binding as the ratio of distribution volume to free fraction (VT /fP ) in 9 patients (5 high affinity and 4 medium affinity binders) and 11 age-matched volunteers (5 high-affinity and 6 medium affinity) who had metabolite-corrected arterial input functions measured. RESULTS: Nine of 11 patients had AIs exceeding control mean 95% confidence intervals in at least one region consistent with the seizure focus. Three of the nine had normal MRI. There was a nonsignificant trend for patients to have higher binding than volunteers both ipsilateral and contralateral to the focus in the group that had absolute binding measured. SIGNIFICANCE: Our study demonstrates the presence of focal and distributed inflammation in neocortical epilepsy. There may be a role for TSPO PET for evaluation of patients with suspected neocortical seizure foci, particularly when other imaging modalities are unrevealing. However, a complex method, inherent variability, and increased binding in regions outside seizure foci will limit applicability.
Asunto(s)
Epilepsia/diagnóstico por imagen , Inflamación/diagnóstico por imagen , Neocórtex/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Receptores de GABA/metabolismo , Acetamidas , Adulto , Edad de Inicio , Electroencefalografía , Epilepsia/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neocórtex/cirugía , Procedimientos Neuroquirúrgicos/métodos , Piridinas , Radiofármacos , Adulto JovenRESUMEN
PURPOSE: Cavernous malformation (CM) in the temporal neocortex causes intractable epilepsy. Whether to resect additional mesial temporal structures in addition to the lesionectomy is a still controversial issue. To clarify the need for the procedure, we retrospectively analyzed pre- and postoperative clinical data of patients with surgically removed CM. SUBJECTS AND METHODS: We included data from 18 patients with CM in the temporal neocortex who presented with intractable epilepsy. Eleven patients of our early series were treated with extended resection, i.e., lesionectomy and the resection of additional mesial temporal structures. Seven patients underwent lesionectomy, i.e., removal of the CM and of hemosiderin-stained surrounding brain tissue. Pathological assessments of the resected hippocampus were performed. Chronic intracranial electroencephalography (EEG) recordings were obtained in 6 patients. We performed perioperative neuropsychological assessments in all patients. RESULTS: The seizure outcome was recorded as Engel class I in 17 patients (94.4%); Iaâ¯=â¯12 (66.7%) Ibâ¯=â¯2 (11.1%), Icâ¯=â¯1 (5.6%), Idâ¯=â¯2 (11.1%), and class IIb in one patient (5.6%). Adding resection of the mesial temporal structures to lesionectomy did not alter the seizure outcome. Pathology of hippocampus revealed limited neuronal loss in CA4. Ictal onsets in the ipsilateral lateral cortex were detected in all 6 patients who underwent intracranial EEG. In 4 patients each, we also detected ictal onsets from the ipsilateral mesial temporal structures and from the contralateral temporal lobe. Postoperatively, in the patients where their CM was located in the language-dominant hemisphere (nâ¯=â¯10), the full-scale intelligence quotient (IQ) and the performance IQ increased (pâ¯<â¯0.05), whereas the verbal memory (WMS-R) deteriorated in two of 5 patients. CONCLUSION: Excellent seizure outcomes were obtained even the lesionectomy alone. To confirm appropriate surgical strategy for lateral temporal CM with intractable epilepsy, further studies in large sample size are needed.
Asunto(s)
Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Neocórtex/cirugía , Convulsiones/cirugía , Lóbulo Temporal/cirugía , Adulto , Epilepsia Refractaria/complicaciones , Epilepsia Refractaria/patología , Epilepsia Refractaria/fisiopatología , Electroencefalografía/efectos adversos , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hipocampo/patología , Hipocampo/fisiopatología , Hipocampo/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/complicaciones , Convulsiones/patología , Convulsiones/fisiopatología , Lóbulo Temporal/patología , Lóbulo Temporal/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: Incomplete resection of neocortical epileptogenic foci correlates with failed epilepsy surgery in children. We often treat patients with neocortical epilepsy with a staged approach using invasive monitoring to localize the focus, resect the seizure onset zone, and, in select cases, post-resection invasive monitoring (PRM). We report the technique and the outcomes of children treated with staged surgery including PRM. METHODS: We retrospectively reviewed the charts of pediatric patients with neocortical epilepsy who underwent resective surgery with PRM. RESULTS: We identified 71 patients, 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions; 64/66 (97%) patients had complete lesionectomy. In 61/71 (86%) patients PRM was associated with positive outcomes. Those findings were: 1) clinical seizures with electrographic involvement at resection margins (47%); 2) subclinical seizures and interictal discharges at resection margins (29%); and 3) clinical and subclinical seizures revealing a new epileptogenic focus (20%). In 55/71 (77%) patients, PRM data led to additional resection (re-resection; RR). Six additional patients had no further resection due to overlap with eloquent cortex. Histopathology showed tuberous sclerosis complex (TSC; n = 46), focal cortical dysplasia (FCD; n = 16)), gliosis (n = 4), tumors (n = 4), and Sturge-Weber syndrome (n = 1). There were no major complications. Seizure-free outcome in children with TSC was 63% at 1-year follow-up and 56% at 2-year follow-up. In FCD, seizure freedom after 1 and 2 years was 85%. SIGNIFICANCE: Post-resection monitoring may provide additional information about the extent of the epileptogenic zone, such as residual epileptogenic activity at the margins of the resection cavity, and may unmask additional seizure foci. This method may be especially useful in achieving long-term stable seizure-free outcome.
Asunto(s)
Epilepsia Refractaria/cirugía , Epilepsias Parciales/cirugía , Neocórtex/cirugía , Monitorización Neurofisiológica , Niño , Preescolar , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/fisiopatología , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neocórtex/diagnóstico por imagen , Procedimientos Neuroquirúrgicos/métodos , Cuidados Posoperatorios , Complicaciones Posoperatorias , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/fisiopatología , Esclerosis Tuberosa/cirugíaRESUMEN
Repair of complex CNS circuitry requires newly incorporated neurons to become appropriately, functionally integrated. One approach is to direct differentiation of endogenous progenitors in situ, or ex vivo followed by transplantation. Prior studies find that newly incorporated neurons can establish long-distance axon projections, form synapses and functionally integrate in evolutionarily old hypothalamic energy-balance circuitry. We now demonstrate that postnatal neocortical connectivity can be reconstituted with point-to-point precision, including cellular integration of specific, molecularly identified projection neuron subtypes into correct positions, combined with development of appropriate long-distance projections and synapses. Using optogenetics-based electrophysiology, experiments demonstrate functional afferent and efferent integration of transplanted neurons into transcallosal projection neuron circuitry. Results further indicate that 'primed' early postmitotic neurons, including already fate-restricted deep-layer projection neurons and/or plastic postmitotic neuroblasts with partially fate-restricted potential, account for the predominant population of neurons capable of achieving this optimal level of integration.
Asunto(s)
Diferenciación Celular/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Neocórtex , Neuronas/fisiología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Animales Recién Nacidos , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de Unión al ADN/metabolismo , Embrión de Mamíferos , Antagonistas de Aminoácidos Excitadores/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neocórtex/citología , Neocórtex/crecimiento & desarrollo , Neocórtex/cirugía , Proteínas del Tejido Nervioso/metabolismo , Proteínas Represoras/metabolismo , Sinaptofisina/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Valina/análogos & derivados , Valina/farmacologíaRESUMEN
This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. Recent technological progress has enabled the fabrication of microelectrode arrays that allow recording the activity of multiple individual neurons in the neocortex of the human brain. These arrays have the potential to bring unique insight onto the neuronal correlates of cerebral function in health and disease. Furthermore, the identification and decoding of volitional neuronal activity opens the possibility to establish brain-computer interfaces, and thus might help restore lost neurological functions. The implantation of neocortical microelectrode arrays is an invasive procedure requiring a supra-centimetric craniotomy and the exposure of the cortical surface; thus, the procedure must be performed by an adequately trained neurosurgeon. In order to provide an opportunity for surgical training, we designed a procedure based on a human cadaver model. The use of a formaldehyde-fixed human cadaver bypasses the practical, ethical and financial difficulties of surgical practice on animals (especially non-human primates) while preserving the macroscopic structure of the head, skull, meninges and cerebral surface and allowing realistic, operating room-like positioning and instrumentation. Furthermore, the use of a human cadaver is closer to clinical daily practice than any non-human model. The major drawbacks of the cadaveric simulation are the absence of cerebral pulsation and of blood and cerebrospinal fluid circulation. We suggest that a formaldehyde-fixed human cadaver model is an adequate, practical and cost-effective approach to ensure proper surgical training before implanting microelectrode arrays in the living human neocortex.
Asunto(s)
Electrodos Implantados , Microelectrodos , Neocórtex/cirugía , Procedimientos Neuroquirúrgicos/métodos , Cadáver , Formaldehído , Humanos , Neurocirugia/educación , Procedimientos Neuroquirúrgicos/instrumentación , Fijación del TejidoRESUMEN
BACKGROUND: Multiple hippocampal transection (MHT) is a surgical treatment for mesial temporal lobe epilepsy associated with improved postoperative neuropsychological outcomes compared with lobectomy. OBJECTIVE: To determine whether resection of the amygdala and anterior temporal neocortex during MHT affects postoperative seizure/memory outcome. METHODS: Seventeen patients with normal magnetic resonance imaging and stereo-electroencephalogram-proven drug-resistant dominant mesial temporal lobe epilepsy were treated with MHT. Nine patients underwent MHT alone (MHT-) and 8 patients underwent MHT plus removal of the amygdala and anterior 4.5 cm of temporal neocortex lateral to the fusiform gyrus (MHT+). Verbal and visual-spatial memory were assessed in all patients preoperatively and in 14 patients postoperatively using the Wechsler Memory Scale. Postoperative seizure control was assessed at 12 months for all patients. RESULTS: Overall, 11 of 17 patients (64.7%) were Engel class 1 at 1 year (6/9 MHT-, 5/8 MHT+, P = .38), and 10 of 14 patients (71.4%) had no significant postoperative decline in either verbal or visual memory (6/8 MHT-, 4/6 MHT+, P = .42). Verbal memory declined in 2 of 8 MHT- and 1 of 6 MHT+ patients, and visual memory declined in 1 of 8 MHT- and 2 of 6 MHT+ patients. Two patients had improved visual memory postoperatively, both in the MHT+ group. CONCLUSION: MHT on the dominant side is associated with high rates of seizure freedom and favorable memory preservation outcomes regardless of the extent of neocortical resection. Preservation of the temporal neocortex and amygdala during MHT does not appear to decrease the risk of postoperative memory decline, nor does it alter seizure outcome.
Asunto(s)
Epilepsia del Lóbulo Temporal/cirugía , Hipocampo/cirugía , Trastornos de la Memoria/etiología , Neocórtex/cirugía , Psicocirugía , Reoperación/métodos , Adolescente , Adulto , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/cirugía , Persona de Mediana Edad , Pruebas Neuropsicológicas , Convulsiones/etiología , Convulsiones/cirugía , Adulto JovenAsunto(s)
Epilepsia Refractaria/enzimología , Epilepsia del Lóbulo Temporal/enzimología , Sistema Límbico/enzimología , Trastornos Mentales/enzimología , Mitocondrias/enzimología , Complejos Multienzimáticos/metabolismo , Adulto , Epilepsia Refractaria/patología , Epilepsia Refractaria/psicología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/psicología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Humanos , Sistema Límbico/patología , Sistema Límbico/cirugía , Masculino , Trastornos Mentales/complicaciones , Neocórtex/enzimología , Neocórtex/cirugía , Datos Preliminares , Estudios Prospectivos , Esclerosis/enzimología , Esclerosis/patología , Esclerosis/psicología , Esclerosis/cirugía , Lóbulo Temporal/enzimología , Lóbulo Temporal/cirugíaRESUMEN
OBJECTIVE: We aimed to validate the usefulness of gradient magnetic-field topography (GMFT) for analysis of ictal magnetoencephalography (MEG) in patients with neocortical epilepsy. METHODS: We identified 13 patients presenting with an ictal event during preoperative MEG. We applied equivalent current dipole (ECD) estimation and GMFT to detect and localize the ictal MEG onset, and compared these methods with the ictal onset zone (IOZ) derived from chronic intracranial electroencephalography. The surgical resection areas and outcomes were also evaluated. RESULTS: GMFT detected and localized the ictal MEG onset in all patients, whereas ECD estimation showed localized ECDs in only 2. The delineation of GMFT was concordant with the IOZ at the gyral-unit level in 10 of 12 patients (83.3%). The detectability and precision of delineation of ictal MEG activity by GMFT were significantly superior to those of ECD (p<0.05 and p<0.01, respectively). Complete resection of the IOZ in the concordant group provided seizure freedom in 3 patients, whereas seizures remained in 9 patients who had incomplete resections. CONCLUSIONS: Because of its higher spatial resolution, GMFT of ictal MEG is superior to conventional ECD estimation in patients with neocortical epilepsy. SIGNIFICANCE: Ictal MEG study is a useful tool to estimate the seizure onset in patients with neocortical epilepsy.
Asunto(s)
Epilepsia/diagnóstico , Epilepsia/fisiopatología , Magnetoencefalografía/métodos , Neocórtex/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Epilepsia/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neocórtex/cirugía , Estudios Retrospectivos , Adulto JovenRESUMEN
The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10 years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step.
Asunto(s)
Epilepsias Parciales/fisiopatología , Hamartoma/fisiopatología , Enfermedades Hipotalámicas/fisiopatología , Animales , Lobectomía Temporal Anterior , Niño , Preescolar , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Dominancia Cerebral/fisiología , Electrodos Implantados , Electroencefalografía , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/cirugía , Femenino , Hamartoma/diagnóstico , Hamartoma/cirugía , Hipocampo/fisiopatología , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/cirugía , Excitación Neurológica/fisiología , Masculino , Neocórtex/fisiopatología , Neocórtex/cirugía , Red Nerviosa/fisiopatología , Red Nerviosa/cirugía , Neuronas/fisiología , Procesamiento de Señales Asistido por Computador , Adulto JovenRESUMEN
This was a prospective observational study to correlate the clinical symptoms, electrophysiology, imaging, and surgical pathology of patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis. We selected consecutive patients with TLE and normal MRI undergoing temporal lobe resection between April and September 2015. Clinical features, imaging, and functional data were reviewed. Intracranial monitoring and language mapping were performed when it was required according to our team recommendation. Prior to hippocampal resection, intraoperative electrocorticography was performed using depth electrodes in the amygdala and the hippocampus. The resected hippocampus was sent for pathological analysis. RESULTS: Five patients with diagnosis with non-lesional TLE were included. We did not find distinctive clinical features that could be a characteristic of non-lesional TLE. The mean follow-up was 13.2months (11-15months); 80% of patients achieved Engel Class I outcome. There was no distinctive electrographic findings in these patients. Histopathologic analysis was negative for mesial temporal sclerosis. A second blinded independent neuropathologist with expertise in epilepsy found ILAE type I focal cortical dysplasia in the parahippocampal gyrus in all patients. A third independent neuropathologist reported changes in layer 2 with larger pyramidal neurons in 4 cases but concluded that none of these cases met the diagnostic criteria of FCD. Subtle pathological changes could be associated with a parahippocampal epileptic zone and should be investigated in patients with MRI-negative TLE. This study also highlights the lack of interobserver reliability for the diagnosis of mild cortical dysplasia. Finally, selective amygdalo-hippocampectomy or laser ablation of the hippocampus may not control intractable epilepsy in this specific population.
Asunto(s)
Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Neocórtex/patología , Neocórtex/cirugía , Adulto , Electrocorticografía/métodos , Electroencefalografía/métodos , Epilepsia del Lóbulo Temporal/psicología , Femenino , Hipocampo/patología , Hipocampo/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Giro Parahipocampal/patología , Giro Parahipocampal/cirugía , Estudios Prospectivos , Reproducibilidad de los Resultados , Lóbulo Temporal/patología , Lóbulo Temporal/cirugíaRESUMEN
Human epilepsy patients suffer from spontaneous seizures, which originate in brain regions that also subserve normal function. Prior studies demonstrate focal, neocortical epilepsy is associated with dysfunction, several hours before seizures. How does the epileptic network perpetuate dysfunction during baseline periods? To address this question, we developed an unsupervised machine learning technique to disentangle patterns of functional interactions between brain regions, or subgraphs, from dynamic functional networks constructed from approximately 100 h of intracranial recordings in each of 22 neocortical epilepsy patients. Using this approach, we found: (1) subgraphs from ictal (seizure) and interictal (baseline) epochs are topologically similar, (2) interictal subgraph topology and dynamics can predict brain regions that generate seizures, and (3) subgraphs undergo slower and more coordinated fluctuations during ictal epochs compared to interictal epochs. Our observations suggest that seizures mark a critical shift away from interictal states that is driven by changes in the dynamical expression of strongly interacting components of the epileptic network.
Asunto(s)
Mapeo Encefálico/métodos , Epilepsia Refractaria/fisiopatología , Neocórtex/fisiopatología , Aprendizaje Automático no Supervisado , Análisis por Conglomerados , Conjuntos de Datos como Asunto , Epilepsia Refractaria/cirugía , Electrocorticografía , Electrodos Implantados , Femenino , Humanos , Masculino , Modelos Neurológicos , Neocórtex/cirugía , Convulsiones/fisiopatología , Convulsiones/cirugía , Factores de TiempoRESUMEN
Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema/increased intracranial pressure modulated and single human pyramidal cell verified gene products identified here might be considered as novel pharmacological targets in cell type specific neuroprotection.
Asunto(s)
Edema Encefálico/metabolismo , Hipertensión Intracraneal/metabolismo , Neocórtex/metabolismo , Neuronas/metabolismo , Adulto , Edema Encefálico/patología , Edema Encefálico/cirugía , Femenino , Regulación de la Expresión Génica , Sustancia Gris/metabolismo , Sustancia Gris/patología , Sustancia Gris/cirugía , Humanos , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Hipertensión Intracraneal/patología , Hipertensión Intracraneal/cirugía , Presión Intracraneal/fisiología , Masculino , Potenciales de la Membrana/fisiología , Persona de Mediana Edad , Neocórtex/patología , Neocórtex/cirugía , Neuronas/patología , ARN Mensajero/metabolismo , Técnicas de Cultivo de TejidosRESUMEN
Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca(2+) imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca(2+) signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo.