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PGAP2 gene has been known to be the cause of "hyperphosphatasia, mental retardation syndrome-3" (HPMRS3). To date, 14 pathogenic variants in PGAP2 have been identified as the cause of this syndrome in 24 patients described in single-case reports or small clinical series with pan-ethnic distribution. We aim to present a pediatric PGAP2-mutated case, intending to further expand the clinical phenotype of the syndrome and to report our experience on a therapeutic approach to drug-resistant epilepsy.We present the clinical, neuroradiological, and genetic characterization of a Caucasian pediatric subject with biallelic pathogenic variants in the PGAP2 gene revealed by next generation sequencing analysis.We identified a subject who presented with global developmental delay and visual impairment. Brain magnetic resonance imaging showed mild hypoplasia of the inferior cerebellar vermis and corpus callosum and mild white matter reduction. Laboratory investigations detected an increase in alkaline phosphatase. At the age of 13 months, he began to present epileptic focal seizures with impaired awareness, which did not respond to various antiseizure medications. Electroencephalogram (EEG) showed progressive background activity disorganization and multifocal epileptic abnormalities. Treatment with high-dose pyridoxine showed partial benefit, but the persistence of seizures and the lack of EEG amelioration prompted us to introduce ketogenic diet treatment.Our case provides a further phenotypical expansion of HPMRS3 to include developmental and epileptic encephalopathy. Due to the limited number of patients reported so far, the full delineation of the clinical spectrum of HPMRS3 and indications for precision medicine would benefit from the description of new cases and their follow-up evaluations.
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Anomalías Múltiples , Epilepsia , Discapacidad Intelectual , Humanos , Lactante , Masculino , Anomalías Múltiples/patología , Encéfalo/patología , Epilepsia/diagnóstico por imagen , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Fenotipo , Convulsiones , SíndromeRESUMEN
PURPOSE: The dysregulation of brain iron homeostasis is closely relevant to a multitude of chronic neurological disorders. This study employed quantitative susceptibility mapping (QSM) to detect and compare whole-brain iron content between childhood epilepsy with centrotemporal spikes (CECTS) children and typically developing children. MATERIALS AND METHODS: 32 children with CECTS and 25 age- and gender-matched healthy children were enrolled. All participants were imaged with 3.0-T MRI to acquire the structural and susceptibility-weighted data. The susceptibility-weighted data were processed using STISuite toolbox to obtain QSM. The magnetic susceptibility difference between the two groups was compared using voxel-wise and region of interest methods. Multivariable linear regression, controlling for age, were employed to investigate the associations between the brain magnetic susceptibility and age at onset. RESULTS: Lower magnetic susceptibility was mainly observed in sensory- and motor-related brain regions in children with CECTS, including bilateral middle frontal gyrus, supplementary motor area, midcingulate cortex, paracentral lobule and precentral gyrus, the magnetic susceptibility of right paracentral lobule, right precuneus and left supplementary motor area were found to have positive correlation with the age at onset. CONCLUSIONS: This study suggests that the potential iron deficiency in certain brain regions is associated with CECTS, which might be helpful for further illumination of potential pathogenesis mechanism of CECTS.
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Epilepsia , Hierro , Humanos , Niño , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Epilepsia/diagnóstico por imagenRESUMEN
Neuromodulation is an increasingly utilized therapy for the treatment of people with drug-resistant epilepsy. To date, the most common and effective target has been the thalamus, which is known to play a key role in multiple forms of epilepsy. Neuroimaging has facilitated rapid developments in the understanding of functional targets, surgical and programming techniques, and the effects of thalamic stimulation. In this review, the role of neuroimaging in neuromodulation is explored. First, the structural and functional changes of the thalamus in common epilepsy syndromes are discussed as the rationale for neuromodulation of the thalamus. Next, methods for imaging different thalamic nuclei are presented, as well as rationale for the need of direct surgical targeting rather than reliance on traditional stereotactic coordinates. Lastly, we discuss the potential role of neuroimaging in assessing the effects of thalamic stimulation and as a potential biomarker for neuromodulation outcomes.
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Conectoma , Epilepsia Refractaria , Epilepsia , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsia/diagnóstico por imagen , Epilepsia/terapia , Humanos , Neuroimagen , Tálamo/diagnóstico por imagenRESUMEN
A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various frequency ranges are coordinated across the space of the human cortex and time of memory processing is inconclusive. They can either be coordinated together across the frequency spectrum at the same cortical site and time or induced independently in particular bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated low frequency theta, intermediate frequency alpha and beta, and high frequency gamma power in a mosaic pattern of discrete cortical sites. A majority of the cortical sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and high frequency activities propagated in independent sequences across the visual, temporal and prefrontal cortical areas throughout subsequent phases of memory encoding. Our results provide a holistic, simplified model of the spectral activities engaged in the formation of human memory, suggesting an anatomically and temporally distributed mosaic of coordinated brain rhythms.
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Electroencefalografía/métodos , Memoria/fisiología , Adulto , Conjuntos de Datos como Asunto , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.
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Encéfalo/fisiopatología , Epilepsia/fisiopatología , Neuronas , Adulto , Benzotiazoles/farmacología , Encéfalo/crecimiento & desarrollo , Señalización del Calcio , Preescolar , Epilepsia/diagnóstico por imagen , Femenino , Humanos , Células Madre Pluripotentes Inducidas , Proteína 2 de Unión a Metil-CpG/genética , Red Nerviosa/fisiopatología , Neurogénesis/genética , Neuroimagen , Síndrome de Rett/diagnóstico por imagen , Síndrome de Rett/fisiopatología , Análisis de la Célula Individual , Sinapsis , Tolueno/análogos & derivados , Tolueno/farmacología , TranscriptomaRESUMEN
OBJECTIVE: To identify magnetic resonance imaging (MRI) biomarkers for post-traumatic epilepsy. METHODS: The EPITARGET (Targets and biomarkers for antiepileptogenesis, epitarget.eu) animal cohort completing T2 relaxation and diffusion tensor MRI follow-up and 1-month-long video-electroencephalography monitoring included 98 male Sprague-Dawley rats with traumatic brain injury and 18 controls. T2 imaging was performed on day (D) 2, D7, and D21 and diffusion tensor imaging (DTI) on D7 and D21 using a 7-Tesla Bruker PharmaScan MRI scanner. The mean and standard deviation (SD) of the T2 relaxation rate, multiple diffusivity measures, and diffusion anisotropy at each time-point within the ventroposterolateral and ventroposteromedial thalamus were used as predictor variables in multi-variable logistic regression models to distinguish rats with and without epilepsy. RESULTS: Twenty-nine percent (28/98) of the rats with traumatic brain injury (TBI) developed epilepsy. The best-performing logistic regression model utilized the D2 and D7 T2 relaxation time as well as the D7 diffusion tensor data. The model distinguished rats with and without epilepsy (Bonferroni-corrected p-value < .001) with a cross-validated concordance statistic of 0.74 (95% confidence interval [CI] 0.60-0.84). In a cross-validated classification test, the model exhibited 54% sensitivity and 91% specificity, enriching the epilepsy rate within the study population from the expected 29% to 71%. A model using the D2 T2 data only resulted in a 73% enriched epilepsy rate (regression p-value .007, cross-validated concordance 0.70, 95% CI 0.56-0.80, sensitivity 29%, specificity 96%). SIGNIFICANCE: An MRI parameter set reporting on acute and subacute neuropathologic changes common to experimental and human TBI presents a diagnostic biomarker for post-traumatic epileptogenesis. Significant enrichment of the study population was achieved even when using a single time-point measurement, producing an expected epilepsy rate of 73%.
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Lesiones Traumáticas del Encéfalo , Epilepsia , Animales , Biomarcadores , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Humanos , Masculino , Pronóstico , Ratas , Ratas Sprague-Dawley , Tálamo/diagnóstico por imagenRESUMEN
OBJECTIVE: The effects of individual cannabinoids on white matter integrity are unclear. Human studies have shown white matter maturation alterations in regular recreational cannabis users with the magnitude of these effects dependent on the age of exposure. However, studies have yet to determine which phytocannabinoids are most responsible for these changes. In the current study, we analyzed the effects of pharmaceutical grade cannabidiol oral solution (CBD; Epidiolex® in the U.S.; Epidyolex® in the EU; 100 mg/mL oral solution) on white matter integrity using diffusion MRI in patients with treatment resistant epilepsy (TRE). METHODS: 15 patients with TRE underwent 3 T diffusion MRI prior to receiving CBD and then again approximately 12 weeks later while on a stable dose of CBD for at least two weeks. DTI analyzes were conducted using DSI Studio and tract-based spatial statistics (TBSS). RESULTS: DTI analysis using DSI Studio showed significant increases in fractional anisotropy (FA) in the right medial lemniscus (p = 0.03), right superior cerebellar peduncle (p = 0.03) and the pontine crossing tract (p = 0.04); decreased mean diffusivity (MD) in the left uncinate fasciculus (p = 0.02) and the middle cerebellar peduncle (p = 0.04); decreased axial diffusivity (AD) in the left superior cerebellar peduncle (p = 0.05), right anterior limb of the internal capsule (p = 0.03), and right posterior limb of the internal capsule (p = 0.02); and decreased radial diffusivity (RD) in the middle cerebellar peduncle (p = 0.03) and left uncinate fasiculus (p = 0.01). The follow-up ANCOVA also yielded significant results when controlling for covariates of CBD dosage, age, sex, change in seizure frequency, and scanner type: FA increased in the pontine crossing tract (p = 0.03); RD decreased in the middle cerebellar peduncle (p = 0.04) and left uncinate fasciculus (p = 0.04). Subsequent TBSS analysis controlling for the same variables yielded no significant white matter differences between groups. CONCLUSION: These findings indicate relatively minor short-term effects of highly-purified plant-derived CBD on white matter structural integrity in patients with TRE.
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Cannabidiol , Epilepsia , Sustancia Blanca , Anisotropía , Encéfalo , Cannabidiol/uso terapéutico , Imagen de Difusión Tensora , Epilepsia/diagnóstico por imagen , Epilepsia/tratamiento farmacológico , Humanos , Sustancia Blanca/diagnóstico por imagenRESUMEN
Pyridoxine-dependent epilepsy (PDE) is a recessive genetic disease characterized by epileptic encephalopathy with therapeutic response to pharmacological doses of pyridoxine and resistance to anti-epileptic treatments. The recent discovery in 2006 of the genetic defect antiquitin (ALDH7A1, OMIM #266100) has helped to understand the underlying mechanism, which is the accumulation of neurotoxic intermediates in the lysine catabolic pathway. The goal of the new therapeutic approach, termed triple therapy (TT) (pyridoxine, lysine-restricted diet and arginine supplementation), is to improve epilepsy control and neurocognitive development in patients with PDE. We present the 3-year treatment outcome for a child with PDE on pyridoxine treatment (started at age 5 months), lysine-restricted diet (started at age 17 months) and arginine supplementation therapy (started at age 19 months). The TT was well-tolerated with good compliance. No adverse events were reported. We observed a neurodevelopmental improvement, significantly fewer seizures, and a reduction of pipecolic acid (PA) as a biomarker of the illness. Our results show an improving clinical evolution, supporting and extending previous studies reporting efficacy of TT.
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Arginina/administración & dosificación , Suplementos Dietéticos , Epilepsia/diagnóstico por imagen , Epilepsia/dietoterapia , Lisina/deficiencia , Piridoxina/administración & dosificación , Biomarcadores/sangre , Preescolar , Epilepsia/sangre , Femenino , Humanos , Ácidos Pipecólicos/sangre , Resultado del TratamientoRESUMEN
Spoken language, both perception and production, is thought to be facilitated by an ensemble of predictive mechanisms. We obtain intracranial recordings in 37 patients using depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. These reveal two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first, localized to bilateral Heschl's gyri and indexed by low-frequency phase, predicts the timing of acoustic events. The second, localized to planum temporale only in language-dominant cortex and indexed by high-gamma power, shows a transient response to acoustic stimuli that is uniquely suppressed during speech production. Chronometric stimulation of Heschl's gyrus selectively disrupts speech perception, while stimulation of planum temporale selectively disrupts speech production. This work illuminates the fundamental acoustic infrastructure-both architecture and function-for spoken language, grounding cognitive models of speech perception and production in human neurobiology.
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Corteza Auditiva/fisiopatología , Epilepsia/fisiopatología , Estimulación Acústica , Adulto , Corteza Auditiva/diagnóstico por imagen , Mapeo Encefálico , Epilepsia/diagnóstico por imagen , Epilepsia/psicología , Femenino , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Habla , Percepción del Habla , Adulto JovenRESUMEN
PURPOSE: The parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between the mediodorsal nucleus and the prefrontal cortex play a major role in cognition, particularly in the rapid processing of behaviorally relevant information. The thalamus is the brain region with the highest density in α4ß2 nicotinic acetylcholine receptors, the main human nicotinic acetylcholine receptor subtype. The aim of this study was to investigate the possible role of the nicotinic cholinergic system in the thalamo-cortical loops measuring receptor density in different subregions of the thalamus, based on their cortical connectivity. PROCEDURES: We studied α4ß2 nicotinic acetylcholine receptors using positron emission tomography and [18F]Fluoro-A-85380, a radiotracer specific for this receptor subtype, in 36 non-smoking male subjects, including 12 healthy controls and 24 patients with epilepsy. [18F]Fluoro-A-85380 ratio index of binding potential was compared by a repeated measures general linear model, including the thalamic subregions and the brain hemisphere as within-subject factor and clinical groups as between-subject factor. RESULTS: The "prefrontal" thalamus, the subregion including the mediodorsal nucleus, had a significantly higher nicotinic acetylcholine receptor density than all other thalamic subregions. These findings were confirmed when analyzing solely the 12 healthy controls. CONCLUSIONS: This particular neurochemical organization of the thalamus supports a major role of the cholinergic system in the loops between the thalamus and the prefrontal cortex. The highest nicotinic acetylcholine receptor density in the « higher-order thalamus ¼ could partly explain the beneficial effect of acute nicotine on attentional and executive functions and possibly the pathophysiology of some neuropsychiatric disorders.
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Epilepsia/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Receptores Nicotínicos/metabolismo , Tálamo/diagnóstico por imagen , Adulto , Mapeo Encefálico , Cognición , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Receptores Nicotínicos/químicaRESUMEN
Memory impairment is common in persons with epilepsy (PWE), and exercise may be a strategy for its improvement. In this pilot study, we hypothesized that exercise rehabilitation would improve physical fitness and verbal memory and induce changes in brain networks involved in memory processes. We examined the effects of combined endurance and resistance exercise rehabilitation on memory and resting state functional connectivity (rsFC). Participants were randomized to exercise (PWE-E) or control (PWE-noE). The exercise intervention consisted of 18 supervised sessions on nonconsecutive days over 6â¯weeks. Before and after the intervention period, both groups completed self-report assessments (Short Form-36 (SF-36), Baecke Questionnaire (BQ) of habitual physical activity, and Profile of Mood States (POMS)), cognitive testing (California Verbal Learning Test-II (CVLT-II)), and magnetic resonance imaging (MRI); PWE-E also completed exercise performance tests. After completing the study, PWE-noE were offered cross-over to the exercise arm. There were no differences in baseline demographic, clinical, or assessment variables between 8 PWE-noE and 9 PWE-E. Persons with epilepsy that participated in exercise intervention increased maximum voluntary strength (all strength tests pâ¯<â¯0.05) and exhibited nonsignificant improvement in cardiorespiratory fitness (pâ¯=â¯0.15). Groups did not show significant changes in quality of life (QOL) or habitual physical activity between visits. However, there was an effect of visit on POMS total mood disturbance (TMD) measure showing improvement from baseline to visit 2 (pâ¯=â¯0.023). There were significant group by visit interactions on CVLT-II learning score (pâ¯=â¯0.044) and total recognition discriminability (d') (pâ¯=â¯0.007). Persons with epilepsy that participated in exercise intervention had significant reductions in paracingulate rsFC with the anterior cingulate and increases in rsFC for the cerebellum, thalamus, posterior cingulate cortex (PCC), and left and right inferior parietal lobule (IPL) (corrected pâ¯<â¯0.05). Change in CVLT-II learning score was associated with rsFC changes for the paracingulate cortex (rSâ¯=â¯-0.67; pâ¯=â¯0.0033), left IPL (rSâ¯=â¯0.70; pâ¯=â¯0.0019), and right IPL (rSâ¯=â¯0.71; pâ¯=â¯0.0015) while change in d' was associated with change in cerebellum rsFC to angular/middle occipital gyrus (rSâ¯=â¯0.68; pâ¯=â¯0.0025). Our conclusion is that exercise rehabilitation may facilitate verbal memory improvement and brain network functional connectivity changes in PWE and that improved memory performance is associated with changes in rsFC. A larger randomized controlled trial of exercise rehabilitation for cognitive improvement in PWE is warranted.
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Encéfalo/fisiología , Entrenamiento Aeróbico/métodos , Epilepsia/terapia , Memoria/fisiología , Red Nerviosa/fisiología , Entrenamiento de Fuerza/métodos , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Entrenamiento Aeróbico/psicología , Epilepsia/diagnóstico por imagen , Epilepsia/psicología , Terapia por Ejercicio/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Proyectos Piloto , Calidad de Vida/psicología , Conducta Verbal/fisiología , Adulto JovenRESUMEN
The field of epilepsy surgery has seen tremendous growth in recent years. Innovative new devices have driven much of this growth, but some has been driven by revisions of existing products. Devices have also helped to rejuvenate existing procedures, as in the case of robotic assistance for electrode placement for stereo-electroencephalography, and these devices have brought significant attention along with their introduction. Other devices, such as responsive neurostimulators or laser interstitial thermal therapy systems, have introduced novel treatment modalities and broadened the surgical indications. Collectively, these advances are rapidly changing much of the landscape in the world of pediatric neurosurgery for medically refractory epilepsy. The foundations for indications for neurosurgical intervention are well supported in strong research data, which has also been expanded in recent years. In this article, the authors review advances in the neurosurgical treatment of pediatric epilepsy, beginning with trials that have repeatedly demonstrated the value of neurosurgical procedures for medically refractory epilepsy and following with several recent advances that are largely focused on less-invasive intervention. ABBREVIATIONS AED = antiepileptic drug; ANT = anterior nucleus of the thalamus; BOLD = blood oxygen level dependent; CCEP = cortico-cortical evoked potential; DBS = deep brain stimulation; ECoG = electrocorticography; ERSET = Early Randomized Surgical Epilepsy Trial; FCD = focal cortical dysplasia; HH = hypothalamic hamartoma; LITT = laser interstitial thermal therapy; RCT = randomized controlled trial; r-fMRI = resting-state functional MRI; RNS = responsive neurostimulation; SEEG = stereo-electroencephalography; VNS = vagus nerve stimulation.
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Epilepsia/cirugía , Procedimientos Neuroquirúrgicos/métodos , Aniversarios y Eventos Especiales , Niño , Cirugía Laser de Córnea , Terapia por Estimulación Eléctrica , Electroencefalografía , Endoscopios , Epilepsia/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7â¯Telsa (7â¯T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (nâ¯=â¯9) or radiological (nâ¯=â¯1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3â¯years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (pâ¯=â¯.001), and increased peritumoural GluCEST contrast was associated with both recent seizures (pâ¯=â¯.038) and drug refractory epilepsy (pâ¯=â¯.029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (Râ¯=â¯0.89, pâ¯=â¯.003) and a positive trend existed in the tumour voxel (Râ¯=â¯0.65, pâ¯=â¯.113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7â¯T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.
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Neoplasias Encefálicas/metabolismo , Epilepsia/metabolismo , Glioma/metabolismo , Ácido Glutámico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Adulto , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Femenino , Glioma/complicaciones , Glioma/diagnóstico por imagen , Glioma/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The purpose of this study was to characterize the reasons, extent, and impact of traditional medicine use among people with epilepsy (PWE) in the Republic of Guinea. METHODS: Guinea is a low-income country in sub-Saharan Africa (SSA) with limited healthcare resources. People with epilepsy and their caregivers were seen at a public referral hospital in Conakry, the capital city, where they completed semi-structured interviews with physicians regarding their beliefs about epilepsy, medical care, and engagement with traditional healers. RESULTS: Of 132 participants (49% children, 44% female, 55% with a university-educated head of household), 79% had seen a traditional healer, and 71% saw a traditional healer before seeing a medical provider for their epilepsy. Participants were treated by a traditional healer for a mean of 39â¯months before seeing a medical provider. By contrast, 58% of participants reported taking antiepileptic drugs (AEDs) regularly; 46% reported having undergone a head computed tomography (CT) scan; 58% reported having had an electroencephalogram, and 4% reported having had a brain magnetic resonance imaging (MRI) scan. CONCLUSIONS: Traditional healers in Guinea provide frontline care for PWE in Guinea with considerable delays in AED initiation, even among a cohort of PWE actively seeking medical care. Engaging with these healers is critical for both influencing community perceptions and appropriately managing epilepsy throughout the country.
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Cuidadores , Epilepsia/etnología , Epilepsia/terapia , Medicinas Tradicionales Africanas/métodos , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Cuidadores/psicología , Niño , Preescolar , Estudios de Cohortes , Electroencefalografía/métodos , Epilepsia/diagnóstico por imagen , Femenino , Guinea/etnología , Humanos , Masculino , Derivación y Consulta , Adulto JovenRESUMEN
Previous studies have shown insular activations involving sensory, motor, and affective processing. However, the functional roles of subdivisions within the human insula are still not well understood. In the present study, we used intracranial electroencephalography and electrical cortical stimulation to investigate the causal roles of subdivisions of the insula in auditory emotion perception in epilepsy patients implanted with depth electrodes in this brain region. The posterior and the anterior subdivisions of the human insula, identified based on structural and functional analyses, showed distinct response properties to auditory emotional stimuli. The posterior insula showed auditory responses that resemble those observed in Heschl's gyrus, whereas the anterior insula (AI) responded to the emotional contents of the auditory stimuli in a similar way as observed in the amygdala. Furthermore, the degree of the differentiation between various emotion types increased from the posterior to the AI. Our findings suggest different roles played by the two regions of the human insula and a transformation from sensory to affective representations in auditory modality along the posterior-to-anterior axis in the human insula.
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Percepción Auditiva/fisiología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiología , Emociones/fisiología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Estimulación Acústica/métodos , Adolescente , Adulto , Imagen de Difusión Tensora/métodos , Electrocorticografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Recent developments of transparent electrode arrays provide a unique capability for simultaneous optical and electrical interrogation of neural circuits in the brain. However, none of these electrode arrays possess the stretchability highly desired for interfacing with mechanically active neural systems, such as the brain under injury, the spinal cord, and the peripheral nervous system (PNS). Here, we report a stretchable transparent electrode array from carbon nanotube (CNT) web-like thin films that retains excellent electrochemical performance and broad-band optical transparency under stretching and is highly durable under cyclic stretching deformation. We show that the CNT electrodes record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. Simultaneous two-photon calcium imaging through the transparent CNT electrodes from cortical surfaces of GCaMP-expressing mice with epilepsy shows individual activated neurons in brain regions from which the concurrent electrical recording is taken, thus providing complementary cellular information in addition to the high-temporal-resolution electrical recording. Notably, the studies on rats show that the CNT electrodes remain operational during and after brain contusion that involves the rapid deformation of both the electrode array and brain tissue. This enables real-time, continuous electrophysiological monitoring of cortical activity under traumatic brain injury. These results highlight the potential application of the stretchable transparent CNT electrode arrays in combining electrical and optical modalities to study neural circuits, especially under mechanically active conditions, which could potentially provide important new insights into the local circuit dynamics of the spinal cord and PNS as well as the mechanism underlying traumatic injuries of the nervous system.
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Electrodos Implantados , Nanotubos de Carbono/química , Red Nerviosa , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/patología , Calcio/análisis , Elasticidad , Estimulación Eléctrica/métodos , Fenómenos Electrofisiológicos , Epilepsia/diagnóstico por imagen , Epilepsia/patología , Ratones , Ratones Transgénicos , Imagen Óptica/métodos , Optogenética/métodos , RatasRESUMEN
OBJECTIVE: The objective of this study was to investigate whether reduction of thalamic volumes in children with early onset epilepsy (CWEOE) is associated with cognitive impairment. METHODS: This is a nested case-control study including a prospectively recruited cohort of 76 children with newly-diagnosed early onset epilepsy (onset <5years age) and 14 healthy controls presenting to hospitals within NHS Lothian and Fife. Quantitative volumetric analysis of subcortical structures was performed using volumetric T1-weighted magnetic resonance imaging (MRI) and correlated with the results of formal neurocognitive and clinical assessment. False discovery rate was used to correct for multiple comparisons as appropriate with q<0.05 used to define statistical significance. RESULTS: Age, gender, and intracranial volume (ICV)-adjusted left thalamic volumes were significantly reduced in CWEOE with cognitive impairment compared to CWEOE without impairment (5295mm3 vs 6418mm3, q=0.008) or healthy controls (5295mm3 vs 6410mm3, q<0.001). The differences in left thalamic volume remained if gray matter or cortical/cerebellar volumes were used as covariates rather than ICV (q<0.05). The degree of volume reduction correlated with the severity of cognitive impairment (q=0.048). SIGNIFICANCE: Reduced left thalamic volume may be a biomarker for cognitive impairment in CWEOE and could help inform the need for further formal cognitive evaluations and interventions.
Asunto(s)
Encéfalo/patología , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Imagen por Resonancia Magnética , Tálamo/diagnóstico por imagen , Estudios de Casos y Controles , Niño , Disfunción Cognitiva/psicología , Epilepsia/patología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
MRI-guided laser interstitial thermal therapy for epilepsy (LITT-E) has become an established, minimally invasive alternative to traditional epilepsy surgery. LITT-E is particularly valuable in cases in which open surgery poses unacceptably high morbidity or patient preference precludes craniotomy. Here we present a focused review of technical details and application of LITT to both focal and generalized epilepsy.
Asunto(s)
Epilepsia/diagnóstico por imagen , Epilepsia/terapia , Hipertermia Inducida/métodos , Terapia por Láser/métodos , Imagen por Resonancia Magnética Intervencional , Craneotomía , Humanos , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVE The ROSA device is a robotic stereotactic arm that uses a laser system to register the patient's head or spine with MR or CT images. In this study, the authors analyze their experience with this system in pediatric neurosurgical applications and present selected cases that exemplify the usefulness of this system. METHODS The authors reviewed all cases that utilized the ROSA system at their institution. Patient demographics, pathology, complications, electrode placement, laser ablation, and biopsy accuracy were analyzed. Patient disposition and condition at follow-up were also analyzed. RESULTS Seventeen patients underwent 23 procedures using the ROSA system. A total of 87 electroencephalography electrodes were placed, with 13% deviating more than 3 mm from target. Six patients underwent stereotactic needle biopsy, and 9 underwent laser interstitial thermotherapy (LITT). One patient who underwent LITT required a subsequent craniotomy for tumor resection. Another patient experienced an asymptomatic extraaxial hematoma that spontaneously resolved. No patient suffered neurological complications during follow-up. Follow-up from the last procedure averaged 180 days in epilepsy patients and 309 days in oncology patients. CONCLUSIONS The precision, ease of use, and versatility of the ROSA system make it well suited for pediatric neurosurgical practice. Further work, including long-term analysis of results and cost-effectiveness, will help determine the utility of this system and if its applications can be expanded.
Asunto(s)
Neoplasias Encefálicas/cirugía , Epilepsia/cirugía , Glioma/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Adolescente , Biopsia , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Preescolar , Electroencefalografía , Epilepsia/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Glioma/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Terapia por Láser/métodos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Técnicas Estereotáxicas , Tomógrafos Computarizados por Rayos X , Adulto JovenRESUMEN
The pioneeristic work of Alexander Romanovic Luria into the field of human neuropsychology offered eminent contributions to clinical praxis by providing theory guided methods and instruments for the study of higher cortical functions. However, lots of this knowledge corpus either remains untranslated and thus inaccessible, or in some cases selectively overlooked by academic authorities and consequently not passed to the future generations of experts. Although Luria was not exclusively devoted to the study of epilepsy, his theories and clinical approaches actually penetrate the whole neuropathology spectrum. His holistic and systemic approach to the brain sounds nowadays more than opportune and consistent with the network approach of the modern neuroimaging era. As to epilepsy, the logic underlying the Lurian approach (cognitive functions organized into complex functional systems with intra- and/or inter-hemispheric distribution, as opposed to the modularistic view of the brain) seems consistent with our current knowledge in epileptology with respect to epileptic networks, as well as the modern construct of the functional deficit zone. These contributions seem to be highly promising for the neuropsychology of epilepsy and epilepsy surgery, since they provide clinicians with valuable methods and theories to assist them in the localization -and lateralization- of cognitive deficits. Consequently they are of great applicability in the context of the preoperative neuropsychological monitoring of patients candidates for epilepsy surgery, where neuropsychologist are called upon to provide surgeons with anatomical data.