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BACKGROUND AND OBJECTIVES: Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months. METHODS: This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records. RESULTS: A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10). DISCUSSION: The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.
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Epilepsias Parciales , Ideación Suicida , Humanos , Adolescente , Masculino , Femenino , Epilepsias Parciales/epidemiología , Epilepsias Parciales/psicología , Epilepsias Parciales/diagnóstico , Prevalencia , Niño , Estudios de Seguimiento , Suicidio/estadística & datos numéricos , Suicidio/psicologíaRESUMEN
BACKGROUND AND OBJECTIVES: Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents. METHODS: This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management. RESULTS: A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings. DISCUSSION: Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.
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Servicio de Urgencia en Hospital , Epilepsias Parciales , Convulsiones , Humanos , Adolescente , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Masculino , Estudios Retrospectivos , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Niño , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatologíaRESUMEN
PURPOSE: Tail-vein catheterization and subsequent in-magnet infusion is a common route of administration of deuterium (2 H)-labeled substrates in small-animal deuterium (D) MR studies. With mice, because of the tail vein's small diameter, this procedure is challenging. It requires considerable personnel training and practice, is prone to failure, and may preclude serial studies. Motivated by the need for an alternative, the time courses for common small-molecule deuterated substrates and downstream metabolites in brain following subcutaneous infusion were determined in mice and are presented herein. METHODS: Three 2 H-labeled substrates-[6,6-2 H2 ]glucose, [2 H3 ]acetate, and [3,4,4,4-2 H4 ]beta-hydroxybutyrate-and 2 H2 O were administered to mice in-magnet via subcutaneous catheter. Brain time courses of the substrates and downstream metabolites (and semi-heavy water) were determined via single-voxel DMRS. RESULTS: Subcutaneous catheter placement and substrate administration was readily accomplished with limited personnel training. Substrates reached pseudo-steady state in brain within â¼30-40 min of bolus infusion. Time constants characterizing the appearance in brain of deuterated substrates or semi-heavy water following 2 H2 O administration were similar (â¼15 min). CONCLUSION: Administration of deuterated substrates via subcutaneous catheter for in vivo DMRS experiments with mice is robust, requires limited personnel training, and enables substantial dosing. It is suitable for metabolic studies where pseudo-steady state substrate administration/accumulation is sufficient. It is particularly advantageous for serial longitudinal studies over an extended period because it avoids inevitable damage to the tail vein following multiple catheterizations.
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Encéfalo , Cola (estructura animal) , Ratones , Animales , Óxido de Deuterio , Deuterio , Cola (estructura animal)/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismoRESUMEN
OBJECTIVE: Accreditation Council for Graduate Medical Education (ACGME)-accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them. METHODS: A work group of nine board-certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach. RESULTS: The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy-specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo-EEG, neurostimulation, genetics, and safety in epilepsy monitoring units. SIGNIFICANCE: Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.
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Epilepsia , Internado y Residencia , Acreditación , Adulto , Niño , Competencia Clínica , Educación de Postgrado en Medicina , Epilepsia/diagnóstico , Epilepsia/terapia , Becas , HumanosRESUMEN
Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m2 at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.
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Epilepsia Generalizada , Epilepsia Refleja , Trastornos por Fotosensibilidad , Electroencefalografía , Epilepsia Refleja/etiología , Humanos , Estimulación Luminosa , Convulsiones/etiologíaRESUMEN
OBJECTIVE: To determine whether familial aggregation of status epilepticus (SE) occurs in a large cohort of familial common epilepsies. METHODS: We used the Epilepsy Phenome/Genome Project dataset, which consisted of 2,197 participants in 1,043 family units with ≥2 members having a common generalized or nonacquired focal epilepsy (NAFE). We identified participants with a history of traditionally defined SE (TSE) (seizures ≥30 minutes) and operationally defined SE (OSE) (seizures ≥10 minutes) by chart review. We assessed familial aggregation of TSE and OSE using χ2 analysis and generalized estimating equations (GEE). RESULTS: One hundred fifty-five (7%) participants in 1,043 families had ≥1 episodes of TSE. Two hundred fifty (11%) had ≥1 episodes of OSE. In a χ2 analysis, the number of family units with ≥2 members having TSE (odds ratio [OR] 4.79, 95% confidence interval [CI] 2.56-8.97) or OSE (OR 4.23, 95% CI 2.67-6.70) was greater than expected by chance. In GEE models adjusted for sex, broad epilepsy class (GE or NAFE), age at onset, and duration of epilepsy, TSE in a proband predicted TSE in a first-degree relative (OR 2.79, 95% CI 1.24-6.22), and OSE in a proband predicted OSE in a first-degree relative (OR 2.91, 95% CI 1.65-5.15). The results remained significant in models addressing epilepsy severity by incorporating the number of antiseizure medications used or epilepsy surgery. CONCLUSIONS: TSE and OSE showed robust familial aggregation in a cohort of familial epilepsy independently of epilepsy severity or class, suggesting that genetic factors contribute to SE independently of the genetic cause of these epilepsies. CLINICALTRIALSGOV IDENTIFIER: NCT00552045.
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Epilepsias Parciales/genética , Epilepsia Generalizada/genética , Salud de la Familia/estadística & datos numéricos , Estado Epiléptico/genética , Adolescente , Adulto , Niño , Bases de Datos Genéticas , Epilepsias Parciales/complicaciones , Epilepsia Generalizada/complicaciones , Femenino , Humanos , Masculino , Estado Epiléptico/complicaciones , Factores de Tiempo , Adulto JovenRESUMEN
This review assesses the risk of a photic-induced seizure in a child during viewing of 3D (binocular 3 dimensional, stereoscopic) movies or games, either on standard video displays or when wearing a virtual reality (VR) headset. Studies published by pediatric epilepsy experts emphasize the low risk of 3D viewing even for children with known photosensitive epilepsy (PSE). The low incidence of PSE is noteworthy because the number of hours devoted to 2D or 3D screen viewing and/or VR headset use by children worldwide has increased markedly over the last decade. The medical literature does not support the notion that VR headset use poses a risk for PSE.
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BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses. SETTING: Multicenter study based in academic pediatric cerebral palsy clinics. PARTICIPANTS: A total of 49 patients with cerebral palsy who had participated in an oral baclofen pharmacokinetic/pharmacodynamic study. METHODS OR INTERVENTIONS: Of 53 participants in a pharmacokinetic/pharmacodynamic trial, 49 underwent genetic analysis of 307 key genes and 4535 single-nucleotide polymorphisms involved in drug absorption, distribution, metabolism, and excretion. Associations between genotypes and phenotypes of baclofen disposition (weight-corrected and allometrically scaled clearance) and clinical endpoints (improvement from baseline in mean hamstring Modified Tardieu Scale scores from baseline for improvement of R1 spastic catch) were determined by univariate analysis with correction for multiple testing by false discovery rate. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were the genotypic and phenotypic variability of oral baclofen in allometrically scaled clearance and change in the Modified Tardieu Scale angle compared to baseline. RESULTS: After univariate analysis of the data, the SNP of ABCC9 (rs11046232, heterozygous AT versus the reference TT genotype) was associated with a 2-fold increase in oral baclofen clearance (mean 0.51 ± standard deviation 0.05 L/h/kg for the AT genotype versus 0.25 ± 0.07 L/h/kg for the TT genotype, adjusted P < .001). Clinical responses were associated with decreased spasticity by Modified Tardieu Scale in allelic variants with SNPs ABCC12, SLC28A1, and PPARD. CONCLUSIONS: Genetic variation in ABCC9 affecting oral baclofen clearance highlights the need for continued studies of genetic polymorphisms to better characterize variable drug response in children with cerebral palsy. Single-nucleotide polymorphisms in ABCC12, SLC28A1, and PPARD were associated with varied responses, which warrants further investigation to determine their effect on spasticity. LEVEL OF EVIDENCE: II.
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Baclofeno/farmacocinética , Parálisis Cerebral/tratamiento farmacológico , Farmacogenética/métodos , Administración Oral , Adolescente , Baclofeno/administración & dosificación , Parálisis Cerebral/genética , Parálisis Cerebral/metabolismo , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Variación Genética , Humanos , Masculino , Relajantes Musculares Centrales/administración & dosificación , Relajantes Musculares Centrales/farmacocinética , Polimorfismo de Nucleótido Simple , Pronóstico , Receptores de Sulfonilureas/genética , Receptores de Sulfonilureas/metabolismoRESUMEN
Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism.
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ADN Complementario/genética , Epilepsia Generalizada/genética , Epilepsia/genética , Mutación con Ganancia de Función/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Electrofisiología , Femenino , Humanos , Masculino , Modelos Biológicos , LinajeRESUMEN
OBJECTIVE: To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. SUBJECTS DESIGN: Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). RESULTS: R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. CONCLUSION: The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.
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Baclofeno/farmacocinética , Parálisis Cerebral/tratamiento farmacológico , Relajantes Musculares Centrales/farmacocinética , Absorción , Administración Oral , Adolescente , Baclofeno/sangre , Baclofeno/uso terapéutico , Peso Corporal , Parálisis Cerebral/sangre , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Modelos Estadísticos , Análisis Multivariante , Relajantes Musculares Centrales/sangre , Relajantes Musculares Centrales/uso terapéuticoRESUMEN
Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-ß mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-ß. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox-Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor.
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Cerebelo/anomalías , Genes Recesivos , Estudios de Asociación Genética , Mutación , Espasmos Infantiles/genética , alfa Carioferinas/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Encéfalo/patología , Niño , Preescolar , Análisis Mutacional de ADN , Electroencefalografía , Exoma , Facies , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Imagen por Resonancia Magnética , Modelos Moleculares , Fenotipo , Conformación Proteica , Espasmos Infantiles/diagnóstico , alfa Carioferinas/químicaRESUMEN
Dr. Masur and colleagues(1) from the Childhood Absence Epilepsy Study Group tried to answer a few important questions regarding childhood absence epilepsy (CAE) in their article "Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy." First, they wanted to know whether children with absence epilepsy have any problems with thinking before starting medications. If the children have problems with thinking, the authors wanted to identify the specific types of thinking problems the children have. The authors also wanted to assess what effect seizure medications have on attention in these children. In principle, medications could improve or worsen attention. The possible effects of medication on attention may or may not depend on whether the medications control the seizures.
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Trastornos del Conocimiento/etiología , Epilepsia Tipo Ausencia/complicaciones , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Estados UnidosRESUMEN
Clinicians typically breathe a sigh of relief when they make the diagnosis of childhood absence epilepsy. The history is classic-a normal young child with myriad brief periods of staring. The clinic visit is powerful when the phenomena are replicated by having the child hyperventilate. Finally, the EEG is definitive. The ability to demonstrate to a family the abrupt eruption and cessation of spike-wave activity provides a framework for them to understand what is happening to their child. Parents are usually reassured that there are very good therapies, that seizures are typically controlled, and that their child will "outgrow" it. However, data from the multicenter Childhood Absence Epilepsy Study Group are rewriting this narrative.(1-3.)
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Epilepsia Tipo Ausencia/diagnóstico , Niño , Electroencefalografía , HumanosRESUMEN
Health-related quality of life (HRQOL) is an important outcome in pediatric epilepsy surgery, but there are few studies that utilize presurgical ratings to assess the effect of surgery on HRQOL. We collected parental ratings on the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 28 children who participated in neuropsychological assessment before and after epilepsy surgery. Our results revealed significant improvements in overall HRQOL after surgery, especially in physical and social activities. These changes were apparent despite generally unchanged intellectual and psychological functioning. Children with better seizure outcome had more improvement in HRQOL; however, improvements were not statistically different among children with Engel class I, II, and III outcomes. Our results suggest that children can experience significant improvements in HRQOL following epilepsy surgery even when neuropsychological functioning remains unchanged. Moreover, improvements in HRQOL appear evident in children who experience any worthwhile improvement in seizure control (Engel class III or better).
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Epilepsia , Estado de Salud , Procedimientos Neuroquirúrgicos/métodos , Calidad de Vida , Ajuste Social , Adolescente , Análisis de Varianza , Niño , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/cirugía , Emociones/fisiología , Epilepsia/complicaciones , Epilepsia/psicología , Epilepsia/cirugía , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Procedimientos Neuroquirúrgicos/clasificación , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They can also have antiepileptogenic properties and can eventually have a role in treating other neurologic and nonneurologic conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for 4 distinct mechanisms that could contribute to the antiseizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)-sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission.
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Dieta Cetogénica/métodos , Epilepsia/dietoterapia , Epilepsia/metabolismo , Animales , Dieta Baja en Carbohidratos , Humanos , Canales de Potasio , Transmisión Sináptica/fisiologíaRESUMEN
OBJECTIVE: To implement an automated analysis of EEG recordings from prematurely-born infants and thus provide objective, reproducible results. METHODS: Bayesian probability theory is employed to compute the posterior probability for developmental features of interest in EEG recordings. Currently, these features include smooth delta waves (0.5-1.5Hz, >100µV), delta brushes (delta portion: 0.5-1.5Hz, >100µV; "brush" portion: 8-22Hz, <75µV), and interburst intervals (<10µV), though the approach taken can be generalized to identify other EEG features of interest. RESULTS: When compared with experienced electroencephalographers, the algorithm had a true positive rate between 72% and 79% for the identification of delta waves (smooth or "brush") and interburst intervals, which is comparable to the inter-rater reliability. When distinguishing between smooth delta waves and delta brushes, the algorithm's true positive rate was between 53% and 88%, which is slightly less than the inter-rater reliability. CONCLUSION: Bayesian probability theory can be employed to consistently identify features of EEG recordings from premature infants. SIGNIFICANCE: The identification of features in EEG recordings provides a first step towards the automated analysis of EEG recordings from premature infants.
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Electroencefalografía/métodos , Recien Nacido Prematuro/fisiología , Procesamiento de Señales Asistido por Computador , Algoritmos , Teorema de Bayes , Humanos , Recién Nacido , Reproducibilidad de los ResultadosRESUMEN
Chromosome 2p15p16.1 microdeletion is an emerging syndrome recently described in patients with dysmorphic facial features, congenital microcephaly, mild to moderate developmental delay and neurodevelopmental abnormalities. Using clinical ultra-high resolution Affymetrix SNP 6.0 array we identified a de novo interstitial deletion on the short arm of chromosome 2, spanning approximately 2.5 Mb in the cytogenetic band position 2p15p16.1, in a female infant with characteristic features of 2p15p16.1 deletion syndrome including severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect. We further redefined the previously reported critical region, supporting the presence of a newly recognized microdeletion syndrome involving haploinsufficiency of one or more genes deleted within at least a 1.1 Mb segment of the 2p15p16.1 region.