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Rhabdomyosarcoma (RMS) is a pediatric malignancy with a variable prognosis depending on tumor stage and genotype. There has been a significant improvement in survival rates over the past decades. However, aggressive variants can metastasize to locations that are difficult to treat. We report a case of prostatic alveolar rhabdomyosarcoma with metastases to the bone marrow and thoracic spine in a child. The patient was treated with a multimodal approach that included surgical resection of the epidural mass; the administration of vincristine, dactinomycin, and cyclophosphamide; and radiotherapy. Unfortunately, after six months, the patient showed disease progression and was started on secondary-line treatment. This case illustrates the difficulties in managing end-stage metastatic rhabdomyosarcoma and is the first report of prostatic rhabdomyosarcoma presenting with spinal cord compression in a child.
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OBJECTIVE: MR-guided laser interstitial thermal therapy (MRgLITT) is associated with lower seizure-free outcome but better safety profile compared to open surgery. However, the predictors of seizure freedom following MRgLITT remain uncertain. This study aimed to use machine learning to predict seizure-free outcome following MRgLITT and to identify important predictors of seizure freedom in children with drug-resistant epilepsy. METHODS: This multicenter study included children treated with MRgLITT for drug-resistant epilepsy at 13 epilepsy centers. The authors used clinical data, diagnostic investigations, and ablation features to predict seizure-free outcome at 1 year post-MRgLITT. Patients from 12 centers formed the training cohort, and patients in the remaining center formed the testing cohort. Five machine learning algorithms were developed on the training data by using 10-fold cross-validation, and model performance was measured on the testing cohort. The models were developed and tested on the complete feature set. Subsequently, 3 feature selection methods were used to identify important predictors. The authors then assessed performance of the parsimonious models based on these important variables. RESULTS: This study included 268 patients who underwent MRgLITT, of whom 44.4% had achieved seizure freedom at 1 year post-MRgLITT. A gradient-boosting machine algorithm using the complete feature set yielded the highest area under the curve (AUC) on the testing set (AUC 0.67 [95% CI 0.50-0.82], sensitivity 0.71 [95% CI 0.47-0.88], and specificity 0.66 [95% CI 0.50-0.81]). Logistic regression, random forest, support vector machine, and neural network yielded lower AUCs (0.58-0.63) compared to the gradient-boosting machine but the findings were not statistically significant (all p > 0.05). The 3 feature selection methods identified video-EEG concordance, lesion size, preoperative seizure frequency, and number of antiseizure medications as good prognostic features for predicting seizure freedom. The parsimonious models based on important features identified by univariate feature selection slightly improved model performance compared to the complete feature set. CONCLUSIONS: Understanding the predictors of seizure freedom after MRgLITT will assist with prognostication.
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Epilepsia Refractaria , Epilepsia , Terapia por Láser , Humanos , Niño , Resultado del Tratamiento , Terapia por Láser/métodos , Convulsiones/cirugía , Epilepsia Refractaria/cirugía , Epilepsia/cirugía , Imagen por Resonancia Magnética/métodos , Rayos Láser , Estudios RetrospectivosRESUMEN
Cerebellar granule neurons (CGNs) are the most abundant neurons in the human brain. Dysregulation of their development underlies movement disorders and medulloblastomas. It is suspected that these disorders arise in progenitor states of the CGN lineage, for which human models are lacking. Here, we have differentiated human hindbrain neuroepithelial stem (hbNES) cells to CGNs in vitro using soluble growth factors, recapitulating key progenitor states in the lineage. We show that hbNES cells are not lineage committed and retain rhombomere 1 regional identity. Upon differentiation, hbNES cells transit through a rhombic lip (RL) progenitor state at day 7, demonstrating human specific sub-ventricular cell identities. This RL state is followed by an ATOH1+ CGN progenitor state at day 14. By the end of a 56-day differentiation procedure, we obtain functional neurons expressing CGN markers GABAARα6 and vGLUT2. We show that sonic hedgehog promotes GABAergic lineage specification and CGN progenitor proliferation. Our work presents a new model with which to study development and diseases of the CGN lineage in a human context.
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Cerebelo , Proteínas Hedgehog , Humanos , Proteínas Hedgehog/metabolismo , Rombencéfalo/metabolismo , Diferenciación Celular/fisiología , Neurogénesis , Células MadreRESUMEN
OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.
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Epilepsia Refractaria , Terapia por Láser , Convulsiones , Niño , Humanos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/terapia , Terapia por Láser/métodos , Imagen por Resonancia Magnética , Estudios Retrospectivos , Convulsiones/prevención & control , Resultado del TratamientoRESUMEN
PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). METHODS: Information was collected on patients with histologically confirmed AT/RT using the NCDB (2004-2016). Kaplan-Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional hazards (CPH) and logistic regression models. RESULTS: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7 ± 2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS = 5.91 months), 51 (27.7%) received surgery and chemotherapy (S + CT) (OS = 11.2 months), and 9 (4.89%) received surgery and radiotherapy (S + RT) (OS = 10.3 months). Forty-five (24.5%) received S + CT + RT combination therapy (OS = 45.4 months), 13 (17.1%) received S + CT + BMT/SCT (bone marrow or stem cell transplant) (OS = 55.5 months), and 16 (8.70%) received S + CT + RT + BMT/SCT (OS = 68.4 months). Bivariate analysis of dichotomized age (HR = 0.550, 95% CI [0.357, 0.847], p = 0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S + CT + RT, S + CT + BMT/SCT, or S + CT + RT + BMT/SCT combination therapy predicted significantly (p < 0.05) increased OS compared to surgery alone. CONCLUSION: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.
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Neoplasias del Sistema Nervioso Central , Tumor Rabdoide , Neoplasias del Sistema Nervioso Central/terapia , Preescolar , Estudios de Cohortes , Terapia Combinada , Femenino , Humanos , Lactante , Masculino , Pronóstico , Tumor Rabdoide/terapiaRESUMEN
This article provides general principles of managing children with central nervous system tumors. The distribution, diagnostic work-up, and key principles of treatment are reviewed, and special circumstances that may be encountered by pediatricians in the community are discussed.
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Neoplasias Encefálicas/terapia , Neoplasias del Sistema Nervioso Central/terapia , Oncología Médica/normas , Atención Primaria de Salud/normas , Neoplasias de la Médula Espinal/terapia , Niño , Humanos , Pediatría/normasRESUMEN
In the twenty-first century, choroid plexus cauterization (CPC) in combination with endoscopic third ventriculostomy (ETV) has emerged as an effective treatment for some infants with hydrocephalus, leading to the favourable condition of 'shunt independence'. Herein we provide a narrative technical review considering the indications, procedural aspects, morbidity and its avoidance, postoperative care and follow-up. The CP has been the target of hydrocephalus treatment for more than a century. Early eminent neurosurgeons including Dandy, Putnam and Scarff performed CPC achieving generally poor results, and so the procedure fell out of favour. In recent years, the addition of CPC to ETV was one of the reasons greater ETV success rates were observed in Africa, compared to developed nations, and its popularity worldwide has since increased. Initial results indicate that when ETV/CPC is performed successfully, shunt independence is more likely than when ETV is undertaken alone. CPC is commonly performed using a flexible endoscope via septostomy and aims to maximally cauterize the CP. Success is more likely in infants aged >1 month, those with hydrocephalus secondary to myelomeningocele and aqueductal obstruction and those with >90% cauterized CP. Failure is more likely in those with post-haemorrhagic hydrocephalus of prematurity (PHHP), particularly those <1 month of corrected age and those with prepontine scarring. High-quality evidence comparing the efficacy of ETV/CPC with shunting is emerging, with data from ongoing and future trials offering additional promise to enhance our understanding of the true utility of ETV/CPC.
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Hidrocefalia , Neuroendoscopía , Tercer Ventrículo , Humanos , Lactante , Cauterización , Plexo Coroideo/cirugía , Hidrocefalia/cirugía , Tercer Ventrículo/cirugía , VentriculostomíaRESUMEN
Choroid plexus cysts rarely grow to be symptomatic. Few large choroid plexus cysts have been reported in the pediatric population. The authors report a 15-month-old boy with increased head circumference and a bony deformity in the left parietal region due to mass effect from a giant choroid plexus cyst. The child had a craniotomy for open resection of the cyst, and made an excellent recovery. The differential diagnosis for intraventricular cysts and the literature surrounding choroid plexus cysts are discussed.
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Encefalopatías , Quistes del Sistema Nervioso Central , Quistes , Encefalopatías/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Niño , Plexo Coroideo/diagnóstico por imagen , Plexo Coroideo/cirugía , Craneotomía , Quistes/complicaciones , Quistes/diagnóstico por imagen , Quistes/cirugía , Humanos , Lactante , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Medulloblastoma is the most common malignant brain tumor in children. Here we describe a medulloblastoma model using Induced pluripotent stem (iPS) cell-derived human neuroepithelial stem (NES) cells generated from a Gorlin syndrome patient carrying a germline mutation in the sonic hedgehog (SHH) receptor PTCH1. We found that Gorlin NES cells formed tumors in mouse cerebellum mimicking human medulloblastoma. Retransplantation of tumor-isolated NES (tNES) cells resulted in accelerated tumor formation, cells with reduced growth factor dependency, enhanced neurosphere formation in vitro, and increased sensitivity to Vismodegib. Using our model, we identified LGALS1 to be a GLI target gene that is up-regulated in both Gorlin tNES cells and SHH-subgroup of medulloblastoma patients. Taken together, we demonstrate that NES cells derived from Gorlin patients can be used as a resource to model medulloblastoma initiation and progression and to identify putative targets.
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Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Células-Madre Neurales/fisiología , Anilidas/farmacología , Animales , Síndrome del Nevo Basocelular/genética , Síndrome del Nevo Basocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Galectina 1/genética , Galectina 1/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas Hedgehog/genética , Humanos , Ratones , Neoplasias Experimentales , Receptor Patched-1/genética , Piridinas/farmacologíaRESUMEN
BACKGROUND: In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. METHODS: A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. RESULTS: A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. CONCLUSIONS: This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.
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PURPOSE: Cerebrospinal fluid (CSF) leak is a major risk factor for external ventricular drain infection. Here, we present a surgical technique to reduce the possibility of CSF leak at the external ventricular drain (EVD) exit site in high-risk patients. METHODS: Vertical mattress sutures are placed circumferentially around the EVD catheter tract as it passes under the skin, so to close off the tract along which CSF may travel toward the exit site. RESULTS: Specific case examples are discussed where the introduction of this technique was found to be helpful in stopping exit-site CSF leak. CONCLUSION: In our experience, these surgical steps are useful adjuncts that should be considered in all high-risk patients undergoing EVD placement.
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Pérdida de Líquido Cefalorraquídeo , Drenaje , Pérdida de Líquido Cefalorraquídeo/etiología , HumanosRESUMEN
OBJECTIVE: Selective dorsal rhizotomy (SDR) is a procedure primarily performed to improve function in a subset of children with limitations related to spasticity. There is substantial variability in operative techniques among centers and surgeons. Here, the authors provide a technical review of operative approaches for SDR. METHODS: Ovid MEDLINE, Embase, and PubMed databases were queried in accordance with PRISMA guidelines. All studies included described a novel surgical technique. The technical nuances of each approach were extracted, including extent of exposure, bone removal, and selection of appropriate nerve roots. The operative approach preferred at the authors' institution (the "2 × 3 exposure") is also detailed. RESULTS: Five full-text papers were identified from a total of 380 articles. Operative approaches to SDR varied significantly with regard to level of exposure, extent of laminectomy, and identification of nerve roots. The largest exposure involved a multilevel laminectomy, while the smallest exposure involved a keyhole interlaminar approach. At the Hospital for Sick Children, the authors utilize a two-level laminoplasty at the level of the conus medullaris. The benefits and disadvantages of the spectrum of techniques are discussed, and illustrative figures are provided. CONCLUSIONS: Surgical approaches to SDR vary considerably and are detailed and illustrated in this review as a guide for neurosurgeons. Future studies should address the long-term impact of these techniques on functional outcomes and complications such as spinal deformity.
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Medulloblastoma (MB), the most frequent malignant childhood brain tumor, can arise from cellular malfunctions during hindbrain development. Here we generate humanized models for Sonic Hedgehog (SHH)-subgroup MB via MYCN overexpression in primary human hindbrain-derived neuroepithelial stem (hbNES) cells or iPSC-derived NES cells, which display a range of aggressive phenotypes upon xenografting. iPSC-derived NES tumors develop quickly with leptomeningeal dissemination, whereas hbNES-derived cells exhibit delayed tumor formation with less dissemination. Methylation and expression profiling show that tumors from both origins recapitulate hallmarks of infant SHH MB and reveal that mTOR activation, as a result of increased Oct4, promotes aggressiveness of human SHH tumors. Targeting mTOR decreases cell viability and prolongs survival, showing the utility of these varied models for dissecting mechanisms mediating tumor aggression and demonstrating the value of humanized models for a better understanding of pediatric cancers.
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Meduloblastoma/metabolismo , Meduloblastoma/patología , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Células Madre/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Línea Celular , Proliferación Celular/genética , Proliferación Celular/fisiología , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Femenino , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Inmunohistoquímica , Meduloblastoma/genética , Ratones , Factor 3 de Transcripción de Unión a Octámeros/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/genéticaRESUMEN
During nervous system development, early neuroepithelial stem (NES) cells with a highly polarized morphology and responsiveness to regionalizing morphogens give rise to radial glia (RG) cells, which generate region-specific neurons. Recently, stable neural cell populations reminiscent of NES cells have been obtained from pluripotent stem cells and the fetal human hindbrain. Here, we explore whether these cell populations, similar to their in vivo counterparts, can give rise to neural stem (NS) cells with RG-like properties and whether region-specific NS cells can be generated from NES cells with different regional identities. In vivo RG cells are thought to form from NES cells with the onset of neurogenesis. Therefore, we cultured NES cells temporarily in differentiating conditions. Upon reinitiation of growth factor treatment, cells were found to enter a developmental stage reflecting major characteristics of RG-like NS cells. These NES cell-derived NS cells exhibited a very similar morphology and marker expression as primary NS cells generated from human fetal tissue, indicating that conversion of NES cells into NS cells recapitulates the developmental progression of early NES cells into RG cells observed in vivo. Importantly, NS cells generated from NES cells with different regional identities exhibited stable region-specific transcription factor expression and generated neurons appropriate for their positional identity. Stem Cells 2019;37:1429-1440.
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Encéfalo/citología , Encéfalo/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Células Ependimogliales/citología , Células Ependimogliales/metabolismo , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Células Neuroepiteliales/citología , Células Neuroepiteliales/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Células Cultivadas , Humanos , Neuronas/citología , Neuronas/metabolismo , Rombencéfalo/citología , Rombencéfalo/metabolismoRESUMEN
Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
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Síndrome del Nevo Basocelular/genética , Neoplasias Encefálicas/genética , Meduloblastoma/genética , Proteína Proto-Oncogénica N-Myc/metabolismo , Células-Madre Neurales/fisiología , Células Neuroepiteliales/fisiología , Células Madre Pluripotentes/fisiología , Animales , Síndrome del Nevo Basocelular/metabolismo , Síndrome del Nevo Basocelular/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Carcinogénesis/genética , ARN Helicasas DEAD-box/genética , Modelos Animales de Enfermedad , Ingeniería Genética , Predisposición Genética a la Enfermedad , Humanos , Meduloblastoma/metabolismo , Meduloblastoma/patología , Ratones , Ratones SCID , Proteína Proto-Oncogénica N-Myc/genética , Proteínas de Neoplasias/genética , Receptor Patched-1/genética , Trasplante de Células Madre , Trasplante HeterólogoRESUMEN
Individuals with lesions in the prefrontal cortex often show impairments with the organisation of their behaviour in everyday life. These difficulties can be hard to detect using structured formal tests. The objective of this study was to use Virtual Reality (VR) to explore the multitasking performance of individuals with focal frontal lobe lesions, specifically using the Jansari assessment of Executive Functions (JEF©). Nineteen individuals with frontal lobe lesions were compared with 19 matched controls on the test and a group of commonly used clinical measures of neuropsychological functioning, as well as questionnaire measures of everyday activity, anxiety and depression. There was a significant difference between groups on the overall JEF© score and on five of the eight individual constructs, namely the planning, creative thinking, adaptive thinking, event-based Prospective Memory (PM) and time-based PM constructs. There were no differences between groups on the non-VR EF individual measures apart from on one EF control measure, Trail Making A. These results demonstrate the potential clinical utility of the JEF© and highlight the value of ecologically valid VR measures in detecting impairments in EF in individuals with frontal lobe lesions.
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Lesiones Encefálicas/patología , Lesiones Encefálicas/rehabilitación , Trastornos del Conocimiento/etiología , Lóbulo Frontal/patología , Terapia de Exposición Mediante Realidad Virtual/métodos , Realidad Virtual , Adulto , Anciano , Lesiones Encefálicas/complicaciones , Trastornos del Conocimiento/rehabilitación , Función Ejecutiva , Femenino , Humanos , Masculino , Memoria Episódica , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Encuestas y CuestionariosRESUMEN
Loss-of-function mutations in the cytosine-5 RNA methylase NSUN2 cause neurodevelopmental disorders in humans, yet the underlying cellular processes leading to the symptoms that include microcephaly remain unclear. Here, we show that NSUN2 is expressed in early neuroepithelial progenitors of the developing human brain, and its expression is gradually reduced during differentiation of human neuroepithelial stem (NES) cells in vitro. In the developing Nsun2-/- mouse cerebral cortex, intermediate progenitors accumulate and upper-layer neurons decrease. Loss of NSUN2-mediated methylation of tRNA increases their endonucleolytic cleavage by angiogenin, and 5' tRNA fragments accumulate in Nsun2-/- brains. Neural differentiation of NES cells is impaired by both NSUN2 depletion and the presence of angiogenin. Since repression of NSUN2 also inhibited neural cell migration toward the chemoattractant fibroblast growth factor 2, we conclude that the impaired differentiation capacity in the absence of NSUN2 may be driven by the inability to efficiently respond to growth factors.
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Diferenciación Celular/genética , Citosina/metabolismo , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , ARN/metabolismo , Animales , Encéfalo/embriología , Encéfalo/metabolismo , Movimiento Celular , Femenino , Técnicas de Inactivación de Genes , Humanos , Metilación , Metiltransferasas/genética , Ratones , Ratones Noqueados , Neuronas/citología , Neuronas/metabolismo , Organogénesis/genética , Ribonucleasa Pancreática/farmacologíaRESUMEN
BACKGROUND: Placement of a subdural drain after drainage of chronic subdural haematoma (CSDH) has been shown to reduce the rate of recurrence in several randomised controlled trials (RCT). The most recently published RCT was from Cambridge, UK, in 2009. Despite class I evidence for the use of subdural drains, it is unclear whether these results have been translated into clinical practice. In this clinical audit we review the use of subdural drains in our institution before and after the publication of the 2009 RCT results. METHODS: A longitudinal retrospective study was performed on all adults having burr holes for CSDH between January 2009 and January 2014. Case notes were analysed to determine subdural drain use, re-operation for CSDH recurrence and post-operative complications. The audit loop was closed with data collected from August 2015 to January 2016. RESULTS: Thirty-one per cent of patients had subdural drains placed at operation. Drain placement was associated with lower reoperation rates (8% vs. 17%, p = 0.021) without increasing complication rates. Drain usage doubled after publication of the Santarius et al. (2009) trial but we observed persisting and significant variability in drain utilisation by supervising consultants. The use of drains in the department increased from 35% to 75% of all cases after presentation of these results. CONCLUSIONS: The use of subdural drains in our unit reduced recurrence rates following drainage of CSDH and reproduced the results of a 2009 clinical trial. Although the use of subdural drains doubled in the post-trial epoch, significant variability remains in practice. Clinical audit provided an effective tool necessary to drive the implementation of subdural drain placement in our unit.