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Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.
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Células-Tronco Pluripotentes Induzidas , Microglia , Humanos , Camundongos , Animais , Redes Reguladoras de Genes , Encéfalo , Regulação da Expressão GênicaRESUMO
OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.
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Carcinoma de Células Renais , Cistos do Sistema Nervoso Central , Cistos , Neoplasias Renais , Humanos , Criança , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Cistos do Sistema Nervoso Central/cirurgiaRESUMO
INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.
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Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/diagnóstico por imagem , Criança , Adolescente , Masculino , Feminino , Procedimentos Endovasculares/métodos , Pré-Escolar , Lactente , Adulto Jovem , Procedimentos Neurocirúrgicos/métodos , Resultado do TratamentoRESUMO
We present 4 children (diagnosed between 1 and 8 y, 3 females and 1 male) with molecularly distinct tectal gliomas (2 KRAS mutant, 1 EGFR mutant, 1 SRGAP3-RAF-1 fusion) that contributes to the growing literature of this uncommonly biopsied tumor. The patient with EGFR R222C mutation had a more severe course, earlier diagnosis, subsequent leptomeningeal metastatic disease, required more aggressive therapies, and died 9 years after diagnosis. Patients with KRAS mutations and SRGAP3-RAF-1 fusion had a more indolent course. Our series expands the molecular phenotype of tectal glioma with the potential for leptomeningeal dissemination. Future studies on establishing genotypic/phenotypic correlation from those who undergo biopsy are needed.
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Neoplasias Encefálicas , Neoplasias do Tronco Encefálico , Glioma , Feminino , Masculino , Humanos , Glioma/genética , Glioma/patologia , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores ErbB/genética , Mutação , Neoplasias Encefálicas/genéticaRESUMO
PURPOSE: Herein lies a brief historical review of the practice of artificial cranial deformation (ACD) in Tiwanaku, Bolivia, a pre-Columbian archeological ruin once regarded as one of the most powerful pre-Inca regions whose influence extended into present-day Peru and Chile from 600 to 1000 AD. We describe the history, purpose, and implications of ACD from both a neuroanatomical and cultural perspective. METHODS: A literature review was conducted through PubMed on the history of artificial cranial deformation in South America, concentrating on the Tiwanaku region. The authors searched all available data with no specific time reference, using the mentioned keywords: ACD, neuroanatomical implications of ACD, cultural and social functions of ACD, Tiwanaku society, and Andean civilization. RESULTS: Early Andean civilization was hierarchical and stratified. In Tiwanaku, the practice of ACD served to delineate one's social class, caste, lineage, and vocation. This was especially useful for warriors, who distinguished their fellow combatants from insurgents by differences in their cranial structure. ACD was usually conducted within the first few months of an infant's life before morphogenetic features became permanent. Two popular cranial styles-tabular and annular-were achieved by applying various mechanical apparatus and resulted in several cranial shapes (conical, box-like, flattened, etc.). Neuroanatomically, each deformation technique and the duration for which mechanical stress was applied influenced the solidification of cranial bones and shaped the frontal, occipital, parietal, and temporal bones differently. Cognitive deficits and plagiocephalic defects were recorded in limitation and may have been overlooked as the era's occupational demands were more labor-intensive than knowledge-driven. CONCLUSION: In Tiwanaku, the custom of ACD was used to demonstrate group identity, with alterations of the cranial shape corresponding to a particular headdress. ACD was used to distinguish an individual's social identity, separating different groups of society into castes, classes, and slaves (Brain, 1979). The custom has also been used to mark territory and emphasize ethnic differences among groups, with potential cognitive implications that were largely unrecorded.
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Arqueologia , Osso Temporal , Lactente , Humanos , Bolívia , América do Sul , Peru , Arqueologia/métodosRESUMO
OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.
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COVID-19 , Otite Média , Trombose dos Seios Intracranianos , Humanos , Criança , Estudos Retrospectivos , Pandemias , COVID-19/complicações , Otite Média/complicações , Otite Média/tratamento farmacológico , Otite Média/cirurgia , Anticoagulantes/uso terapêutico , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Trombose dos Seios Intracranianos/cirurgiaRESUMO
PURPOSE: To highlight the clinical, neuroradiographic, neuropathologic, and molecular features of histologically identified neurocytoma in a pediatric cohort and highlight the evolving use methylation profiling in providing diagnostic clarity in difficult to diagnosis pediatric brain tumors. METHODS: Five consecutive children (ages 9-13, 2 girls 3 boys) were histologically diagnosed with neurocytoma at Rady Children's Hospital San Diego from 2012 to 2018. Clinical and molecular features were analyzed with regards to treatment course and outcome. RESULTS: Presenting symptoms included seizures (n = 2), syncope (n = 1), headache (n = 2), visual disturbances (n = 2) and emesis (n = 2). Tumor location included intraventricular (n = 2), intraventricular with parenchymal spread (n = 1), and extraventricular (n = 2). Magnetic resonance imaging demonstrated reduced diffusivity (2/5), signal abnormality on susceptibility-weighted sequences (3/5), and varying degrees of contrast enhancement (4/5). All patients underwent surgical resection alone. Recurrence occurred in four children that were treated with surgery (4/4), adjuvant radiation (2/4), and chemoradiation (1/4). Neuropathologic features included positivity for GFAP (4/5), synaptophysin (4/5), NSE (2/2), NeuN (4/4), and variable Ki-67 (< 1% to 15%). Next generation sequencing (3/5) and microarray (3/5) collectively were abnormal in four of five tumors. Methylation profiling was successfully performed on four of five samples which led to modification of diagnosis in two patients and the others were either unclassifiable or confirmatory with the histologic diagnosis. Mean time to follow up was 77 months (range 44-112 months). Mean progression free survival and overall survival were 24 months (range 6 to 52 months) and 100% respectively. CONCLUSION: Neurocytomas are a rare clinical entity that warrants further investigation into molecular and pathologic prognosticating features. Methylation profiling may aid in differentiation of neurocytoma from other difficult to diagnose tumors who share similar histologic features.
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Neoplasias Encefálicas , Neurocitoma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Criança , Feminino , Humanos , Antígeno Ki-67 , Imageamento por Ressonância Magnética , Masculino , Metilação , Neurocitoma/patologia , SinaptofisinaRESUMO
BACKGROUND: Ventriculoperitoneal shunt (VPS) placement into the reoperative abdomen can be challenging due to intraperitoneal adhesions. Laparoscopic guidance may provide safe abdominal access and identify an area for optimal cerebrospinal fluid drainage. The study aim was to compare laparoscopic-assisted VPS placement to an "open" approach in patients with prior abdominal surgery. MATERIALS AND METHODS: A retrospective review was performed of children undergoing VPS placement into a reoperative abdomen from 2009-2019. Clinical data were collected, and patients undergoing laparoscopy (LAP) were compared to those undergoing an open approach (OPEN). RESULTS: A total of 120 children underwent 169 VPS placements at a median age of 8 y (IQR 2-15 y), and a mean number of two prior abdominal operations (IQR 1-2). Laparoscopy was used in 24% of cases. Shunt-related complications within 30 d were lower in the LAP group (0% versus 19%, P = 0.001), as were VPS-related postoperative emergency department visits (0% versus 13%, P = 0.003) and readmissions (0% versus 13%, P = 0.013). Shunt malfunction rates were higher (42% OPEN versus 25% LAP, P = 0.03) and occurred sooner in the OPEN group (median 26 versus 78 wk, P = 0.01). The LAP group demonstrated shorter operative times (63 versus 100 min, P < 0.0001), and the only bowel injury. Time to feeds, length of stay, and mortality were similar between groups. CONCLUSIONS: Laparoscopic guidance during VPS placement into the reoperative abdomen is associated with a decrease in shunt-related complications, longer shunt patency, and shorter operative times. Prospective study may clarify the potential benefits of laparoscopy in this setting.
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Hidrocefalia , Laparoscopia , Abdome/cirurgia , Criança , Humanos , Hidrocefalia/cirurgia , Laparoscopia/efeitos adversos , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS). MATERIAL AND METHODS: We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3. RESULTS: We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19 months (range: 12-51 months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9 years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS. CONCLUSIONS: Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.
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Neoplasias do Sistema Nervoso Central , Neoplasias Meníngeas , Neoplasias Neuroepiteliomatosas , Neoplasias do Sistema Nervoso Central/patologia , Criança , Humanos , Antígeno Ki-67 , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Neuroepiteliomatosas/patologia , PrognósticoRESUMO
PURPOSE: Compared to adult AVMs, there is a paucity of data on the microsurgical treatment of pediatric AVMs. We report our institutional experience with pediatric AVMs treated by microsurgical resection with or without endovascular embolization and radiation therapy. METHODS: We retrospectively reviewed all patients ≤ 18 years of age with cerebral AVMs that underwent microsurgical resection at Rady Children's Hospital 2002-2019. RESULTS: Eighty-nine patients met inclusion criteria. The mean age was 10.3 ± 5.0 years, and 56% of patients were male. In total, 72 (81%) patients presented with rupture. Patients with unruptured AVMs presented with headache (n = 5, 29.4%), seizure (n = 9, 52.9%), or incidental finding (n = 3, 17.7%). The mean presenting mRS was 2.8 ± 1.8. AVM location was lobar in 78%, cerebellar/brainstem in 15%, and deep supratentorial in 8%. Spetzler-Martin grade was I in 28%, II in 45%, III in 20%, IV in 6%, and V in 1%. Preoperative embolization was utilized in 38% of patients and more frequently in unruptured than ruptured AVMs (62% vs. 32%, p = 0.022). Radiographic obliteration was achieved in 76/89 (85.4%) patients. Complications occurred in 7 (8%) patients. Annualized rates of delayed rebleeding and recurrence were 1.2% and 0.9%, respectively. The mean follow-up was 2.8 ± 3.1 years. A good neurological outcome (mRS score ≤ 2) was obtained in 80.9% of patients at last follow-up and was improved relative to presentation for 75% of patients. CONCLUSIONS: Our case series demonstrates high rates of radiographic obliteration and relatively low incidence of neurologic complications of treatment or AVM recurrence.
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Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Radiocirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Hospitais Pediátricos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Masculino , Microcirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this study is to use imaging data to determine if endoscopic endonasal surgery (EES) for skull base tumor resection interrupts skull base growth and development, resulting in an atrophic midface skeletal structure, compared to matched normal controls. METHODS: Data were collected by a retrospective chart review done on children aged 16 years and below who underwent endoscopic tumor resection and had pre- and postoperative magnetic resonance imaging with relevant midface anatomy. 121 normal controls were matched to 20 EES patients by age and gender. Three measurements related to midface anatomy were taken from 1 sagittal T1 slice and 1 axial T2 slice of each scan. Statistical analysis was used to compare growth measures between cases and controls. RESULTS: Twenty patients who underwent EES between November 2015 and April 2018 met our inclusion criteria. The mean age of the patients, 11 males and 9 females, was 10 years, and 8 patients (38%) were aged 7 years or younger. Six patients who had a high-flow CSF leak obtained a nasoseptal flap. A student T test and multivariate regression analysis found that EES did not affect midface and skull base growth. Among the variables assessed, age appears to be the only driver of growth. CONCLUSION: There were no identified differences in craniofacial growth in pediatric patients undergoing EES for skull base tumor resection as compared to the control group. EES does not appear to significantly interfere with midface/skull base development and is a good surgical option for pediatric patients.
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Procedimentos de Cirurgia Plástica , Neoplasias da Base do Crânio , Criança , Endoscopia , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Retalhos CirúrgicosRESUMO
INTRODUCTION: Nasal chondromesenchymal tumors (NCMT) are rare benign neoplasms that usually present in children <1 year of age. They can display rapid growth and significant local bony remodeling that can mimic a malignant process. Of the â¼50 published cases to date, few have documented the need for neurosurgical intervention. We herein report a NCMT in an infant treated with a staged cranial and transnasal approach, as well as summarize the available literature on this pathology. CASE REPORT: A newborn male with a compromised airway was noted to have a large sinonasal lesion. After stabilization, MRI demonstrated a 4-cm enhancing mass with diffuse sinus involvement and significant extension into the anterior cranial fossa, with displacement of the optic apparatus and hypothalamic pituitary axis. After an initial biopsy, the patient underwent a bifrontal craniofacial approach at 2 months of age, followed by a second-stage transnasal endoscopic approach at 15 months which resulted in a complete resection. There were no neurosurgical complications. Pathology was consistent with a NCMT. DISCUSSION: Although rare, neurosurgical involvement is critical for the treatment of NCMTs with intracranial extension. Staged cranial and endonasal endoscopic approaches may be needed for complete resection of such lesions.
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Neoplasias Encefálicas , Procedimentos Neurocirúrgicos , Biópsia , Neoplasias Encefálicas/cirurgia , Criança , Endoscopia , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
Background and Purpose- Stroke is a leading cause of long-term disability. Limited treatment options exist for patients with chronic stroke and substantial functional deficits. The current study examined safety and preliminary efficacy estimates of intravenous allogeneic mesenchymal stem cells in this population. Methods- Entry criteria included ischemic stroke >6 months prior and substantial impairment (National Institutes of Health Stroke Scale score ≥6) and disability. Enrollees received a single intravenous dose of allogeneic ischemia-tolerant mesenchymal stem cells. Phase 1 used a dose-escalation design (3 tiers, n=5 each). Phase 2 was an expanded safety cohort. The primary end point was safety over 1-year. Secondary end points examined behavioral change. Results- In phase 1 (n=15), each dose (0.5, 1.0, and 1.5 million cells/kg body weight) was found safe, so phase 2 subjects (n=21) received 1.5 million cells/kg. At baseline, subjects (n=36) averaged 4.2±4.6 years poststroke, age 61.1±10.8 years, National Institutes of Health Stroke Scale score 8 (6.5-10), and Barthel Index 65±29. Two were lost to follow-up, one was withdrawn and 2 died (unrelated to study treatment). Of 15 serious adverse events, none was possibly or probably related to study treatment. Two mild adverse events were possibly related to study treatment, a urinary tract infection and intravenous site irritation. Treatment was safe based on serial exams, electrocardiograms, laboratory tests, and computed tomography scans of chest/abdomen/pelvis. All behavioral end points showed significant gains over the 12-months of follow-up. For example, Barthel Index scores increased by 6.8±11.4 points (mean±SD) at 6-months (P=0.002) and by 10.8±15.5 points at 12-months (P<0.001) post-infusion; the proportion of patients achieving excellent functional outcome (Barthel score ≥95) increased from 11.4% at baseline to 27.3% at 6-months and to 35.5% at 12-months. Conclusions- Intravenous transfusion of allogeneic ischemia-tolerant mesenchymal stem cell in patients with chronic stroke and substantial functional deficits was safe and suggested behavioral gains. These data support proceeding to a randomized, placebo-controlled study of this therapy in this population. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01297413.
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Transplante de Células-Tronco Mesenquimais/métodos , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Doença Crônica , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recuperação de Função FisiológicaAssuntos
Astrocitoma/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Hidrocefalia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Pré-Escolar , Feminino , Humanos , Hidrocefalia/etiologia , Hidrocefalia/terapia , Imageamento por Ressonância Magnética/métodos , Espaço Subaracnóideo/diagnóstico por imagem , VentriculostomiaRESUMO
Treatment for medulloblastoma carries significant risks, particularly in resource-constrained settings. We report a case of a Mexican infant with desmoplastic/nodular medulloblastoma. Given the nature of her tumor, we developed a tailored regimen following subtotal resection to avoid both radiation therapy and the high-dose cisplatin therapy offered at most centers in the United States. The patient is in remission 4 years after the initial diagnosis. This case suggests an alternative treatment plan for this particular tumor variant that accommodates the limited resources of many centers around the world and avoids the risks associated with radiation therapy at a young age.
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Neoplasias Cerebelares/patologia , Meduloblastoma/patologia , Antineoplásicos/uso terapêutico , Neoplasias Cerebelares/cirurgia , Neoplasias Cerebelares/terapia , Feminino , Humanos , Lactente , Meduloblastoma/cirurgia , Meduloblastoma/terapia , MéxicoAssuntos
Lobo Frontal/diagnóstico por imagem , Lobo Frontal/lesões , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Ferimentos por Arma de Fogo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/etiologia , Pré-Escolar , Evolução Fatal , Armas de Fogo , Humanos , Masculino , Ferimentos por Arma de Fogo/complicaçõesRESUMO
There is an increased risk of cerebrovascular accidents (CVA) in individuals with PHACES, yet the precise causes are not well understood. In this analysis, we aimed to examine the role of arteriopathy in PHACES syndrome as a potential contributor to CVA. We analyzed clinical and radiological data from 282 patients with suspected PHACES syndrome. We analyzed clinical features, including the presence of infantile hemangioma and radiological features based on magnetic resonance angiography or computed tomography angiography, in individuals with PHACES syndrome according to the Garzon criteria. To analyze intravascular blood flow, we conducted a simulation based on the Fluid-Structure Interaction (FSI) method, utilizing radiological data. The collected data underwent statistical analysis. Twenty patients with PHACES syndrome were included. CVAs were noted in 6 cases. Hypoplasia (p = 0.03), severe tortuosity (p < 0.01), absence of at least one main cerebral artery (p < 0.01), and presence of persistent arteries (p = 0.01) were associated with CVAs, with severe tortuosity being the strongest predictor. The in-silico analysis showed that the combination of hypoplasia and severe tortuosity resulted in a strongly thrombogenic environment. Severe tortuosity, combined with hypoplasia, is sufficient to create a hemodynamic environment conducive to thrombus formation and should be considered high-risk for cerebrovascular accidents (CVAs) in PHACES patients.
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Hemangioma , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Artérias Cerebrais/patologia , Angiografia por Ressonância Magnética , Hemangioma/patologia , Tomografia Computadorizada por Raios XRESUMO
Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams.
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OBJECTIVE: Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers. METHODS: Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed. RESULTS: Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals. CONCLUSIONS: In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.
Assuntos
Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/terapia , Malformações Arteriovenosas Intracranianas/epidemiologia , Masculino , Feminino , Criança , Estudos Retrospectivos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Adolescente , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Resultado do Tratamento , Pré-Escolar , Procedimentos Endovasculares , Estados Unidos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Estudos de Coortes , Lactente , Craniotomia/estatística & dados numéricosRESUMO
Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.