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1.
Immunity ; 56(9): 2152-2171.e13, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37582369

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas , Microglia , Humanos , Camundongos , Animais , Redes Reguladoras de Genes , Encéfalo , Regulação da Expressão Gênica
2.
Childs Nerv Syst ; 40(5): 1501-1506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240787

RESUMO

OBJECTIVE: To describe the rare complication of cerebral pseudoaneurysm formation following stereotactic electroencephalography (sEEG) lead implantation in children. METHODS: A retrospective chart review of all pediatric patients undergoing sEEG procedures between 2015 and 2020 was performed. Cases of pseudoaneurysm were identified and reviewed. RESULTS: Cerebral pseudoaneurysms were identified in two of 58 total cases and 610 implanted electrodes. One lesion was detected 1 year after sEEG explantation and required craniotomy and clipping. The other was detected 3 months post-explantation and underwent coil embolization. Neither patient had any neurologic deficits associated with the pseudoaneurysm before or after treatment. CONCLUSIONS: Pseudoaneurysm formation post-sEEG explantation is rare and likely underreported. Routine, post-explantation/treatment imaging is warranted to detect this rare but potentially lethal complication.


Assuntos
Falso Aneurisma , Humanos , Criança , Estudos Retrospectivos , Eletroencefalografia/métodos , Técnicas Estereotáxicas , Imageamento Tridimensional , Eletrodos Implantados
3.
Childs Nerv Syst ; 40(4): 1111-1120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38072858

RESUMO

PURPOSE: Tethered cord syndrome (TCS) is characterized by abnormal attachment of the spinal cord neural elements to surrounding tissues. The most common symptoms include pain, motor or sensory dysfunction, and urologic deficits. Although TCS is common in children, there is a significant heterogeneity in outcomes reporting. We systematically reviewed surgical indications and postoperative outcomes to assess the need for a grading/classification system. METHODS: PubMed and EMBASE searches identified pediatric TCS literature published between 1950 and 2023. Studies reporting surgical interventions, ≥ 6-month follow-up, and ≥ 5 patients were included. RESULTS: Fifty-five studies representing 3798 patients were included. The most commonly reported non-urologic symptoms were nonspecific lower-extremity motor disturbances (36.4% of studies), lower-extremity/back pain (32.7%), nonspecific lower-extremity sensory disturbances (29.1%), gait abnormalities (29.1%), and nonspecific bowel dysfunction/fecal incontinence (25.5%). Urologic symptoms were most commonly reported as nonspecific complaints (40.0%). After detethering surgery, retethering was the most widely reported non-urologic outcome (40.0%), followed by other nonspecific findings: motor deficits (32.7%), lower-extremity/back/perianal pain (18.2%), gait/ambulation function (18.2%), sensory deficits (12.7%), and bowel deficits/fecal incontinence (12.7%). Commonly reported urologic outcomes included nonspecific bladder/urinary deficits (27.3%), bladder capacity (20.0%), bladder compliance (18.2%), urinary incontinence/enuresis/neurogenic bladder (18.2%), and nonspecific urodynamics/urodynamics score change (16.4%). CONCLUSION: TCS surgical literature is highly variable regarding surgical indications and reporting of postsurgical outcomes. The lack of common data elements and consistent quantitative measures inhibits higher-level analysis. The development and validation of a standardized outcomes measurement tool-ideally encompassing both patient-reported outcome and objective measures-would significantly benefit future TCS research and surgical management.


Assuntos
Incontinência Fecal , Defeitos do Tubo Neural , Incontinência Urinária , Humanos , Criança , Incontinência Fecal/cirurgia , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Dor , Avaliação de Resultados em Cuidados de Saúde , Defeitos do Tubo Neural/cirurgia , Estudos Retrospectivos
4.
Childs Nerv Syst ; 40(1): 153-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37462812

RESUMO

PURPOSE: Understanding the complication profile of craniosynostosis surgery is important, yet little is known about complication co-occurrence in syndromic children after multi-suture craniosynostosis surgery. We examined concurrent perioperative complications and predictive factors in this population. METHODS: In this retrospective cohort study, children with syndromic diagnoses and multi-suture involvement who underwent craniosynostosis surgery in 2012-2020 were identified from the National Surgical Quality Improvement Program-Pediatric database. The primary outcome was concurrent complications; factors associated with concurrent complications were identified. Correlations between complications and patient outcomes were assessed. RESULTS: Among 5,848 children identified, 161 children (2.75%) had concurrent complications: 129 (2.21%) experienced two complications and 32 (0.55%) experienced ≥ 3. The most frequent complication was bleeding/transfusion (69.53%). The most common concurrent complications were transfusion/superficial infection (27.95%) and transfusion/deep incisional infection (13.04%) or transfusion/sepsis (13.04%). Two cardiac factors (major cardiac risk factors (odds ratio (OR) 3.50 [1.92-6.38]) and previous cardiac surgery (OR 4.87 [2.36-10.04])), two pulmonary factors (preoperative ventilator dependence (OR 3.27 [1.16-9.21]) and structural pulmonary/airway abnormalities (OR 2.89 [2.05-4.08])), and preoperative nutritional support (OR 4.05 [2.34-7.01]) were independently associated with concurrent complications. Children who received blood transfusion had higher odds of deep surgical site infection (OR 4.62 [1.08-19.73]; p = 0.04). CONCLUSIONS: Our results indicate that several cardiac and pulmonary risk factors, along with preoperative nutritional support, were independently associated with concurrent complications but procedural factors were not. This information can help inform presurgical counseling and preoperative risk stratification in this population.


Assuntos
Craniossinostoses , Procedimentos Neurocirúrgicos , Humanos , Criança , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/métodos , Infecção da Ferida Cirúrgica/etiologia , Craniossinostoses/complicações , Craniossinostoses/cirurgia , Fatores de Risco , Suturas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
5.
PLoS Comput Biol ; 18(8): e1010401, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939509

RESUMO

In analyzing the neural correlates of naturalistic and unstructured behaviors, features of neural activity that are ignored in a trial-based experimental paradigm can be more fully studied and investigated. Here, we analyze neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings, and reveal that multiple neural signal characteristics exist that discriminate between unstructured and naturalistic behavioral states such as "engaging in dialogue" and "using electronics". Using the high gamma amplitude as an estimate of neuronal firing rate, we demonstrate that behavioral states in a naturalistic setting are discriminable based on long-term mean shifts, variance shifts, and differences in the specific neural activity's covariance structure. Both the rapid and slow changes in high gamma band activity separate unstructured behavioral states. We also use Gaussian process factor analysis (GPFA) to show the existence of salient spatiotemporal features with variable smoothness in time. Further, we demonstrate that both temporally smooth and stochastic spatiotemporal activity can be used to differentiate unstructured behavioral states. This is the first attempt to elucidate how different neural signal features contain information about behavioral states collected outside the conventional experimental paradigm.


Assuntos
Eletrocorticografia , Eletroencefalografia , Mapeamento Encefálico , Humanos , Distribuição Normal
6.
Stereotact Funct Neurosurg ; 101(3): 179-187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062282

RESUMO

INTRODUCTION: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. METHODS: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. RESULTS: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. CONCLUSION: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.


Assuntos
Epilepsia Resistente a Medicamentos , Hemisferectomia , Terapia a Laser , Criança , Masculino , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Resultado do Tratamento , Imageamento por Ressonância Magnética/métodos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Convulsões/cirurgia , Terapia a Laser/efeitos adversos , Hemisferectomia/efeitos adversos , Hemisferectomia/métodos , Espectroscopia de Ressonância Magnética/efeitos adversos
7.
Neurosurg Focus ; 55(4): E8, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37778041

RESUMO

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.


Assuntos
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/cirurgia
8.
Pediatr Emerg Care ; 39(6): 402-407, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730955

RESUMO

BACKGROUND: Optimal treatment of children with traumatic intracranial epidural hematomas (EDHs) is unknown. We sought to identify clinical and radiographic predictors of delayed surgical intervention among children with EDH admitted for observation. METHODS: We retrospectively identified patients younger than 15 years with acute traumatic EDHs evaluated at our level 1 pediatric trauma center. We excluded patients with penetrating head injuries, recent surgical evacuation of EDH, or depressed skull fracture requiring surgical repair and assigned the remaining subjects to the immediate surgery group if they underwent immediate surgical evacuation, to the supportive-therapy-only group if they underwent observation only, and to the delayed surgery group if they underwent surgery after observation. We abstracted clinical and laboratory findings, surgical interventions, and neurological outcome and measured EDH dimensions and volumes, adjusting for cranial size. We compared clinical and radiographic characteristics among groups and performed receiver-operator characteristic analyses of predictors of delayed surgery. RESULTS: Of 172 patients with EDH, 103 patients met the inclusion criteria, with 6 (6%) in the immediate surgery group, 87 (84%) in the supportive-therapy-only group, and 10 (10%) in the delayed surgery group. Headache, prothrombin time of >14 seconds, EDH maximal thickness of ≥1.1 cm, volume of ≥14 mL, EDH thickness/cranial width index of ≥0.08 and EDH volume/cranial volume index of ≥0.18, and mass effect were associated with delayed surgical intervention. There was no difference in length of stay or functional impairment between the immediate and delayed surgery groups. However, patients in delayed surgery group were more likely to have subjective symptoms at discharge than those in immediate surgery group. CONCLUSIONS: Among patients with EDH admitted for observation, larger EDH, mass effect, headaches, and prothrombin time of >14 seconds were associated with delayed surgical intervention. A larger-scale study is warranted to identify independent predictors of delayed surgery in children under observation for EDH.


Assuntos
Lesões Encefálicas Traumáticas , Hematoma Epidural Craniano , Humanos , Criança , Hematoma Epidural Craniano/cirurgia , Atraso no Tratamento , Lesões Encefálicas Traumáticas/complicações , Craniotomia , Centros de Traumatologia , Estudos Retrospectivos , Masculino , Feminino
9.
J Surg Res ; 269: 212-217, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600330

RESUMO

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.


Assuntos
Hidrocefalia , Laparoscopia , Abdome/cirurgia , Criança , Humanos , Hidrocefalia/cirurgia , Laparoscopia/efeitos adversos , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Derivação Ventriculoperitoneal/efeitos adversos
10.
Childs Nerv Syst ; 38(9): 1663-1673, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35867118

RESUMO

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.


Assuntos
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 , Prognóstico
11.
Childs Nerv Syst ; 37(4): 1267-1277, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33404725

RESUMO

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.


Assuntos
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 Tratamento
12.
Childs Nerv Syst ; 36(7): 1367-1377, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32399800

RESUMO

INTRODUCTION: The Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS. METHODS: We explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion. RESULTS: Our systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS. CONCLUSION: Spinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management.


Assuntos
Obstrução das Vias Respiratórias , Síndrome de Pierre Robin , Doenças da Coluna Vertebral , Adolescente , Deleção Cromossômica , Cromossomos Humanos Par 10 , Feminino , Humanos , Lactente , Recém-Nascido , Síndrome de Pierre Robin/complicações , Síndrome de Pierre Robin/diagnóstico por imagem , Síndrome de Pierre Robin/genética
13.
Stereotact Funct Neurosurg ; 97(1): 10-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943498

RESUMO

BACKGROUND: Nonlesional cingulate gyrus epilepsy is rare, difficult to diagnose, and challenging to treat. METHODS: We report the use of ROSA (Medtech Surgical, Inc., New York, NY, USA) robotic assistance for stereotactic EEG (S-EEG) localization and therapeutic thermal laser ablation of a nonlesional cingulate gyrus epileptogenic zone in a 17-year-old female with intractable partial epilepsy. RESULTS: After an inconclusive exhaustive initial workup, robotic-assisted S-EEG localized the patient's seizure focus to the right cingulate gyrus. Robotic-assisted lesioning of the cingulate gyrus was performed via 5 total ablations with 3 minimally invasive catheters. There were no perioperative complications. The patient was discharged home on postoperative day 2 at her neurologic baseline. She was seizure free for 8 months postoperatively, with a sustained partial response through the 23-month follow-up. CONCLUSIONS: This report expands the technical uses, pathologies, and patient populations being treated via robotic-assisted neurosurgery.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Epilepsias Parciais/cirurgia , Giro do Cíngulo/cirurgia , Terapia a Laser/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos
14.
Proc Natl Acad Sci U S A ; 112(30): E4055-64, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26159421

RESUMO

The available evidence suggests that the lethality of glioblastoma is driven by small subpopulations of cells that self-renew and exhibit tumorigenicity. It remains unclear whether tumorigenicity exists as a static property of a few cells or as a dynamically acquired property. We used tumor-sphere and xenograft formation as assays for tumorigenicity and examined subclones isolated from established and primary glioblastoma lines. Our results indicate that glioblastoma tumorigenicity is largely deterministic, yet the property can be acquired spontaneously at low frequencies. Further, these dynamic transitions are governed by epigenetic reprogramming through the lysine-specific demethylase 1 (LSD1). LSD depletion increases trimethylation of histone 3 lysine 4 at the avian myelocytomatosis viral oncogene homolog (MYC) locus, which elevates MYC expression. MYC, in turn, regulates oligodendrocyte lineage transcription factor 2 (OLIG2), SRY (sex determining region Y)-box 2 (SOX2), and POU class 3 homeobox 2 (POU3F2), a core set of transcription factors required for reprogramming glioblastoma cells into stem-like states. Our model suggests epigenetic regulation of key transcription factors governs transitions between tumorigenic states and provides a framework for glioblastoma therapeutic development.


Assuntos
Neoplasias Encefálicas/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Histona Desmetilases/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias/metabolismo , Processos Estocásticos
15.
Neurosurg Focus ; 38(4): E13, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25828489

RESUMO

Upper airway obstruction resulting from overflexion of the craniocervical junction after occipitocervical fusion is a rare but potentially life-threatening complication and is associated with morbidity. The authors retrospectively reviewed the medical records and diagnostic images of 2 pediatric patients who underwent occipitocervical fusion by the Neuro-Spine Program at Texas Children's Hospital and experienced dyspnea and/or dysphagia from new upper airway obstruction in the postoperative period. Patient demographics, operative data, and preoperative and postoperative occiput-C2 angles were recorded. A review of the literature for similar complications after occipitocervical fusion was performed. A total of 13 cases of prolonged upper airway obstruction after occipitocervical fusion were analyzed. Most of these cases involved adults with rheumatoid arthritis. To the best of the authors' knowledge, there have been no previous reports of prolonged upper airway obstruction in children after an occipitocervical fusion. Fixation of the neck in increased flexion (-18° to -5°) was a common finding among these adult and pediatric cases. The authors' cases involved children with micrognathia and comparatively large tongues, which may predispose the oropharynx to obstruction with even the slightest amount of increased flexion. Close attention to a satisfactory fixation angle (occiput-C2 angle) is necessary to avoid airway obstruction after an occipitocervical fusion. Children with micrognathia are particularly sensitive to changes in flexion at the craniocervical junction after occipitocervical fixation.


Assuntos
Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/etiologia , Transtornos de Deglutição/etiologia , Dispneia/etiologia , Complicações Pós-Operatórias/fisiopatologia , Fusão Vertebral/efeitos adversos , Adolescente , Articulação Atlantoaxial/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Osso Occipital/cirurgia
17.
Neurosurg Focus ; 36(4): E23, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24812719

RESUMO

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Mutação/genética , Proteína Supressora de Tumor p53/genética , Ilhas de CpG , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Estudos de Associação Genética , Glioma/diagnóstico , Humanos , Isocitrato Desidrogenase/genética , Masculino , MicroRNAs/genética , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo
18.
J Neurosurg Pediatr ; : 1-10, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788230

RESUMO

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.

19.
World Neurosurg ; 185: e1230-e1243, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38514037

RESUMO

BACKGROUND: For patients with medically refractory epilepsy, newer minimally invasive techniques such as laser interstitial thermal therapy (LITT) have been developed in recent years. This study aims to characterize trends in the utilization of surgical resection versus LITT to treat medically refractory epilepsy, characterize complications, and understand the cost of this innovative technique to the public. METHODS: The National Inpatient Sample database was queried from 2016 to 2019 for all patients admitted with a diagnosis of medically refractory epilepsy. Patient demographics, hospital length of stay, complications, and costs were tabulated for all patients who underwent LITT or surgical resection within these cohorts. RESULTS: A total of 6019 patients were included, 223 underwent LITT procedures, while 5796 underwent resection. Significant predictors of increased patient charges for both cohorts included diabetes (odds ratio: 1.7, confidence interval [CI]: 1.44-2.19), infection (odds ratio: 5.12, CI 2.73-9.58), and hemorrhage (odds ratio: 2.95, CI 2.04-4.12). Procedures performed at nonteaching hospitals had 1.54 greater odds (CI 1.02-2.33) of resulting in a complication compared to teaching hospitals. Insurance status did significantly differ (P = 0.001) between those receiving LITT (23.3% Medicare; 25.6% Medicaid; 44.4% private insurance; 6.7 Other) and those undergoing resection (35.3% Medicare; 22.5% Medicaid; 34.7% private Insurance; 7.5% other). When adjusting for patient demographics, LITT patients had shorter length of stay (2.3 vs. 8.9 days, P < 0.001), lower complication rate (1.9% vs. 3.1%, P = 0.385), and lower mean hospital ($139,412.79 vs. $233,120.99, P < 0.001) and patient ($55,394.34 vs. $37,756.66, P < 0.001) costs. CONCLUSIONS: The present study highlights LITT's advantages through its association with lower costs and shorter length of stay. The present study also highlights the associated predictors of LITT versus resection, such as that most LITT cases happen at academic centers for patients with private insurance. As the adoption of LITT continues, more data will become available to further understand these issues.


Assuntos
Bases de Dados Factuais , Complicações Pós-Operatórias , Humanos , Estados Unidos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/economia , Epilepsia Resistente a Medicamentos/economia , Epilepsia Resistente a Medicamentos/cirurgia , Tempo de Internação/economia , Pacientes Internados , Idoso , Terapia a Laser/economia , Adulto Jovem , Procedimentos Neurocirúrgicos/economia , Custos de Cuidados de Saúde , Epilepsia/economia , Epilepsia/cirurgia , Adolescente
20.
Spine Deform ; 12(3): 727-738, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38334901

RESUMO

PURPOSE: There is limited information on the clustering or co-occurrence of complications after spinal fusion surgery for neuromuscular disease in children. We aimed to identify the frequency and predictive factors of co-occurring perioperative complications in these children. METHODS: In this retrospective database cohort study, we identified children (ages 10-18 years) with neuromuscular scoliosis who underwent elective spinal fusion in 2012-2020 from the National Surgical Quality Improvement Program-Pediatric database. The rates of co-occurring complications within 30 days were calculated, and associated factors were identified by logistic regression analysis. Correlation between a number of complications and outcomes was assessed. RESULTS: Approximately 11% (709/6677 children with neuromuscular scoliosis undergoing spinal fusion had co-occurring complications: 7% experienced two complications and 4% experienced ≥ 3. The most common complication was bleeding/transfusion (80%), which most frequently co-occurred with pneumonia (24%) and reintubation (18%). Surgical time ≥ 400 min (odds ratio (OR) 1.49 [95% confidence interval (CI) 1.25-1.75]), fusion ≥ 13 levels (1.42 [1.13-1.79]), and pelvic fixation (OR 1.21 [1.01, 1.44]) were identified as procedural factors that independently predicted concurrent complications. Clinical risk factors for co-occurring complications included an American Society of Anesthesiologist physical status classification ≥ 3 (1.73 [1.27-2.37]), structural pulmonary/airway abnormalities (1.24 [1.01-1.52]), impaired cognitive status (1.80 [1.41-2.30]), seizure disorder (1.36 [1.12-1.67]), hematologic disorder (1.40 [1.03-1.91], preoperative nutritional support (1.34 [1.08-1.72]), and congenital malformations (1.20 [1.01-1.44]). Preoperative tracheostomy was protective against concurrent complications (0.62 [0.43-0.89]). Significant correlations were found between number of complications and length of stay, non-home discharge, readmissions, and death. CONCLUSION: Longer surgical time (≥ 400 min), fusion ≥ 13 levels and pelvic fixation are surgical risk factors independently associated with co-occurring complications, which were associated with poorer patient outcomes. Recognizing identified nonmodifiable risk factors might also be important for preoperative planning and risk stratification of children with neuromuscular scoliosis requiring spinal fusion. LEVEL OF EVIDENCE: Level IV evidence.


Assuntos
Complicações Pós-Operatórias , Escoliose , Fusão Vertebral , Humanos , Fusão Vertebral/efeitos adversos , Escoliose/cirurgia , Criança , Adolescente , Feminino , Masculino , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Doenças Neuromusculares/complicações , Doenças Neuromusculares/epidemiologia , Fatores de Risco , Fatores de Tempo , Duração da Cirurgia , Pneumonia/epidemiologia , Pneumonia/etiologia
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