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OBJECTIVE: Posterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement. MATERIAL AND METHODS: We analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata. RESULTS: The mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression. CONCLUSION: The first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.
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Pediatric low-grade gliomas (PLGGs) comprise a heterogeneous set of low-grade glial and glioneuronal tumors, collectively representing the most frequent CNS tumors of childhood and adolescence. Despite excellent overall survival rates, the chronic nature of the disease bears a high risk of long-term disease- and therapy-related morbidity in affected patients. Recent in-depth molecular profiling and studies of the genetic landscape of PLGGs led to the discovery of the paramount role of frequent upregulation of RAS/MAPK and mTOR signaling in tumorigenesis and progression of these tumors. Beyond, the subsequent unveiling of RAS/MAPK-driven oncogene-induced senescence in these tumors may shape the understanding of the molecular mechanisms determining the versatile progression patterns of PLGGs, potentially providing a promising target for novel therapies. Recent in vitro and in vivo studies moreover indicate a strong dependence of PLGG formation and growth on the tumor microenvironment. In this work, we provide an overview of the current understanding of the multilayered cellular mechanisms and clinical factors determining the natural progression patterns and the characteristic biological behavior of these tumors, aiming to provide a foundation for advanced stratification for the management of these tumors within a multimodal treatment approach.
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Senescência Celular , Progressão da Doença , Glioma , Humanos , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Criança , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Microambiente Tumoral , Animais , Gradação de Tumores , Transdução de SinaisRESUMO
PURPOSE: Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) in pLGG is the most important prognostic factor. There are multiple intraoperative tools to optimize the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of pLGG. METHODS: The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. RESULTS: We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep-seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (chi-square test, p < 0.01). CONCLUSION: iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long-term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent and iMRI if locally available.
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INTRODUCTION: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies. PATIENTS AND METHODS: Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age. RESULTS: The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres. CONCLUSIONS: The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals.
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Neoplasias Encefálicas , Glioma , Procedimentos Neurocirúrgicos , Humanos , Criança , Glioma/cirurgia , Glioma/patologia , Feminino , Masculino , Procedimentos Neurocirúrgicos/métodos , Alemanha , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Adolescente , Pré-Escolar , Lactente , Gradação de TumoresRESUMO
Within the past decade, incremental integration of molecular characteristics into the classification of central nervous system neoplasms increasingly facilitated precise diagnosis and advanced stratification, beyond potentially providing the foundation for advanced targeted therapies. We report a series of three cases of infant-type hemispheric glioma (IHG) involving three infants diagnosed with neuroepithelial tumors of the cerebral hemispheres harboring a novel, recurrent TRIM24::MET fusion. Histopathology showed glial tumors with either low-grade or high-grade characteristics, while molecular characterization found an additional homozygous CDKN2A/B deletion in two cases. Two patients showed leptomeningeal dissemination, while multiple supra- and infratentorial tumor manifestations were found in one case. Following subtotal resection (two cases) and biopsy (one case), treatment intensity of adjuvant chemotherapy regimens did not reflect in the progression patterns within the reported cases. Two patients showed progression after first-line treatment, of which one patient died not responding to tyrosine kinase inhibitor cabozantinib. As the detection of a recurrent TRIM24::MET fusion expands the spectrum of renowned driving fusion genes in IHG, this comparative illustration may indicate a distinct clinico-pathological heterogeneity of tumors bearing this driver alteration. Upfront clinical trials of IHG promoting further characterization and the implementation of individualized therapies involving receptor tyrosine kinase inhibition are required.
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Neoplasias Encefálicas , Glioma , Proteínas Proto-Oncogênicas c-met , Humanos , Proteínas Proto-Oncogênicas c-met/genética , Glioma/genética , Glioma/patologia , Masculino , Feminino , Lactente , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Transporte/genéticaRESUMO
OBJECTIVE: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach. We report our retrospective experience from two centers on surgical options and their impact on long-term outcomes. METHODS: Medical records of surgically treated pediatric CHG patients between 2004 and 2022 were analyzed. Patient characteristics, surgical interventions, histology, and non-surgical therapy were retrieved together with outcome measures such as visual acuity, endocrine function, and survival. RESULTS: A total of 63 patients (33 female, NF-1, n = 8) were included. Age at first diagnosis was 4.6 years (range 0.2-16.9) and cohort follow-up was 108 ± 72 months. Twenty patients were surgically treated with a biopsy and 43 patients with debulking at a median age of 6.5 years (range 0.16-16.9). Patients received a median of 2 tumor surgeries (range 1-5). Cyst drainage was accomplished in 15 patients, and 27 patients had ventriculoperitoneal shunt implantation. Non-surgical therapy was given in 69.8%. At the end of follow-up, 74.6% of patients had stable disease. The cohort had a median Karnofsky score of 90 (range 0-100). Four patients died. Hormone substitution was necessary in 30.2%, and visual acuity was impaired in 66% of patients. CONCLUSION: Pediatric CHG is a chronic disease due to overall high survival with multiple progressions. Surgical therapy remains a key treatment option offering biopsy, limited tumor-debulking, cyst fenestration, and hydrocephalus management in the framework of MDT decision-making. Team experience contributes to reducing possible deficits in this challenging cohort.
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Methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" was recently defined based on methylation profiling and tSNE analysis of a series of 21 neuroepithelial tumors with predominant presence of a BCOR fusion and/or characteristic CNV breakpoints at chromosome 22q12.31 and chromosome Xp11.4. Clear diagnostic criteria are still missing for this tumor type, specially that BCOR/BCOR(L1)-fusion is not a consistent finding in these tumors despite being frequent and that none of the Heidelberger classifier versions is able to clearly identify these cases, in particular tumors with alternative fusions other than those involving BCOR, BCORL1, EP300 and CREBBP. In this study, we introduce a BCOR::CREBBP fusion in an adult patient with a right temporomediobasal tumor, for the first time in association with methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" in addition to 35 cases of CNS neuroepithelial tumors with molecular and histopathological characteristics compatible with "CNS tumor with BCOR/BCOR(L1)-fusion" based on a comprehensive literature review and data mining in the repository of 23 published studies on neuroepithelial brain Tumors including 7207 samples of 6761 patients. Based on our index case and the 35 cases found in the literature, we suggest the archetypical histological and molecular features of "CNS tumor with BCOR/BCOR(L1)-fusion". We also present four adult diffuse glioma cases including GBM, IDH-Wildtype and Astrocytoma, IDH-Mutant with CREBBP fusions and describe the necessity of complementary molecular analysis in "CNS tumor with BCOR/BCOR(L1)-alterations for securing a final diagnosis.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Neoplasias Neuroepiteliomatosas , Adulto , Humanos , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/genética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Metilação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/genética , Proteína de Ligação a CREB/genéticaRESUMO
PURPOSE: The prognostic utility of MIB-1 labeling index (LI) in pediatric low-grade glioma (PLGG) has not yet conclusively been described. We assess the correlation of MIB-1 LI and tumor growth velocity (TGV), aiming to contribute to the understanding of clinical implications and the predictive value of MIB-1 LI as an indicator of proliferative activity and progression-free survival (PFS) in PLGG. METHODS: MIB-1 LI of a cohort of 172 nonependymal PLGGs were comprehensively characterized. Correlation to TGV, assessed by sequential MRI-based three-dimensional volumetry, and PFS was analyzed. RESULTS: Mean MIB-1 LI accounted for 2.7% (range: < 1-10) and showed a significant decrease to 1.5% at secondary surgery (p = .0013). A significant difference of MIB-1 LI in different histopathological types and a correlation to tumor volume at diagnosis could be shown. Linear regression analysis showed a correlation between MIB-1 LI and preoperative TGV (R2 = .55, p < .0001), while correlation to TGV remarkably decreased after incomplete resection (R2 = .08, p = .013). Log-rank test showed no association of MIB-1 LI and 5-year PFS after incomplete (MIB-1 LI > 1 vs ≤ 1%: 48 vs 46%, p = .73) and gross-total resection (MIB-1 LI > 1 vs ≤ 1%: 89 vs 95%, p = .75). CONCLUSION: These data confirm a correlation of MIB-1 LI and radiologically detectable TGV in PLGG for the first time. Compared with preoperative TGV, a crucially decreasing correlation of MIB-1 LI and TGV after surgery may result in limited prognostic capability of MIB-1 LI in PLGG.
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Neoplasias Encefálicas , Glioma , Criança , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Antígeno Ki-67 , Prognóstico , Estudos RetrospectivosRESUMO
Background: Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm. Methods: We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment. Results: MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control. Conclusion: Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.
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BACKGROUND: Idiopathic intracranial hypertension in children often presents with non-specific symptoms found in conditions such as hydrocephalus. For definite diagnosis, invasive intracranial pressure measurement is usually required. Ultrasound (US) of the optic nerve sheath diameter provides a non-invasive method to assess intracranial pressure. Transtemporal US allows imaging of the third ventricle and thus assessment for hydrocephalus. OBJECTIVE: To investigate whether the combination of US optic nerve sheath and third ventricle diameter can be used as a screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure and exclude hydrocephalus as an underlying pathology. Further, to analyze whether both parameters can be used to monitor treatment outcome. MATERIALS AND METHODS: We prospectively included 36 children with idiopathic intracranial hypertension and 32 controls. Using a 12-Mhz linear transducer and a 1-4-Mhz phased-array transducer, respectively, optic nerve sheath and third ventricle diameters were determined initially and during the course of treatment. RESULTS: In patients, the mean optic nerve sheath diameter was significantly larger (6.45±0.65 mm, controls: 4.96±0.32 mm) and the mean third ventricle diameter (1.69±0.65 mm, controls: 2.99±1.31 mm) was significantly smaller compared to the control group, P<0.001. Optimal cut-off values were 5.55 mm for the optic nerve sheath and 1.83 mm for the third ventricle diameter. CONCLUSIONS: The combined use of US optic nerve sheath and third ventricle diameter is an ideal non-invasive screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure while ruling out hydrocephalus. Treatment can effectively be monitored by repeated US, which also reliably indicates relapse.
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Nervo Óptico , Pseudotumor Cerebral , Humanos , Feminino , Masculino , Criança , Pseudotumor Cerebral/diagnóstico por imagem , Nervo Óptico/diagnóstico por imagem , Adolescente , Pré-Escolar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Seguimentos , Terceiro Ventrículo/diagnóstico por imagem , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , LactenteRESUMO
Introduction: Dilatation of the optic nerve sheath diameter and swelling of the optic disc are known phenomena associated with intracranial pressure elevation. Research question: Do sex and disease etiology have an impact on the development of optic disc elevation and optic nerve sheath extension in children in the setting of ICP elevation? Fundoscopic papilledema and point-of-care-ultrasound techniques-optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE) - were compared in this regard. Material and methods: 72 children were included in this prospective study; 50 with proven pathology (e.g. pseudotumor cerebri, tumor), 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array-transducer. This was compared with fundoscopic optic disc findings and in 28 patients with invasive ICP values, stratified for sex and etiology. Results: In patients with proven disease, significant more girls (69%) had fundoscopic papilledema compared with boys (37%, p < 0.05). Girls had also larger US-ODE values (0.86 ± 0.36 mm vs. 0.65 ± 0.40 mm in boys). 80% of tumor patients had initial papilledema (100% girls, 79% boys), compared with 50% in pseudotumor cerebri (PTC) (83% girls, 30% boys). US-ONSD had no sex- and no etiology-specificity. Discussion and conclusion: Presence of papilledema appears to be influenced by sex and etiology, whereas US-ONSD is not. Girls seem more likely to develop papilledema under similar conditions. Male sex and PTC appear as risk factors for being undetected by fundoscopic findings. US-ONSD and US-ODE seem useful tools to identify pathologies with potentially increased ICP requiring treatment in children regardless of sex and etiology.
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A 14-year-old boy presented with a 2-year history of slowly increasing weakness and atrophy in the right forearm and leg. Magnetic resonance imaging (MRI) revealed an intramedullary diffusely infiltrating lateralized tumor at C3-7. An extended biopsy was planned. After laminotomy and durotomy, the swollen spinal cord was noted to be rotated by 45° with the right dorsal root entry zone being in the midline. A 15 MHz linear ultrasound probe was used to identify the midline by visualizing the dorsal median sulcal vein within the midline raphe. A myelotomy was made in that zone without deterioration of somatosensory evoked potentials (SEPs) and an extended biopsy was performed. Histological examination revealed a pilocytic astrocytoma. Modern intraoperative high-resolution color-coded ultrasound enables the identification of the midline in intramedullary spinal cord lesions even when the spinal cord anatomy is distorted.
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Neoplasias da Medula Espinal , Masculino , Humanos , Adolescente , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Procedimentos Neurocirúrgicos , Potenciais Somatossensoriais Evocados/fisiologia , Raízes Nervosas EspinhaisRESUMO
Solid tumors of the cervicothoracic junction, the posterior mediastinum, or bilateral dorsal thoracic tumors represent a challenge in pediatric surgical oncology. The aim of this study was to evaluate trap-door thoracotomy and clamshell thoracotomy as surgical approaches. A single-center retrospective study of children with solid tumors in these specific localizations was performed. From 2015 to 2023, 26 children (17 girls; 9 boys) were treated at a median age of 54 months (range 8-229). Tumor resection was performed for neuroblastoma (n = 11); metastatic disease (n = 7); malignant rhabdoid tumor (n = 4); Ewing sarcoma (n = 1); inflammatory myofibroblastic tumor (n = 1); rhabdomyosarcoma (n = 1); and neurofibroma (n = 1). The surgical goal of macroscopic complete excision was achieved in all of the 14 children who underwent trap-door thoracotomy and in 11 of the 12 children who underwent clamshell thoracotomy. There were no major complications. At a median follow-up of 8 months (range 0-60), the disease was under local control or in complete remission in 66.7% of the children. In conclusion, surgical resection of solid tumors of the cervicothoracic junction in children can be performed safely and successfully with trap-door thoracotomy and with clamshell thoracotomy for posterior mediastinal or bilateral dorsal thoracic tumors.
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INTRODUCTION: Cerebral oxygen desaturation during pediatric surgery has been associated with adverse perioperative outcomes. The aim of this pilot study was to analyze the frequency and severity of intraoperative cerebral oxygen desaturations and their impact on postoperative cerebral oxygen metabolism in neonates and infants undergoing pediatric surgery. METHODS: In a prospective pilot study, intra- and postoperative regional cerebral oxygen saturation and blood flow were measured noninvasively using a device combining laser Doppler flowmetry and white-light-spectrometry. Thirty-seven consecutive neonates and infants undergoing noncardiac surgery under general anesthesia for more than 30 min and necessity for invasive arterial blood pressure monitoring were included. Patients with pre-known congenital structural heart disease or cerebral disease were excluded. Continuously brain monitor recording was started in sedated patients before induction of anesthesia (preoperative baseline) and was completed 1 h postoperatively in the PICU in sedated, intubated, and mechanically ventilated states at the PICU (postoperative state). Baseline and postoperative state for cerebral fractional tissue oxygen extraction and approximated cerebral metabolic rate of oxygen were calculated. RESULTS: Seventeen (46%) of the 37 studied neonates and infants suffered from intraoperative periods of regional cerebral oxygen desaturation below 20% of the baseline (event group). Severity of cerebral desaturations was median 4.0%min/h [range 0.1-58.7; interquartile range [IQR] 0.99-21.29]. In the event group, the duration of surgery was significantly longer (median 135 min [range 11-260; IQR 113.5-167.0] vs median 46.5 min [range 11-180; IQR 30.5-159.3]; difference of -62.94; 95% confidence interval [CI] -105.17 to -20.71; p = .021). In the event group, cerebral fractional tissue oxygen extraction (median 0.41 [range 0.20-0.55; IQR 0.26-0.44] vs. median 0.27 [range 0.11-0.41; IQR 0.20-0.31]; difference of -0.11; 95% CI -0.17 to -0.05; p = .001) and approximated cerebral metabolic rate of oxygen (median 6.15 arbitrary unit [range 2.69-12.07; IQR 5.12-7.21] vs. median 4.14 arbitrary unit [range 1.78-7.86; IQR 3.82-6.31]; difference of -1.76; 95% CI -3.03 to -0.49; p = .009) were significantly higher and the cerebral regional oxygen saturation (median 58.99% [range 44.87-79.1; IQR 54.26-72.61] vs median 70.94% [range 57.9-86.13; IQR 67.07-76.59]; difference of 10.01; 95% CI 4.13-15.90; p = .002) significantly lower after surgery compared to the nonevent group. DISCUSSION: The increase of approximated cerebral metabolic rate of oxygen could indicate an elevated oxidative energy metabolism in the "stressed" brain, due to repair processes. The increased cerebral fractional tissue oxygen extraction fits with the decreased NIRS cerebral oxygenation. Our data suggest that an increase in cerebral oxygen metabolism was the cause. CONCLUSION: Cerebral oxygen desaturation during major surgery in neonates and infants is associated with early postoperative increased cerebral oxygen extraction and possibly increased cerebral oxygen metabolism.
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Cardiopatias Congênitas , Oxigênio , Lactente , Recém-Nascido , Criança , Humanos , Estudos Prospectivos , Projetos Piloto , Cardiopatias Congênitas/cirurgia , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologiaRESUMO
PURPOSE: To compare transorbital point-of-care ultrasound techniques -optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE)- with fundoscopic papilledema to detect potentially raised intracranial pressure (ICP) with treatment indication in children. METHODS: In a prospective study, 72 symptomatic children were included, 50 with later proven disease associated with raised ICP (e.g. pseudotumour cerebri, brain tumour, hydrocephalus) and 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array transducer. This was compared to fundoscopic optic disc findings (existence of papilledema) and, in 28 cases, invasively measured ICP values. RESULTS: The sensitivity and specificity of a cut-off value of US-ONSD (5.73 mm) to detect treatment indication for diseases associated with increased ICP was 92% and 86.4%, respectively, compared to US-ODE (0.43 mm) with sensitivity: 72%, specificity: 77.3%. Fundoscopic papilledema had a sensitivity of 46% and a specificity of 100% in this context. Repeatability and observer-reliability of US-ODE examination was eminent (Cronbach's α = 0.978-0.989). Papilledema was detected fundoscopically only when US-ODE was > 0.67 mm; a US-ODE > 0.43 mm had a positive predictive value of 90% for potentially increased ICP. CONCLUSION: In our cohort, transorbital point-of-care US-ONSD and US-ODE detected potentially elevated ICP requiring treatment in children more reliably than fundoscopy. US-ONSD and US-ODE indicated the decrease in ICP after treatment earlier and more reliably than fundoscopy. The established cut-off values for US-ONSD and US-ODE and a newly developed US-based grading of ODE can be used as an ideal first-line screening tool to detect or exclude conditions with potentially elevated ICP in children.
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Hipertensão Intracraniana , Papiledema , Criança , Humanos , Papiledema/complicações , Papiledema/diagnóstico por imagem , Estudos Prospectivos , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Pressão Intracraniana/fisiologia , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Hipertensão Intracraniana/complicações , Hipertensão Intracraniana/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
INTRODUCTION: Glioblastoma (GBM) is a tumor with rapid growth and a possible relationship to elevated intracranial pressure (ICP). High ICP may not always be associated with clinical signs. A non-invasive technique for assessment of ICP is measuring the optic nerve sheath diameter (ONSD). Identifying patients who need immediate intervention is of importance in neuro-oncological care. The goal of this study is to assess the available magnetic resonance imaging (MRI) of patients with GBM with respect to pre- and postoperative ONSD. METHODS AND MATERIALS: Retrospective data analysis was performed on all patients operated for GBM at a tertiary care center between 2010 and 2020. Two pre and one postoperative MRI had to be available. Clinical data and ONSD at multiple time points were analyzed and correlated, as well as preoperative volumetrics. RESULTS: Sixty-seven patients met the inclusion criteria. Clinical signs of elevated ICP were seen in 25.4% (n = 17), while significant perifocal edema was present in 67.2% (n = 45) of patients. Clinical signs of preoperatively elevated ICP were associated with significantly elevated ONSD at diagnosis (p < 0.001) as well as preoperative tumor volume (p < 0.001). Significant perifocal edema at the time of diagnosis was associated with elevated ONSD (p = 0.029) and higher tumor volume (p = 0.003). In patients with significant edema, ONSD increased significantly between preoperative MRIs (p = 0.003/005). In patients with clinical signs of raised ICP, ONSD also increased, whereas it was stable in asymptomatic patients (yes: 5.01+/-4.17 to 5.83+/-0.55 mm, p = 0.010, no: 5.17+/-0.46 mm to 5.38+/-0.41 mm, p = 0.81). A significant increase of ONSD from diagnosis to preoperative MRI and a significant decrease until 3 months postoperatively were observed (p < 0.001). CONCLUSIONS: ONSD might help identify high ICP in patients with GBM. In this first-of-its kind study, we observed a significant increase of ONSD preoperatively, likely associated with edema. Postoperatively, ONSD decreased significantly until 3 months after surgery and increased again at 12 months. Further prospective data collection is warranted.
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Glioblastoma , Glioma , Hipertensão Intracraniana , Humanos , Estudos Retrospectivos , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Pressão Intracraniana/fisiologia , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/patologia , Glioma/patologia , Glioblastoma/patologia , Edema/patologia , Ultrassonografia/métodosRESUMO
BACKGROUND AND OBJECTIVE: Although an increased intracranial pressure (ICP) is a known problem in children with syndromic craniosynostosis, it remains unclear whether elevated ICP and impaired cerebral perfusion exist in nonsyndromic synostosis and should be defined as targets of primary treatment. This study aimed to investigate ICP, cerebral autoregulation (CAR), and brain perfusion in infants with nonsyndromic craniosynostosis at first surgical intervention. METHODS: Forty-three infants were prospectively included. The patients underwent perioperative measurement of mean arterial blood pressure, ICP, and brain perfusion before and after cranial vault decompression. Physiological parameters with possible influences on ICP and autoregulation/brain perfusion were standardized for age. CAR was assessed by the pressure reactivity index (PRx), calculated using the mean arterial blood pressure and ICP. RESULTS: Biparietal decompression was performed in 29 infants with sagittal synostosis (mean age, 6.1 ± 1.3 months). Fronto-orbital advancement was performed in 10 and 4 infants with metopic and unilateral coronal synostosis, respectively (mean age, 11.6 ± 2.1 months). An elevated ICP (>15 mm Hg) was found in 20 of 26 sagittal (mean, 21.7 ± 4.4 mm Hg), 2 of 8 metopic (mean, 17.1 ± 0.4 mm Hg), and 2 of 4 unilateral coronal synostosis cases (mean, 18.9 ± 2.5 mm Hg). Initial ICP was higher in sagittal synostosis than in metopic/coronal synostosis (P = .002). The postdecompression ICP was significantly reduced in sagittal synostosis cases (P < .001). The relative cerebral blood flow and blood flow velocity significantly increased after decompression. Impaired CAR was found in infants with a mean ICP >12 mm Hg (PRx, 0.26 ± 0.32), as compared with those with a mean ICP ≤ 12 mm Hg (PRx, -0.37 ± 0.07, P = .001). CONCLUSION: Contrary to common belief, an elevated ICP and significantly impaired CAR can exist early in single suture synostosis, particularly sagittal synostosis. Because an influence of raised ICP on long-term cognitive development is known in other diseases, we suggest that preventing increased ICP during the phase of maximal brain development may be a goal for decompressive surgery, at least for sagittal synostosis cases.
RESUMO
PURPOSE: Although pediatric low-grade gliomas (pLGG) are the most common pediatric brain tumors, patient-derived cell lines reflecting pLGG biology in culture are scarce. This also applies to the most common pLGG subtype pilocytic astrocytoma (PA). Conventional cell culture approaches adapted from higher-grade tumors fail in PA due to oncogene-induced senescence (OIS) driving tumor cells into arrest. Here, we describe a PA modeling workflow using the Simian Virus large T antigen (SV40-TAg) to circumvent OIS. METHODS: 18 pLGG tissue samples (17 (94%) histological and/or molecular diagnosis PA) were mechanically dissociated. Tumor cell positive-selection using A2B5 was perfomed in 8/18 (44%) cases. All primary cell suspensions were seeded in Neural Stem Cell Medium (NSM) and Astrocyte Basal Medium (ABM). Resulting short-term cultures were infected with SV40-TAg lentivirus. Detection of tumor specific alterations (BRAF-duplication and BRAF V600E-mutation) by digital droplet PCR (ddPCR) at defined time points allowed for determination of tumor cell fraction (TCF) and evaluation of the workflow. DNA-methylation profiling and gene-panel sequencing were used for molecular profiling of primary samples. RESULTS: Primary cell suspensions had a mean TCF of 55% (+/- 23% (SD)). No sample in NSM (0/18) and ten samples in ABM (10/18) were successfully transduced. Three of these ten (30%) converted into long-term pLGG cell lines (TCF 100%), while TCF declined to 0% (outgrowth of microenvironmental cells) in 7/10 (70%) cultures. Young patient age was associated with successful model establishment. CONCLUSION: A subset of primary PA cultures can be converted into long-term cell lines using SV40-TAg depending on sample intrinsic (patient age) and extrinsic workflow-related (e.g. type of medium, successful transduction) parameters. Careful monitoring of sample-intrinsic and extrinsic factors optimizes the process.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Criança , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Fluxo de Trabalho , Astrocitoma/patologia , Glioma/patologia , Neoplasias Encefálicas/patologiaRESUMO
BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.