Search

Background: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017–2019), COVID (2020–2021), and post-COVID period (2022–June 2023) looking for possible epidemiological and/or clinical changes. Material and methods: An English language questionnaire was sent to ESPN members about year of the event, patient’s age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. Results: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution. Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks. Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain. Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique.

Achondroplasia is an autosomal dominant genetic disease representing the most common form of human skeletal dysplasia: almost all individuals with achondroplasia have identifiable mutations in the fibroblast growth factor receptor type 3 (FGFR3) gene. The cardinal features of this condition and its inheritance have been well-established, but the occurrence of feeding and nutritional complications has received little prominence. In infancy, the presence of floppiness and neurological injury due to foramen magnum stenosis may impair the feeding function of a newborn with achondroplasia. Along with growth, the optimal development of feeding skills may be affected by variable interactions between midface hypoplasia, sleep apnea disturbance, and structural anomalies. Anterior open bite, prognathic mandible, retrognathic maxilla, and relative macroglossia may adversely impact masticatory and respiratory functions. Independence during mealtimes in achondroplasia is usually achieved later than peers. Early supervision of nutritional intake should proceed into adolescence and adulthood because of the increased risk of obesity and respiratory problems and their resulting sequelae. Due to the multisystem involvement, oral motor dysfunction, nutrition, and gastrointestinal issues require special attention and personalized management to facilitate optimal outcomes, especially because of the novel therapeutic options in achondroplasia, which could alter the progression of this rare disease.

The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5–6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

PurposeImage processing plays a fundamental role in the study of central nervous system, for example in the analysis of the vascular network in neurodegenerative diseases. Synchrotron X-ray Phase-contrast micro-Tomography (SXPCT) is a very attractive method to study weakly absorbing samples and features, such as the vascular network in the spinal cord (SC). However, the identification and segmentation of vascular structures in SXPCT images is seriously hampered by the presence of image noise and strong contrast inhomogeneities, due to the sensitivity of the technique to small electronic density variations. In order to help with these tasks, we implemented a user-friendly ImageJ plugin based on a 3D Gaussian steerable filter, tuned up for the enhancement of tubular structures in SXPCT images.MethodsThe developed 3D Gaussian steerable filter plugin for ImageJ is based on the steerability properties of Gaussian derivatives. We applied it to SXPCT images of ex-vivo mouse SCs acquired at different experimental conditions.ResultsThe filter response shows a strong amplification of the source image contrast-to-background ratio (CBR), independently of structures orientation. We found that after the filter application, the CBR ratio increases by a factor ranging from ~6 to ~60. In addition, we also observed an increase of 35% of the contrast to noise ratio in the case of injured mouse SC.ConclusionThe developed tool can generally facilitate the detection/segmentation of capillaries, veins and arteries that were not clearly observable in non-filtered SXPCT images. Its systematic application could allow obtaining quantitative information from pre-clinical and clinical images.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.

A crucial issue in the development of therapies to treat pathologies of the central nervous system is represented by the availability of non-invasive methods to study the threedimensional morphology of spinal cord, with a resolution able to characterize its complex vascular and neuronal organization. X-ray phase contrast micro-tomography enables a highquality, 3D visualization of both the vascular and neuronal network simultaneously without the need of contrast agents, destructive sample preparations or sectioning. Until now, high resolution investigations of the post-mortem spinal cord in murine models have mostly been performed in spinal cords removed from the spinal canal. We present here post-mortem phase contrast micro-tomography images reconstructed using advanced computational tools to obtain high-resolution and high-contrast 3D images of the fixed spinal cord without removing the bones and preserving the richness of micro-details available when measuring exposed spinal cords. We believe that it represents a significant step toward the in-vivo application. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Recent trends in hard X-ray micro-computed tomography (microCT) aim at increasing both spatial and temporal resolutions. These challenges require intense photon beams. Filtered synchrotron radiation beams, also referred to as 'pink beams', which are emitted by wigglers or bending magnets, meet this need, owing to their broad energy range. In this work, the new microCT station installed at the biomedical beamline ID17 of the European Synchrotron is described and an overview of the preliminary results obtained for different biomedical-imaging applications is given. This new instrument expands the capabilities of the beamline towards sub-micrometre voxel size scale and simultaneous multi-resolution imaging. The current setup allows the acquisition of tomographic datasets more than one order of magnitude faster than with a monochromatic beam configuration.

AIM: To analyze the current literature on neurocutaneous melanosis (NCM), as well as, our cases, in order to better define the prognosis and the presence of risk factors affecting it, thus, offering better information to the parents. MATERIAL and METHODS: Two cases observed at the Pediatric Neurosurgery Unit of the Catholic University Medical School in Rome are described. Both of them had cutaneous stigmata and cerebral MR evidence of intracranial melanin deposits. These two children showed a very different clinical course. RESULTS: The present study enlighten the differences among the two cases and review the literature on the subject, with the attempt to understand which are clinical and disease related factors that might influence the prognosis. CONCLUSION: Beside malignant features of cutaneous melanotic lesions, the presence of hydrocephalus at diagnosis and the early appearance of clinical symptoms, when appearing contemporarily, are predicting the rapid progression of the disease and a worse prognosis.

Background: Pediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool. Methods: We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres. Results: These microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant (p < 0.001) prognostic performance for miR-1248 was reported with an area under the curve (AUC) of 1.00. We also highlighted a critical oncogenic role for miR-1248 in gliomas tumours. Indeed, high miR-1248 levels maintain low its validated target genes (CDKN1A (p21)/FRK/SPOP/VHL/MTAP) and consequently sustain the activation of oncogenic pathways. Conclusions: Altogether, we provide a novel molecular biomarker able to successfully identify pLGG patients associated with disease progression that could support the clinicians in the decision-making strategy, advancing personalized medicine.

Background: Diffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy. Methods: Immunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function. Results: GD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo. Conclusion: Our study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.

This narrative review highlights the latest achievements in the field of post-surgical rehabilitation of posterior fossa tumors. Studies investigating the effects of cognitive rehabilitation programs have been considered, following a comprehensive literature search in the scientific electronic databases: Pubmed, Scopus, Plos One, and ScienceDirect. This review investigates the effects of cognitive remediation, with specific highlights for single cognitive domains. The results revealed that in spite of the increasing number of children who survive into adulthood, very few studies investigated the effects of rehabilitation programs in this specific population. This study details new, promising therapeutic opportunities for children after brain surgery. More research in this filed is needed to identify the most effective protocols for clinical use.

Background: High-grade pineal region tumors are rare and heterogeneous types of primary central nervous system neoplasms; radiological differential diagnosis is challenging but it is important because it has a therapeutic relevance. Purpose: To discriminate among high-grade pineal region tumors by combining apparent diffusion coefficient (ADC) volumetric values and qualitative features in order to predict their histology. Material and Methods: Twenty-two patients with high-grade pineal region tumors were assessed by qualitative and quantitative analysis. Margins, T2-weighted signal intensity, contrast enhancement, hemorrhage, calcifications, different volumetric ADC fractions (ADCmean, ADCmax, ADCmin) were evaluated and were compared to the histopathologic findings (cell count and proliferation index). Results: Our qualitative imaging data showed that only margins were different among different tumors and each tumor type showed peculiar age onset. ADCmean was found the best quantitative value to discriminate high-grade tumors of the pineal region. ADCmean correlated with proliferation index but not with cell count. ADCmean values were lower in tumors with higher proliferation rate and a significant difference in ADCmean values were found between germinomas and pineoblastomas, between germinomas and papillary tumors and between papillary tumors and pineoblastomas. Moreover, the cut-off value of 0.865 × 10–3 mm2/s for ADCmean (ADC mean threshold value) could differentiate germinoma from pineoblastomas with the best combination of sensitivity and specificity. Conclusion: The ADCmean value measured on the whole tumor, reflecting tumor proliferative activity, may be a practical and non-invasive marker for predicting tumor histology in high-grade pineal region lesions and might be useful in preoperative assessment.