Arterial spin labelling: predictive role in surgical bleeding of paediatric optic pathway gliomas.

AIM: To analyse the performance of arterial spin labelling (ASL) in predicting surgical bleeding in a paediatric cohort of optic pathway glioma (OPG). MATERIALS AND METHODS: Preoperative ASL data were obtained for 51 OPG in 40 patients, aged from 9 months to 16 years. The relative cerebral blood flow (rCBF) in the tumour areas with the highest CBF (maximum rCBF) was measured and then correlated with qualitative local bleeding (graded no, moderate, and major by the neurosurgeon) and quantitative global surgical bleeding (assessed in millilitres using haematocrit data). RESULTS: Intratumoural maximum rCBF was significantly higher when qualitative local bleeding was high (median value in the no, moderate, and major bleeding groups equal to 0.81, 1.39 and 4.22, respectively, p=0.004), but there was no difference in global quantitative bleeding (p=0.7 for the total blood loss). The maximum tumour rCBF cut-off value of 1.1 yielded a sensitivity of 73%, a specificity of 78%, and an accuracy of 76% (39/51 tumours) in detecting haemorrhagic OPG. Choosing a maximum tumour rCBF cut-off value > 1.7 improved the specificity in diagnosing tumours with high bleeding risk with a specificity of 94%, a sensitivity of 53%, and an accuracy of 82% (42/51 tumours). CONCLUSION: ASL tumoural rCBF is a useful and simple diagnostic tool to help predict high intraoperative tumoural bleeding risk in paediatric OPG.

Financial fallout from the COVID-19 pandemic:Report from a high-volume academic neurosurgery.

BACKGROUND: The global healthcare system has been overwhelmed by the Coronavirus disease-2019 (COVID-19). In order to mitigate the risk of spread of the virus, most elective surgical procedures have been cancelled especially during the lockdown periods. The purpose of this study was to assess the financial impact of the COVID outbreak due to the supposed reduced workload from our neurosurgery department in 2020. METHODS: Number of neurosurgical procedures (NSP) within the Department of Neurosurgery and their associated estimated income were retrospectively reviewed globally and month wise from administrative records of billing in 2020 and 2019 based on the Diagnosis related group (DRG) and severity of illness (4 levels). RESULTS: Overall, 824 and 818 inpatient surgical procedures were performed in 2019 and 2020 respectively. The total estimate revenue generated from inpatient surgeries was moderately decreased (3%): 9 498 226.41 euros in 2020 versus 9 817 361.65 euros in 2019 without significant difference across DRG (P=0.96) and severity of illness. CONCLUSIONS: Our data suggests a moderate negative impact of the COVID-19 pandemic had on neurosurgical and financial activity. However, a more in-depth medico-economic analysis need to be performed to assess the real financial impact.

Imaging features of medulloblastoma: Conventional imaging, diffusion-weighted imaging, perfusion-weighted imaging, and spectroscopy: From general features to subtypes and characteristics.

Medulloblastoma is a frequent high-grade neoplasm among pediatric brain tumours. Its classical imaging features are a midline tumour growing into the fourth ventricle, hyperdense on CT-scan, displaying a hypersignal when using diffusion-weighted imaging, with a variable contrast enhancement. Nevertheless, atypical imaging features have been widely reported, varying according to the age of the patient, and histopathological subtype. In this study, we review the classical and atypical imaging features of medulloblastomas, with emphasis on advanced MRI techniques, histopathological and molecular subtypes and characteristics, and follow-up modalities.

CT and Multimodal MR Imaging Features of Embryonal Tumors with Multilayered Rosettes in Children.

BACKGROUND AND PURPOSE: Embryonal tumors with multilayered rosettes, C19MC-altered, are brain tumors occurring in young children, which were clearly defined in the 2016 World Health Organization classification of central nervous system neoplasms. Our objective was to describe the multimodal imaging characteristics of this new entity. MATERIALS AND METHODS: We performed a retrospective monocentric review of embryonal brain tumors and looked for embryonal tumors with multilayered rosettes with confirmed C19MC alteration. We gathered morphologic imaging data, as well as DWI and PWI data (using arterial spin-labeling and DSC). RESULTS: We included 16 patients with a median age of 2 years 8 months. Tumors were both supratentorial (56%, 9/16) and infratentorial (44%, 7/16). Tumors were large (median diameter, 59 mm; interquartile range, 48-71 mm), with absent (75%, 12/16) or minimal (25%, 4/16) peritumoral edema. Enhancement was absent (20%, 3/15) or weak (73%, 11/15), whereas intratumoral macrovessels were frequently seen (94%, 15/16) and calcifications were present in 67% (10/15). Diffusion was always restricted, with a minimal ADC of 520 mm2/s (interquartile range, 495-540 mm2/s). Cerebral blood flow using arterial spin-labeling was low, with a maximal CBF of 43 mL/min/100 g (interquartile range, 33-55 mL/min/100 g 5). When available (3 patients), relative cerebral blood volume using DSC was high (range, 3.5-5.8). CONCLUSIONS: Embryonal tumors with multilayered rosettes, C19MC-altered, have characteristic imaging features that could help in the diagnosis of this rare tumor in young children.

Immunomagnetic selective donor-derived CD4+CCR7+ T cell depletion procedure for peripheral blood stem cells graft.

PURPOSE OF THE STUDY: While acute graft-versus-host-disease (GVHD) is a T cell-mediated disease caused by alloreactive donor T cells, we and others have highlighted that patients who received higher proportion of donor CD4+ naïve and central memory T cells expressing the chemokine receptor 7 (CCR7) more often developed acute GVHD than those who did not. Consequently, we then investigated in vitro the impact of selective CD4+ CCR7+ T cell depletion on immune reactions and showed that such a depletion reduced alloreactivity without altering acquired anti-infectious reactions. In order to translate these findings to clinic, we now developed a compliant procedure for a selective reduction of the CD4+ naïve and central memory T cell subset relevant to peripheral blood stem cell (PBSC) allografts. PATIENTS AND METHODS: We performed a two-step immunomagnetic depletion of CD4+ CCR7+ T cells from ten G-CSF-mobilized PBSC apheresis samples. RESULTS: A median of 89% (82-94%) of CD4+ CCR7+ T cells could be depleted. This allowed a marked reduction of the alloreactive immune response against allogenic dendritic cells compared with unmanipulated cells. The preservation of CD34+ cell number and the hematopoietic progenitor function were controlled. Functional tests showed that the selection procedure did not interfere with the capacity of pathogen-specific T cells to produce interferon-gamma in response to certain viral pathogens. CONCLUSION: Our results pave the way to a feasible procedure that can be used in patients undergoing allo-hematopoietic cell transplantation and particularly for improving haploidentical transplant results by controlling GVHD, the main immune complication.

The Impact of Compressed Femtosecond Laser Pulse Durations on Neuronal Tissue Used for Two-Photon Excitation Through an Endoscope.

Accurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo. For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo, the effect of short laser pulse durations (40-340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.

Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.

Optical properties, spectral, and lifetime measurements of central nervous system tumors in humans.

A key challenge of central nervous system tumor surgery is to discriminate between brain regions infiltrated by tumor cells and surrounding healthy tissue. Although monitoring of autofluorescence could potentially be an efficient way to provide reliable information for these regions, we found little information on this subject, and thus we conducted studies of brain tissue optical properties. This particular study focuses on the different optical quantitative responses of human central nervous system tumors and their corresponding controls. Measurements were performed on different fixed human tumoral and healthy brain samples. Four groups of central nervous system tumors (glioblastoma, diffuse glioma, meningioma and metastasis) were discriminated from healthy brain and meninx control tissues. A threshold value was found for the scattering and absorption coefficient between tumoral and healthy groups. Emission Spectra of healthy tissue had a significant higher intensity than tumoral groups. The redox and optical index ratio were thenn calculated and these also showed significant discrimination. Two fluorescent molecules, NADH and porphyrins, showed distinct lifetim values among the different groups of samples. This study defines several optical indexes that can act as combinated indicators to discriminate healthy from tumoral tissues.

Surgery for dysembryoplastic neuroepithelial tumors and gangliogliomas in eloquent areas. Functional results and seizure control.

INTRODUCTION: Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas. METHODS: Among 150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors. RESULTS: New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor (n=2) and moderate language disturbance (n=1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma. CONCLUSION: Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome.

Meningeal SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1)-deficient tumours: an emerging group of meningeal tumours.

AIMS: Bi-allelic inactivation of SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1; also known as INI1) and loss of immunohistochemical expression of SMARCB1 define the group of SMARCB1-deficient tumours. Initially highlighted in malignant rhabdoid tumours, this inactivation has subsequently been observed in several intra and extracranial tumours. To date, primary meningeal SMARCB1-deficient tumours have not been described. We report two cases of meningeal SMARCB1-deficient tumours occurring in adults. METHODS: We performed immunohistochemical analyses, comparative genomic hybridization, fluorescence in situ hybridization and targeted next-generation sequencing. RESULTS: The first meningeal tumour was a solitary mass, composed of rhabdoid, adenoid, chordoid and sarcomatoid areas. The second case presented as multiple, bilateral, supra and infratentorial nodules, was composed of fusiform and ovoid cells embedded in a myxoid stroma. Tumour cells were positive for epithelial membrane antigen (EMA), vimentin and CD34 and negative for SMARCB1 and meningothelial, melanocytic, muscular, glial markers. In the first case, one allele of SMARCB1 was completely deleted, whereas in the second case, loss of expression of SMARCB1 was observed as a consequence of a homozygous deletion of SMARCB1. CONCLUSIONS: The phenotype and genotype of these two cases did not fit diagnostically with entities already known to be SMARCB1-deficient tumours. As both tumours shared common features, they are regarded as belonging to an emerging group of primary meningeal SMARCB1-deficient tumours, not described to date. To facilitate the identification and characterization of these tumours, we recommend SMARCB1 immunohistochemistry for primary meningeal tumours which are difficult to classify, especially if immunopositive for EMA and CD34.

Spectral and fluorescence lifetime endoscopic system using a double-clad photonic crystal fiber.

We present a customized small-core double-clad photonic crystal fiber for spectral and fluorescence lifetime measurements of human samples. In this Letter, the new fiber has been characterized on different fluorophores and samples of human brain tumor; a comparison to a bi-fiber homemade system and a commercial fiber probe was made.

Choroid Plexus Neoplasms: Toward a Distinction between Carcinoma and Papilloma Using Arterial Spin-Labeling.

Pediatric choroid plexus papillomas and carcinomas are highly vascularized neoplasms, which are difficult to distinguish with conventional imaging. We aimed to analyze the diagnostic accuracy of PWI, by using both pseudocontinuous arterial spin-labeling and DSC-PWI. We reviewed the PWI of 13 children with choroid plexus neoplasms (7 papillomas and 6 carcinomas). We quantified CBF, relative CBF, and relative CBV in each lesion and compared papillomas and carcinomas. Relative CBF values by using arterial spin-labeling were significantly higher for carcinomas (P = .028). The median value of relative CBF was 1.7 (range, 1.4-1.9) for carcinomas and 0.4 (range, 0.3-0.6) for papillomas. The CBF median value was 115 mL/min/100 g (range, 90-140 mL/min/100 g) for carcinomas and 41 mL/min/100 g (range, 10-73 mL/min/100 g) for papillomas (P = .056). Measures with DSC-PWI were more variable and not significantly different (P = .393). Arterial spin-labeling is a promising technique to differentiate choroid plexus carcinomas and papillomas.

The novel HLA-B*39:93 allele was identified by sequence-based typing in a French family.

A novel HLA-B allele, B*39:93, was identified in a French family.

Oedema-based model for diffuse low-grade gliomas: application to clinical cases under radiotherapy.

OBJECTIVES: Diffuse low-grade gliomas are characterized by slow growth. Despite appropriate treatment, they change inexorably into more aggressive forms, jeopardizing the patient's life. Optimizing treatments, for example with the use of mathematical modelling, could help to prevent tumour regrowth and anaplastic transformation. Here, we present a model of the effect of radiotherapy on such tumours. Our objective is to explain observed delay of tumour regrowth following radiotherapy and to predict its duration. MATERIALS AND METHODS: We have used a migration-proliferation model complemented by an equation describing appearance and draining of oedema. The model has been applied to clinical data of tumour radius over time, for a population of 28 patients. RESULTS: We were able to show that draining of oedema accounts for regrowth delay after radiotherapy and have been able to fit the clinical data in a robust way. The model predicts strong correlation between high proliferation coefficient and low progression-free gain of lifetime, due to radiotherapy among the patients, in agreement with clinical studies. We argue that, with reasonable assumptions, it is possible to predict (precision ~20%) regrowth delay after radiotherapy and the gain of lifetime due to radiotherapy. CONCLUSIONS: Our oedema-based model provides an early estimation of individual duration of tumour response to radiotherapy and thus, opens the door to the possibility of personalized medicine.

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model.

This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.