Embolization as adjunctive treatment to achieve complete cure of ruptured arachnoid cyst associated with chronic subdural hematoma.

INTRODUCTION: Chronic Subdural Hematoma (CSDH) is a rare but classical evolutive complication of arachnoid cysts (AC). Its management has rarely been evaluated to date. Several approaches have been proposed including conservative and surgical treatments. Endovascular treatment in such CSDH subtype remains poorly reported. CASE PRESENTATION: We present here an original case of a 16 years-old-boy suffering from ruptured AC responsible for CSDH successfully treated with embolization. CONCLUSION: Endovascular approach may be considered in the treatment of CSDH related to arachnoid cyst rupture.

Descriptive Epidemiology of Ependymal Tumors in Gironde, France: Results from the Gironde Registry for the 2000-2018 Period.

BACKGROUND: The Gironde Central Nervous System (CNS) Tumor Registry, in collaboration with the French National Cancer Institute, is the largest population-based registry focused exclusively on primary CNS tumors in France and represents a population of 1.62 million. This report focuses on ependymal tumors to refine current knowledge and provide up-to-date data on the epidemiology of these rare tumors. MATERIAL AND METHODS: All of the ependymal tumors were extracted from the Gironde CNS Tumor Registry for the years 2000-2018. Demographic and clinical characteristics, incidence rates, and time trends as well as survival outcomes were analyzed. RESULTS: One hundred forty-four ependymal tumors were retrieved, which represented 2.3% of all the CNS tumors recorded in the same period. Histological subtype was significantly dependent on age and topography in the CNS. The median age at diagnosis was 46 years. The annual incidence rates varied between 0.15/100,000 (2004) and 0.96/100,000 (2016), with a significant increase over the study period by 4.67% per year. Five-year and 10-year OS rates were 87% and 80%, respectively. CONCLUSION: An increase in the incidence of ependymal tumors was observed over the past two decades. Further studies are needed to confirm this result and provide etiological clues.

Skin landmarks to main cerebral structures: how to identify the main cerebral sulci? An anatomical study.

PURPOSE: Neuronavigation is used in neurosurgical practice to locate the cortical structures. If this tool is unavailable, basic anatomical knowledge should be used. Craniometry has been rarely detailed in recent literature, systematically using bony landmarks. The aim of this study is to describe skin landmarks for neurosurgical practice. METHODS: Dissection of 10 hemispheres with insertion of radio-opaque markers within the limits of lateral sulcus, central and pre-central sulci, and preoccipital notch. Computed tomography was performed in all cases and multiplanar reconstructions were performed. Maximal intensity projection (MIP) fusion images were used for measurements between known skin landmarks and sulci of interests. RESULTS: The Anterior Sylvian Point is measured 31.8 ± 2.8 mm behind the orbital wall, 36.9 ± 3 mm above the zygomatic arch. The horizontal part of the lateral sulcus is measured 59 ± 6 mm above the tragus. The Superior Rolandic Point is measured 190.7 ± 4.5 mm behind the nasion. The Pre-occipital Notch is measured 37.0 ± 6.9 mm above the tragus and 67.1 ± 6.4 mm behind. The Ideal Entry Points (IEP) for ventricular punctures are measured 120.2 ± 7 mm behind the nasion and 33.8 ± 3 mm laterally for the frontal IEP, and 61.3 mm ± 2.5 mm above and 64.7 ± 6.8 mm behind the tragus for the parieto-occipital IEP. CONCLUSION: In this study, we described simple skin landmarks for lateral sulcus, central sulcus, preoccipital notch, and an IEP for ventricular drainage. Precise knowledge of brain sulcal anatomy will guide patient's positioning, skin incision, and craniotomies; and permits checking of imaging data provided by neuronavigation systems.

Decompressive craniectomy and CSF disorders in children.

INTRODUCTION: Decompressive craniectomy (DC) is a lifesaving procedure but is associated to several post-operative complications, namely cerebrospinal fluid (CSF) dynamics impairment. The aim of this multicentric study was to evaluate the incidence of such CSF alterations after DC and review their impact on the overall outcome. MATERIAL AND METHODS: We performed a retrospective multicentric study to analyze the CSF disorders occurring in children aged from 0 to 17 years who had undergone a DC for traumatic brain injury (TBI) in the major Departments of Pediatric Neurosurgery of France between January 2006 and August 2016. RESULTS: Out of 150 children, ranging in age between 7 months and 17 years, mean 10.75 years, who underwent a DC for TBI in 10 French pediatric neurosurgical centers. Sixteen (6 males, 10 females) (10.67%) developed CSF disorders following the surgical procedure and required an extrathecal CSF shunting. External ventricular drainage increased the risk of further complications, especially cranioplasty infection (p = 0.008). CONCLUSION: CSF disorders affect a minority of children after DC for TBI. They may develop early after the DC but they may develop several months after the cranioplasty (8 months), consequently indicating the necessity of clinical and radiological close follow-up after discharge from the neurosurgical unit. External ventricular drainage and permanent CSF shunt placement increase significantly the risk of cranioplasty infection.

When to discharge patients following a neuronavigation-assisted brain biopsy for supratentorial lesion? A single-center experience.

OBJECTIVE: Most brain biopsies are performed using the frame-based stereotactic technique and several studies describe the time taken and rate of complications, often allowing an early discharge. In comparison, neuronavigation-assisted biopsies are performed under general anesthesia and their complications have been poorly described. We examined the complication rate and determined which patients will worsen clinically. METHODS: All adults who underwent a neuronavigation-assisted brain biopsy for a supratentorial lesion from Jan, 2015, to Jan, 2021, in the Neurosurgical Department of the University Hospital Center of Bordeaux, France, were analyzed retrospectively in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement. The primary outcome of interest was short-term (7 days) clinical deterioration. The secondary outcome of interest was the complication rate. RESULTS: The study included 240 patients. The median postoperative Glasgow score was 15. Thirty patients (12.6 %) showed acute postoperative clinical worsening, including 14 (5.8 %) with permanent neurological worsening. The median delay was 22 h after the intervention. We examined several clinical combinations that allowed early postoperative discharge. A preoperative Glasgow prognostic score of 15, Charlson Comorbidity Index ≤ 3, preoperative World Health Organization Performance Status ≤ 1, and no preoperative anticoagulation or antiplatelet treatment predicted postoperative worsening (negative predictive value, 96.3 %). CONCLUSION: Optical neuronavigation-assisted brain biopsies might require longer postoperative observation than frame-based biopsies. Based on strict preoperative clinical criteria, we consider to plan postoperative observation for 24 h a sufficient hospital stay for patients who undergo these brain biopsies.

A novel LARGE1-AFF2 fusion expanding the molecular alterations associated with the methylation class of neuroepithelial tumors with PATZ1 fusions.

A novel DNA methylation class of tumor within the central nervous system, the "neuroepithelial tumor (NET), PATZ1 fusion-positive" has recently been identified in the literature, characterized by EWSR1- and MN1-PATZ1 fusions. The cellular origin of this tumor type remains unknown, wavering between glioneuronal or mesenchymal (as round cell sarcomas with EWSR1-PATZ1 of the soft tissue). Because of the low number of reported cases, this tumor type will not be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS). Herein, we report one case of a CNS tumor classified by DNA methylation analysis as NET-PATZ1 but harboring a novel LARGE1-AFF2 fusion which has until now never been described in soft tissue or the CNS. We compare its clinical, histopathological, immunophenotypical, and genetic features with those previously described in NET-PATZ1. Interestingly, the current case presented histopathological (astroblastoma-like features, glioneuronal phenotype), clinical (with a favorable course), genetic (1p loss), and epigenetic (DNA-methylation profiling) similarities to previously reported cases of NET-PATZ1. Our results added data suggesting that different histomolecular tumor subtypes seem to be included within the methylation class "NET, PATZ1 fusion-positive", including non PATZ1 fusions, and that further cases are needed to better characterize them.

An EZH2 blocker sensitizes histone mutated diffuse midline glioma to cholesterol metabolism inhibitors through an off-target effect.

Background: Diffuse Midline Glioma, H3K27M-mutant (DMG) is a rare, highly aggressive pediatric tumor affecting the brainstem, and is one of the deadliest cancers. Currently available treatment options such as chemotherapy and radiotherapy do only modestly prolong survival. In this pathology, H3K27 mutations deregulate Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2, which is therefore under investigation as a therapeutic target. Methods: We used a chemical EZH2 inhibitor, GSK126, small interfering RNAs, and a CRISPR/Cas9 knockout approaches in a series of DMG tumor cell lines to investigate metabolic treatment responses by proteomic analysis. A combination strategy was elaborated and studied in primary and established DMG cells, spheroid 3D cultures, and in vivo in a chick chorio-allantoic membrane DMG assay and an orthotopic intracranial DMG mouse model. Results: GSK126 shows significant (P < .05-.001) inhibitory effects in in vitro cell proliferation assays and induces apoptosis. Chemical targeting of EZH2 induced expression of proteins implicated in cholesterol metabolism. Low-dose GSK126 treatment together with statins revealed strong growth inhibition in combinatorial treatments, but not in single treatments, both in DMG cells in vitro, in DMG spheroid cultures, and in chick and mouse in vivo models (P < .05). All statistical tests were two-sided. Conclusions: Our results reveal an unexpected GSK126-inducible sensitivity to cholesterol biosynthesis inhibitors in highly aggressive pediatric glioma that warrants further evaluation as treatment strategy. This combinatorial therapy should have few side effects because of the low doses used to achieve significant anti-tumor activity.

Intramedullary Spinal Cord Lesions: A Single-Center Experience.

OBJECTIVE: Spinal cord tumors constitute a small part of spinal surgery owing to their rarity. This retrospective study describes their current management. METHODS: Forty-eight patients were treated for an intramedullary tumor between 2014 and 2020 at a single institution. Patients' files were retrospectively studied. We detailed clinical status according to neurological deficit and ambulatory ability using the modified McCormick Scale, radiological features like number of levels, associated syringomyelia, surgical technique with or without intraoperative electrophysiological monitoring, pathological findings, and postoperative outcome. RESULTS: The median age of this population was 43 years, including 5 patients under 18 years. The median delay before first neurosurgical contact was 3 months after the first clinical complaint. Treatment was gross total resection in 43.8%, subtotal resection in 50.0%, and biopsy in 6.2%. A laminectomy was performed for all the patients except 2 operated using the laminoplasty technique. Pathological findings were ependymoma in 43.8%, hemangioblastoma in 20.8%, and pilocytic astrocytoma in 10.4%. Six patients were reoperated for a tumor recurrence less than 2 years after the first surgical resection. One patient was reoperated for a postoperative cervical kyphosis. CONCLUSION: Intramedullary tumors are still a challenging disease and they are treated by various surgical techniques. They must be managed in a specialized center including a trained surgical, radiological, electrophysiological, and pathological team. Arthrodesis must be discussed before performing extensive laminectomy to avoid postoperative kyphosis.

Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

Increased Incidence of Intracranial Meningiomas in Patients With Acromegaly.

BACKGROUND: An increased incidence of various neoplasms has been described in patients with acromegaly, and there is evidence to suggest that growth factors are risk factors for the development of meningiomas. OBJECTIVE: To study if patients with acromegaly are more at risk for developing intracranial meningiomas. METHODS: We conducted an observational study on 221 consecutive acromegalic patients recruited between January 1, 2000 and December 31, 2015, and 357 consecutive patients with a nonsomatotropic pituitary adenoma recruited between March 1, 2015 and December 31, 2016, in our institution. Patients underwent a gadolinium-enhanced 3D T1 brain magnetic resonance imaging to look for meningiomas. The proportion of meningiomas was compared between the 2 groups, and the standardized incidence ratio (SIR) was computed from the incidence rates of meningiomas observed in the population of acromegalic patients and compared to that of the general population given by the local registry of central nervous system tumors. RESULTS: Patients with acromegaly had a significant risk for developing intracranial meningiomas as compared to patients without acromegaly (7.7% vs 2.2%, P = .005, OR = 3.45 [1.46; 8.15]). There was a significant increased incidence of intracranial meningiomas in patients with acromegaly (SIR = 126 [25; 367]) as compared to the general population. CONCLUSION: Our study suggests strongly that patients with acromegaly are more at risk for developing intracranial meningiomas.

Ependymoma of the Spinal Cord in Children: A Retrospective French Study.

BACKGROUND: Ependymoma is the most frequent spinal tumor in adults but it is rather uncommon in children. The aim of the present study was to retrospectively summarize the clinical and therapeutic experience in the treatment of pediatric spinal ependymomas in France. METHODS: In the present retrospective multicenter study, data from patients aged <18 years who had been treated from 2000 to 2010 for spinal ependymomas were collected. Epidemiologic and tumor- and treatment-related data were analyzed. The prognostic factors for progression-free survival (PFS) were assessed. RESULTS: We identified 28 patients (22 males, 6 females). Their median age at surgery was 13.67 years (range, 0.7-17.6). Initial gross total resection (GTR) was achieved in 22 children and subtotal resection (STR) in 6. Histologically, 15 tumors were myxopapillary ependymomas and 11 were grade II and 2 grade III ependymomas. Adjuvant initial radiotherapy (RT) was performed in 6 patients. The median follow-up period was of 40 months (range, 2.3-127.5). The 5-year PFS rate was 51% (95% confidence interval, 26.3%-71.2%), and the overall survival rate was 100%. On univariate analysis, only GTR had a significant influence on PFS (P = 0.0013). A subgroup analysis showed a benefit of RT delivered to patients with GTR; however, RT failed to prevent relapse in the group with initial STR. CONCLUSIONS: Our data suggest that initial adjuvant RT might improve PFS after GTR but will not prevent relapse in patients with STR. Further studies are needed to define more specific treatments for the latter group.

Combining 3'-Deoxy-3'-[18F] fluorothymidine and MRI increases the sensitivity of glioma volume detection.

OBJECTIVE: 3'-Deoxy-3'-[18F] fluorothymidine (18F-FLT) is a marker of cell proliferation and displays a high tumor-to-background ratio in brain tumor lesions. We determined whether combining 18F-FLT PET and MRI study improves the detection of tumoral tissue compared to MRI alone and whether 18F-FLT uptake has a prognostic value by studying its association with histopathological features. METHODS: Thirteen patients with a supratentorial malignant glioma were recruited and scheduled for surgery. The tumor volume was defined in all patients on both 18F-FLT PET and MRI images. The images were coregistered and uploaded onto a neuronavigation system. During surgery, an average of 11 biopsies per patient were taken in regions of the brain that were positive to one or both imaging modalities, as well as from control peritumoral regions. The standardized uptake values (SUVs) of each biopsy region were correlated to histopathological data (i.e., proliferation index and number of mitoses) and the SUV values of high and low-grade samples were compared. RESULTS: Out of a total of 149 biopsies, 109 contained tumoral tissue at histopathological analysis. The positive predictive value was 93.1% for MRI alone and 78.3% for MRI and PET combined. In addition, 40% of the biopsy samples taken from areas of the brain that were negative at both PET and MRI had evidence of malignancy at pathology. The SUV values were not significantly correlated to either the proliferation index or the number of mitoses, and could not differentiate between high- and low-grade samples. CONCLUSION: In patients with newly diagnosed glioma, a combination of MRI and 18F-FLT-PET detects additional tumoral tissue and this may lead to a more complete surgical resection. Also, the addition of a negative PET to a negative MRI increases the negative predictive value. However, 18F-FLT still underestimated the margins of the lesion and did not correlate with histopathological features.

Decompressive Craniectomy in Children with Severe Traumatic Brain Injury: A Multicenter Retrospective Study and Literature Review.

BACKGROUND: Severe traumatic brain injury (TBI) is the most common cause of disability in children. Refractory increased intracranial pressure can be a therapeutic challenge. Decompressive craniectomy can be proposed when medical management is insufficient, but its place is not clearly defined in guidelines. The aim of this study was to identify prognostic factors in children with TBI. METHODS: We performed a retrospective, multicenter study to analyze long-term outcomes of 150 children with severe TBI treated by decompressive craniectomy and to identify prognostic factors. RESULTS: A satisfactory neurologic evolution (represented by a King's Outcome Scale for Childhood Head Injury score >3) was observed in 62% of children with a mean follow-up of 3.5 years. Mortality rate was 17%. Prognostic factors associated with outcome were age, initial Glasgow Coma Scale score, presence of mydriasis, neuromonitoring values (maximal intracranial pressure >30 mm Hg), and radiologic findings (Rotterdam score ≥4). CONCLUSIONS: This study in a large population confirms that children with severe TBI treated by decompressive craniectomy can achieve a good neurologic outcome. Further studies are needed to clarify the use of this surgery in the management of children with severe TBI.

Pediatric Chordomas: Results of a Multicentric Study of 40 Children and Proposal for a Histopathological Prognostic Grading System and New Therapeutic Strategies.

Pediatric chordomas are rare malignant neoplasms, and few data are available for optimizing therapeutic strategies and outcome. This study aimed at evaluating how best to manage them and to identify prognostic factors. This multicentric retrospective study included 40 children diagnosed with chordomas between 1966 and 2012. Clinical, radiological, and histopathological data, treatment modalities, and outcomes were reviewed. The median age was 12 years old. Most chordomas were histologically classical forms (45.5%) and were mostly located at the skull base (72.5%). The overall survival (OS) was 66.6% and 58.6%, and progression-free survival (PFS) was 55.7% and 52% at 5 and 10 years, respectively. Total resection was correlated with a better outcome (p = 0.04 for OS and PFS, log-rank). A histopathological/immunohistochemical grading system recently crafted for adults was applied. In a multivariate analysis, it significantly correlated with outcome (PFS and OS, p = 0.004), and the loss of BAF47 immunoexpression appeared to be a significant independent prognostic factor (PFS, p = 0.033). We also identified clinical and histopathological parameters that correlated with prognosis. A new grading system combined with the quality of surgical resection could help classify patients to postpone radiotherapy in case of low risk. Targeted therapy and reirradiation at recurrence may be considered as potential therapeutic strategies.

Assessment of Abdominal Fat Graft to Repair Anterior Skull Base after Malignant Sinonasal Tumor Extirpation.

OBJECTIVE: Adult abdominal fat, which is known to contain pluripotent stem cells, is frequently used to treat cerebrospinal fluid leak. The aim of this study was to assess the efficacy and reliability of abdominal fat graft to close large skull base defects after extirpation of malignant sinonasal tumors. STUDY DESIGN: Case series with chart review performed between 2009 and 2014. SUBJECTS AND METHODS: Twenty-nine cases were included of consecutive patients who were suffering from malignant sinonasal tumors, operated by an endoscopic endonasal approach with anterior skull base extirpation and surgically induced cerebrospinal fluid leak. Skull base was repaired by 1 layer of "en bloc" autologous fat graft used as a plug in the onlay position. Epidemiologic data, medical history, defect size, length of hospitalization, and morbidity were analyzed. RESULTS: Radiotherapy was given pre- and postoperatively in 4 (13.8%) and 23 (79.3%) patients, respectively. Mean defect size was 4.47 ± 2.9 cm(2) (range, 0.24-9.1 cm(2)). Mean operative time was 210 ± 86 minutes. Mean length of hospitalization was 8.6 ± 3.7 days and 4.9 ± 2 days in the intensive care unit. No lumbar drain was used in this study. There was 1 case of cerebrospinal fluid leak (3.5%) and 2 cases of meningitis (6.9%), which resolved after medical treatment. Mean follow-up was 17 ± 13 months (range, 3-53 months). CONCLUSION: Abdominal fat graft is a safe and reliable material to close the anterior skull base after extirpation of malignant sinonasal tumors.

Responses of heart rate variability to acute pain after minor spinal surgery: optimal thresholds and correlation with the numeric rating scale.

BACKGROUND: The autonomic nervous system is influenced by many stimuli including pain. Heart rate variability (HRV) is an indirect marker of the autonomic nervous system. Because of paucity of data, this study sought to determine the optimal thresholds of HRV above which the patients are in pain after minor spinal surgery (MSS). Secondly, we evaluated the correlation between HRV and the numeric rating scale (NRS). METHODS: Following institutional review board approval, patients who underwent MSS were assessed in the postanesthesia care unit after extubation. A laptop containing the HRV software was connected to the ECG monitor. The low-frequency band (LF: 0.04 to 0.5 Hz) denoted both sympathetic and parasympathetic activities, whereas the high-frequency band (HF: 0.15 to 0.4 Hz) represented parasympathetic activity. LF/HF was the sympathovagal balance. Pain was quantified by the NRS ranging from 0 (no pain) to 10 (worst imaginable pain). Simultaneously, HRV parameters were noted. Optimal thresholds were calculated using receiver operating characteristic curves with NRS>3 as cutoff. The correlation between HRV and NRS was assessed using the Spearman rank test. RESULTS: We included 120 patients (64 men and 56 women), mean age 51±14 years. The optimal pain threshold values were 298 ms for LF and 3.12 for LF/HF, with no significant change in HF. NRS was correlated with LF (r=0.29, P<0.005) and LF/HF (r=0.31, P<0.001) but not with HF (r=0.09, NS). CONCLUSIONS: This study suggests that, after MSS, values of LF>298 m and LF/HF>3.1 denote acute pain (NRS>3). These HRV parameters are significantly correlated with NRS.