Prognostic significance of MRI contrast enhancement in newly diagnosed glioblastoma, IDH-wildtype according to WHO 2021 classification.

BACKGROUND AND OBJECTIVES: Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. METHODS: We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. RESULTS: We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm3, and postoperative residual contrast enhancement were independent predictors of shorter overall survival. CONCLUSION: A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).

Radiographic growth rate as a predictor of aggressiveness of diffuse gliomas without 1p19q codeletion.

OBJECTIVE: The 2021 WHO classification of CNS tumors has refined the definition of adult-type diffuse gliomas without 1p19q codeletion. Nevertheless, the aggressiveness of gliomas is based exclusively on histomolecular criteria performed on a limited sample of the tumor. The authors aimed to assess whether the spontaneous radiographic tumor growth rate is associated with tumor aggressiveness and allows preoperative identification of malignancy grade of adult-type diffuse gliomas without 1p19q codeletion. METHODS: The authors retrospectively reviewed the records of adult patients harboring a newly diagnosed supratentorial diffuse glioma without 1p19q codeletion, with available preoperative MRI follow-up between January 2008 and April 2022. The spontaneous radiographic tumor growth rate was quantified by tumor volume segmentation and regression of the evolution of the mean tumor diameter over time and was compared with clinical, imaging, histomolecular, and survival data. RESULTS: Ninety-six patients were included. The spontaneous radiographic tumor growth rates (mean 17.8 ± 38.8 mm/year, range 0-243.5 mm/year) significantly varied according to IDH1/2 mutation (p < 0.001), grade of malignancy (p < 0.001), and presence of microvascular proliferation (p < 0.001). The spontaneous radiographic tumor growth rate allowed preoperative identification of high-grade cases: 100% of grade 3 and 4 IDH-mutant diffuse astrocytomas had a spontaneous radiographic tumor growth rate ≥ 8.0 mm/year, and 100% of IDH-wild-type glioblastomas had a spontaneous radiographic tumor growth rate ≥ 42.0 mm/year. A spontaneous radiographic growth rate ≥ 8.0 mm/year was an independent predictor of shorter progression-free (p = 0.014) and overall (p = 0.007) survival. A mitotic count threshold ≥ 4 mitoses was the optimal threshold for identifying aggressive IDH-mutant astrocytomas based on spontaneous radiographic tumor growth. CONCLUSIONS: The spontaneous radiographic tumor growth rates could be used as an additional tool to preoperatively screen tumor aggressiveness of adult-type diffuse gliomas without 1p19q codeletion.

Safety and efficacy of frameless stereotactic robot-assisted intraparenchymal brain lesion biopsies versus image-guided biopsies: a bicentric comparative study.

PURPOSE: User-friendly robotic assistance and image-guided tools have been developed in the past decades for intraparenchymal brain lesion biopsy. These two methods are gradually becoming well accepted and are performed at the discretion of the neurosurgical teams. However, only a few data comparing their effectiveness and safety are available. METHODS: Population-based parallel cohorts were followed from two French university hospitals with different surgical methods and defined geographical catchment regions (September 2019 to September 2022). In center A, frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies were performed, while image-guided intraparenchymal brain lesion biopsies were performed in center B. Pre-and postoperative clinical, radiological, and histomolecular features were retrospectively collected and compared. RESULTS: Two hundred fifty patients were included: 131 frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies in center A and 119 image-guided biopsies in center B. The clinical, radiological, and histomolecular features were comparable between the two groups. The diagnostic yield (96.2% and 95.8% respectively; p = 1.000) and the overall postoperative complications rates (13% and 14%, respectively; p = 0.880) did not differ between the two groups. The mean duration of the surgical procedure was longer in the robot-assisted group (61.9 ± 25.3 min, range 23-150) than in the image-guided group (47.4 ± 11.8 min, range 25-81, p < 0.001). In the subgroup of patients with anticoagulant and/or antiplatelet therapy administered preoperatively, the intracerebral hemorrhage > 10 mm on postoperative CT scan was higher in the image-guided group (36.8%) than in the robot-assisted group (5%, p < 0.001). CONCLUSION: In our bicentric comparative study, robot-assisted stereotactic and image-guided biopsies have two main differences (shorter time but more frequent postoperative hematoma for image-guided biopsies); however, both techniques are demonstrated to be safe and efficient.

Predictors of postoperative epidural hematomas after custom-made porous hydroxyapatite cranioplasty: a single-center experience of 194 consecutive cases.

Cranioplasty is important for improving cosmesis and functional recovery after decompressive craniectomy. We assessed the incidence and predictors of post-cranioplasty epidural hematomas requiring surgical evacuation. A single-institution, retrospective study enrolled 194 consecutive patients who underwent a cranioplasty using custom-made hydroxyapatite between February 2008 and April 2022. Variables associated with postoperative epidural hematoma requiring surgical evacuation at the p < 0.1 level in unadjusted analysis were entered into multivariable analyses. Nine patients (4.6%) experienced postoperative epidural hematomas requiring evacuation, with time interval between craniectomy and cranioplasty <6 months (adjusted odds ratio (aOR), 20.75, p = 0.047), cranioplasty-to-bone shift > half of the bone thickness (aOR, 17.53, p = 0.008), >10 mm difference between pre-cranioplasty and post-cranioplasty midline brain shift contralateral to the cranioplasty (aOR, 17.26, p < 0.001), and non-resorbable duraplasty (aOR, 17.43, p = 0.011) identified as independent predictors. Seventeen patients (8.8%) experienced post-cranioplasty hydrocephalus requiring shunt placement. Twenty-six patients (13.4%) experienced postoperative infection. Sixteen patients (8.2%) had postoperative epileptic seizures. The identification of independent predictors of post-cranioplasty epidural hematomas requiring surgical evacuation will help identify at-risk patients, guide prophylactic care, and reduce morbidity of this common and important procedure.

Accuracy and safety of 101 consecutives neurosurgical procedures for newly diagnosed central nervous system lymphomas: a single-institution experience.

INTRODUCTION: Brain surgery is required to ascertain the diagnosis of central nervous system lymphoma. We assessed the diagnostic yield and safety of the surgical procedures, the predictors of postoperative morbidity, and of overall survival. METHODS: Observational single-institution retrospective cohort study (1992-2020) of 101 consecutive adult patients who underwent stereotactic biopsy, open biopsy, or resection for a newly diagnosed central nervous system lymphoma. RESULTS: The diagnostic yield was 100% despite preoperative steroid administration in 48/101 cases (47.5%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.006) was an independent predictor of a new postoperative focal neurological deficit (7/101 cases, 6.9%). A previous history of hematological malignancy (p = 0.049), age 65 years or more (p = 0.031), and new postoperative neurological deficit (p < 0.001) were independent predictors of a Karnofsky Performance Status score decrease 20 points or more postoperatively (13/101 cases, 12.9%). A previous history of hematological malignancy (p = 0.034), and preoperative Karnofsky Performance Status score less than 70 (p = 0.024) were independent predictors of postoperative hemorrhage (13/101 cases, 12.9%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.019), and a previous history of hematological malignancy (p = 0.014) were independent predictors of death during hospital stay (8/101 cases, 7.9%). In the 82 immunocompetent patients harboring a primary central nervous system lymphoma, age 65 years or more (p = 0.044), and time to hematological treatment more than 21 days (p = 0.008), were independent predictors of a shorter overall survival. A dedicated hematological treatment (p < 0.001) was an independent predictor of a longer overall survival. CONCLUSION: Brain biopsy is feasible with low morbidity for central nervous system lymphomas. Postoperatively, patients should be promptly referred for hematological treatment initiation.

Neurosurgical developments of Thierry de Martel (1875-1940), French neurosurgery pioneer, during World Wars I and II.

Following France's entry into World War I on August 3, 1914, Thierry de Martel (1875-1940), the French neurosurgery pioneer, served on the front line and was wounded on October 3, 1914. He was then assigned as a surgeon in temporary hospitals in Paris, where he published his first observations of cranioencephalic war wounds. In 1915, de Martel met Harvey Cushing at the American Hospital in Neuilly, where de Martel was appointed chief surgeon in 1916. In 1917, he published with the French neurologist Charles Chatelin a book (Blessures du crâne et du cerveau. Clinique et traitement) with the aim to optimize the practice of wartime brain surgery. This book, which included the results of more than 5000 soldiers with head injuries, was considered the most important ever written on war neurology at that time and was translated into English in 1918 (Wounds of the Skull and Brain; Their Clinical Forms and Medical and Surgical Treatment). In this book, de Martel detailed the fundamentals of skull injuries, classified the various craniocerebral lesions, recommended exploratory craniectomy for cranioencephalic injuries, recommended the removal of metal projectiles from the brain using a magnetic nail, and advocated for the prevention of infectious complications. Between the World Wars, de Martel undertook several developments for neurosurgery in France alongside neurologists Joseph Babinski and Clovis Vincent. Following France's entry into World War II on September 3, 1939, de Martel took over as head of the services of the American Hospital of Paris in Neuilly. He updated his work on war surgery with the new cases he personally treated. Together with Vincent, de Martel presented his new approach in "Le traitement des blessures du crâne pendant les opérations militaires" ("The treatment of skull injuries during military operations") on January 30, 1940, and published his own surgical results in April 1940 in "Plan d'un travail sur le traitement des plaies cranio-cérébrales de guerre" ("Work Plan on the Treatment of Cranio-Cerebral Wounds of War"), intended for battlefield surgeons. On June 14, 1940, the day German troops entered Paris, de Martel injected himself with a lethal dose of phenobarbital. Thierry de Martel played a central role in establishing modern neurosurgery in France. His patriotism led him to improve the management of wartime cranioencephalic injuries using his own experience acquired during World Wars I and II.

MRI-based and robot-assisted stereotactic biopsy with intraoperative CT imaging.

BACKGROUND: As a pioneer center in the field of stereotaxy, Sainte-Anne school has always advocated the use of intraoperative imaging for stereotactic procedures to optimize both safety and accuracy. With the advent of intraoperative mobile CT unit, the robot-assisted stereotactic biopsy procedure has been recently updated. METHOD: Herein, we aim at describing our new surgical procedure that combines robotic assistance (NeuroMate, Renishaw) and intraoperative cone beam CT imaging (O-Arm, Medtronic). CONCLUSION: Intraoperative imaging with the O-Arm was efficiently incorporated into the workflow. This new equipment leads to optimizing operative time and an easier realization of intraoperative imaging.

Investigating Glioblastoma Multiforme Sub-Proteomes: A Computational Study of CUSA Fluid Proteomic Data.

Based on our previous proteomic study on Cavitating Ultrasound Aspirator (CUSA) fluid pools of Newly Diagnosed (ND) and Recurrent (R) glioblastomas (GBMs) of tumor core and periphery, as defined by 5-aminolevulinc acid (5-ALA) metabolite fluorescence, this work aims to apply a bioinformatic approach to investigate specifically into three sub-proteomes, i.e., Not Detected in Brain (NB), Cancer Related (CR) and Extracellular Vesicles (EVs) proteins following selected database classification. The study of these yet unexplored specific datasets aims to understand the high infiltration capability and relapse rate that characterizes this aggressive brain cancer. Out of the 587 proteins highly confidently identified in GBM CUSA pools, 53 proteins were classified as NB. Their gene ontology (GO) analysis showed the over-representation of blood coagulation and plasminogen activating cascade pathways, possibly compatible with Blood Brain Barrier damage in tumor disease and surgery bleeding. However, the NB group also included non-blood proteins and, specifically, histones correlated with oncogenesis. Concerning CR proteins, 159 proteins were found in the characterized GBM proteome. Their GO analysis highlighted the over-representation of many pathways, primarily glycolysis. Interestingly, while CR proteins were identified in ND-GBM exclusively in the tumor zones (fluorescence positive core and periphery zones) as predictable, conversely, in R-GBM they were unexpectedly characterized prevalently in the healthy zone (fluorescence negative tumor periphery). Relative to EVs protein classification, 60 proteins were found. EVs are over-released in tumor disease and are important in the transport of biological macromolecules. Furthermore, the presence of EVs in numerous body fluids makes them a possible low-invasive source of brain tumor biomarkers to be investigated. These results give new hints on the molecular features of GBM in trying to understand its aggressive behavior and open to more in-depth investigations to disclose potential disease biomarkers.

Improving the Accuracy of Neuronavigation in Cerebral Cavernous Malformation: A Technical Note on 68 Cases.

Cavernous malformations (CM) are benign, low-flow vascular lesions that account for 5% - 13% of all cerebrovascular malformations. Surgery remains the most important treatment strategy, and many different approaches have been developed. We present here our institutional experience with 68 cases using a transcortical neuronavigation approach with some technical nuances to improve navigation accuracy during resection. The technique and clinical outcomes are discussed, with a specific focus on seizure sequels. Demographic data were collected, along with information on clinical and seizure characteristics at presentation, localization and size of CM, presence of multiple localizations, evidence of recent CM-related bleeding on MRI, intervention features, postoperative complications, prescription of anti-epileptic drugs at discharge and seizure outcome. We assume that surgery through a narrow well-defined working corridor would limit brain exposure and manipulation, and hence could significantly affect not only general complications, but also seizure control. The technique is feasible and associated with relatively low rates of minor and major procedure-related complications. It is also a valid method for surgeons in training since the trajectory is planned preoperatively with a senior consultant and the working corridor always follows the catheter, which directly leads to the cavernoma.

Robot-assisted stereotactic electroencephalography using 3-dimensional intraoperative imaging and frameless registration tool.

Stereoelectroencephalography (SEEG) is the gold standard to investigate the epileptic network in cases of drug-resistant epilepsy. Robot-assisted SEEG is increasingly being used; however, its installation process in the operating room is more difficult than that of the stereotactic frame procedure. New robotic tools and 3D intraoperative imaging ease the setup while achieving the same mechanical precision and a lower complication rate. In this video, the authors illustrate the surgical technique and step-by-step workflow using a robotic arm (neuromate) guided by a frameless registration system (neurolocate), registered with an intraoperative flat-panel CT scanner (O-arm). The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2419.

Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults.

BACKGROUND AND OBJECTIVES: We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults. METHODS: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021. RESULTS: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142). CONCLUSION: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.

Feasibility and Accuracy of Robot-Assisted, Stereotactic Biopsy Using 3-Dimensional Intraoperative Imaging and Frameless Registration Tool.

BACKGROUND: Robot-assisted stereotactic biopsy is evolving: 3-dimensional intraoperative imaging tools and new frameless registration systems are spreading. OBJECTIVE: To investigate the accuracy and effectiveness of a new stereotactic biopsy procedure. METHODS: Observational, retrospective analysis of consecutive robot-assisted stereotactic biopsies using the Neurolocate (Renishaw) frameless registration system and intraoperative O-Arm (Medtronic) performed at a single institution in adults (2019-2021) and comparison with a historical series from the same institution (2006-2016) not using the Neurolocate nor the O-Arm. RESULTS: In 100 patients (55% men), 6.2 ± 2.5 (1-14) biopsy samples were obtained at 1.7 ± 0.7 (1-3) biopsy sites. An histomolecular diagnosis was obtained in 96% of cases. The mean duration of the procedure was 59.0 ± 22.3 min. The mean distance between the planned and the actual target was 0.7 ± 0.7 mm. On systematic postoperative computed tomography scans, a hemorrhage ≥10 mm was observed in 8 cases (8%) while pneumocephalus was distant from the biopsy site in 76%. A Karnofsky Performance Status score decrease ≥20 points postoperatively was observed in 4%. The average dose length product was 159.7 ± 63.4 mGy cm. Compared with the historical neurosurgical procedure, this new procedure had similar diagnostic yield (96 vs 98.7%; P = .111) and rate of postoperative disability (4.0 vs 4.2%, P = .914) but was shorter (57.8 ± 22.9 vs 77.8 ± 20.9 min; P < .001) despite older patients. CONCLUSION: Robot-assisted stereotactic biopsy using the Neurolocate frameless registration system and intraoperative O-Arm is a safe and effective neurosurgical procedure. The accuracy of this robot-assisted surgery supports its effectiveness for daily use in stereotactic neurosurgery.

A Preoperative Scoring System to Predict Function-Based Resection Limitation Due to Insufficient Participation During Awake Surgery.

BACKGROUND: Failure in achieving a function-based resection related to the insufficient patient's participation is a drawback of awake surgery. OBJECTIVE: To assess preoperative parameters predicting the risk of patient insufficient intraoperative cooperation leading to the arrest of the awake resection. METHODS: Observational, retrospective, multicentric cohort analysis enrolling 384 (experimental dataset) and 100 (external validation dataset) awake surgeries. RESULTS: In the experimental data set, an insufficient intraoperative cooperation occurred in 20/384 patients (5.2%), leading to awake surgery failure in 3/384 patients (ie, no resection, 0.8%), and precluded the achievement of the function-based resection in 17/384 patients (ie, resection limitation, 4.4%). The insufficient intraoperative cooperation significantly reduced the resection rates (55.0% vs 94.0%, P < .001) and precluded a supratotal resection (0% vs 11.3%, P = .017). Seventy years or older, uncontrolled epileptic seizures, previous oncological treatment, hyperperfusion on MRI, and mass effect on midline were independent predictors of insufficient cooperation during awake surgery ( P < .05). An Awake Surgery Insufficient Cooperation score was then assessed: 96.9% of patients (n = 343/354) with a score ≤2 presented a good intraoperative cooperation, while only 70.0% of patients (n = 21/30) with a score >2 presented a good intraoperative cooperation. In the experimental data set, similar date were found: 98.9% of patients (n = 98/99) with a score ≤2 presented a good cooperation, while 0% of patients (n = 0/1) with a score >2 presented a good cooperation. CONCLUSION: Function-based resection under awake conditions can be safely performed with a low rate of insufficient patient intraoperative cooperation. The risk can be assessed preoperatively by a careful patient selection.

Glioblastoma CUSA Fluid Protein Profiling: A Comparative Investigation of the Core and Peripheral Tumor Zones.

The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGFß signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic sur.

Use of Neuronavigation System for Superficial Vein Identification: Safe and Quick Method to Avoid Intraoperative Bleeding and Vein Closure: Technical Note.

BACKGROUND: Contributions on using navigation in neurosurgery have been shared widely. However, few authors have reported their experience identifying superficial vessels before dural opening using indocyanine green-video angiography. Furthermore, this technique has shown some limitations. METHODS: For many years, each time we planned a needle biopsy for brain tumors, we set the entry point and trajectory on the navigator before surgery. Regarding the target, we systematically chose both a trajectory, which should avoid any crossing with vessels, and an entry far from veins or granulations. Gadolinium-enhanced magnetic resonance imaging T1-weighted sequences have been demonstrated to be adequate for this purpose. Note that we used the Medtronic StealthStation S8 (Minneapolis, Minnesota, USA) and gadolinium-enhanced magnetic resonance imaging T1-weighted sequences to plan 4 different surgical procedures (needle biopsy, parasagittal meningioma, double metastases, and high-grade glioma). Intraoperatively, after craniotomy and dural exposure, a Passive Planar Blunt Probe and dermographic pen were used to mark superficial vessels on the basis of navigational images. The dura was opened far from any marked line, vessels were dissected, and the dura was opened by a Penfield dissector and Metzenbaum scissors. RESULTS: The mean planning time length was 7 minutes, and the marking procedure time length was 3 minutes. Dural marks perfectly corresponded to the underlying vessels. The correspondence rate of marks to underlying vessels was 100%. No one vessel unmarked was noticed. No superficial vessel injuries were reported. CONCLUSIONS: This technique provides a safe and fast method to avoid vessel injuries during dural opening. Furthermore, it could be useful as an educational tool.