The impact of the European Society of Cardiology guidelines and whole exome sequencing on genetic testing in hereditary cardiac diseases.

In the last decade, an incredible improvement has been made in elucidating the genetic bases of cardiomyopathies. Here we report the impact of either the European Society of Cardiology (ESC) guidelines or the use of whole exome sequencing (WES) in terms of a number of variants of uncertain significance (VUS) and missed diagnoses in a series of 260 patients affected by inherited cardiac disorders. Samples were analyzed using a targeted gene panel of 128 cardiac-related genes and/or WES in a subset of patients, with a three-tier approach. Analyzing (i) only a subset of genes related to the clinical presentation, strictly following the ESC guidelines, 20.77% positive test were assessed. The incremental diagnostic rate for (ii) the whole gene panel, and (iii) the WES was 4.71% and 11.67%, respectively. The diverse analytical approaches increased the number of VUSs and incidental findings. Indeed, the use of WES highlights that there is a small percentage of syndromic conditions that standard analysis would not have detected. Moreover, the use of targeted sequencing coupled with "narrow" analytical approach prevents the detection of variants in actionable genes that could allow for preventive treatment. Our data suggest that genetic testing might aid clinicians in the diagnosis of inheritable cardiac disorders.

Predictors of functional outcomes following spinal meningioma surgery. A single-center retrospective experience of 59 cases.

BACKGROUND: To better predict the postoperative functional outcomes of patients operated on for a spinal meningioma, we assessed: 1) the prevalence of good and poor postoperative functional outcomes following surgery; 2) the impact of age and frailty on postoperative functional outcomes. METHODS: In this retrospective cohort study, we screened adult patients operated on for a spinal meningioma from 2005 to 2022. Inclusion criteria were: 1) patients ≥18 years; 2) histopathological diagnosis of meningioma; 3) location to the cervical, thoracic or lumbar spine (foramen magnum meningioma excluded); 4) surgery as first-line treatment; and 5) available postoperative follow-up ≥1 year. Clinical outcomes were assessed using the modified McCormick scale preoperatively and at one-year of postoperative follow-up. RESULTS: In this single institution experience of 59 cases, we found that: 1) surgical resection positively impacts patients' functional outcomes, 91.2% either showing an improved or maintained good postoperative neurological status defined by a modified McCormick scale score ≤ II; 2) a good modified McCormick scale status was achieved in 84.2% of patients at one postoperative year; 3) 87.5% of patients who were not improved postoperatively maintained an overall good neurological status defined by a modified McCormick scale score ≤ II; and 4) frail or aged patients were not at a higher risk of poor postoperative functional outcomes. CONCLUSION: Surgical resection positively impacts outcomes of patients operated for a spinal meningioma. Sex, presence of a meningioma-related myelopathy, extent of resection, and occurrence of surgery-related postoperative complications, but not age or frailty, predict postoperative functional outcomes.

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).

Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer.

INTRODUCTION: The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. MATERIALS AND METHODS: Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. RESULTS: Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). CONCLUSION: In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.

Impact of frailty on survival glioblastoma, IDH-wildtype patients.

PURPOSE: Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. METHODS: We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. RESULTS: A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). CONCLUSION: In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

A bird's eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases.

Phenotypic and genotypic heterogeneity in congenital ocular diseases, especially in anterior segment dysgenesis (ASD), have created challenges for proper diagnosis and classification of diseases. Over the last decade, genomic research has indeed boosted our understanding in the molecular basis of ASD and genes associated with both autosomal dominant and recessive patterns of inheritance have been described with a wide range of expressivity. Here we describe the molecular characterization of a cohort of 162 patients displaying isolated or syndromic congenital ocular dysgenesis. Samples were analyzed with diverse techniques, such as direct sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing (WES), over 20 years. Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome). Our data clearly suggest that WES allows expanding the analytical portfolio of ocular dysgenesis, both isolated and syndromic, and that is pivotal for the differential diagnosis of those conditions in which there may be phenotypic overlaps and in general in ASD.

Filamin C (FLNC) truncating mutation in a fatal arrhythmogenic left ventricular cardiomyopathy (ALVC).

Forensic pathologists are frequently asked to investigate cases of sudden death (SD), and identifying the cause of death can be of particular importance, especially where it may be necessary to perform family screening among the relatives of the victim. A multidisciplinary approach inclusive of genetic analysis is therefore strongly recommended. According to forensic practice, arrhythmogenic cardiomyopathy (ACM) is a well-known cause of SD. However, cases of SD caused by a left ventricular pattern of ACM diagnosed at autopsy are rarely reported in the literature. We present the case of an apparently healthy, 37-year-old male found dead at his home. At autopsy, multiple foci of epicardial and mid-wall fibrous and fibro-adipose tissue were observed within the left ventricle and, to a lesser extent, within the interventricular septum. Toxicology was negative, whereas a filamin C truncating mutation was detected through genetic analysis. To our knowledge, this is the first instance of arrhythmogenic left ventricular cardiomyopathy being diagnosed at autopsy.

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.

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.

Presentation and Management of Cerebral Venous Sinus Thrombosis After Supratentorial Craniotomy.

BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) after supratentorial craniotomy is a poorly studied complication, for which there are no management guidelines. This study assessed the incidence, associated risk factors, and management of postoperative CVST after awake craniotomy. METHODS: This is an observational, retrospective, monocentric analysis of patients who underwent a supratentorial awake craniotomy. Postoperative CVST was defined as a flow defect on the postoperative contrast-enhanced 3D T1-weighted sequence and/or as a T2* hypointensity within the sinus. RESULTS: In 401 supratentorial awake craniotomies (87.3% of diffuse glioma), the incidence of postoperative CVST was 4.0% (95% CI 2.5-6.4): 14/16 thromboses located in the superior sagittal sinus and 12/16 located in the transverse sinus. A venous sinus was exposed during craniotomy in 45.4% of cases, and no intraoperative injury to a cerebral venous sinus was reported. All thromboses were asymptomatic, and only two cases were diagnosed at the time of the first postoperative imaging (0.5%). Postoperative complications, early postoperative Karnofsky Performance Status score, and duration of hospital stay did not significantly differ between patients with and without postoperative CVST. Adjusted independent risk factors of postoperative CVST were female sex (adjusted Odds Ratio 4.00, 95% CI 1.24-12.91, P = .021) and a lesion ≤1 cm to a venous sinus (adjusted Odds Ratio 10.58, 95% CI 2.93-38.20, P < .001). All patients received standard prophylactic-dose anticoagulant therapy, and none received treatment-dose anticoagulant therapy. No thrombosis-related adverse event was reported. All thromboses presented spontaneous sinus recanalization radiologically at a mean of 89 ± 41 days (range, 7-171). CONCLUSION: CVST after supratentorial awake craniotomy is a rare event with satisfactory clinical outcomes and spontaneous sinus recanalization under conservative management without treatment-dose anticoagulant therapy. These findings are comforting to neurosurgeons confronted with postoperative MRI reports suggesting CVST.

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.

Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma.

BACKGROUND AND OBJECTIVES: Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, isocitrate dehydrogenase (IDH)-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy. METHODS: We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, IDH-wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ2 or Fisher exact tests for categorical variables and the unpaired t test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models. RESULTS: One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; p < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and MGMT promoter methylation. DISCUSSION: The progression of tumor-related epilepsy with the evolution of glioblastoma, IDH-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.

Robot-assisted endoscopic third ventriculostomy under intraoperative CT imaging guidance.

BACKGROUND: The robot-assisted neurosurgical procedures have recently benefited of the evolution of intraoperative imaging, including mobile CT unit available in the operating room. This facilitated use paved the way to perform more neurosurgical procedures under robotic assistance. Endoscopic third ventriculocisternostomy requires both a safe transcortical trajectory and a smooth manipulation. METHOD: We describe our technique of robot-assisted endoscopic third ventriculocisternostomy combining robotic assistance and intraoperative CT imaging. CONCLUSION: Robot-assisted endoscopic third ventriculocisternostomy using modern intraoperative neuroimaging can be easily implemented and prevented erroneous trajectory and abrupt endoscopic movements, reducing surgically induced brain damages.

Carmustine wafer implantation for supratentorial glioblastomas, IDH-wildtype in "extreme" neurosurgical conditions.

We assessed the feasibility of Carmustine wafer implantation in "extreme" conditions (i.e. patients > 80 years and Karnofsky Performance Status score < 50) and of implantation ≥ 12 Carmustine wafers in adult patients harbouring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We performed an observational, retrospective single-centre cohort study at a tertiary surgical neuro-oncological centre between January 2006 and December 2021. Four hundred eighty patients who benefited from a surgical resection at first-line treatment were included. We showed that Carmustine wafer implantation in patients > 80 years, in patients with a Karnofsky performance status score < 50, and that implantation ≥ 12 Carmustine wafers (1) did not increase overall postoperative complication rates, (2) did not affect the completion of standard radiochemotherapy protocol, (3) did not worsen the postoperative Karnofsky Performance Status scores, and (4) did not significantly affect the time to oncological treatment. We showed that the implantation of ≥ 12 Carmustine wafers improved progression-free survival (31.0 versus 10.0 months, p = 0.025) and overall survival (39.0 versus 16.5 months, p = 0.041) without increasing postoperative complication rates. Carmustine wafer implantation during the surgical resection of a newly diagnosed supratentorial glioblastoma, IDH-wildtype is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50. The number of Carmustine wafers should be adapted (up to 16 in our experience) to the resection cavity to improve survival without increasing postoperative overall complication rates.

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.

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.