Papers by Rina Bonaventura
Neuro-Oncology
BACKGROUND Cerebellopontine angle (CPA) surgery for extra-axial lesions in elderly patients could... more BACKGROUND Cerebellopontine angle (CPA) surgery for extra-axial lesions in elderly patients could be hampered by concerns regarding functional outcomes. However, an overall ageing society warrants an improved approach. Intraoperative neuromonitoring is crucial for facial nerve (FN) preservation: intraoperative cortico-bulbar facial motor evoked potentials (FMEPs) can be effectively coupled to standard techniques. In a previous work, we validated the use of FMEPs as preditors of early and late post-operative FN function (FNF). Aim of this study was to re-evaluate FMEP role in patients beyond 65 years of age. METHODS An institutional series of 83 patients was reported. A pair of needle electrodes was used to record FMEP from orbicularis oculi (OOc) and orbicularis oris (OOr) muscles; baseline, final and minimum values were recorded. From FMEP amplitudes, minimum-to-baseline (MBR) and final-to-baseline (FBR) amplitude ratios, and recovery value (RV=FBR-MBR), were calculated. These indi...
Journal of Neurosurgical Sciences, 2020
BACKGROUND Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably r... more BACKGROUND Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably related to the enrollment of molecularly unselected patients. In this study we report the results of a precision medicine protocol in recurrent GBM. METHODS We prospectively evaluated 34 patients with recurrent GBM. We determined the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor variant III (EGFRvIII), and phosphatase and tensin homolog (PTEN). According to the molecular pattern we administered bevacizumab alone in patients with VEGF overexpression, absence of EGFRvIII, and normal PTEN (group A; n=16); bevacizumab + erlotinib in patients with VEGF overexpression, expression of EGFRvIII, and normal PTEN (group B; n=14); and bevacizumab + sirolimus in patients with VEGF overexpression and loss of PTEN, irrespective of the EGFRvIII status (group C; n=4). We evaluated the response rate, the clinical benefit rate, the 6-month progression-free survival (PFS-6), the 12-month PFS (PFS-12) and the safety profile of the treatment. Moreover we compared our results with the ones of EORTC 26101 trial. RESULTS Response rate was 50% in the whole cohort with the highest rate in group C (75%). Clinical benefit rate was 71% with the highest rate in group C (75%). PFS-6 was 56% in the whole cohort with the highest rate in group B (64%). PFS-12 was 21% in the whole cohort with the highest rate in group B (29%). When comparing our results with those from the combination arm of the EORTC 26101 trial we found a significantly higher PFS-6 and PFS-12 in our cohort. CONCLUSIONS The precision medicine protocol for recurrent GBM is feasible and leads to improved results if compared with studies lacking molecular selection.
Neurosurgical Review
Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies ... more Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies able to assess ischemia and aimed to improve surgical outcome reducing the treatment related morbidity in surgery for intracranial aneurysms. Many studies analyzing the impact of IONM are poised by the heterogeneity bias affecting the cohorts. We report our experience with IONM for surgery of unruptured middle cerebral artery (MCA) aneurysm in order to highlight its influence on functional and radiological outcome and surgical strategy. We retrospectively reviewed all MCA unruptured aneurysms treated between January 2013 and June 2021 by our institutional neurovascular team. Patients were divided into 2 groups according to the use of IONM. A total of 153 patients were included in the study, 52 operated on without IONM and 101 with IONM. The groups did not differ preoperatively regarding clinical status and aneurysm characteristics. Patients operated with IONM had better functional outcom...
Life
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Neuro-Oncology
INTRODUCTION Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably... more INTRODUCTION Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably due to the enrollment of molecularly unselected patients. In preliminary studies, we prospectively selected recurrent GBM patients on the basis of molecular pattern and administered targeted therapy accordingly. This tailored approach gave encouraging results in term of low recurrence rate (RR) and high 6-month progression free survival (PFS-6). Here, we present the long-term results of our work. METHODS On recurrent tumor samples of 34 adult patients, we assessed the expression of VEGF and PTEN through immunohistochemistry and of EGFRvIII through RT-PCR. Patients with VEGF overexpression were treated with bevacizumab (10 mg/Kg i.v. every 2 weeks in 6-week cycles). Patients with EGFRvIII expression and normal PTEN expression added erlotinib (150 mg/day orally). Patients with loss of PTEN expression, irrespective of EGFRvIII status, added sirolimus (1–10 mg/day orally). RESULTS Sixteen p...
Operative Neurosurgery
Since the dawn of antiquity, scientists, philosophers, and artists have pondered the nature of op... more Since the dawn of antiquity, scientists, philosophers, and artists have pondered the nature of optical stereopsis-the perception of depth that arises from binocular vision. The early 19th century saw the advent of stereoscopes, devices that could replicate stereopsis by producing a 3D illusion from the super-imposition of 2D photographs. This phenomenon opened up a plethora of possibilities through its usefulness as an educational tool-particularly in medicine. Before long, photographers, anatomists, and physicians were collaborating to create some of the first stereoscopic atlases available for the teaching of medical students and residents. In fields like neurosurgery-where a comprehensive visuospatial understanding of neuro-anatomical correlates is crucial-research into stereoscopic modalities are of fundamental importance. Already, medical institutions all over the world are capitalizing on new and immersive technologies-such as 3D intraoperative recording, and 3D endoscopes-to refine their pedagogical efforts as well as improve their clinical capacities. The present paper surveys the history of stereoscopy from antiquity to the modern era-with a focus on its role in neurosurgery and medical education. Through the tracking of this evolution, we can discuss potential benefits, future directions, and highlight areas in which further research is needed. By anticipating these factors, we may strive to take full advantage of an emergent field of technology, for our ultimate goal of improving patient care.
Interdisciplinary Neurosurgery
Operative Neurosurgery
Dural arteriovenous fistulas (dAVFs) are acquired dural shunts between an artery and a vein witho... more Dural arteriovenous fistulas (dAVFs) are acquired dural shunts between an artery and a vein without parenchymal nidus. DAVFs represent 10%-15% of intracranial arteriovenous malformations, and their manifestations vary from asymptomatic to devastating intracranial hemorrhage.1 They are classified according to their drainage and presence/absence of cortical venous reflux (CVR).2,3 The junction between transverse and sigmoid sinus (SS) is the most common location, and their treatment in case of CVR can involve the sacrifice of the sinus. DAVF occlusion may be achieved with both endovascular and surgical technique and frequently with combined techniques. This video demonstrates the management of a left dAVF of the SS in a 54-yr-old male with recent onset of diplopia and imbalance with venous congestion seen in the left cerebellum on T2 sequence MRI. Angiography revealed a Borden grade 2, Cognard grade IIa + b left SS dAVF supplied by the jugular and hypoglossal branches of the neuromeni...
29th Annual Meeting North American Skull Base Society
Neuro-Oncology
The greatest clinical challenge faced in meningioma is the inability to predict recurrence for in... more The greatest clinical challenge faced in meningioma is the inability to predict recurrence for individual patients, limiting the ability to select patients who would benefit from adjuvant radiation therapy to prevent recurrence. Therefore, in this multi-center cohort study, we utilized global epigenome DNA methylation profiles from human meningioma samples to generate and validate a methylome-based predictor of recurrence-free survival (RFS) and a meningioma recurrence score. Cox modeling of individual probes was used for feature selection in a training set (N=228 patients) which was then applied to two independent validation sets (N=54; N=140 patients). Geneexpression analysis was correlated to DNA methylation profiles using two published microarray datasets (GSE16581;GSE9438). Finally, penalized Cox modeling was used to generate a 5-year meningioma recurrence score based on a nomogram that integrated our validated methylome-based predictor with established clinical factors. The methlyome-based predictor was independently associated with RFS in each of the two validation sets, after adjusting for tumor grade and extent of resection (EOR; HR 4.0, 95%CI 1.4-11.5, P = 0.01 and HR 2.3, 95%CI 1.4-3.8, P=0.002). Using a 5-year RFS metric, the methylome-based predictor performed favourably compared to a grade-based predictor in both validation cohorts (ΔAUC =15%; ΔAUC=12%). Functional annotation of the included probes implicated the homeobox gene family. A nomogram constructed using the validated methylome-predictor with WHO grade and EOR demonstrated greater predictive performance than a nomogram using clinical factors alone (ΔAUC = 7.7%) and resulted in two different risk groups with distinct recurrence patterns (P <0.001). The methylome-based predictor and meningioma recurrence score developed and validated in this study provide important prognostic information not captured by established clinical factors and represent the first combined molecular and clinical prognostic tool that is individualized for patients with meningiomas, and hence an advance towards precision medicine in meningiomas MNGI-06. MENINGIOMA METASTASES: INCIDENCE AND SCREENING IN 1203 PATIENTS
Operative neurosurgery (Hagerstown, Md.), Jan 13, 2018
Arteriovenous malformations (AVMs) of the trigeminal root entry zone are rare and can be associat... more Arteriovenous malformations (AVMs) of the trigeminal root entry zone are rare and can be associated with neurovascular compression syndromes as well as intracranial hemorrhage.1 They generally have a small nidus located on and around the pial surface of the brainstem; thus, they are feasible for surgery. Nevertheless, they represent a challenge given the vicinity and involvement of cranial nerves and brainstem perforators.2-4This video demonstrates the case of a 57-yr-old man with new onset of a severe headache without neurological deficit associated with MRI evidence of a vascular malformation around the cisternal right trigeminal nerve. The nerve showed an altered signal on the MRI. Angiography revealed a Spetzler-Martin grade II AVM with a 16-mm nidus supplied by basilar artery perforators, right anterior inferior cerebellar artery, and the superior cerebellar artery (SCA), with drainage into the superior petrosal vein and sigmoid sinus. After an unsuccessful attempted embolizati...
Acta neurochirurgica. Supplement, 2017
Spinal cord stimulation (SCS) is well known for its early role in the management of chronic pain,... more Spinal cord stimulation (SCS) is well known for its early role in the management of chronic pain, mainly failed back surgery syndrome (FBSS), spasticity, and bowel and bladder dysfunction. In more recent years, SCS has been proposed for patients suffering from refractory angina or peripheral vasculopathies in order to gain symptom relief, thus indicating some hemodynamic effect on the peripheral circulation. Taking into account this scientific observation, since the late1980s, researchers have started to investigate the potential effect of SCS on cerebral blood flow (CBF) regulation and its possible application in certain pathological settings dealing with vascular pattern dysfunction, such as ischemia, subarachnoid hemorrhage, head trauma, and brain tumors. The aim of this study was to review the scientific literature about SCS and its effect on CBF, evaluating the results both in "physiological" experimental models and clinical studies, as well as in the particular patho...
Therapeutics and Clinical Risk Management, 2015
Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgi... more Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields.
Therapeutics and Clinical Risk Management, 2015
Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgi... more Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields.
Background: Primary intramedullary neurocytoma is extremely rare. Due to its rarity, it is diffic... more Background: Primary intramedullary neurocytoma is extremely rare. Due to its rarity, it is difficult to collect a wide series in a single institution to perform a survival analysis and give indications about prognosis and treatment. Case Description: Here, we report on a case of a 37-year-old woman with primary intramedullary neurocytoma and perform a systematic statistical analysis of cases reported in the literature. Of 21 articles found, 15 studies and the present case (22 patients) were eligible for the analysis. We studied the impact of age, sex, number of involved levels (≤2 vs. >2), entity of resection, postoperative radiotherapy (RT), proliferation index (Ki67) on the neurological outcome of patients, and on the recurrence of the tumor. Comparison of categorical variables was performed by the χ 2 statistic. The Kaplan-Meier curves were plotted to calculate the progression-free survival (PFS) of these patients. P < 0.05 was considered as statistically significant. The 1-year PFS was 95.45% and the 2-year PFS was 86.36%. A gross total resection was associated to a worsening of the neurological function with no impact on the tumor recurrence. Adjuvant RT significantly improved the neurological function. A lower Ki67 was strongly associated with a lower tumor recurrence. Conclusions: We think that the goal of the surgery should be to preserve a good neurological function even if a residual tumor has to be left. Ki67 should be always evaluated due to its impact on the prognosis. Although adjuvant RT significantly improved the neurological function, its role in preventing the tumor recurrence is not clearly defined.
Journal of neurosurgery, Jan 4, 2015
OBJECT Only a few published studies of the surgical treatment of benign peripheral nerve sheath t... more OBJECT Only a few published studies of the surgical treatment of benign peripheral nerve sheath tumors (BPNSTs), malignant peripheral nerve sheath tumors (MPNSTs), and peripheral non-neural sheath tumors (PNNSTs) have analyzed the results and possible prognostic factors using multivariate analysis. The authors report on their surgical series of cases of BPNSTs, MPNSTs, and PNNSTs with long-term follow-up and analyze the role of selected factors with respect to the prognosis and risk of recurrence of these tumors using multivariate analysis. They also review the pertinent literature and discuss their results in its context. METHODS The authors retrospectively reviewed data from cases involving patients who underwent resection of a peripheral nerve tumor between January 1983 and December 2013 at their institution. Of a total of 200 patients, 150 patients (with 173 surgically treated tumors) had adequate follow-up data available for analysis. Pain was assessed using a visual analog sca...
Surgical Neurology International, 2015
Primary intramedullary neurocytoma is extremely rare. Due to its rarity, it is difficult to colle... more Primary intramedullary neurocytoma is extremely rare. Due to its rarity, it is difficult to collect a wide series in a single institution to perform a survival analysis and give indications about prognosis and treatment. Here, we report on a case of a 37-year-old woman with primary intramedullary neurocytoma and perform a systematic statistical analysis of cases reported in the literature. Of 21 articles found, 15 studies and the present case (22 patients) were eligible for the analysis. We studied the impact of age, sex, number of involved levels (≤2 vs. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2), entity of resection, postoperative radiotherapy (RT), proliferation index (Ki67) on the neurological outcome of patients, and on the recurrence of the tumor. Comparison of categorical variables was performed by the χ (2) statistic. The Kaplan-Meier curves were plotted to calculate the progression-free survival (PFS) of these patients. P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 was considered as statistically significant. The 1-year PFS was 95.45% and the 2-year PFS was 86.36%. A gross total resection was associated to a worsening of the neurological function with no impact on the tumor recurrence. Adjuvant RT significantly improved the neurological function. A lower Ki67 was strongly associated with a lower tumor recurrence. We think that the goal of the surgery should be to preserve a good neurological function even if a residual tumor has to be left. Ki67 should be always evaluated due to its impact on the prognosis. Although adjuvant RT significantly improved the neurological function, its role in preventing the tumor recurrence is not clearly defined.
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Papers by Rina Bonaventura