Publications by authors named "Alberto Feletti"

59 Publications

Spinal hemangioblastomas: analysis of surgical outcome and prognostic factors.

Neurosurg Rev 2021 Nov 25. Epub 2021 Nov 25.

Unit of Neurosurgery, Department of Biomedicine, Metabolic Sciences and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.

The prognostic factors for surgically removed spinal hemangioblastomas, the impact of VHL disease on outcome, and the role of intraoperative neuromonitoring are still not completely clear. The aim of this study was to review our experience with spinal hemangioblastomas in order to assess potential predictors of neurological outcome after surgery. All cases of spinal hemangioblastomas removed at two Italian academic institutions from 1985 to 2020 were reviewed. Data about clinical presentation and symptom duration, diagnosis of VHL, surgical approach, use of IONM, duration of hospital stay, follow-up, and modified McCormick grade before and after surgery were extracted. Sixty-one patients (31 F, 30 M) underwent 69 surgeries to remove 74 spinal hemangioblastomas (37 cervical, 32 thoracic, 5 lumbar). Improvement was found in 32.3% of cases, neurological condition remained stable in 51.6% of cases, and deteriorated in 16.1% of patients. A worsening trend in VHL patients and an improvement trend in non-VHL patients were detected, despite the lack of statistical significance. Laminotomy and use of IONM were found to be associated with better outcome, although no association was found between surgery without IONM and worse outcome. In most cases, patients affected by spinal hemangioblastomas can expect a good long-term outcome. In our experience, laminotomy seems to be associated with better outcome compared to laminectomy. While its absence is not associated with worse outcome, IONM seems to be associated with a better neurological outcome. Our study suggests that the more impaired the preoperative neurological condition, the worse the outcome.
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http://dx.doi.org/10.1007/s10143-021-01696-xDOI Listing
November 2021

GD2 CAR T cells against human glioblastoma.

NPJ Precis Oncol 2021 Oct 27;5(1):93. Epub 2021 Oct 27.

Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.
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http://dx.doi.org/10.1038/s41698-021-00233-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551169PMC
October 2021

Where the central canal begins: endoscopic in vivo description.

J Neurosurg 2021 Aug 13:1-10. Epub 2021 Aug 13.

4Department of Neurosciences, Biomedicine, and Movement Sciences, Institute of Neurosurgery, University of Verona, Italy.

Objective: Although evidence and descriptions of the central canal (CC) along the medulla oblongata and the spinal cord have been provided by several anatomical and radiological studies, a clear picture and assessment of the opening of the CC, or apertura canalis centralis (ACC), into the fourth ventricle is lacking, due to its submillimetric size and hidden position in the calamus scriptorius.

Methods: The authors reviewed all of their cases in which patients underwent ventricular transaqueductal flexible endoscopic procedures and selected 44 cases in which an inspection of the region of the calamus scriptorius had been performed and was suitable for study inclusion. Patients were divided into different groups, based on the presence or absence of a chronic pathological process involving the fourth ventricle. In each case, the visual appearance of the opening of the CC of the ACC was classified as no evidence (A0), indirect evidence (A1), or clear evidence (A2). Morphometric measurements were inferred from surrounding structures and the size of surgical tools visible in the field.

Results: The opening of the CC could be clearly observed in all cases (A1 4.5%, A2 95.5%). In normal cases, a lanceolate shape along the median sulcus was most frequently found, with an average size of 600 × 250 µm that became rounded and smaller in size in cases of hydrocephalus. The distance between the caudal margin of the ACC and the obex was about 1.8 mm in normal cases, 2.1 mm in cases of obstructive hydrocephalus, and 1 mm in cases of normal pressure hydrocephalus. The two wings of the area postrema, variable in size and shape, were sited just caudal to the opening.

Conclusions: A flexible scope inserted through the cerebral aqueduct can approach the hidden calamus scriptorius like a pen fits into an inkpot. With this privileged viewpoint, the authors provide for the first time, to their knowledge, a clear and novel vision of the opening of the CC in the fourth ventricle, along with the precise location of this tiny structure compared to other anatomical landmarks in the inferior triangle.
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http://dx.doi.org/10.3171/2020.12.JNS203649DOI Listing
August 2021

Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and adult populations: a systematic review and meta-analysis.

Neurosurg Rev 2021 Jun 25. Epub 2021 Jun 25.

Computational Neurosciences Outcomes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days-87 years]. Although flexible ETV had a higher incidence of failure in adults (flexible: 54%, 95%CI: 22-82% vs rigid: 20%, 95%CI: 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus.
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http://dx.doi.org/10.1007/s10143-021-01590-6DOI Listing
June 2021

The extent of resection of T2-flair hyperintense area for eloquent glioblastomas: outcomes analysis between awake and general anesthesia patients.

J Neurosurg Sci 2021 Jun 10. Epub 2021 Jun 10.

Department of Neuroscience, University of Padova, Padova, Italy.

Background: Maximum safe resection for eloquent areas glioblastomas is the greatest tumor resection achievable without causing neurological deficits. This study aims to assess, through quantitative volumetric analysis, the outcomes of patients with eloquent areas glioblastomas and correlate the extent of resection (EOR), based on MRI T1-contrast enhanced (CE) and T2- fluid-attenuated inversion recovery (FLAIR) sequences, with patient outcomes and overall survival.

Methods: We prospectively collected and analyzed patients with a diagnosis of primary GBM located in an eloquent area operated between January 2012 and April 2018. We examined 295 consecutive patients' records with GBM and identified 82 eloquent GBMs who met inclusion criteria. We stratified our patients by type of treatment - awake surgery (AS) and general anesthesia (GA) craniotomies. The kind of treatment was correlated with EOR, focusing on exeresis over the limit of the contrast-enhanced signal intensity, including both T1-CE and T2-FLAIR MRI signal alterations.

Results: The overall mean EOR value was higher in AS than in GA on T1-CE (p-value: 0.010) and T2-Flair MRI images (p-value: 0.007). Also, patients who had at least 30% of T2-FLAIR signal resection (EOR ≥ 30%) had a significantly lower risk of death and recurrence (p-value: 0.020), independent of residual T1-CE tumor volume.

Conclusions: Extensive T2-Flair resection and AS improve overall survival and reduce risk of recurrence while simultaneously minimizing surgical and medical complications among patients with GBMs in eloquent areas.
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http://dx.doi.org/10.23736/S0390-5616.21.05342-XDOI Listing
June 2021

Hemangioblastoma with Contrast-Enhanced Cystic Wall: When the Surgical Rule Must Not Be Respected.

World Neurosurg 2021 05 5;149:190-194. Epub 2021 Mar 5.

Department of Neurosciences, Biomedicine, and Movement Sciences, Institute of Neurosurgery, University of Verona, Italy.

Objective: The purpose of this paper is to describe the variation of surgical plan and technique required in a rare subset of hemangioblastomas compared with the accepted general strategy. The established rule in hemangioblastoma surgery is to avoid cyst wall removal, as it is not neoplastic, and it will not recur if mural nodule is completely removed. However, the wall of the associated cyst is occasionally enhanced by gadolinium on preoperative magnetic resonance imaging.

Methods: We present the case of a patient with a hemangioblastoma that was progressively compressed by a growing cyst, with the final appearance of a contrast-enhanced cyst wall. We collected similar cases reported in the literature.

Results: Our study points out the need for a tailored preoperative strategy, the usefulness of intraoperative fluorescent dyes, and the crucial role of frozen section histopathologic analysis to confirm diagnosis and optimize treatment.

Conclusions: When a hemangioblastoma is associated with a contrast-enhanced cyst, care must be taken to intraoperatively confirm the presence of neoplastic cells and eventually remove the neoplastic cyst wall to reduce the risk of recurrence.
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http://dx.doi.org/10.1016/j.wneu.2021.02.111DOI Listing
May 2021

How I do it: flexible endoscopic aspiration of intraventricular hemorrhage.

Acta Neurochir (Wien) 2020 12 23;162(12):3141-3146. Epub 2020 Jul 23.

Unit of Neurosurgery, Spedali Civili, University of Brescia, Brescia, Italy.

Background: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension.

Method: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained.

Conclusion: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency.
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http://dx.doi.org/10.1007/s00701-020-04499-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593288PMC
December 2020

A light on the dark side: in vivo endoscopic anatomy of the posterior third ventricle and its variations in hydrocephalus.

J Neurosurg 2020 Jul 3:1-9. Epub 2020 Jul 3.

2Department of Neurosciences, Neurosurgical Unit, University of Modena.

Objective: Despite the technological advancements of neurosurgery, the posterior part of the third ventricle has always been the "dark side" of the ventricle. However, flexible endoscopy offers the opportunity for a direct, in vivo inspection and detailed description of the posterior third ventricle in physiological and pathological conditions. The purposes of this study were to describe the posterior wall of the third ventricle, detailing its normal anatomy and surgical landmarks, and to assess the effect of chronic hydrocephalus on the anatomy of this hidden region.

Methods: The authors reviewed the video recordings of 59 in vivo endoscopic explorations of the posterior third ventricle to describe every identifiable anatomical landmark. Patients were divided into 2 groups based on the absence or presence of a chronic dilation of the third ventricle. The first group provided the basis for the description of normal anatomy.

Results: The following anatomical structures were identified in all cases: adytum of the cerebral aqueduct, posterior commissure, pineal recess, habenular commissure, and suprapineal recess. Comparing the 2 groups of patients, the authors were able to detect significant variations in the shape of the adytum of the cerebral aqueduct and in the thickness of the habenular and posterior commissures. Exploration with sodium fluorescein excluded the presence of any fluorescent area in the posterior third ventricle, other than the subependymal vascular network.

Conclusions: The use of a flexible scope allows the complete inspection of the posterior third ventricle. The anatomical variations caused by chronic hydrocephalus might be clinically relevant, in light of the commissure functions.
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http://dx.doi.org/10.3171/2020.4.JNS20493DOI Listing
July 2020

Myelomeningocele Repair Combining a Double Cryopreserved Amniotic Membrane Homograft and the Keystone Flap in a 3-Year-Old Child: A Case Report.

Pediatr Neurosurg 2020 26;55(2):106-112. Epub 2020 May 26.

Plastic Surgery Unit, Department of Medical and Surgical Sciences of the Mother, Children and Adult, Modena University Hospital, Modena, Italy.

Introduction: Early repair in patients affected by myelomeningocele (MMC) is of paramount importance in order to prevent infection, minimize neural tissue damage, and reduce mortality. Treatment must include duraplasty and possibly an adequate soft tissue coverage. Delayed surgery in MMC patients can be more tedious due to the less clear borders between the placode and the skin. Moreover, the risks of wound infection and breakdown increase significantly.

Case Presentation: We present the unusual case of a large MMC in a 3-year-old patient treated by combining the recently described cryopreserved amniotic membrane (AM) as homograft for dural reconstruction and a bilateral Keystone flap for soft tissue reconstruction.

Discussion: Thanks to its anti-inflammatory and elastic proprieties, the AM can play an important role in preventing adhesion between the reconstructed layers, thus reducing the risk of spinal cord tethering. The Keystone flap, at the same time, allows the wound tension to be distributed widely over the flap margins and not only along the midline, which overlies the duraplasty, enhancing the scar quality and lowering the risk of cerebrospinal fluid recurrence and wound dehiscence, with no donor site morbidity.
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http://dx.doi.org/10.1159/000507715DOI Listing
June 2021

Over ten years overall survival in glioblastoma: A different disease?

J Neurol Sci 2020 Jan 1;408:116518. Epub 2019 Nov 1.

Department of Neurosciences, Biomedicine and Movement Sciences, Neurosurgery Unit, University of Verona, Italy.

Purpose: The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine which genetic alterations or patient's characteristics influence survival time.

Methods: We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20 years, stratifying patients in three groups: those with a survival time ≥ 36 months and < 120 months (LTS), ≥120 months (VLTS), and < 36 months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival.

Results: Younger age at presentation (HR = 0.36, 95% CI 0.21-0.67, p = .001), and MGMT promoter [(MGMTp), methylated, HR = 0.57, CI 0.34-0.96, p = .034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (< 50 years), Ki-67 < 10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HR = 0.10, CI 0.01-0.74, p = .025).

Conclusions: We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors.
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http://dx.doi.org/10.1016/j.jns.2019.116518DOI Listing
January 2020

Neuroendoscopic Aspiration of Blood Clots in the Cerebral Aqueduct and Third Ventricle During Posterior Fossa Surgery in the Prone Position.

Oper Neurosurg (Hagerstown) 2019 08;17(2):143-148

Department of Neurosciences, Neurosurgery Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Background: During surgery in the posterior fossa in the prone position, blood can sometimes fill the surgical field, due both to the less efficient venous drainage compared to the sitting position and the horizontally positioned surgical field itself. In some cases, blood clots can wedge into the cerebral aqueduct and the third ventricle, and potentially cause acute hydrocephalus during the postoperative course.

Objective: To illustrate a technique that can be used in these cases: the use of a flexible scope introduced through the opened roof of the fourth ventricle with a freehand technique allows the navigation of the fourth ventricle, the cerebral aqueduct, and the third ventricle in order to explore the cerebrospinal fluid pathways and eventually aspirate blood clots and surgical debris.

Methods: We report on one patient affected by an ependymoma of the fourth ventricle, for whom we used a flexible neuroendoscope to explore and clear blood clots from the cerebral aqueduct and the third ventricle after the resection of the tumor in the prone position. Blood is aspirated with a syringe using the working channel of the scope as a sucker.

Results: A large blood clot that was lying on the roof of the third ventricle was aspirated, setting the ventricle completely free. Other clots were aspirated from the right foramen of Monro and from the optic recess.

Conclusion: We describe this novel technique, which represents a safe and efficient way to clear the surgical field at the end of posterior fossa surgery in the prone position. The unusual endoscopic visual perspective and instrument maneuvers are easily handled with proper neuroendoscopic training.
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http://dx.doi.org/10.1093/ons/opy324DOI Listing
August 2019

Targeting GD2-positive glioblastoma by chimeric antigen receptor empowered mesenchymal progenitors.

Cancer Gene Ther 2020 08 22;27(7-8):558-570. Epub 2018 Nov 22.

Department of Medical and Surgical Sciences for Children and Adults, Division of Oncology, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Tumor targeting by genetically modified mesenchymal stromal/stem cells (MSCs) carrying anti-cancer molecules represents a promising cell-based strategy. We previously showed that the pro-apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be successfully delivered by MSCs to cancer sites. While the interaction between TRAIL and its receptors is clear, more obscure is the way in which MSCs can selectively target tumors and their antigens. Several neuroectoderm-derived neoplasms, including glioblastoma (GBM), sarcomas, and neuroblastoma, express high levels of the tumor-associated antigen GD2. We have already challenged this cell surface disialoganglioside by a chimeric antigen receptor (CAR)-T cell approach against neuroblastoma. With the intent to maximize the therapeutic profile of MSCs delivering TRAIL, we here originally developed a bi-functional strategy where TRAIL is delivered by MSCs that are also gene modified with the truncated form of the anti-GD2 CAR (GD2 tCAR) to mediate an immunoselective recognition of GD2-positive tumors. These bi-functional MSCs expressed high levels of TRAIL and GD2 tCAR associated with a robust anti-tumor activity against GD2-positive GBM cells. Most importantly, the anti-cancer action was reinforced by the enhanced targeting potential of such bi-functional cells. Collectively, our results suggest that a truncated anti-GD2 CAR might be a powerful new tool to redirect MSCs carrying TRAIL against GD2-expressing tumors. This affinity-based dual targeting holds the promise to combine site-specific and prolonged retention of MSCs in GD2-expressing tumors, thereby providing a more effective delivery of TRAIL for still incurable cancers.
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http://dx.doi.org/10.1038/s41417-018-0062-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445885PMC
August 2020

Adenosine-induced Flow Arrest to Facilitate Intracranial Complex Aneurysm Clip Ligation: Review of the Literature.

Asian J Neurosurg 2018 Jul-Sep;13(3):539-545

Department of Neurosurgery, Banbuntane Hotokukai Hospital, Fujita Health University, Nagoya, Japan.

Complex intracranial aneurysms (CIAs) rank high among the most technically demanding neurosurgical pathologies. Microsurgery and clip ligation can be challenging in CIAs as circumferential visualization of the aneurysm, parent vessels, branches, perforators, and other neurovascular structures is important to prevent residual aneurysms or strokes from vessel or perforator occlusion. Decompression of the aneurysm sac is often required for CIAs. We reviewed the literature and PubMed advanced search showed 13 results of adenosine-induced flow arrest to facilitate intracranial complex aneurysm clip ligation which included three independent case reports and ten cases in a case series from 1999 to May 2016. Few case series have described the use of adenosine in intracranial aneurysm surgery. Satisfactory aneurysm decompression was achieved in all cases, and all aneurysms were clipped successfully. We recommend that adenosine cardiac arrest is a relatively novel method for decompression of intracranial aneurysms to facilitate clip application. With appropriate safety precautions, it is a reasonable alternative method when temporary clipping of proximal vessels is not desirable or not possible.
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http://dx.doi.org/10.4103/ajns.AJNS_207_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159025PMC
October 2018

Computational Fluid Dynamics Analysis and Correlation with Intraoperative Aneurysm Features.

Acta Neurochir Suppl 2018;129:3-9

Department of Neurosurgery, Fujita Health University Hospital, Nagoya, Japan.

Introduction: There are many controversies about computational fluid dynamics (CFD) findings and aneurysm initiation, growth, and ultimate rupture. The aim of our work was to analyze CFD data in a consecutive series of patients and to correlate them with intraoperative visual aneurysm findings.

Methods: Hemoscope software (Amin, Ziosoft Corporation, Minato ward, Tokyo, Japan) was used to process images from 17 patients who underwent clipping of 18 aneurysms. Pressure (P), wall shear stress (WSS) gradient and vectors, normalized WSS, and streamlines (SL) direction and velocity were assessed. CFD data were compared to intraoperative visual findings. A total of 39 aneurysm wall areas were assessed.

Results: Red, thin aneurysm wall areas were more often associated with low WSS. However, the association of low WSS with high P, diverging WSS vectors, direct impact of SL, and high SL velocity more frequently matched with yellow, atherosclerotic aneurysm walls.

Conclusions: Low WSS alone is not sufficient to determine the thickness of an aneurysm wall. Its association with other parameters might enable one to distinguish preoperatively atherosclerotic, thick areas (high P, diverging WSS vectors, high flow velocity) from thin areas with higher rupture risk (parallel WSS vectors, lower flow velocity). The changing balance between these parameters can modify the features and the risk of rupture of aneurysm wall over time.
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http://dx.doi.org/10.1007/978-3-319-73739-3_1DOI Listing
January 2019

Ventriculoperitoneal Shunt Complications in the European Idiopathic Normal Pressure Hydrocephalus Multicenter Study.

Oper Neurosurg (Hagerstown) 2019 07;17(1):97-102

Neurologiska kliniken, Akademiska Sjukhuset, Uppsala, Sweden.

Background: Ventriculoperitoneal shunt (VP-shunt) is the standard of treatment for idiopathic normal pressure hydrocephalus (iNPH). However, a thorough investigation of VP-shunt complications in this population is lacking.

Objective: To present the analysis and the rates of complications progressively occurring during the first year after shunt surgery in the patients with iNPH included in the European multicenter (EU-iNPH) study.

Methods: Patients (n = 142) were prospectively included in the EU-iNPH study by 13 institutions. All patients received a programmable VP-shunt. One hundred fifteen patients completed the 12-mo follow-up. Reexaminations were performed 1, 3, and 12 mo after surgery. Data regarding symptomatic over- or underdrainage, infections, malposition, subdural collections, and shunt surgery were collected and analyzed.

Results: Thirty patients (26%) experienced symptoms due to shunt underdrainage. Symptomatic overdrainage was reported in 10 (9%). Shunt adjustments were made in 43 (37%). Shunt malposition was recognized as the primary cause of shunt malfunction in 8 (7%), while only 1 infection (0.9%) occurred. Subdural hematoma was diagnosed in 7 (6%) and was treated by increasing the opening pressure of the valve in 5 patients. Hygroma was diagnosed in 10 (9%), requiring surgery in 1 patient. Overall, 17 patients (15%) underwent 19 shunt surgeries.

Conclusion: The advances in valve technology, a careful opening pressure setting, and rigorous follow-up allow a significant reduction of complications, which can be usually managed nonsurgically within the first 3 to 6 mo.
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http://dx.doi.org/10.1093/ons/opy232DOI Listing
July 2019

Congenital Arteriovenous Malformation of the Scalp Involving the Orbit.

J Neurol Surg A Cent Eur Neurosurg 2018 Nov 15;79(6):541-549. Epub 2018 Jun 15.

Department of Neurosurgery, Azienda Ospedaliero-Universitaria di Modena, Via Giardini 1355, 41121 Modena, Italy.

Background:  Arteriovenous malformations (AVMs) of the scalp are rare and infrequently encountered by the neurosurgeon.

Case Description:  We report a unique case of a 42-year-old patient who presented with a progressive worsening of visual acuity in the right eye (lower quadrantanopia) and palpebral ptosis. Physical examination revealed a right exophthalmos and a right frontoparietal scalp soft swelling when the patient was in the supine position. Neurologic work-up showed a scalp AVM extending into the orbit and connected to an intraorbital cavernous angioma. The patient was treated with a frontotemporal craniotomy and decompression of the orbit.

Conclusions:  In the rare case of intraorbital extension of a scalp AVM, neurologic symptoms may appear when the size of the vascular malformation increases with age. The aims of surgery should be decompression of the orbit and aesthetic preservation, rather than complete excision. A review of the literature is also provided.
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http://dx.doi.org/10.1055/s-0038-1641178DOI Listing
November 2018

High speed flow cytometry allows the detection of circulating endothelial cells in hemangioblastoma patients.

Methods 2018 02 10;134-135:3-10. Epub 2017 Nov 10.

Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Circulating endothelial cells (CECs) detach from the intima monolayer after endothelial damages. Their circulating endothelial progenitors (CEPs) represent less than 0.01% of nucleated blood cells. Increased levels of CECs and CEPs have been detected in patients with several types of cancer, suggesting that they could be a useful blood-based marker for detecting a tumor, or for monitoring its clinical course. However, their routine monitoring is time consuming and technically challenging. Here, we present a flow cytometry method for quantifying such cells in a cohort of patients with hemangioblastoma (HB). HB is a rare benign tumor, responsible for 1-2.5% of primary intracranial tumors and up to 10% of spinal cord tumors, and for which no tools are available to predict the onset or recurrence in patients undergoing surgical removal of tumor mass. This method allowed us to accurately quantifying CEC and CEP before and after surgery. CEPs are present at high levels in HB patients than control before intervention, and decrease after tumor removal, suggesting that their percentage could represent a valid tool to monitor the disease onset and recurrence.
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http://dx.doi.org/10.1016/j.ymeth.2017.11.002DOI Listing
February 2018

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil.

Drug Des Devel Ther 2017 3;11:593-598. Epub 2017 Mar 3.

Department of Neurosurgery, Nuovo Ospedale Civile SAgostino-Estense.

Introduction: Awake craniotomy allows continuous monitoring of patients' neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic-sedative medication is increasing.

Methods: Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management.

Results: The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure.

Conclusion: In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used.
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http://dx.doi.org/10.2147/DDDT.S124736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344434PMC
December 2017

Indocyanine green videoangiography: the thin border between a useful tool and an illusion of safety.

J Neurosurg Sci 2017 Jun;61(3):348-351

Department of Neurosurgery, Nuovo Ospedale Civile S. Agostino Estense, Modena, Italy.

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http://dx.doi.org/10.23736/S0390-5616.16.03258-6DOI Listing
June 2017

Expanded transcanal transpromontorial approach to the internal auditory canal: Pilot clinical experience.

Laryngoscope 2017 11 8;127(11):2608-2614. Epub 2017 Mar 8.

Otolaryngology-Head and Neck Surgery Department, University Hospital of Verona, Verona, Italy.

Objectives/hypothesis: The aim of this study was to describe and evaluate the feasibility of an expanded transcanal transpromontorial approach, developed from the exclusive endoscopic transcanal transpromontorial approach.

Study Design: Retrospective case series.

Methods: Retrospective chart review of 10 patients operated by an expanded transcanal transpromontorial approach in two tertiary referral centers (University Hospital of Modena, Italy and University Hospital of Verona, Italy). Data from charts and video documentation were collected and analyzed.

Results: Between April 2015 and January 2016, 10 patients underwent an expanded transcanal transpromontorial approach for vestibular schwannoma Koos stage I or II and were enrolled in the study. The size of the tumors ranged from 7 to 19 mm in maximum diameter. A gross total resection was achieved in all cases. One subject experienced postoperative cerebrospinal fluid otorhinorrhea and three subjects experienced temporary postoperative facial weakness, all of which completely resolved. The mean follow-up was 5 months.

Conclusions: The expanded transcanal transpromontorial approach allowed bimanual dissection using a microscopic technique for the treatment of pathologies of the internal auditory canal and cerebellopontine angle. This novel approach resulted in minimal morbidity and comparable facial nerve preservation rates to the traditional approaches to the internal auditory canal. The expanded transpromontorial approach to the internal auditory canal holds promise for addressing pathology in this region of the temporal bone from the external auditory canal.

Level Of Evidence: 4. Laryngoscope, 127:2608-2614, 2017.
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http://dx.doi.org/10.1002/lary.26559DOI Listing
November 2017

Dual-Image Videoangiography During Intracranial Microvascular Surgery.

World Neurosurg 2017 Mar 23;99:572-579. Epub 2016 Dec 23.

Department of Neurosurgery, Fujita Health University Hospital, Nagoya, Japan.

Objective: Indocyanine green videoangiography (ICG-VA) is a valuable tool to assess vessel and aneurysm patency during neurovascular surgical procedures. However, ICG-VA highlights vascular structures, which appear white over a black background. Anatomic relationships are sometimes difficult to understand at first glance. Dual-image videoangiography (DIVA) enables simultaneous visualization of light and near-infrared fluorescence images of ICG-VA.

Methods: The DIVA system was mounted on an OPMI Pentero Flow 800 intraoperative microscope. DIVA was used during microsurgical procedures on 5 patients who were operated for aneurysm clipping and superficial temporal artery-middle cerebral artery bypass.

Results: DIVA provides real-time simultaneous visualization of aneurysm and vessels and surrounding structures including brain, nerves, and surgical clips. Although visual contrast between vessels and background is higher with standard black-and-white imaging, DIVA makes it easier to understand anatomic relationships between intracranial structures. DIVA also provides better vision of the depth of field.

Conclusions: DIVA has the potential to become a widely used intraoperative tool to check patency of intracranial vessels. It should be considered as an adjunct to standard ICG-VA for better understanding of vascular anatomy in relation to surrounding structures and can have an impact on decision making during surgery.
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http://dx.doi.org/10.1016/j.wneu.2016.12.070DOI Listing
March 2017

Cavernous Angioma of the Cerebral Aqueduct.

World Neurosurg 2017 Feb 24;98:876.e15-876.e22. Epub 2016 Nov 24.

Department of Neurosurgery, NOCSAE Hospital of Modena, Modena, Italy.

Background: Among the rare intraventricular cavernomas, purely intra-aqueductal cavernomas are exceptionally rare.

Case Description: A 62-year-old patient presented with progressive headache, memory loss, gait instability, and urinary incontinence. Magnetic resonance imaging showed the presence of a mass lesion located in the lumen of the cerebral aqueduct, associated with triventricular hydrocephalus.

Conclusions: We discuss the rationale that led us to treat hydrocephalus with neuroendoscopy, which offered the possibility to directly inspect the intra-aqueductal lesion, make the diagnosis of cavernoma, and treat symptoms resulting from hydrocephalus without increasing the risk of bleeding.
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http://dx.doi.org/10.1016/j.wneu.2016.11.096DOI Listing
February 2017

If it can be done, it should be done,… or not? Response to Prof. Grotenhuis.

Acta Neurochir (Wien) 2016 06 23;158(6):1203-4. Epub 2016 Apr 23.

Unit of Neurosurgery, Department of Neurosciences, NOCSAE Modena Hospital, Modena, Italy.

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http://dx.doi.org/10.1007/s00701-016-2814-4DOI Listing
June 2016

Aspiration of parafalcine empyemas with flexible scope.

Childs Nerv Syst 2016 Jun 13;32(6):1123-9. Epub 2016 Apr 13.

Department of Neurosurgery, Treviso Regional Hospital, University of Padova, Treviso, Italy.

Purpose: Subdural empyemas are considered neurosurgical emergencies, and the parafalcine location is particularly insidious. We revised the experience of general surgeons who are used to manage chronic pleural purulent collections with video-assisted thoracoscopy.

Methods: With a similar technique, we successfully aspirated a parafalcine empyema using a flexible scope avoiding a more invasive craniotomy. A review of the treatment options of empyematous collections is also provided, focusing particularly on the hazardous parafalcine location.

Results: The management of subdural empyemas poses different decision-making problems compared to common brain abscesses, urging a more rapid and holistic surgical treatment with minimally invasive approach. Endoscopic aspiration of parafalcine empyema was followed by complete recovery in our patient.

Conclusions: Flexible endoscopy is a promising method to obtain complete pus removal even from loculated collections through a bur hole, avoiding large craniotomies and consequent potential complications.
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http://dx.doi.org/10.1007/s00381-016-3082-6DOI Listing
June 2016

Transaqueductal trans-Magendie fenestration of arachnoid cyst in the posterior fossa.

Acta Neurochir (Wien) 2016 Apr 17;158(4):655-662. Epub 2016 Feb 17.

Unit of Neurosurgery, Department of Neurosciences, NOCSAE Modena Hospital, Via Giardini 1355, 41126, Baggiovara (MO), Italy.

Background: Neuroendoscopy is currently recommended as the first choice to treat posterior fossa arachnoid cysts. It has proven to be effective, providing improved outcome, and safe, having a low complication rate. Compared to craniotomy and shunt placement, it has lower surgical morbidity, minimizing or avoiding risks of subdural fluid collections, shunt infection, malfunction, overdrainage, and dependence. Usually, rigid scopes maneuvered through a suboccipital approach are used. When symptomatic obstructive hydrocephalus develops, CSF diversion is the first aim of surgery.

Methods: In these patients, a flexible scope introduced through a frontal burr hole allows not only immediate and efficient management of hydrocephalus with endoscopic third-ventriculostomy, but in selected cases also direct cyst inspection and fenestration. Navigation of an enlarged cerebral aqueduct is actually safe when performed by experienced neurosurgeons.

Results: We describe the cystocisternostomy of a cisterna magna arachnoid cyst using a transaqueductal trans-Magendie approach.

Conclusions: This minimally invasive technique gives the possibility of performing both endoscopic third-ventriculostomy and cyst fenestration, which alone may not be enough to efficiently treat hydrocephalus.
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http://dx.doi.org/10.1007/s00701-016-2734-3DOI Listing
April 2016

Management of Subarachnoid Hemorrhage in Two Important Italian Political Leaders: A Paradigm of Ethical and Technological Evolution of Neurosurgery During the Past Half-Century.

World Neurosurg 2016 Aug 14;92:559-564. Epub 2016 Jan 14.

Department of Neurosciences, Unit of Neurosurgery, NOCSAE Modena Hospital, Baggiovara, Italy. Electronic address:

For a curious and extraordinary coincidence, 5 of the 7 most relevant leaders of the Italian Communist Party (Partito Comunista Italiano, which was established in 1921, has been the biggest Communist Party in Western Countries) suffered a cerebral stroke. Cerebrovascular diseases afflicted also Stalin and Lenin, and a number of Presidents of the United States. We present the stories of 2 important Italian political leaders who shared both the leadership role of the major left Italian Party and the dramatic experience of a subarachnoid hemorrhage. Retracing their medical incidents, separated by 50 years of history, we show how a fatal medical disease has become neurosurgical and successfully cured thanks to the advances of neurosurgery, neuroradiology, and hospital organization. A neurologic disease that was disgraceful 50 years ago has lost any disquieting and embarrassing significance in the present time to the light of evolution of vascular neurosurgery.
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http://dx.doi.org/10.1016/j.wneu.2015.12.089DOI Listing
August 2016

Von Hippel-Lindau disease: an evaluation of natural history and functional disability.

Neuro Oncol 2016 07 12;18(7):1011-20. Epub 2016 Jan 12.

Department of Neurosciences, Neurosurgery Unit, NOCSAE Modena Hospital, Modena, Italy (A.F., G.P.); Department of Medicine-DIMED, Section of Radiology, University of Padova, Italy (M.A.); Department of Statistical Sciences, University of Padova, Italy (B.S.); Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, Padova, Italy (F.S., F.B., S.Z., E.T., G.O.); Department of Urology, Ospedale Sant'Antonio, Padova, Italy (M.G.); Department of Neurosciences, Otosurgery Unit, University of Padova, Italy (E.Z.); Department of Neurosciences, Ophthalmology Unit, University of Padova, Italy (S.P.); Department of Women's and Children's Health, Pediatric Neurology Unit, University of Padova, Italy (A.M.); Department of Medicine-DIMED, University of Padova, Italy (G.O.).

Background: Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly.

Methods: We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease.

Results: Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities.

Conclusions: Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function.
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http://dx.doi.org/10.1093/neuonc/nov313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896541PMC
July 2016

Split cerebral aqueduct: a neuroendoscopic illustration.

Childs Nerv Syst 2016 Jan 1;32(1):199-203. Epub 2015 Aug 1.

Department of Neurosurgery, Treviso Hospital-University of Padova, Treviso, Italy.

Purpose: Forking of the cerebral aqueduct is a developmental malformation that is infrequently encountered by neurosurgeons as a rare cause of hydrocephalus, sometimes with a delayed onset. The etiology of an apparently forked aqueduct might be different. However, neuroendoscopy can often be the optimal treatment. The purpose of this study was to review the literature by analyzing the anatomical, functional, diagnostic, and therapeutic features of this unusual condition and adding our personal cases.

Methods: We present a case of forking of the cerebral aqueduct that was detected in vivo and treated with a flexible scope. A thorough review of the pertinent literature is also discussed. In the past years, diagnosis of forked aqueduct was possible only postmortem.

Results: A forked aqueduct is occasionally encountered in patients when a delayed hydrocephalic decompensation occurs.

Conclusions: Flexible neuroendoscopy enables for a direct, in vivo diagnosis and immediate treatment through a third ventriculostomy.
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http://dx.doi.org/10.1007/s00381-015-2827-yDOI Listing
January 2016
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