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Background Microvascular decompression (MVD) represents a milestone for the treatment of trigeminal neuralgia (TN). Nevertheless, several complications still occur and may negatively affect the outcome. We recently proposed some technical nuances for complication avoidance related to MVD. Objective To verify the efficacy of the proposed refinement of the standard MVD technique in terms of resolution of the pain and reduction of complication rates. Methods We analyzed surgical and outcome data of patients with TN using a novel surgical refinement to MVD, over the last 4 yr. Outcome variables included pain relief, facial numbness, muscular atrophy, local cutaneous occipital and temporal pain or numbness, cerebellar injury, hearing loss, cranial nerve deficits, wound infection, and cerebrospinal fluid (CSF) leak. Overall complication rate was defined as the occurrence of any of the aforementioned items. Results A total of 72 consecutive patients were enrolled in the study. Pain relief was achieved in 91.6% and 88.8% of patients at 1- and 4-yr follow-up, respectively. No patient reported postoperative facial numbness during the entire follow-up period. The incidence of CSF leak was 1.4%. One patient developed a complete hearing loss and another a minor cerebellar ischemia. There was no mortality. The overall complication rate was 5.6%, but only 1.4% of patients experienced permanent sequelae. Conclusion The proposed refinement of the standard MVD technique has proved effective in maintaining excellent results in terms of pain relief while minimizing the overall complication rate associated with this surgical approach.

In Italy, vaccination against COVID-l 9 began on December 27, 2020. To date, 13,7 13,224 people in Italy are fully vaccinated, which accounts îor 25.3 oh of the general population, and 44.804 received at least one vaccination dose. Thc prescnt study aim to investigate willingness to receive COVID-I9 vaccination in costumers accessing a sample of community pharmacies in the Province of Palermo, Italy. A self- administered and anon),rnous questionnaire was carried out among costumers older than 18 ycars old between Dcccmbcr 2020 atrd March 2021. Three hundred and sixty-three subjects were enrolled in the study, 259 (71.3%) expressed their willingness to receive COVID-19 vaccination. The main dctcrminants associated with vaccination acccptance resulted "trust in safety and eflectiveness ofvaccinations" and the absence of any previous negative vaccination experience. Unfavourable information on COVID-I9 vaccination obtained through intemelmedia/social media and lack ofconfidence in COVID-I9 vaccines and in the Italian national healthcare system are the main determinants associated with vaccine refusal. Male gender, younger age classes and influenza vaccination acceptance due to the impact of COVID pandemic were significantly associated with willingness to be vaccinated against COVID-Ì9. In order to promote COVID-I9 vaccination campaign accumte, infomrative and communicative campaigr dedicated to subjects that are more hesitant regarding COVID-I9 vaccination (e.g. female sex, adults, people that usually do not adhere to influenza vaccination campaign) should be implemented.

Vaccine hesitancy (VH) is known to play a relevant role in thwarting the efforts toward reaching satisfactory influenza vaccination coverage, and has caused similar difficulties during the COVID-19 pandemic. This study aims to describe the phenomenon and produce insights on the reasons behind VH. A survey was administered between December 2020 and February 2021 to adults living in the cities of Bologna and Palermo. Of the 443 subjects enrolled, 47.3% were likely to get the influenza vaccination, while 75.6% were willing to receive the COVID-19 vaccination. The most frequent determinants that motivated the willingness to get the COVID-19 vaccine were trust in the safety of vaccines and belief that the vaccine is an effective tool. As for people’s unwillingness to be vaccinated, being exposed to information that produced doubts about the vaccine and lack of trust in a newly developed vaccine were the most frequently involved determinants. Statistically significant positive associations were found between the willingness to be vaccinated and postgraduate education and the propensity towards influenza vaccination. A negative association with being over 40 years old and of female gender was also found. These results might have an impact in better understanding individual reasons behind VH, identifying which categories are more exposed to it and which strategies should be implemented.

A variety of neurosurgical disorders affect the anterior cranial base and require an anterior cranial fossa approach. As neurosurgeons, we usually deal with the treatment of benign neoplasms, in particular meningiomas. Nonetheless, other common neurosurgical pathologies include traumatic injuries, craniofacial malformations (i.e., hypertelorism, craniosynostosis), cerebrospinal fluid (CSF) fistulas, and vascular lesions (i.e., arterio-venous fistulas). Although surgery of benign lesions of the anterior cranial fossa is a relatively common procedure, tumors like meningiomas can reach huge sizes and encase vital neurovascular structures, making surgery in the area a real challenge. Furthermore, the anterior cranial base is also involved by malignant tumors. With some notable exceptions (leukemia, lymphoma, myeloma, metastases), malignant neoplasms are treated surgically but require adjuvant radiation or chemotherapy. Malignant lesions are generally challenging lesions that require a multidisciplinary approach to achieve an en bloc resection with margins of uninvolved tissue after broad circumferential exposure whenever possible.1 Indications for surgical treatment of malignant tumors are influenced by the extent of the lesion taken together with clinical data, including age and performance. Surgical morbidity must be weighed against the anticipated natural course of the lesion and results of nonsurgical treatments, when applicable. Here we briefly describe the transcranial approaches to the anterior cranial fossa and discuss complications commonly encountered in anterior cranial fossa surgery and their avoidance.

Background: Stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) is well-established. Radiographic advantages exist for 3-dimensional rotational digital subtraction angiography (3DRA) over 2-dimensional digital subtraction angiography (2D DSA) in delineating AVM nidus structure for SRS treatment planning. However, currently there is limited to no data directly comparing 2D DSA versus 3DRA in terms of patient outcomes. Objective: To investigate whether the use of 3DRA over 2D DSA in radiosurgical treatment planning for AVMs associates with improved clinical outcomes. Methods: All AVM patients treated with SRS at our institution between the years 2000 and 2018 were identified. Primary outcomes were obliteration rates and time to obliteration (TTO); secondary outcomes included rates of post-SRS hemorrhage, salvage therapy, and symptomatic radionecrosis. A minimum of 12 mo of follow-up imaging/angiogram post-SRS was required, or alternatively evidence of obliteration on angiogram prior to 12 mo post-SRS. Single predictor and multivariable Cox regression and logistic regression models were constructed to test for association between radiographic, clinical, and treatment factors with outcomes. Results: A total of 75 patients were included. Total 17 patients received 3DRA and 58 patients received 2D DSA, with a median follow-up of 3.29 yr. The 3DRA is significantly associated with improved TTO on single predictor (HR 2.87, 1.29-6.12; P = .0109) and multivariable analysis (HR 2.448, 1.076-5.750; P = .0330) and increased odds of achieving obliteration by 3 yr post-SRS on single predictor analysis (OR 6.044, 1.405-26.009; P = .0157). Conclusion: The 3DRA over 2D DSA in SRS treatment planning for AVMs may result in improved TTO and 3-yr obliteration rates. Further investigation and prospective study are warranted.

BACKGROUND: Gelatin-thrombin hemostatic matrix (FloSeal®) use is associated with shorter surgical times and less blood loss, parameters that are highly valued in neurosurgical procedures. We aimed to assess the effectiveness of gelatin-thrombin in neurosurgical procedures and estimate its economic value. METHODS: In a 6-month retrospective evaluation at 2 hospitals, intraoperative and postoperative information were collected from patients undergoing neurosurgical procedures where bleeding was controlled with gelatin-thrombin matrix or according to local bleeding control guidelines (control group). Study endpoints were: length of surgery, estimated blood loss, hospitalization duration, blood units utilized, intensive care unit days, postoperative complications, and time to recovery. Statistical methods compared endpoints between the gelatin-thrombin and control groups and resource utilization costs were estimated. RESULTS: Seventy-eight patients (38 gelatin-thrombin; 40 control) were included. Gelatin-thrombin was associated with a shorter surgery duration than control (166±40 versus 185±55 minutes, P=0.0839); a lower estimated blood loss (185±80 versus 250±95 mL; P=0.0017); a shorter hospital stay (10±3 versus 13±3 days; P

Comment on Microneurosurgical Removal of a Globus Pallidus Tumor With Cottonoid-Guided Intraoperative Ultrasonography: 2-Dimensional Operative Video. Keleş A, Harput MV, Türe U. Oper Neurosurg (Hagerstown). 2020 Aug 1;19(2):E154. doi: 10.1093/ons/opz348. PMID: 31768549

Background Since January 2020, when the pathogen causing the coronavirus disease was identified in humans, the literature on coronavirus disease 2019 (COVID-19) has grown exponentially to more than 4000 publications. There is the need to provide an update for each single medical discipline, including neurosurgery, to be used by single professionals or to be distributed through the neurosurgical community and to be used by governments in designing new scenario of care. Methods A review of the MEDLINE database was performed on April 13, 2020. Search terms included “COVID-19,” “neurosurgery,” and “surgery.” A review of documents published on the webpage of the WFNS (World Federation of Neurosurgical Societies) and of the 5 continental associations of neurosurgical societies, AANS (American Association of Neurological Surgeons), AASNS (Asian Australasian Society of Neurological Surgeons), CAANS (Continental Association of African Neurosurgical Societies), EANS (European Association of Neurosurgical Societies), and FLANC (Latin American Federation of Neurosurgical Societies), representing the 119 national neurosurgical societies around the world, was performed. Results The literature search yielded 38 results that were manually reviewed. Fourteen manuscripts were considered eligible. They described suggestions and considerations to optimize care of neurosurgical patients, editorials on operational models, perspectives from neurosurgical departments, letters to the editor describing experiences on how to help medical staff to be prepared in advance for pandemic situations, and descriptions of regional or departmental models and/or organizational schemes. The webpages of the searched societies reported a total of 57 documents. Conclusions The neurosurgical scientific community has promptly reacted to the COVID-19 outbreak by producing a growing number of documents that could serve as guidance for neurosurgeons all over the world. Neurosurgical societies will represent the key institutions for guiding the neurosurgical community to overcome the COVID-19 crisis.

Background Microvascular decompression (MVD) represents the most effective and safe surgical option for the treatment of trigeminal neuralgia since it was first popularized by Jannetta 50 years ago. Despite several advances, complications such as cerebellar and vascular injury, hearing loss, muscular atrophy, cerebrospinal fluid (CSF) leak, postoperative cutaneous pain, and sensory disturbances still occur and may negatively affect the outcome. We propose some technical nuances of the surgical procedure that were used in our recent series. Methods We used a novel hockey stick−shaped retromastoid skin incision, preserving the major nerves of the occipital and temporal areas. Microsurgical steps were performed without the use of retractors. CSF leakage was prevented with a watertight dural closure and multilayer osteodural reconstruction. Results The refined surgical steps were perfected in the last consecutive 15 cases of our series. In these cases we did not record any cutaneous pain, sensory disturbances, or CSF leakage. The average diameter of the craniectomy was 18 mm. No patient reported major complications related to the intradural microsurgical maneuvers. In all cases the neurovascular conflict was found and solved with a good outcome in terms of pain disappearance. Conclusions Our minimally invasive approach was demonstrated to guarantee an optimal exposure of the cerebellopontine angle and minimize the rate of complications related to skin incision and muscular dissection, microsurgical steps, and closure.

Objective A modification of other reported endoscopic techniques for intracerebral clot evacuation is described and illustrated. Methods From January 2014 to December 2014, we operated on 6 patients harboring a spontaneous supratentorial intracerebral hemorrhage using a fully endoscopic freehand technique. Clinical chart and surgical videos were analyzed. Volumetric evaluation of the clot preoperatively and the residual hematoma postoperatively was performed. Clinical outcome was measured using the modified Rankin Scale and Glasgow Outcome Scale. Results The mean operative time was 96 minutes (range, 72–125 minutes). Clot evacuation was >90% in all patients. No patient experienced rebleeding after surgery. Two patients died. The Glasgow Outcome Scale score at 6 months was 4 in 2 patients, 3 in 2 patients, and 1 (death) in 2 patients. The modified Rankin Scale score at 6 months was 6 (death) in 2 patients, 4 in 2 patients, 3 in 1 patient and 2 in 1 patient. Conclusions The proposed minimally invasive technique allows a good rate of hematoma evacuation and intraoperative bleeding control. Further studies in large series are needed to confirm the role of this freehand endoscopic technique.

The need to improve surgical efficacy in patients affected by high-grade gliomas has led to development of advanced pre-surgical MRI-based techniques such as tractography. This study investigates pre-surgical planning of optic radiations (ORs) in patients affected by occipito-temporo-parietal high-grade gliomas, by means of constrained spherical deconvolution (CSD) and diffusion tensor imaging (DTI) tractography. Twelve patients with occipito-temporo-parietal high-grade gliomas were recruited and analyzed using a 3 T MRI scanner. Diffusion-weighted imaging (DWI) was conducted with 64 gradient diffusion directions. OR alterations were assessed qualitatively and quantitatively to evaluate the effectiveness of CSD- and DTI-based pre-surgical planning. CSD-based tractography provided better qualitative evaluation of affected white matter tracts when compared to DTI; by thresholding tractographic probabilistic maps coming from all reconstructions, we detected, at the highest cutoff level, OR involvement in 75 % of patients (vs 41.67 % of patients with probabilistic DTI). Quantitative analysis of diffusion parameters revealed a statistically significant decrease in fractional anisotropy (FA) in the affected side following CSD-based reconstructions; on the contrary, DTI-based reconstructions did not show any significant quantitative alteration. Our results showed improvement in pre-surgical planning of high-grade gliomas involving ORs with use of CSD-based tractography. This technique provided more useful information regarding the white matter spatial relationship with brain neoplasm and its involvement in the glioma, when compared to DTI. Using CSD model for OR evaluation may optimize safe surgical resection margins, helping to reduce risk of post-operative visual deficits.

The authors of this elegant study1 retrospectively reviewed the clinical characteristics of 40 gliomas IDH-wild-type pTERT-mutant astrocytomas (World Health Organization [WHO] grade II [n = 19] and grade III [n = 21]) and compared them to the outcome of 114 IDH-mutant and pTERTwild- type lower grade gliomas (LGG), of 92 IDH-wild-type pTERT-mutant glioblastoma multiforme (GBM), and of 15 IDH-wild-type pTERT-wild-type astrocytomas. The authors showed that IDH-wild-type pTERT-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or, in some instances, as gliomatosis cerebri in patients aged >50 yr. Accordingly, although these tumors often display an initial, falsely reassuring, LGG-like appearance, they indeed present a typically aggressive behavior and in the absence of treatment, grow rapidly, and develop GBMlike characteristics.

Petrous meningiomas (PMs) represent a subset of posterior fossa tumors accounting for ∼8% of all intracranial meningiomas. Surgical treatment of PMs is challenging because of their relationships with vital neurovascular structures of the cerebellopontine angle. OBJECTIVE: To investigate independent pre- and intraoperative predictors of PM surgery outcome. METHODS: We reviewed the surgical and outcome data of patients who underwent microsurgical resection of PMs from 1997 to 2016. From 2007 onward, a multimodal intraoperative protocol consisting of intraoperative neuromonitoring (IONM), endoscopy, and indocyanine green (ICG) videoangiography was applied. Outcome variables included extent of resection, Karnofsky performance status (KPS), overall survival, and progression-free survival (PFS). RESULTS: A total of 54 patients were included. Independent predictors of gross total resection (GTR) included retromeatal location (P < .0175; odds ratio [OR] 4.05), absence of brainstem compression (P < .02; OR 3.55), and histological WHO grade I (P < .001; OR 3.47). Nongiant size (P < .012; OR 4.38), and WHO grade I (P < .0001; OR 7.7) were independent predictors of stable or improved KPS. The use of multimodal intraoperative tools to assist surgery independently predicted GTR (P < .002; OR 6.8) and good KPS (P < .018; OR 4.23). Nongiant size (P = .01) and WHO grade I (P = .002) were significantly associated with increased PFS. CONCLUSION: Notwithstanding the limitations of a retrospective study, our results suggest that support of microsurgery by a combination of IONM, endoscopy, and ICG videoangiography may improve patient outcome in PM surgery.

The Neurosurgical Operative Atlas: Vascular Neurosurgery edited by R. Loch MacDonald is the third edition of an authored book composed of 3 separate sections: the first section covers intracranial aneurysm surgery, the second section covers brain and spine vascular malformations, the third section addresses surgical procedures for cerebral ischemia. Ten years after the previous edition, the editor and the authors have considerably changed the book by discarding some out-of-date aspects while adding entirely new chapters. Almost all the chapters have been substan- tially updated with respect to the last edition. Each chapter is meant to address each key operative aspect of the procedures or diseases that are discussed. In general, each chapter includes: patient selection, indications for surgery, preoperative investi- gations, surgical planning, positioning, step-by-step description of the surgical procedure, and postoperative complications. The book includes 39 authored chapters that are accompanied by 38 videos included.

We had the great opportunity to review the study entitled: “Big Data Defined: A Practical Review for Neurosurgeons.” In their article, Bydon et al1 reviewed and discussed data science in relationship to the modern neurosurgical practice, providing new useful information for bridging the gap between the theory of “Big Data” and neurosurgical practice.

Background Unruptured intracranial aneurysms (UIAs) are increasingly identified and are an important health-care burden; in the past they were commonly treated by surgical clipping, but nowadays endovascular coil embolization is increasingly employed as an alternative. Methods The Unruptured Aneurysms Italian Study (UAIS) is a multicentric cooperative prospective study aimed to delineate the "State of the Art" of UIAs treatment in Italy. 51 Italian Neurosurgical and Neuroradiological Units, representatives of all 20 Italian regions are involved in the Study. Results UAIS started on June 2003 and ended on July 2007. 1138 patients were collected by that date, but 181 were ruled-out due to severe violation of the protocol; 957 had complete data and could be statistically evaluated. Conclusions UAIS demonstrates that the treatment of UAs, as performed in Italy as a Nation, is effective in improving long-term outcome vs. natural history, particularly in aneurysms larger than 7 mm.

Background Navigated transcranial magnetic stimulation (nTMS) enables preoperative mapping of the motor cortex (M1). The combination of nTMS with diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST) has been described; however, its impact on surgery of motor-eloquent lesions has not been addressed. Objective To analyze the impact of nTMS-based mapping on surgery of motor-eloquent lesions. Methods In this retrospective case-control study, we reviewed the data of patients operated for suspected motor-eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group. Results We included 35 patients who underwent nTMS mapping of M1 (group A), 35 patients who also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperative motor performance (P = .04) and Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A. Conclusion nTMS-based mapping enables a tailored surgical approach for motor-eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed.

In reviewing the seventh edition of the Neurological Surgery by Youmans and Winn, the first question arising is whether we still need an all-encompassing textbook, an opera omnia, on Neurosurgery. Ours is an age of specialization and even of ultraspecialization. Being early addressed to a subspecialty is a today’s general trend for young neurosurgeons and this is certainly functional to the rapid gathering of a wealth of experience to ensure optimal patient outcome. Nevertheless neurosurgeons, especially those young doctors who did not live in a time when neurosurgeons were able to deal with most of the neurosurgical diseases, run the risk of losing a more comprehensive understanding of our discipline—its great beauty as well as its pitfalls. The intent of providing an encyclopedic overview of neurological surgery is clearly stated by the authors, and we recognize that this textbook is, in its own right, an essential reference guide to both the experienced and nascent clinician. The first edition of Neurological Surgery by Julian Youmans appeared in 1973. Since then on, and for each generation of neurosurgeons, the “Youmans” represented a comprehensive textbook highlighting the state of the art of neurosurgery, the techniques and technology of that generation’s contribution to neurosurgery. Almost 5 decades have passed from that first edition, and the textbook has expanded to 415 chapters and 5000 pages. By looking through all the editions, we can understand the long journey made by our knowledge and the breadth reached by our current practice of neurosurgery. The second question concerns what a textbook, with ambition to be considered the bible of the craft of neurosurgery of the present and next generation, should communicate. If great attention should be paid to the rise of the technological aspects on which our discipline is increasingly dependent, all these innovations make sense if able to improve patient safety and postoperative quality of life. To this purpose, this seventh edition dedicates a good number of pages to relevant, but elsewhere overlooked, themes such as “Improving patient safety,” “Complication avoidance in neurosurgery,” or “Coagulation in neurosurgery.” Also, more traditional issues are discussed under original and modern perspectives (ie, chapter 24, “Brain Retraction”). The description of pitfalls and complications is always very difficult. Summarizing in few pages all the circumstances in which minimal variations from what we plan may result in an unexpected event with serious implications on the patient’s healing perspectives, is a great challenge. Equally complicated would be trying to describe the emotional consequences that these events may have in the immediacy and on the subsequent choices. Can a textbook explain to young neurosurgeons that mastering surgical techniques is sometimes insufficient and that our results depend substantially on our decision-making? Probably no. Nonetheless, Neurological Surgery by Youmans and Winn makes an attempt to explain to the reader this fundamental issue of the discipline with its “complication avoidance” sections and especially with the foreword of Henry Marsh, a wonderful declaration of love and an epitome of the essence of neurosurgery. A wide section is dedicated to the surgical anatomy as crafted by Albert Rhoton and his colleagues. The section is combined with relevant clinical cases and relative videos that make surgical anatomy much more intelligible. The majority of chapters also contain related surgical videos, which are all very well prepared with a suitable length, correct magnification, and appropriate commentaries. Even though an increasing number of video collections and multimedia publications are available on the web, this selected well-prepared electronic material remarkably helps the understanding of several neurosurgical procedures. Videos on perioperative techniques such as patient positioning are also provided, as well as other supplementing basic sciences and clinical topics. Great attention is paid by the authors to radiological anatomy, with introductory overviews of brain and spine imaging and other relevant techniques for diagnosis contained within each subspecialty section.Other investigational techniques and, in particular, those that are ancillary to the surgical procedure such as neurophysiology and functional neuroimaging are also described in detail. Controversies in clinical practice, an issue that is really relevant in this textbook, are presented very clearly in a dedicated section and at the beginning of all introductory chapters for each of the 12 sections. These introductory chapters, written by each section editor, review the contents of the section and provide thoughtful comments while presenting main controversies on the topic. The textbook contains interesting incursions in the fields of neuroanesthesia, neurointensive care, and neurourology. All this material represents an important contribution that can greatly help the cultural growth of neurosurgeons. Being able to understand and even handle anesthesiology techniques is crucial to recognize the risks of surgery and greatly improve surgical performance. Similarly, a chapter dedicated to the role of the neurosurgeon in intensive care reminds us that such medical expertise is a basic and indispensable requirement. The textbook also tries to dominate the uncountable knowledge provided by basic science investigations through some chapters that address themes of obvious interest. Of course, this is an overwhelming task and well beyond the purpose of the authors.

Objectives Awake surgery and intraoperative monitoring represent the gold standard for surgery of brain tumors located in the perisylvian region of the dominant hemisphere due to their ability to map and preserve the language network during surgery. Nevertheless, in some cases awake surgery is not feasible. This could increase the risk of postoperative language deficit. Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI fiber tracking (DTI-FT) provide a preoperative mapping and reconstruction of the cortico-subcortical language network. This can be used to plan and guide the surgical strategy to preserve the language function. The objective if this study is to describe the impact of a non-invasive preoperative protocol for mapping the language network through the nTMS and nTMS-based DTI-FT in patients not eligible for awake surgery and thereby operated under general anesthesia for suspected language-eloquent brain tumors. Patients and methods We reviewed clinical data of patients not eligible for awake surgery and operated under general anaesthesia between 2015 and 2016. All patients underwent nTMS language cortical mapping and nTMS-based DTI-FT of subcortical language fascicles. The nTMS findings were used to plan and guide the maximal safe resection of the tumor. The impact on postoperative language outcome and the accuracy of the nTMS-based mapping in predicting language deficits were evaluated. Results Twenty patients were enrolled in the study. The nTMS-based reconstruction of the language network was successful in all patients. Interestingly, we observed a significant association between tumor localization and the cortical distribution of the nTMS errors (p = 0.004), thereby suggesting an intra-hemispheric plasticity of language cortical areas, probably induced by the tumor itself. The nTMS mapping disclosed the true-eloquence of lesions in 12 (60%) of all suspected cases. In the remaining 8 cases (40%) the suspected eloquence of the lesion was disproved. The nTMS-based findings guided the planning and surgery through the visual feedback of navigation. This resulted in a slight reduction of the postoperative language performance at discharge that was completely recovered after one month from surgery. The accuracy of the nTMS-based protocol in predicting postoperative permanent deficits was significantly high, especially for false-eloquent lesions (p = 0.04; sensitivity 100%, specificity 57.14%, negative predictive value 100%, positive predicitive value 50%). Conclusions The nTMS-based preoperative mapping allows for a reliable visualization of the language network, being also able to identify an intra-hemispheric tumor-induced cortical plasticity. It allows for a customized surgical strategy that could preserve post-operative language function. This approach should be considered as a support for neurosurgeons whenever approaching patients affected by suspected language-eloquent tumors but not eligible for awake surgery.

Commentary: Iterative Surgical Resections of Diffuse Glioma with Awake Mapping: How to Deal with Cortical Plasticity and Connectomal Constraints?

Comment on Misclassification of Case-Control Studies in Neurosurgery and Proposed Solutions.

OBJECTIVE: The pterional approach represents the standard approach for most lesions of the anterior and middle cranial fossa. It requires some degree of frontal lobe retraction, which may result in temporary or permanent damage of olfaction because of nerve avulsion or mechanical compression. The purpose of this study, based on microanatomic dissection of human cadaveric specimens, was to review the microsurgical anatomic features of the nerve and suggest operative nuances that may contribute to reducing the rate of postoperative olfactory dysfunction. METHODS: Twenty olfactory nerves and tracts were examined in 10 human cadaveric heads obtained from three fresh and seven formalin-fixed adult cadavers. A standard pterional craniotomy was performed. The olfactory nerve was dissected from its arachnoidal envelopes and then mobilized for an average length of 30 mm (range, 25–35 mm). RESULTS: The possible retraction of the frontal lobe was 10 to 15 mm. More retraction invariably resulted in nerve disruption. CONCLUSION: The standard sylvian and basal cistern opening may be insufficient to guarantee preservation of olfactory function. Early identification and arachnoidal dissection of the nerve may reduce the rate of olfaction compromise. The opening of the subarachnoidal space should be performed in a proximal-to-distal manner to allow early visualization of the olfactory bulb and its dissection. The arachnoidal dissection should be performed with sharp instruments, avoiding any traction on the posterior portion of the olfactory tract. Any direct retractor compression should also be avoided to spare the microvasculature lying on the dorsal surface of the nerve.

Background: The most common etiology of classic trigeminal neuralgia (TN) is vascular compression. However, other causes must be considered. Among these, spontaneous hematoma of the Meckel′s cave (MC) causing symptomatic TN is very rare. Case Description: We present the case of a 60-year-old woman with a 2-month history of left TN and diplopia. Neuroradiological examinations revealed a well-defined hematoma in the left MC. The patient underwent surgical decompression with a progressive neurological improvement. Conclusion: Despite the number of lesions potentially affecting the MC, spontaneous hemorrhage is rare but should be taken into account in the differential diagnosis.

Object Surgical treatment of parasagittal meningiomas is challenging. Preserving the venous outflow is the key point, but this may preclude radical resection. Different surgical strategies have been proposed. To contribute to the debate on the optimal strategy for treating these tumors, a single-institutional, single-surgeon series of patients with parasagittal meningiomas was analyzed and the available literature reviewed. Methods Clinical charts of patients with parasagittal meningioma, managed at the University of Messina between 1988 and 2008, were retrospectively reviewed. A microsurgical resection, the goal of which was to preserve the venous outflow, was performed. Only if the superior sagittal sinus (SSS) was angiographically occluded, but if alternative venous outflow was clearly recognized, was the tumor resected, together with the sinus without further flow restoration. A MEDLINE review of the literature published between 1955 and 2011 was performed. Results Long-term follow-up (mean 80 months) data obtained in 67 patients with meningiomas involving the SSS were analyzed. The recurrence rate was 10.4%; the morbidity and mortality rates were 10.4% and 4.5%, respectively. The authors identified in the literature 19 relevant studies on this issue, and based on their review of the literature, there is no evidence that aggressive management offers an advantage in terms of recurrence rate. Conclusions Analysis of the data obtained in the 67 patients confirmed good outcome and long-term tumor control following a surgical strategy aimed to preserve venous outflow. These findings and the results of the authors' analysis of the literature emphasize that the goal of radical tumor resection should be balanced by an awareness of the increased surgical risk attendant on aggressive management of the SSS and bridging veins.

Although there is recent evidence for the role of intraoperative neurophysiological monitoring (IONM) in spine surgery, there are no uniform opinions on the optimal combination of the different tools. At our institution, multimodal IONM (mIONM) approach in spine surgery involves the evaluation of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) with electrical transcranial stimulation, including the use of a multipulse technique with multiple myomeric registration of responses from limbs, and a single-pulse technique with D-wave registration through epi- and intradural recording, and free running and evoked electromyography (frEMG and eEMG) with bilateral recording from segmental target muscles. We analyzed the impact of the mIONM on the preservation of neuronal structures and on functional restoration in a prospective series of patients who underwent spine surgery. We observed an improvement of neurological status in 50 % of the patients. The D-wave registration was the most useful intraoperative tool, especially when MEP and SEP responses were absent or poorly recordable. Our preliminary data confirm that mIONM plays a fundamental role in the identification and functional preservation of the spinal cord and nerve roots. It is highly sensitive and specific for detecting and avoiding neurological injury during spine surgery and represents a helpful tool for achieving optimal postoperative functional outcome.

Background Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The nonisocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. Methods Twenty-seven patients with refractory TN and MS were treated. A nonisocentric beams distribution was chosen; the maximal target dose was 72.5 Gy. The maximal dose to the brainstem was

Although there is recent evidence for the role of intraoperative neurophysiological monitoring (IONM) in spine surgery, there are no uniform opinions on the optimal combination of the different tools. At our institution, multimodal IONM (mIONM) approach in spine surgery involves the evaluation of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) with electrical transcranial stimulation, including the use of a multipulse technique with multiple myomeric registration of responses from limbs, and a single-pulse technique with D-wave registration through epi- and intradural recording, and free running and evoked electromyography (frEMG and eEMG) with bilateral recording from segmental target muscles. We analyzed the impact of the mIONM on the preservation of neuronal structures and on functional restoration in a prospective series of patients who underwent spine surgery. We observed an improvement of neurological status in 50 % of the patients. The D-wave registration was the most useful intraoperative tool, especially when MEP and SEP responses were absent or poorly recordable. Our preliminary data confirm that mIONM plays a fundamental role in the identification and functional preservation of the spinal cord and nerve roots. It is highly sensitive and specific for detecting and avoiding neurological injury during spine surgery and represents a helpful tool for achieving optimal postoperative functional outcome.

Background: Although pituitary adenomas are considered benign lesions, a small group may exhibit a clinically aggressive behavior, sometimes independently from the classic markers of aggressiveness, including the Ki67 labeling index and/or p53 expression. Methods: We selected 7 subjects harboring a pituitary tumor with clinical features of aggressiveness. Patients underwent a full preoperative and postoperative endocrinological and neuroradiological work-up. Two were nonfunctioning, two PRL-secreting, two ACTH-secreting, and one a GH-secreting adenoma. Results: The 7 patients underwent a total of 17 surgical procedures. At the first surgical procedure in none of the patients a gross total removal was achieved, whereas a subtotal removal - > 90% of tumor removed - was achieved in 4/7 cases, and a partial removal - < 90% of tumor removed - was achieved in 3/7 cases. At first operation, 4/7 patients showed a Ki67 ≤ 3%, 2/7 > 3% ; it was not available in one patient. Postoperatively, all patients underwent radiation therapy. Three patients received chemotherapy with temozolomide. Three patients underwent peptide receptor radionuclide therapy (PRRT). To date, 1 patient died from tumor progression, two patients are in poor general conditions. The remaining 4 patients are in fair/good conditions, without any major complaints. The mean follow-up is 43.42 months. Conclusions: Aggressive pituitary adenomas represent a specific and still underestimated entity, often diagnosed late. Clinical and neuroradiological rapid progression is often the only marker of aggressiveness. Surgical debulking remains first therapeutic option. Multidisciplinary management is mandatory to offer to these patients targeted therapeutic options.

Brain metastases (BM) are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood–brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented.

Gliomas account for around 45% of primary brain tumors. The treatment of malignant gliomas depend on the person’s age, the type of tumor, and the location of the tumor. These tumors tend to grow into the normal brain tissue, with the result that complete surgical removal can be very difficult to reach. Current therapy is unsatisfactory due to low therapeutic efficiency and strong systemic side effects of chemo- and/or radiotherapy protocols.The standard protocol includes maximal surgical resection with postoperative combination of radiation therapy with concomitant and adjuvant chemotherapy. Surgical treatment represents the first initial treatment. However, in spite of the recent innovations in surgical techniques, including intraoperative mapping, we only got a slight improvement of the prognosis. Additionally, radiation therapy is also used to treat gliomas in locations where surgery is not safe and for recurrent gliomas. Chemotherapy is recommended for some high-grade gliomas after surgery and radiation therapy. The presence of the blood-brain barrier impedes the passage of a large number of molecules into the brain. However, most of the current drugs show limited solubility, high toxicity and have a nonspecific delivery. Targeted drugs delivery systems can convey drugs more effectively and increase patient compliance. Recent advances in molecular and biological techniques have evidence new glioma-associated biomarkers and their implications for gliomas progression. The possibility to block contemporary more pathways into glioma by molecular-based targeted approaches, using a nanocarrier loaded with anticancer agent, represent a promising therapeutic strategy.Nanomedicine holds great promise for evolutionizing medical treatments, imaging and drug delivery. Nanoparticles provide better penetration of therapeutic agents and a reduced risk in comparison to conventional treatments. By using nanotechnology it is possible to deliver the drug to the targeted tissue across the blood-brain barrier and release the drug at a controlled rate. Graphene is a versatile two-dimensional nanomaterial thanks to its unique physical and chemical characteristics. Numerous experimental studies have also been made to employ graphene as a vehicle for antitumoral therapies. We think that, using the intrinsic capacity of graphene, should be very interesting to structure a new nanoparticle-based molecular approach against molecular targets, contemporary. In our laboratories, we are trying to create a carrier loaded with an antisense molecule against hypoxic ischemic factor-1α (HIF-1 α) and IL-8. However, there is currently no definitive study regarding the therapeutic potentialities or risks of graphene nanoparticles. They offer many opportunities for cancer therapy, but their interaction with biological tissues has not yet been fully elucidated.

Malignant brain tumors are difficult to manage clinically and are associated with high rates of morbidity and mortality. Late diagnosis and the limitations of conventional therapies that may result from inefficient delivery of the therapeutic or contrast agent to brain tumors due to the blood-brain barrier and nonspecificity of the agents, are major reasons for this unsolved clinical problem. Nanotechnology involves the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer scale. The nanoparticle has emerged as a potential vector for brain delivery, able to overcome the difficulties of modern strategies. Moreover, multifunctionality can be engineered into a single nanoplatform so that it can provide tumor-specific detection, treatment, and follow-up monitoring. This review reports the latest research in nanoparticle-based glioma treatment. From the Clinical Editor In recent years, nanoparticles have emerged as potential delivery vectors targeting brain tumors, including multifunctional NP-s allowing tumor-specific detection, treatment, and follow-up monitoring. This review summarizes the latest research in nanoparticle-based glioma treatment.

Purpose: Accuracy in delineating the target volume is a major issue for successful stereotactic radiosurgery for arteriovenous malformations. The aim of the present study was to describe a method to integrate threedimensional (3D) rotational angiography (3DRA) into CyberKnife treatment planning and to investigate its potential advantages compared with computed tomography angiography (CTA) and magnetic resonance angiography. Methods and Materials: A total of 20 patients with a diagnosis of cerebral arteriovenous malformation were included in the present study. All patients underwent multislice computed tomography and 3D-volumetric CTA, 3DRA, and 3D magnetic resonance angiography. The contouring of the target and critical volumes was done separately using CTA and thereafter directly using 3DRA. The composite, conjoint, and disjoint volumes were measured. Results: The use of CTA or 3DRA resulted in significant differences in the target and critical volumes. The target volumeaveraged3.49±3.01mLmeasuredusingCTAand3.26±2.93mLmeasuredusing3DRA,foradifferenceof 8% (p< .05). The conjoint and disjoint volume analysis showed an 88% volume overlap. The qualitative evaluation showed that the excess volume obtained using CTAwas mostly tissue surrounding the nidus and venous structures. The mean contoured venous volume was 0.67 mL measured using CTA and 0.88 mL (range, 0.1‐2.7) measured using 3DRA (p < .05). Conclusions:3DRAisavolumetricangiographicstudythatcanbeintegratedintocomputer-basedtreatmentplanning. Although whether 3DRA provides superior accuracy has not yet been proved, its high spatial resolution is attractive and offers a superior 3D view. This allows a better 3D understanding of the target volume and distribution of the radiation doses within the volume. Additional technical efforts to improve the temporal resolution and the development of software tools aimed at improving the performance of 3D contouring are warranted. 2011 Elsevier Inc. Three-dimensional rotational angiography, Stereotactic radiosurgery, CyberKnife, Robotic radiosurgery, Cerebral arteriovenous malformations.

The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.

Objective To analyze the risk factors of worst outcome associated with moderate head injury. Methods Data on patients with moderate head injury were collected prospectively in 11 Italian neurosurgical units over a period of 18 months. Patients older than 18 years with blunt head injury and at least one Glasgow Coma Scale (GCS) score between 9 and 13 were enrolled. The outcome was determined at 6 months using the Glasgow Outcome Scale. Results We analyzed 315 patients. Initial computed tomographic scans showed a diffuse injury type I or II in 63%, a mass lesion in 35%, and traumatic subarachnoid hemorrhage in 42% of the patients. The risk of progression toward a mass lesion was 23% when the admission computed tomographic scan showed diffuse injury type I or II. An emergency craniotomy was performed in 22% of the patients, delayed surgery was performed in 14%, and both were performed in 25%. A favorable outcome was obtained in 74% of the patients. When the GCS score was 9 or 10, the predictor of worst outcome was a motor GCS score of 4 or lower (odds ratio [OR], 8.08; 95% confidence interval [CI], 1.22-67.35; P = 0.008), but when the GCS score was 11 to 13, the factors associated with worst outcome were neuroworsening (OR, 3.43; 95% CI, 1.45-8.17; P = 0.002), seizures (OR, 7.94; 95% CI, 1.18-64.48; P = 0.02), and medical complications (OR, 4.24; 95% CI, 1.74-10.33; P = 0.0006). Conclusion There is a high percentage of surgery and worsening on computed tomographic scans in patients with moderate head injury. Neuroworsening, seizures, and medical complications as outcome predictors were more strongly associated with a GCS score of 11 to 13, whereas a low motor GCS score was more outcome-related in patients with GCS scores of 9 and 10.

BACKGROUND Antiapoptotis resulting from hyperactivation of the transcription factor NF-κB has been described in several cancer types. It is triggered by the interaction of the tumor necrosis factor (TNF) with its receptors and recruitment of the intermediate factor TNF-receptor associated factor (TRAF) 2. The NF-κB transcriptional activity could amplify the expression of antiapoptotic genes. The authors investigated the activity of NF-κB, and the mRNA expression of TNFα, TNFα receptor, TRAF1, TRAF2, and TRAF-associated NF-κB activator (TANK), and the antiapoptotic genes Bcl-2, c-IAP 1 and 2, and Survivin in human astrocytic tumors. METHODS Eight low-grade astrocytomas (LGA), 10 anaplastic astrocytomas (AAs), 10 glioblastoma multiforme (GBM) samples were used; 4 samples of normal brain tissue were used as controls. The NF-κB activation was analyzed by electrophoretic mobility shift assay; TRAF1, TRAF2, TANK/I-TRAF, Bcl-2, c-IAP 1 and 2, and Survivin mRNA expressions were studied using real-time quantitative reverse-transcriptase polymerase chain reaction. RESULTS NF-κB hyperactivity was detected in tumor samples. mRNA of antiapoptotic genes, particularly BCL-2 and Survivin, was hyperexpressed in gliomas. Interestingly, BCL-2 was hyperexpressed in LGAs, whereas a very high level of Survivin featured high-grade gliomas. The differential expression of antiapoptotic genes yielded a tight clustering of all LGA and nearly all GBM samples in cluster analysis. CONCLUSIONS NF-κB and factors involved in its intracellular activation were up-regulated in gliomas. NF-κB-activated antiapoptotic genes were hyperexpressed in tumor samples, but showed a differential expression with higher levels of Bcl-2 in LGAs and higher levels of Survivin in GBMs. Cancer 2008. © 2008 American Cancer Society.

Object Meningiomas constitute 25% of primary spinal tumors and predominantly involve the thoracic spinal cord. Although calcifications are commonly seen in intracranial meningiomas, gross calcifications are observed in only 1–5% of all spinal meningiomas. We report the clinical findings, surgical strategy and histological features of 9 patients with ossified spinal meningiomas (OSMs). Patients and methods Clinical and surgical features of 9 patients with ossified spinal meningiomas were retrospectively reviewed. Results There were 8 women and 1 man with a mean age of 59 years. In 7 patients, the lesions were localized in the thoracic segment of the spine while in 2 patients in the lower cervical segment. All patients presented with weakness of the lower limbs and hypoesthesia below the site level of the lesion. Only 2 patients presented with urinary incontinence. Gross-total resection of the tumor was achieved in 6 patients while in 3 a subtotal removal of the meningioma was obtained. In all patients the postoperative course was uneventful. Six patients presented with a significant neurological improvement while in 3 patients a mild improvement was observed. Microscopically, all tumors showed typical histological pattern of ossified meningioma. Conclusions OSMs are amenable to surgery if the complete removal can be achieved. Because of their hard-rock consistency complete resection can be challenging. In difficult cases, subtotal removal can be advised and follow-up imaging is mandatory. Overall, the risk of long-term recurrence of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected.

As well known, from a scientific point of view, the product of 3D printing is the result of the perfect superimposition of layers of condensed polymers of various nature that aggregate to form true solid matter. The previously created computer model is accomplished in accordance with the 3D of the real world. The materials produced may be of different nature (i.e., cardboard, plastic materials, wood, metal) according to the production standards. Because of the big variety of materials and technologies that occur within the concept of 3D printing, this innovation is receiving a huge success, but is defying a simple definition. 3D printing is promising something as big as a new industrial revolution. If computers and the web had allowed the “dematerialization” and the subsequent widespread diffusion of knowledge, the 3D printers allow the “materialization” of innovative ideas with potentially huge economic, social, and political consequences. Furthermore, new products can be now prototyped and built out, using this technology, in a very short time and, through self-funding, paving the way to a “democratization” of innovation