Search

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging.

Intra-operative contrast-enhanced ultrasound (CEUS) is a relatively standardized procedure in brain neurosurgery, but it is still underused in spinal cord and intramedullary tumor evaluation. We reviewed and analyzed the intra-operative data from a surgical series of patients harboring intramedullary spinal cord tumors who underwent surgery under CEUS guidance. CEUS was performed in 12 patients (age range: 13–55 y); all lesions had ill-defined boundaries or peritumoral cysts at preliminary intra-operative B-mode ultrasound. CEUS highlighted the tumors in all cases. The contrast agent's spinal distribution revealed different phases (arterial, peak, washout), as observed in the brain, but these appeared to be slower and less intense. In our experience, intra-operative CEUS allows surgeons to assess spinal cord perfusion and highlight intramedullary tumors in real time. As for other imaging modalities, ultrasound contrast agents add valuable information over baseline imaging, and their use should be fostered to better understand microbubble distribution dynamics.

Nowadays, most of the patients affected by psychiatric disorders are successfully treated with psychotherapy and pharmacotherapy. Nevertheless, according to the disease, a variable percentage of patients results resistant to such modalities, and alternative methods can then be considered. The purpose of this review is to summarize the techniques and results of invasive modalities for several treatment-resistant psychiatric diseases. A literature search was performed to provide an up-to-date review of advantages, disadvantages, efficacy, and complications of Deep-Brain Stimulation, Magnetic Resonance-guided Focused-Ultrasound, radiofrequency, and radiotherapy lesioning for depression, obsessive-compulsive disorder, schizophrenia, addiction, anorexia nervosa, and Tourette’s syndrome. The literature search did not strictly follow the criteria for a systematic review: due to the large differences in methodologies and patients’ cohort, we tried to identify the highest quality of available evidence for each technique. We present the data as a comprehensive, narrative review about the role, indication, safety, and results of the contemporary instrumental techniques that opened new therapeutic fields for selected patients unresponsive to psychotherapy and pharmacotherapy.

OBJECTIVEBenign peripheral nerve sheath tumors (PNSTs) include mainly schwannomas—the most common tumors arising from peripheral nerves—and neurofibromas. Due to their origin, distinguishing between functional intact nerve and the fibers from whence the PNST arose may not always be easy to perform. The introduction of intraoperative tools to better visualize these tumors could be helpful in achieving a gross-total resection. In this study, the authors present a series of patients harboring PNST in which the surgery was performed under fluorescein guidance.METHODSBetween September 2018 and February 2019, 20 consecutive patients with a total of 25 suspected PNSTs underwent fluorescein-guided surgery performed under microscopic view with a dedicated filter integrated into the surgical microscope (YELLOW 560) and with intraoperative monitoring. All patients presented with a different degree of contrast enhancement at preoperative MRI. Fluorescein was intravenously injected after intubation at a dose of 1 mg/kg. Preoperative clinical and radiological data, intraoperative fluorescein characteristics, and postoperative neurological and radiological outcomes were collected and analyzed.RESULTSSix patients were affected by neurofibromatosis or schwannomatosis. There were 14 schwannomas, 8 neurofibromas, 1 myxoma, 1 reactive follicular hyperplasia, and 1 giant cell tumor of tendon sheath. No patient experienced worsening of neurological status after surgery. No side effects related to fluorescein injection were found in this series. Fluorescein allowed an optimal intraoperative distinction between tumor and surrounding nerves in 13 of 14 schwannomas and in all neurofibromas. In 6 neurofibromas and in 1 schwannoma, the final YELLOW 560 visualization showed the presence of small tumor remnants that were not visible under white-light illumination and that could be removed, obtaining a gross-total resection.CONCLUSIONSFluorescein was demonstrated to be a feasible, safe, and helpful intraoperative adjunct to better identify and distinguish PNSTs from intact functional nerves, with a possible impact on tumor resection, particularly in diffuse neurofibromas.

To evaluate and characterize cases of brain abscess in immunocompetent patients due to Gemella morbillorum, an opportunistic Gram-positive coccus. Two cases of brain abscess due to this pathogen which occurred at the authors’ native institution in 2013 and 2016 were analyzed. Moreover, a literature search regarding brain abscess surgically treated due to this pathogen was performed in PubMed database, following PRISMA statement. The final review comprised ten articles for a total of 11 patients—all immunocompetent—with a median age of 50.2 years (range 28–77); almost total were males. Neurological deficits and fever were the most common initial signs; seizures were present only in two cases. Surgical treatment was based on craniotomy and excision in six cases; the remaining five underwent stereotactic aspiration. The antibiotic initial therapy was intravenous in all cases. The average duration of therapy was of six weeks with a minimum of four and maximum of ten. One patient died, while in the other cases, a complete or partial regression of presenting symptoms and disappearing of MRI signs at intermediate follow-up were obtained. In eight patients (72%), it was possible to identify a primary infection or a predisposing factor (as cardiac diseases or septic arthritis). G. morbillorum is an emerging pathogen involved in brain abscesses. Even if it is infrequently reported, the identification of specific characteristics that may increase its neurotropism and virulence also in immunocompetent patients can help to better understand such a rare pathology.

BACKGROUND Sonoelastography is an ultrasound imaging technique able to assess mechanical properties of tissues. Strain elastography (SE) is a qualitative sonoelastographic modality with a wide range of clinical applications, but its use in brain tumor surgery has been so far very limited. OBJECTIVE To describe the first large-scale implementation of SE in oncological neurosurgery for lesions discrimination and characterization. METHODS We analyzed retrospective data from 64 patients aiming at (i) evaluating the stiffness of the lesion and of the surrounding brain, (ii) assessing the correspondence between B-mode and SE, and (iii) performing subgroup analysis for gliomas characterization. RESULTS (i) In all cases, we visualized the lesion and the surrounding brain with SE, permitting a qualitative stiffness assessment. (ii) In 90% of cases, lesion representations in B-mode and SE were superimposable with identical morphology and margins. In 64% of cases, lesion margins were sharper in SE than in B-mode. (iii) In 76% of cases, glioma margins were sharper in SE than in B-mode. Lesions morphology/dimensions in SE and in B-mode were superimposable in 89%. Low-grade (LGG) and high-grade (HGG) gliomas were significantly different in terms of stiffness and stiffness contrast between tumors and brain, LGG appearing stiffer while HGG softer than brain (all P

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice.

Objective Large interhemispheric cysts (IHC) with partial or complete agenesis of corpus callosum (ACC) constitute a heterogeneous group of rare disorders. Neurosurgical treatment, in the terms of if, when and how to operate, remains unclear Methods We performed a surgical literature review of series or reports of IHCs with callosal anomalies; we evaluated whether revision surgeries were necessary and considered the dimensional change in the cyst postoperatively and the developmental outcome. We also reported our experience with sfour patients treated by programmable cysto-peritoneal (CP) shunting. Patients’ clinical history, neuroradiological and neuropsychological performances were evaluated pre and post operatively. Results The review included 133 patients with surgically-treated IHCs. Although most authors are in agreement to perform surgery if the patients present signs of raised ICP and to not intervene in those completely asymptomatic, for other signs and symptoms the debate is still open; only few authors performed cognitive tests pre and post-operatively. Shunting procedures were successful in 60% of our reviewed cases and often lead to a major cyst collapse. Craniotomy achieves good results but is extremely invasive. Endoscopy is minimally invasive and our review demonstrated a success rate of 66%. However, endoscopy does not ensue a complete cyst collapse. Our series and review seem to suggest a possible link between parenchymal re-expansion and cognitive outcome. Conclusions Early and effective surgery seems to obtain a greater cerebral parenchyma re-expansion and long-term cognitive evolution. Endoscopy is safe and reliable, but more data is needed on the impact of uncomplete cyst collapse on neurocognitive outcome.

B-mode represents the main imaging modality used during neurosurgical procedures. This chapter reviews our previous experiences in adult neurosurgery, in particular regarding intraoperative neoplastic evaluation, characterization and vessel visualization, applied during different paediatric neurosurgical procedures. We illustrate how CEUS can be employed in different intra-operative settings in paediatric neurosurgical patients and describe various conditions in which CEUS proved to be feasible and useful for cerebral and spinal cord malformation, neoplastic and vascular diseases. As contrast media is beneficial for the diagnosis and understanding with traditional neuroradiological imaging, ultrasound contrast agents should be included for completeness in most ultrasound studies, particularly in the paediatric population.

Glioblastoma extensively infiltrates the brain; despite surgery and aggressive therapies, the prognosis is poor. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of glioblastoma evolution in every single patient, with the aim of tailoring therapeutic weapons. In particular, the ultimate goal of biomathematics for cancer is the identification of the most suitable theoretical models and simulation tools, both to describe the biological complexity of carcinogenesis and to predict tumor evolution. In this report, we describe the results of a critical review about different mathematical models in neuro-oncology with their clinical implications. A comprehensive literature search and review for English-language articles concerning mathematical modelling in glioblastoma has been conducted. The review explored the different proposed models, classifying them and indicating the significative advances of each one. Furthermore, we present a specific case of a glioblastoma patient in which our recently proposed innovative mechanical model has been applied. The results of the mathematical models have the potential to provide a relevant benefit for clinicians and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis. Further prospective comparative trials, however, are still necessary to prove the impact of mathematical neuro-oncology in clinical practice.

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.

Background: Peripheral schwannomas can be misdiagnosed or mistreated as they can mimic other subcutaneous lesions, leading to wrong diagnosis and, therefore, to improper treatment. Case Description: A 23-years-old male presented a painful growing nodule at the left popliteal fossa, with distally irradiated pain. A first magnetic resonance imaging depicted a heterogeneous lesion between common peroneal and sural nerves but, surprisingly, the patient was submitted to perilesional injection of ozone-oxygen mixture, causing the onset of intense neuropathic pain. A second MRI showed a morphological change of tumor characteristics. He finally underwent surgery but, intraoperatively, inter-fascicular fibrous adherences were noticed, making the tumor removal more difficult and riskier. The histopathological diagnosis was of schwannoma with areas of foreign body reaction. Conclusion: The injection of ozone or other substances within a subcutaneous swelling should be avoided, before a complete imaging assessment; because of such swelling could be a peripheral nerve schwannoma. The correct assessment of a lesion of the limbs determining radiating pain should be carefully demanded to a thorough history, clinical examination, and appropriate imaging technique. To avoid incorrect management, the treatment of such tumors should be performed in the first place by dedicated equips with proven expertise in this field.

Background Despite surgical and endovascular technical improvements over the last decades, the treatment of complex aneurysms of the distal anterior cerebral artery (ACA) is very challenging for both vascular neurosurgeons and interventional neuroradiologists. Furthermore, the interpersonal anatomic variability requires, most of the time, a tailored planning. Objective To describe a novel technique of bypasses in the territory of ACA to protect the brain territory distal to the aneurysm. Methods A 53-yr-old male with a large complex fusiform aneurysm of the left distal A2 segment of the ACA, involving the origin of the callosomarginal and pericallosal arteries, was judged not suitable for a single procedure (endovascular or neurosurgical). Two side-to-side bypasses were performed in a single surgery to connect the pericallosal and callosomarginal arteries of both sides, distally to the aneurysm. Subsequently, an endovascular embolization of the aneurysm was achieved with coils. Results The patency of the microanastomoses, performed in the anterior interhemispheric fissure, was positively evaluated intraoperatively with indocyanine green and fluorescein videoangiography. The aneurysm sac, together with proximal A2 segment, was completely occluded with platinum coils. At the last follow-up, computed tomography angiography confirmed the patency of both bypasses, without any sign of aneurysm recanalization. The patients never complained of any focal neurological deficits or worsening of clinical status. Conclusion We present an elegant and innovative solution to completely protect the distal ACA territory in cases of complex aneurysm involving the origin of both callosomarginal and pericallosal arteries.

Background Surgery for peripheral nerve sheath tumors aims to preserve functional fascicles achieving gross-total resection. Increasing the visualization of anatomic details helps to identify the different layers and the tumor-nerve interface. The traditional microscope can present some limitations in this type of surgery, such as its physical obstruction. Objective To present a proof-of-concept study about exoscope-guided surgery for schwannomas of the lower limbs, to analyze the advantages and disadvantages of the 4K, high-quality, 3-dimensional (3D) imaging. Methods We analyzed 2 consecutive surgical cases of suspected schwannomas of the lower limbs using the ORBEYE™ exoscope (Olympus). A standard operative microscope was also available in the operating room. All procedures were performed with neurophysiological monitoring, to identify functioning nerves and to localize the tumor capsule safest entry point. The cases are reported according to the PROCESS guidelines. Results In both cases, we achieved a gross total resection of the schwannomas; the exoscope provided an excellent view of the anatomic details at tumor-nerve interface, as visible in intraoperative images and in the 3D-4K video supporting these findings. The surgeon's position was comfortable in both cases, although if the co-surgeon positioned himself in front of the first surgeon, the comfort was slightly reduced. The 4K monitor allowed a realistic, nontiring 3D vision for all the team. Conclusion The ORBEYETM, after an adequate learning curve, can represent a feasible and comfortable instrument for nerve tumor surgery, which is usually performed in a single horizontal plane. Further and wider clinical series are necessary to confirm this first impression.

The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 &plusmn, 11.7, 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD, p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

Background Surgery has a fundamental role in central nervous system (CNS) tumors in the pediatric population, as aggressive resection correlates with prognosis. Due to its accumulation in areas with damaged blood brain barrier, sodium fluorescein (SF) could be a valid tool to improve the extent of resection in tumors enhancing at preoperative MRI. This study is aimed to systematically assess the utility of SF in a pediatric population. Methods Patient data were collected in two centers, one in Italy and the other in Germany. At the induction of anesthesia, SF was administered intravenously (5 mg/kg). Surgery was performed using a YELLOW560 filter. Fluorescence intensity was graduated as bright, moderate or absent based on surgeon's opinion; furthermore, SF use was judged as "helpful," "not helpful" or "not essential" in tumor removal. Results Twenty-four patients for 27 surgical procedures were identified. In 21 of 27 (77.8%) procedures fluorescence was reported as bright or moderate, in two of 27 (7.4%) absent and in four of 27 (14.8%) data were unavailable. Intraoperative fluorescence was reported in 21 of 25 (84%) surgeries whose corresponding preoperative MRI had shown contrast enhancement. In 14 of 27 (51.8%) surgical procedures SF was considered "helpful"; in two of 27 (7.4%) not "helpful"; in seven of 27 (25.9%) "not essential." In four of 27 (14.8%) data were unavailable. No adverse effect to SF was registered. Conclusions SF could be considered a valid and safe tool to improve visualization of tumors enhancing at preoperative MRI also in pediatric patients. Future prospective studies are needed to confirm these preliminary data.

Whereas several studies have been so far presented about the surgical outcomes in terms of mortality and perioperative complications for elderly patients submitted to neurosurgical treatments, the management of elderly moyamoya patients is unclear. This review aims to explore the available data about the clinical manifestation, characteristics, and outcome after surgery of older patients with moyamoya arteriopathy (MA). We found only two articles strictly concerning elderly patients with MA. We have also evaluated other reported adult series of moyamoya patients, including elderly cases in their analysis. Patients with MA above 50 years old may be considered a peculiar subset in which patients are often presenting with ischemic symptoms and a higher Suzuki grade. Conservative treatment may be proposed in asymptomatic or stable cases due to their fragility and possible increase of post-operative complications, while the best surgical options in symptomatic cases are still under investigation, although we believe that a minimal invasive superficial temporal artery—middle cerebral artery bypass could be considered the treatment of choice for the immediate effect on brain perfusion with a limited rate of post-operative complications.

The decision of whether to operate on elderly patients with brain tumors is complex, and influenced by pathology-related and patient-specific factors. This retrospective cohort study, based on a prospectively collected surgical database, aims at identifying possible factors predicting clinical worsening after elective neuro-oncological surgery in elderly patients. Therefore, all patients ≥65 years old who underwent BT resection at a tertiary referral center between 01/2018 and 12/2019 were included. Age, smoking, previous radiotherapy, hypertension, preoperative functional status, complications occurrence, surgical complexity and the presence of comorbidities were prospectively collected and analyzed at discharge and the 3-month follow-up. The series included 143 patients (mean 71 years, range 65–86). Sixty-five patients (46%) had at least one neurosurgical complication, whereas 48/65 (74%) complications did not require invasive treatment. Forty-two patients (29.4%) worsened at discharge, these patients had a greater number of complications compared to patients with unchanged/improved performance status. A persistent worsening at three months of follow-up was noted in 20.3% of patients, again, this subgroup presented more complications than patients who remained equal or improved. Therefore, postoperative complications and surgical complexity seem to influence significantly the early outcome in elderly patients undergoing brain tumor surgery. In contrast, postoperative complications alone are the only factor with an impact on the 3-month follow-up.

Objective: Sodium fluorescein, a green, water soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier (BBB) disruption. The authors report the preliminary results of a prospective observational study regarding the use of fluorescein-guided technique for the resection of suspected malignant neoplasms of the central nervous system (CNS), contrast enhancing at preoperative magnetic resonance imaging (MRI), using a dedicated filter on the surgical microscope. Methods: In March 2016 the authors started a prospective, observational trial to evaluate intraoperative fluorescence's characteristics of CNS tumors, the percentage of extent of resection thanks to fluorescein aid and side effects related to fluorescein administration. This report is based on a preliminary analysis of the results of first 279 enrolled patients. Fluorescein was intravenously injected after intubation or immediately at the entrance in the operating room for awake procedures; the tumor was removed using a dedicated filter on the surgical microscope in an inside-out fashion until all fluorescent tissue was removed, as considered feasible by the surgeon. Results: The 279 patients finally enrolled in the trial, both firstly diagnosed and recurrent, were categorized according to WHO pathological classification and there were 212 neuroepithelial tumors, 25 brain metastases, 10 cerebral lymphomas, 7 hemangioblastomas, or hemangioendotheliomas and 25 other tumors and conditions. No adverse reaction related to the administration of fluorescein or to the combined use of fluorescein with other fluorophores was registered. Fluorescein accumulated in cerebral regions where the BBB was damaged, representing a significant surgical aid in most of the CNS tumors with contrast enhancement. In cases of complete removal of all fluorescent tissue, as intraoperatively judged by the surgeon, postoperative MRI revealed a gross total resection in 181/198 patients (91.4%). Conclusions: Based on these preliminary results, fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration.

Chiari malformation type I (CMI) is a common pediatric neurologic anomaly that can be associated with a variety of genetic disorders; however, it is not always clear whether the observed associations are real or random. The knowledge of the real associations could provide useful guidance to clinicians. Furthermore, it could be of help to better understand the still unknown genetic etiology of CMI. With the aim of implementing such insights, we retrospectively reviewed clinical, neuroradiological, and genetic data of patients harboring CMI evaluated at the Child Neurology Unit of our institution between January 2008 and December 2018. The cohort consists of 205 patients (111 males and 94 females), with a mean age at diagnosis of 6.3 years (range 0–18 years). 188 patients completed an average follow-up period of 5.2 years (range one month–18 years). Mean age at last assessment was 11.4 years (range nine months–23 years). 127 (62%) children have been classified as syndromic due to the presence of neurodevelopmental disorders, phenotypic anomalies, or malformations. Among syndromic CMI children, a molecular diagnosis was identified in 35/127 (27.6%) (20 males and 15 females). The most common diagnoses were syndromic craniosynostosis in 8/35 children (22.9%), among which sevenare FGFR-related and one ERF-related craniosynostosis; disorders of the RAS/MAPK pathway, termed RASopathies or RAS/MAPK syndromes in 9/35 (25.7%); disorders of the PTEN-PI3K/AKT signal transduction cascade, termed PTENopathies in 3/35 children (8.6%); and chromosomal rearrangements in 6/35 patients (17.1%), two of whom with del16p11.2. We polarized our attention on the defined genetic diagnoses focusing not only on the phenotypic hallmarks but also on the phenotypic overlapping features. In addition, we discussed the pathophysiological mechanisms leading to progressive cerebellar ectopia and the involved molecular pathways. Along with the recent literature evidence, we suppose that interactions between FGFR and RAS/MAPK pathway and between RAS/MAPK and PTEN-PI3K/AKT pathways could explain some phenotypic overlapping features and could have a significant role in the pathogenesis of CMI.

Background Distal outflow occlusion and extracranial-intracranial bypass represent a possible option for the surgical management of complex middle cerebral artery (MCA) aneurysm. A limitation of the distal clipping strategy combined to bypass is related to the difficulties in predicting intraoperatively the good blood flow supply to the brain territory distal to the aneurysm and the extent and speed of aneurysmal thrombosis. Methods We present an innovative approach in which contrast-enhanced ultrasound (CEUS) and indocyanine green videoangiography (ICG-VA) have been synergistically used to study the effect of distal clipping on the aneurysm flow and the parenchymal blood flow after the bypass. We used this approach in a patient harboring a fusiform, partially thrombosed distal left MCA aneurysm. Results The patient was treated by a superficial temporal artery–MCA bypass, followed by MCA clipping immediately distally to the aneurysm. ICG-VA was used to evaluate bypass patency and brain perfusion in the area supplied by the bypass. CEUS was used to confirm the characteristics of the aneurysm and to explore the proximal MCA compartment immediately after dural opening, and to verify in real time the effect on aneurysm flow determined by distal outflow occlusion. Postoperative imaging confirmed aneurysm occlusion and patency of the bypass. The patient did not experience any neurologic sequelae. Conclusions We present the first report of a synergistic intraoperative utilization of ICG-VA and CEUS in studying parenchymal perfusion and aneurysm flow in complex neurovascular procedures.

In multiple sclerosis (MS) patients, trigeminal neuralgia (TN) represents a challenging syndrome to treat, often refractory to medical therapy and percutaneous techniques. Despite the frequent lack of a neurovascular conflict, the trigeminal nerve’s axons are often damaged, with the myelin sheath permanently degenerated, thus explaining the difficulty in treating TN in MS.The authors illustrate trigeminal interfascicular neurolysis (the combing technique) to control refractory recurrent TN in MS: the nerve is longitudinally divided along its fibers from the root entry zone, determining good pain relief.The video can be found here: https://youtu.be/o1XksPW5fMY

Objective Piezoelectric surgery represents an innovative technique to perform safe and effective osteotomies and is an alternative to traditional bony tissue management using rotating or perforating instruments. We evaluated the safety and feasibility of craniotomies using an ultrasonic device that allows the selective cut of mineralized structures, avoiding damages to the vascular, dural, and parenchymal structures. Methods We analyzed a series of 300 patients (age range, 1–81 years; SD ± 15.2) who underwent elective cranial surgery for brain tumors, in which the craniotomy was performed using a piezoelectric device. Pre- and postoperative imaging, clinical notes, and intraoperative details were collected. Results There were 197 patients (66%) who underwent surgery for supratentorial tumors; the remaining 103 patients (34%) underwent surgery for infratentorial ones. Tumors involved the skull base in 125 cases. Meningiomas, gliomas, and schwannomas represented the most common histotypes. Duraplasty for dural damages was not necessary in all cases; no venous sinuses or parenchymal injuries were reported during bone work. We noted in 13 cases (4.3%) a minor dural tear, requiring only direct sutures. Bone flaps were always intact after craniotomy. No subgaleal cerebrospinal fluid (CSF) collection or CSF leak was recorded. Because of the minimal bone gap, we always achieved correct bone flap ossification. No reabsorption or mobilization of bone flap was noted. Conclusions We illustrate the feasibility and safety of a piezosurgical cutter to perform craniotomies. This alternative technique appears to be safe, with excellent cosmetic effects, adding another tool to the neurosurgical armamentarium.

Objective: Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage. Methods: a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain. Results: FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment. Conclusion: In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.

Purpose: Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound (US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions. Materials and Methods: We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image. Results: 58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was Conclusion: Neuro-navigation using intraoperative US integrated with preoperative MRI is reliable, accurate and user-friendly. Moreover, the adjustments are very helpful in correcting brain shift and tissue distortion. This integrated system allows true real-time feedback during surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and orientation.

The outcome of headache in a series of 135 operated CM1 is presented. Favorable results were obtained in 85% of atypical and 93% typical headache with the support of a multidisciplinary approach that restricted the indications for surgery.

Chiari type 1 Malformation (CM 1) is a structural defect consisting of a displacement of the cerebellar tonsils through the foramen magnum causing obstruction of cerebrospinal fluid (CSF) outflow. CM 1 has a variety of presentation with headache being the most common symptom. The evaluation and treatment of headache related to CM 1 are often difficult, because the pain in the occipital-suboccipital region or headache that is of cough-type suggests symptomatic CM 1, but patients suffering from CM 1 can also report migraine or tension-type headache. In 2015 we started a collaborative project in which our group of neurologists, neurosurgeons and neuroradiologists contribute to create a Chiari Special Outpatient Service; this was set up to provide a multidisciplinary evaluation, treatment and follow-up of patient suffering from CM 1. 201 patients (58 males, 143 females) suffering from CM 1 were multidisciplinary evaluated. Headache characteristics, clinical features, and treatment of patients are discussed. Further progress in multidisciplinary care of headache and CM 1 should be performed to define guidelines.

Background. Contrast enhanced ultrasound (CEUS) is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before.Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas.Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology.Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns.Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors’ biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

Objective Peripheral nerve sheath tumors (PNSTs) are tumors arising from the neural sheath cells. Surgery plays a central role in the management of this disease, with the purpose of obtaining radical tumor's resection and at the same time providing the best outcome. We retrospectively analyzed 53 PNSTs in 42 patients in an attempt to identify some factors that may improve surgical outcome. Material and Methods Clinical, histologic, and imaging data of 42 patients with PNSTs treated at our Institute between 2001 and 2012 were collected and analyzed. We evaluated the outcome 1 month and 6 month after surgery using three clinical parameters (pain, motor deficits, and sensory deficits) in relation to different histotypes, the presence of neurofibromatosis type 1, tumor location, and duration of symptoms before treatment. Results The best functional results were observed in patients having neurofibromas; the worst outcomes were observed in patients with malignant PNSTs. The other factors were not associated with outcome. Conclusion The timing of surgery is the most important predictive factor of surgical outcome, being the only factor that allows to improve the outcome. With the current study, we want to stress the importance of treating PNSTs as soon as possible to provide the best outcome possible.

Ultrasonographic appearance of spinal tumors has been described in few studies until now, and the role of intraoperative ultrasound is not yet well standardized in spinal tumor surgery.

OBJECTIVEThe best management of veins encountered during the neurosurgical approach is still a matter of debate. Even if venous sacrifice were to lead to devastating consequences, under certain circumstances, it might prove to be desirable, enlarging the surgical field or increasing the extent of resection in tumor surgery. In this study, the authors present a large series of patients with vascular or oncological entities, in which they used indocyanine green videoangiography (ICG-VA) with FLOW 800 analysis to study the patient-specific venous flow characteristics and the management workflow in cases in which a venous sacrifice was necessary.METHODSBetween May 2011 and December 2017, 1972 patients were admitted to the authors’ division for tumor and/or neurovascular surgery. They retrospectively reviewed all cases in which ICG-VA and FLOW 800 were used intraoperatively with a specific target in the venous angiographic phase or for the management of venous sacrifice, and whose surgical videos and FLOW 800 analysis were available.RESULTSA total of 296 ICG-VA and FLOW 800 studies were performed intraoperatively. In all cases, the venous structures were clearly identifiable and were described according to the flow direction and speed. The authors therefore defined different patterns of presentation: arterialized veins, thrombosed veins, fast-draining veins with anterograde flow, slow-draining veins with anterograde flow, and slow-draining veins with retrograde flow. In 16 cases we also performed a temporary clipping test to predict the effect of the venous sacrifice by the identification of potential collateral circulation.CONCLUSIONSICG-VA and FLOW 800 analysis can provide complete and real-time intraoperative information regarding patient-specific venous drainage pattern and can guide the decision-making process regarding venous sacrifice, with a possible impact on reduction of surgical complications.

OBJECTIVEIndocyanine green videoangiography (ICG-VA) is an intraoperative technique used to highlight vessels in neurovascular surgery. Its application in the study of the vascular pathophysiology in CNS tumors and its role in their surgical management are still rather limited. A recent innovation of ICG-VA (i.e., the FLOW 800 algorithm integrated in the surgical microscope) allows a semiquantitative evaluation of cerebral blood flow. The aim of this study was to evaluate for the first time the systematic application of ICG-VA and FLOW 800 analysis during surgical removal of CNS tumors.METHODSBetween May 2011 and December 2017, all cases in which ICG-VA and FLOW 800 analysis were used at least one time before, during, or after the tumor resection, and in which surgical videos were available, were retrospectively reviewed. Results of the histological analysis were analyzed together with the intraoperative ICG-VA with FLOW 800 in order to investigate the tumor-related videoangiographic features.RESULTSSeventy-one patients who underwent surgery for cerebral and spinal tumors were intraoperatively analyzed using ICG-VA with FLOW 800, either before or after tumor resection, for a total of 93 videoangiographic studies. The histological diagnosis was meningioma in 25 cases, glioma in 14, metastasis in 7, pineal region tumor in 5, hemangioblastoma in 4, chordoma in 3, and other histological types in 13 cases. The authors identified 4 possible applications of ICG-VA and FLOW 800 in CNS tumor surgery: extradural surveys allowed exploration of sinus patency and the course of veins before dural opening; preresection surveys helped in identifying pathological vascularization (arteriovenous fistulas and neo-angiogenesis) and regional venous outflow, and in performing temporary venous clipping tests, when necessary; postresection surveys were conducted to evaluate arterial and venous patency and parenchymal perfusion after tumor removal; and a premyelotomy survey was conducted in intramedullary tumors to highlight the posterior median sulcus.CONCLUSIONSThe authors found ICG-VA with FLOW 800 to be a useful method to monitor blood flow in the exposed vessels and parenchyma during microsurgical removal of CNS tumors in selected cases. In particular, a preresection survey provides useful information about pathophysiological changes of brain vasculature related to the tumor and aids in the individuation of helpful landmarks for the surgical approach, and the postresection survey helps to prevent potential complications associated with the resection (such as local hypoperfusion or venous infarction).