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Moyamoya angiopathy (MMA) is an uncommon cerebrovascular disease characterized by a progressive steno-occlusive lesion of the internal carotid artery and the compensatory development of an unstable network of collateral vessels. These vascular hallmarks are responsible for recurrent ischemic/hemorrhagic strokes. Surgical treatment represents the preferred procedure for MMA patients, and indirect revascularization may induce a spontaneous angiogenesis between the brain surface and dura mater (DM), whose function remains rather unknown. A better understanding of MMA pathogenesis is expected from the molecular characterization of DM. We performed a comprehensive, label-free, quantitative mass spectrometry-based proteomic characterization of DM. The 30 most abundant identified proteins were located in the extracellular region or exosomes and were involved in extracellular matrix organization. Gene ontology analysis revealed that most proteins were involved in binding functions and hydrolase activity. Among the 30 most abundant proteins, Filamin A is particularly relevant because considering its well-known biochemical functions and molecular features, it could be a possible second hit gene with a potential role in MMA pathogenesis. The current explorative study could pave the way for further analyses aimed at better understanding such uncommon and disabling intracranial vasculopathy.

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood–brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016–2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3–78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma.

ObjectivePleomorphic xanthoastrocytoma (PXA) is a rare brain tumor, most commonly affecting children and young adults. Surgical resection represents the mainstay of treatment, and extent of resection is associated with improved survival. In this study, we analyzed the role of sodium fluorescein (SF) in improving intraoperative visualization easing resection.MethodsSurgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find pleomorphic xanthoastrocytomas and anaplastic xanthoastrocytomas, according to WHO-2016/2021 classification, surgically removed by a fluorescein-guided technique from March 2016 to February 2022. SF was intravenously injected (5mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW 560 filter (Carl Zeiss Meditec, Oberkochen, Germany).ResultsTwelve patients (7 males and 5 females; 3 pediatric patients, mean age 10 years, range 5 to 13 years and 9 adult patients, mean age 50.6 years, range 35 to 63 years) underwent fluorescein-guided surgery. No side effects related to SF occurred. In all tumors, contrast enhancement on preoperative MRI correlated with intense, heterogeneous yellow fluorescence with bright fluorescent cystic fluid. Fluorescein was considered helpful in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 8 cases (66.7%); in 4 cases, otherwise, the resection was subtotal with fluorescent residual spots to avoid neurological worsening (33.3%).ConclusionsThe use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data documented a positive effect of fluorescein-guided surgery on intraoperative visualization, suggesting a probable role in improving the extent of resection during yellow surgery of PXA.

Hemangioblastomas (HBs) are rare, benign tumors often related to von Hippel–Lindau disease. They represent the most frequent primary cerebellar tumors in adults. Neurosurgical procedures aim to obtain a gross-total resection of tumor nodules, avoiding intra-postoperative hemorrhage. The introduction of new intraoperative imaging techniques has considerably changed surgical strategies in neuro-oncology. We present an overview of clinical and radiological data of a mono-institutional retrospective cohort, focusing on the role of intraoperative multimodal imaging in surgical strategy. From 2015 to 2021, we identified 64 (81%) cranial (42 cerebellar, 8 supratentorial, and 14 of the brainstem) HBs and 15 (19%) spinal (4 cervical and 11 dorsal) HBs in 79 patients. Intraoperatively, indocyanine green videoangiography with FLOW800 was used in 62 cases (52 cranial and 10 spinal), intraoperative ultrasound and contrast-enhanced ultrasounds in 22 cases (18 cranial and 4 spinal HBs), and fluorescein in 10 cases (in 6 cranial and 2 spinal cases used as SF-VA). Gross total resection was achieved in 100% of the cases (53 mural nodule removal and 26 complete resections of the solid tumor). No side effects were reported following the combination of these tools. Multimodal intraoperative techniques provide valuable and reliable information to identify the tumor and its vasculature, guiding a more precise and safer resection and reducing the risk of recurrence.

Occult spinal dysraphism (OSD) comprises different forms of failure in embryogenic development that can lead to genitourinary, spinal, or lower limb alterations, thus determining progressive neurological deterioration. The correct management of children harboring OSD represents a significant issue during their life up to adulthood. However, patients often have to entertain individual consultations with each specialist. We settled on a multidisciplinary team comprising pediatric neurosurgeons, urologists, neurologists, orthopedists, and other supporting physicians. We present the results of such actions by analyzing a series of 141 children with OSD subjected to neurosurgical procedures, evaluating the impact of multidisciplinary management on outcomes. We also evaluated the specific actions according to the different ages of OSD patients from birth to adulthood to provide a schematic plan that could represent a basis for establishing and disseminating the need for a multidisciplinary approach in OSD management. The multidisciplinary team allows all consultants to see the patient together, covering specific aspects of history and examination pertinent to their management. Offering a one-stop service prevents coordination issues between the different medical teams, avoids delays or cancellations of the various appointments, optimizes cost-effectiveness, and improves efficiency and parents’ satisfaction.

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.

ObjectivePilocytic astrocytomas (PAs) are relatively benign tumors, usually enhancing on post-contrast MRI and often characterized by a mural nodule within a cystic component. Surgical resection represents the mainstay of treatment, and extent of resection (EOR) is associated with improved survival. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of these circumscribed astrocytic gliomas.MethodsSurgical databases at two neurosurgical departments (Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy and Department of Neurosurgery, University Medical Center Regensburg, Regensburg, Germany) were retrospectively reviewed to identify the cohort of patients with pilocytic astrocytoma who had undergone fluorescein-guided tumor resection at any of the centers between March 2016 and February 2022. SF was intravenously injected (5 mg/kg) immediately after the induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW 560 filter (Carl Zeiss Meditec, Oberkochen, Germany).ResultsForty-four patients (25 males and 19 females; 26 pediatric patients, mean age of 9.77 years, range 2 to 17 years; and 18 adult patients, mean age of 34.39 years, range 18 to 58 years) underwent fluorescein-guided surgery. No side effects related to SF occurred. In all tumors, contrast enhancement on preoperative MRI was correlated with intense, heterogeneous yellow fluorescence with bright fluorescent cystic fluid. Fluorescein was considered helpful in distinguishing tumors from viable tissue in all cases except three patients due to faint fluorescein enhancement. Biopsy was intended in two operations, and partial resection was intended in three operations. Gross total resection was achieved in 24 cases out of 39 patients scheduled for tumor removal (61.54%), in five cases a minimal residual volume was highlighted by postoperative MRI despite the intraoperative subjective evaluation of complete tumor removal (12.82%); in the other 10 cases, the resection was subtotal with fluorescent residual spots to avoid neurological worsening (25.64%).ConclusionsThe use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data showed a positive effect of fluorescein-guided surgery on intraoperative visualization during resection of Pas, suggesting a possible role in improving the extent of resection of these lesions.

Nowadays, most of patients affected by psychiatric disorders are successfully treated with conservative therapies. Still, a variable percentage of them demonstrate resistance to conventional treatments, and alternative methods can then be considered. During the last 20 years, there is a progressive interest in use of deep brain stimulation (DBS) in mental illnesses. It has become clear nowadays, that this modality may be effectively applied under specific indications in some patients with major depressive disorder, obsessive-compulsive disorder, anorexia nervosa and other eating disorders, Tourette syndrome, schizophrenia, substance use disorder, and even pathologically aggressive behavior. Despite the fact that the efficacy of neuromodulation with DBS, as well as of various lesional interventions, in cases of mental illnesses is still not fully established, there are several premises for wider applications of such "unclassical" psychiatric treatments in the future. Novel technologies of DBS, developments in non-invasive lesioning using stereotactic radiosurgery and transcranial magnetic resonance-guided focused ultrasound, and advances of neurophysiological and neuroimaging modalities may bolster further clinical applications of psychiatric neurosurgery, improve its results, and allow for individually selected treatment strategies tailored to specific needs of the patient.

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.

Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease’s pathogenesis. In these patients, MMA’s clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients.

Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.

BACKGROUND Decompression and, when necessary, neurolysis in entrapment neuropathies of upper limbs are effective and safe procedures, but their correlation with the variation of compound muscle action potentials (CMAPs) is still unclear, based in particular on experimental models. In addition, there are few data regarding the efficacy of intraoperative neurophysiologic monitoring (IOM) to predict clinical early and late outcome after surgery in term of pain control and sensitive/motor recovery. We report about the association between the intraoperative anatomical and neurophysiological findings and the mid- and long-term postoperative clinical course in a surgical series. METHODS We retrospectively reviewed clinical data of 24 patients among 68 admitted at our Institution for upper limb neuropathies from September 2012 to May 2015. All patients completed two preoperative questionnaires for assessing the level of disability (DASH) and of pain/discomfort (NRS). CMAPs' amplitudes were intraoperatively detected, before and after decompression and neurolysis and the variations were then related to clinical outcome, evaluated through DASH and NRS questionnaires at 6-, 9- and 12-months follow-up. RESULTS A statistically significant difference was noted in CMAPs amplitudes before and after decompression (P

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: Neurothekeomas are slow-growing, well-circumscribed benign neoplasms. They usually involve cutaneous or subcutaneous tissues. Although originally described as myxomas deriving from nerve sheath cells, their exact histological classification is still uncertain. Peripheral nerve localization is rarely reported. Here, we describe a unique case of sleeve-shaped neurothekeoma of the ulnar nerve, which was incidentally discovered during a cubital tunnel release surgery. Methods: A 57-year-old man was admitted at our institution with clinical, ultrasonographic, and electromyographic findings highly suggestive of cubital tunnel syndrome. During ulnar nerve decompression surgery, however, no bony or ligament compression was noticed, but a segment of the nerve wrapped by a thick sleeve-shaped tissue, which had no clear-cut cleavage plane from the nerve. Given this unexpected finding, the en bloc excision of the lesion was avoided. A nerve decompression with biopsy of the swelling portion of the lesion was performed instead. Results: Histological examination described abundant myxoid stroma, with epithelioid and ring-shaped cells arranged in cords, negative to S100 protein at immunohistochemical analysis. This pattern was suggestive of neurothekeoma. The patient showed improvement in hypermyotrophy and intrinsic weakness of the hand. Conclusions: To the best of our knowledge, this is the first report of a sleeve-shaped neurothekeoma of the ulnar nerve. The exact pathological characterization of such rare entities remains uncertain. In case of peripheral nerve localization, and when a clear cleavage plane is absent, the correct management of these lesions should be that of simple nerve decompression followed by biopsy.

Background Meningioma are the second most common brain tumors in adults and can cause significant morbidity and mortality. The scarcity of in vitro and in vivo models represents the major obstacle to understand the molecular basis of meningioma tumorigenesis. The main aim of this study was to assess a method for radiobiology of meningioma cells colture by means of well-known meningioma lines. New method We carried out a protocol of cells culture for irradiation of meningioma cells. We used the immortalized cell lines IOMM-Lee and CH-157 to study their radiation-reponse by means of clonogenic assays and to evaluate their proliferation and apoptosis. We irradiated the cells with different total doses using two different linear accelerators. Results We observed a more radiation resistance of the IOMM-Lee than the CH-157. Indeed, the cellular death of CH-157 was obtained at a very low dose irradiation. Moreover, we showed a dose-response effect due to the early and late apoptosis, in fact the rate of apoptotic cells is greater than that of the necrotic cells at any dose of irradiation and at any time of analysis. Comparison with existing methods There is not a standardized method for radiobiology of meningioma experiments. Conclusions Our method of cells culture appears suitable for radiosensitivity studies on meningioma. We can confirm that the response to radiotherapy depends not only on irradiation features, but also on tumor radiosensitivity.

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.

BackgroundConfocal laser endomicroscopy (CLE) allowing intraoperative near real-time high-resolution cellular visualization is a promising method in neurosurgery. We prospectively tested the accuracy of a new-designed miniatured CLE (CONVIVO® system) in giving an intraoperative first-diagnosis during glioblastoma removal.MethodsBetween January and May 2018, 15 patients with newly diagnosed glioblastoma underwent fluorescein-guided surgery. Two biopsies from both tumor central core and margins were harvested, dividing each sample into two specimens. Biopsies were firstly intraoperatively ex vivo analyzed by CLE, subsequently processed for frozen and permanent fixation, respectively. Then, a blind comparison was conducted between CLE and standard permanent section analyses, checking for CLE ability to provide diagnosis and categorize morphological patterns intraoperatively.ResultsBlindly comparing CONVIVO® and frozen sections images we obtained a high rate of concordance in both providing a correct diagnosis and categorizing patterns at tumor central core (80 and 93.3%, respectively) and at tumor margins (80% for both objectives). Comparing CONVIVO® and permanent sections, concordance resulted similar at central core (total/partial concordance in 80 and 86.7% for diagnosis and morphological categorization, respectively) and lower at tumor margins (66.6% for both categories). Time from fluorescein injection and time from biopsy sampling to CONVIVO® scanning was 134 ± 31 min (122–214 min) and 9.23 min (1–17min), respectively. Mean time needed for CONVIVO® images interpretation was 5.74 min (1–7 min).ConclusionsThe high rate of diagnostic/morphological consistency found between CONVIVO® and frozen section analyses suggests the possibility to use CLE as a complementary tool for intraoperative diagnosis of ex vivo tissue specimens during glioblastoma surgery.

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.

Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.

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.