Revitalizing neurosurgical frontiers: The EANS frontiers in neurosurgery committee's strategic framework.

Introduction: The field of neurosurgery faces challenges with the increasing involvement of other medical specialties in areas traditionally led by neurosurgeons. This paper examines the implications of this development for neurosurgical practice and patient care, with a focus on specialized areas like pain management, peripheral nerve surgery, and stereotactic radiosurgery. Research question: To assess the implications of the expanded scope of other specialties for neurosurgical practice and to consider the response of the EANS Frontiers in Neurosurgery Committee to these challenges. Materials and methods: Analysis of recent trends in neurosurgery, including the shift in various procedures to other specialties, demographic challenges, and the emergence of minimally invasive techniques. This analysis draws on relevant literature and the initiatives of the Frontiers in Neurosurgery Committee. Results: We explore a possible decrease in neurosurgical involvement in certain areas, which may have implications for patient care and access to specialized neurosurgical interventions. The Frontiers in Neurosurgery Committee's role in addressing these concerns is highlighted, particularly in terms of training, education, research, and networking for neurosurgeons, especially those early in their careers. Discussion and conclusion: The potential decrease in neurosurgical involvement in certain specialties warrants attention. This paper emphasizes the importance of carefully considered responses by neurosurgical societies, such as the EANS, to ensure neurosurgeons continue to play a vital role in managing neurological diseases. Emphasis on ongoing education, integration of minimally invasive techniques, and multidisciplinary collaboration is essential for maintaining the field's competence and quality in patient care.

Angiopoietin-2 associates with poor prognosis in Moyamoya angiopathy.

OBJECTIVE: Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients. METHODS: The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real-time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model. RESULTS: We detected a statistically significant (p < 0.000001) up-regulation of Angiopoietin-2 (Ang-2) in CSF and stenotic middle cerebral arteries (RQ >2) of MA patients compared to controls. A high Ang-2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang-2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable-from-progressive MA. Consistently, MA cellular model showed a significant up-regulation (RQ >2) of Ang-2 in RNF213 silenced condition. INTERPRETATION: Our results pointed out Ang-2 as a reliable biomarker mirroring arterial steno-occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.

Surgical Management of Chiari 1.5 in Children: A Truly Different Disease?

Background: In patients with Chiari 1.5 malformation (CM1.5), a more aggressive disease course and an increased association with craniovertebral junction (CVJ) anomalies has been suggested. The best management of this subgroup of patients is not clearly defined, also due to the lack of specific series elucidating this anomaly's peculiar characteristics. Methods: We evaluated a series of 33 patients (25 females, 8 males; mean age at surgery: 13 years) fulfilling the criteria for Chiari 1.5 diagnosis who underwent posterior fossa decompression and duraplasty (PFDD) between 2006 and 2021. Results: Headache was present in all children, five presented central apnea, five had dysphagia, and three had rhinolalia. Syringomyelia was present in 19 (58%) children. Twenty patients (61%) showed various CVJ anomalies, but only one child presented instability requiring arthrodesis. The mean tonsil displacement below the foramen magnum was 19.9 mm (range: 12-30), without significant correlation with the severity of symptoms. Syringomyelia recurred or was unchanged in three patients, and one needed C1-C2 fixation. The headache disappeared in 28 children (84%). Arachnoid opening and tonsil coagulation or resection was necessary for 19 children (58%). Conclusions: In our pediatric CM series, the need for tonsil resection or coagulation was higher in CM1.5 children due to a more severe crowding.

What have we learned in fluorescein-guided resection of brain metastases? An update after 79 consecutive cases.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. Individualized treatment of CM still represents a challenge for neuro-oncological teams: in patient eligible for surgery, complete tumor removal is the most relevant predictor of overall survival (OS) and neurological outcome. The development of surgical microscopes harboring specific filter able to elicit the fluorescent response from sodium fluorescein (SF) has facilitated fluorescein-guided microsurgery and the identification of pathological tumor tissue, especially at the tumor margins. In this study, we analyzed the effect of SF on the visualization and resection of a large monoinstitutional cohort of CM. METHODS: Surgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find CM surgically removed with a fluorescein-guided technique from March 2016 to December 2022. SF was intravenously injected (5 mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW560 filter (Carl Zeiss Meditec, Oberkochen, Germany). In the most recent cases, biopsies at the tumor margins were performed to evaluate the ability of fluorescein to discriminate between fluorescent and nonfluorescent tissue at the lesion borders. RESULTS: Seventy-nine patients were included; most of them showed a bright, diffuse fluorescent staining that markedly enhanced tumor visibility; 11 melanomas presented a specific faint enhancement of the black pigmented central nodule with high fluorescence at tumor boundaries. Only in a minimal percentage of cases (N.=4-5.1%), fluorescein enhancement was tenuous, thus not providing a significant help during tumor resection. Altogether, in more than 90% of cases, SF was considered useful in the identification of tumoral tissue and in achieving a high rate of CM resection; thus, gross total resection was achieved in 96.2% (N.=76) of patients and in no case the detection of tumor remnants was an unexpected event. The resulted sensitivity and specificity of fluorescein in identifying tumor tissue at the tumor margin was 88.9% with a predictive positive value of 88.9%. No adverse event was registered during the postoperative course. CONCLUSIONS: The 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 CM, suggesting a role in improving the extent of resection of these lesions.

Proteome Profiling of the Dura Mater in Patients with Moyamoya Angiopathy.

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.

Hemangioblastomas and Other Vascular Origating Tumors of Brain or Spinal Cord.

Hemangioblastomas (HBs) are highly vascularized, slow-growing, rare benign tumors (WHO grade I). They account for about 2% of intracranial neoplasms; however, they are the most common primary cerebellar tumors in adults. Another frequent seat is the spinal cord (2-10% of primary spinal cord tumors). HBs are constituted by stromal and capillary vascular cells; macroscopically, HBs appear as nodular tumors, with or without cystic components. Although most of the HBs are sporadic (57-75%), they represent a particular component of von Hippel-Lindau disease (VHL), an autosomal dominant syndrome with high penetrance, due to a germline pathogenic mutation in the VHL gene, which is a tumor suppressor with chromosomal location on the short arm of chromosome three. VHL disease determines a variety of malignant and benign tumors, most frequently HBs, renal cell carcinomas, pheochromocytomas/paragangliomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors. Up to 20% of cases are due to de novo pathogenic variants without a family history. Many epidemiologic details of these tumors, especially the sporadic forms, are not well known. The median age of patients with sporadic HBS is about 40 years. More than two-third of VHL patients develop one or more central nervous system HBs during their lifetime; in case of VHL, patients at first diagnosis are usually younger than the patients with sporadic tumors. The most common presenting signs and symptoms are related to increased intracranial pressure, cerebellar signs, or spinal cord alterations in case of spinal involvement. Magnetic resonance imaging is the gold standard for the diagnosis, assessment, and follow-up of HBs, both sporadic and syndrome-related; angiography is rarely performed because the diagnosis is easily obtained with magnetic resonance. However, the diagnosis of an asymptomatic lesion does not automatically result in therapeutic actions, as the risks of treatment and the onset of possible neurological deficit need to be balanced, considering that HBs may remain asymptomatic and have a static or slow-growing behavior. In such cases, regular follow-up can represent a valid therapeutic option until the patients remain asymptomatic. There are no actual pharmacological therapies that are demonstrated to be effective for HBs. Surgery represents the primary therapeutic approach for these tumors. Observation or radiotherapy also plays a role in the long-term management of patients harboring HBs, especially in VHL; in few selected cases, endovascular treatment has been suggested before surgical removal. This chapter presents a systematic overview of epidemiology, clinical appearance, histopathological and neuroradiological characteristics of central nervous system HBs. Moreover, the genetic and molecular biology of sporadic and VHL HBS deserves special attention. Furthermore, we will describe all the available therapeutic options, along with the follow-up management. Finally, we will briefly report other vascular originating tumors as hemangioendotheliomas, hemangiomas, or angiosarcomas.

A Brief Explanation on Surgical Approaches for Treatment of Different Brain Tumors.

The main goal of brain tumor surgery is to achieve gross total tumor resection without postoperative complications and permanent new deficits. However, when the lesion is located close or within eloquent brain areas, cranial nerves, and/or major brain vessels, it is imperative to balance the extent of resection with the risk of harming the patient, by following a so-called maximal safe resection philosophy. This view implies a shift from an approach-guided attitude, in which few standard surgical approaches are used to treat almost all intracranial tumors, to a pathology-guided one, with surgical approaches actually tailored to the specific tumor that has to be treated with specific dedicated pre- and intraoperative tools and techniques. In this chapter, the basic principles of the most commonly used neurosurgical approaches in brain tumors surgery are presented and discussed along with an overview on all available modern tools able to improve intraoperative visualization, extent of resection, and postoperative clinical outcome.

Magnetic resonance imaging characteristics of pediatric pilocytic astrocytoma.

PURPOSE: MRI has an important role in diagnosing pilocytic astrocytoma and post-surgical follow-up since the surgical approach has a leading role in its treatment. The purpose of our study is to provide an overview of the typical and atypical MRI findings in a series of pediatric patients with isolated-not NF1-related-pilocytic astrocytomas and to correlate specific MRI patterns with clinical variables. METHODS: This is a cross-sectional retrospective study providing the analysis of several clinical and neuroradiological findings from a cohort of pediatric pilocytic astrocytoma, starting from the data collected in the Fondazione IRCCS Istituto Neurologico Carlo Besta (FINCB) internal Cancer Registry during an 11-year time period (January 2008-January 2019). RESULTS: Fifty-six patients were included in the study. Median age at diagnosis was 9.4 years; a slight female prevalence was noticed (m/f ratio 44.6%/55.4%). The majority of pPAs had well-defined contours: 51 (91.1%), 47 (88.7%) were hypointense on T1-wi, all of them were hyperintense on T2-wi, 46 (90.2%) were hyperintense on FLAIR, and 48 (85.7%) were heterogeneous on T1-wi and T2-wi sequences. We found positive correlation between pPAs location and age (r = 0.017), and small degree of connection between pPAs location and gender (Cramer's V = 0.268). CONCLUSIONS: We presented typical and atypical pPAs MRI findings. Age and tumor location were positevely correlated, while degree of connection between gender and pPAs location was small. All of this may aid clinicians, most of all neuroradiologists, neurosurgeons, and neurologists in proper diagnoses and follow-up of these specific patient population.

Increase of Circulating Endothelial Progenitor Cells and Released Angiogenic Factors in Children with Moyamoya Arteriopathy.

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.

Fluorescein sodium in the surgical treatment of pleomorphic xanthoastrocytomas: Results from a retrospective study.

Objective: Pleomorphic 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. Methods: Surgical 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). Results: Twelve 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%). Conclusions: The 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.

Sporadic and von Hippel-Lindau Related Hemangioblastomas of Brain and Spinal Cord: Multimodal Imaging for Intraoperative Strategy.

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.

Multidisciplinary Management of Children with Occult Spinal Dysraphism: A Comprehensive Journey from Birth to Adulthood.

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.

Fluorescein-guided surgery for the resection of pilocytic astrocytomas: A multicentric retrospective study.

Objective: Pilocytic 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. Methods: Surgical 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). Results: Forty-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%). Conclusions: The 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.

Role of deep brain stimulation in management of psychiatric disorders.

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.

Assessing the role of sodium fluorescein in peripheral nerve sheath tumors and mimicking lesions surgery: An update after 142 cases.

Objective: Peripheral nerve sheath tumors (PNST) include mainly schwannomas and neurofibromas. Surgical resection represents the mainstay of treatment but due to their pathogenesis, distinguishing between intact functional nerve and the fibers from whence the PNST arose may not always be easy to perform, constituting the most relevant risk factor in determining a worsening in neurological condition. The introduction of intraoperative tools to better visualize these tumors could help achieve a gross-total resection. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of a large cohort of PNST. Methods: Between September 2018 and December 2021, 142 consecutive patients harboring a suspected PNST underwent fluorescein-guided surgery at the Department of Neurosurgery of the Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. All patients presented with a different degree of contrast enhancement at preoperative MRI. SF was intravenously injected after intubation at 1 mg/kg. Intraoperative fluorescein characteristics and postoperative neurological and radiological outcomes were collected, analyzed, and retrospectively compared with a historical series. Results: 142 patients were included (42 syndromic and 100 sporadic); schwannoma was the predominant histology, followed by neurofibroma (17 neurofibroma e 12 plexiform neurofibroma) and MPNST. Bright fluorescence was present in all cases of schwannomas and neurofibromas, although with a less homogeneous pattern, whereas it was significantly less evident for malignant PNST; perineurioma and hybrid nerve sheath tumors were characterized by a faint fluorescence enhancement. The surgical resection rate in the general population and even among the subgroups was about 66.7%; from the comparative analysis, we found a consistently higher rate of complete tumor removal in plexiform neurofibromas, 66% in the "fluorescent" group vs 44% in the "historical" group (p-value < 0.05). The rate of complications and mean surgical time were superimposable among the two populations. Conclusions: SF is a valuable method for safe fluorescence-guided PNST and mimicking lesions resection. Our data showed a positive effect of fluorescein-guided surgery in increasing the rate of surgical resection of plexiform neurofibromas, suggesting a possible role in improving the functional and oncological outcome of these lesions.

Towards an Established Intraoperative Oncological Favorable Tool: Results of Fluorescein-Guided Resection from a Monocentric, Prospective Series of 93 Primary Glioblastoma Patients.

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.

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy.

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.