Surgery versus endovascular treatment for spinal dural arteriovenous fistulas: a multicenter experience and systematic literature review.

Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications.

Interscapular Pain after Anterior Cervical Discectomy and Fusion: Does Zygapophyseal Joints over Distraction Play a Role?

Introduction: Anterior cervical discectomy and fusion (ACDF) for cervical disc herniation (CDH) is commonly performed. Specific post-operative complications include dysphagia, dysphonia, cervicalgia, adjacent segment disorder, cage subsidence, and infections. However, interscapular pain is commonly reported by these patients after surgery, although its mechanisms have not been clarified yet. Methods: This retrospective series of 31 patients undergoing ACDF for CDH at a single Academic Hospital. Baseline and post-operative clinical, radiological, and surgical data were analyzed. The linear regression analysis was conducted to identify any factor independently influencing the incidence rate of post-operative interscapular pain. Results: The mean age was 57.6 ± 10.8 years, and the M:F ratio was 2.1. Pre-operative mean VAS-arm was 7.15 ± 0.81 among the 20 patients reporting brachialgia, and mean VAS-neck was 4.36 ± 1.43 among those 9 patients reporting cervicalgia. At 1 month, interscapular pain was still reported by 8 out of the 17 patients who experienced it post-operatively, and it was recovered in all patients after 2 months. The regression analysis showed that interscapular pain was not directly associated with age (p = 0.74), gender (p = 0.46), smoking status (p = 0.44), diabetes (0.42), pre-operative brachialgia (p = 0.21) or cervicalgia (p = 0.48), symptoms duration (p = 0.13), baseline VAS-arm (p = 0.11), VAS-neck (p = 0.93), or mJOA (p = 0.63) scores, or disc height modification (p = 0.90). However, the post-operative increase in the mean zygapophyseal joint rim distance was identified as an independent factor in determining interscapular pain (p = 0.02). Conclusions: Our study revealed that the onset of interscapular pain following ACDF may be determined by over distraction of the zygapophyseal joint rim. Then, proper sizing of prosthetic implants could reduce this painful complication.

Hydrocephalus and the First Report of an External Ventriculostomy: The Contributions of Fabrici d'Acquapendente in the Italian Renaissance.

In our historical study, we are unveiling one of the very first surgical treatments of hydrocephalus originally scripted in Latin by Fabrici d'Acquapendente and then transcribed into the French language by Chez Pierre Ravaud. During the European Renaissance, Italian pioneering surgeon Fabricid'Acquapendente illustrated the technique performed at that time. Fabrici described the drainage of fluid for hydrocephalus using the insertion of a cannula. The cannula was kept in place for several days and the fluid was drained slowly and in regulated controlled amounts. Layers of bandage drapes were applied to prevent the leakage of fluid escaping from the wound. Unfortunately, we are missing some significant information regarding the surgical techniques as these were not documented by Fabrici. Although skull trephination was relatively well known, it is unsure whether at the time the cannula was inserted deep within the ventricles. Drainage of the fluid may have still occurred from the extracranial space. Moreover, we are unaware of how long the cannula was kept in place. Nonetheless, Fabrici d'Acquapendente may be considered among the first in Italy and possibly in Europe to lay down the foundations for external ventricular drainage system for hydrocephalus.

Quantitative Anatomical Comparison of Surgical Approaches to Meckel's Cave.

BACKGROUND: Meckel's cave is a challenging surgical target due to its deep location and proximity to vital neurovascular structures. Surgeons have developed various microsurgical transcranial approaches (MTAs) to access it, but there is no consensus on the best method. Newer endoscopic approaches have also emerged. This study seeks to quantitatively compare these surgical approaches to Meckel's cave, offering insights into surgical volumes and exposure areas. METHODS: Fifteen surgical approaches were performed bilaterally in six specimens, including the pterional approach (PTA), fronto-temporal-orbito-zygomatic approach (FTOZA), subtemporal approach (STA), Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), endoscopic endonasal transpterygoid approach (EETPA), inferolateral transorbital approach (ILTEA) and superior eyelid approach (SEYA). All the MTAs were performed both with 10 mm and 15 mm of brain retraction, to consider different percentages of surface exposure. A dedicated navigation system was used to quantify the surgical working volumes and exposure of different areas of Meckel's cave (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Microsurgical transcranial approaches were quantified with two different degrees of brain retraction (10 mm and 15 mm). Statistical analysis was performed using a mixed linear model with bootstrap resampling. RESULTS: The RSAS with 15 mm of retraction offered the maximum exposure of the trigeminal stem (TS). If compared to the KWA, the RSA exposed more of the TS (69% vs. 46%; p = 0.01). The EETPA and ILTEA exposed the Gasserian ganglion (GG) mainly in the anteromedial portion, but with a significant 20% gain in exposure provided by the EETPA compared to ILTEA (42% vs. 22%; p = 0.06). The STA with 15 mm of retraction offered the maximum exposure of the GG, with a significant gain in exposure compared to the STA with 10 mm of retraction (50% vs. 35%; p = 0.03). The medial part of the three trigeminal branches was mainly exposed by the EETPA, particularly for the ophthalmic (66%) and maxillary (83%) nerves. The EETPA offered the maximum exposure of the medial part of the mandibular nerve, with a significant gain in exposure compared to the ILTEA (42% vs. 11%; p = 0.01) and the SEY (42% vs. 2%; p = 0.01). The FTOZA offered the maximum exposure of the lateral part of the ophthalmic nerve, with a significant gain of 67% (p = 0.03) and 48% (p = 0.04) in exposure compared to the PTA and STA, respectively. The STA with 15 mm of retraction offered the maximum exposure of the lateral part of the maxillary nerve, with a significant gain in exposure compared to the STA with 10 mm of retraction (58% vs. 45%; p = 0.04). The STA with 15 mm of retraction provided a significant exposure gain of 23% for the lateral part of the mandibular nerve compared to FTOZA with 15 mm of retraction (p = 0.03). CONCLUSIONS: The endoscopic approaches, through the endonasal and transorbital routes, can provide adequate exposure of Meckel's cave, especially for its more medial portions, bypassing the impediment of major neurovascular structures and significant brain retraction. As far as the most lateral portion of Meckel's cave, MTA approaches still seem to be the gold standard in obtaining optimal exposure and adequate surgical volumes.

Liquid Biopsy in Low-Grade Glioma: A Systematic Review and a Proposal for a Clinical Utility Score.

Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.

The impact of COVID-19 pandemic on surgical neuro-oncology: A survey from the Italian society of neurosurgery (SINch).

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

Tumor Microenvironment and Glioblastoma Cell Interplay as Promoters of Therapeutic Resistance.

The invasive nature of glioblastoma is problematic in a radical surgery approach and can be responsible for tumor recurrence. In order to create new therapeutic strategies, it is imperative to have a better understanding of the mechanisms behind tumor growth and invasion. The continuous cross-talk between glioma stem cells (GSCs) and the tumor microenvironment (TME) contributes to disease progression, which renders research in this field difficult and challenging. The main aim of the review was to assess the different possible mechanisms that could explain resistance to treatment promoted by TME and GSCs in glioblastoma, including the role of M2 macrophages, micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) from exosomes from the TME. A systematic review of the literature on the role of the TME in developing and promoting radioresistance and chemoresistance of GBM was performed according to PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. A dedicated literature review search was also performed on the immunotherapeutic agents against the immune TME. We identified 367 papers using the reported keywords. The final qualitative analysis was conducted on 25 studies. A growing amount of evidence in the current literature supports the role of M2 macrophages and non-coding RNAs in promoting the mechanisms of chemo and radioresistance. A better insight into how GBM cells interact with TME is an essential step towards comprehending the mechanisms that give rise to resistance to standard treatment, which can help to pave the way for the development of novel therapeutic strategies for GBM patients.

Delayed onset of fatal encephalitis in a COVID-19 positive patient.

BACKGROUND: The SARS-nCoV-2019 epidemic has spread since December 2019, quickly gaining worldwide attention. Symptoms consist of fever, cough and breathing difficulties. An increasing number of studies are focusing on neurological manifestations. In addition to the typical ageusia and anosmia, up to 30% of cases can present headache, nausea and vomiting. More serious neurological manifestations, such as encephalitis, thrombosis and cerebral haemorrhage have been reported. CASE DESCRIPTION: We described the case of a 47-year-old man who tested positive for COVID-19 virus in early March 2020. After two negative nasopharyngeal swabs, 41 days after the diagnosis of COVID-19 infection, he developed intense headache with fever, and he was hospitalized. He had subsequent generalized epileptic seizures and intubation was necessary. Contrast Head MRI was negative for brain abscesses or tumours but detected severe vasogenic oedema of the white matter with 10 mm shift of the midline and compression of the right lateral ventricle. Massive cortisone support therapy was ineffective. We diagnosed brain death on day 43 from the infection diagnosis. DISCUSSION: COVID-19 virus can reach the brain, penetrating into the neuronal cells through the interaction between the spike protein S1 and the host ACE-2 receptor, expressed in the capillary endothelium. We believe that in this infection, the pro-inflammatory state induced by the cytokine storm can cause a cerebral cell-mediated response, with subsequent vasodilatation and brain oedema. CONCLUSION: To our knowledge, this is the first description of a delayed onset cell-mediated encephalitis caused by COVID-19 virus after more than 40 days from the diagnosis.

Endoscopic Evacuation of Massive Intraventricular Hemorrhages Reduces Shunt Dependency: A Meta-Analysis.

Intraventricular hemorrhage (IVH) is characterized by severe prognosis. The amount of intraventricular blood is the most important, disease-specific, prognostic factor, as acute complications are strictly dependent on clot formation. Although external ventricular drain (EVD) placement is the standard treatment, in the past 15 years neuroendoscopic (NE) evacuation of IVH has been advocated, but available comparative data are limited. A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included articles compare the treatment of primary and secondary IVH with NE and EVD. The meta-analysis was performed in terms of shunt dependency. Cochran's Q-test and I2 statistics were used to assess heterogeneity in the studies. No heterogeneity was considered for p greater than 0.05 and I2 less than 20%. A random-effect model was used, with restricted maximum likelihood to estimate the heterogeneity variance. After screening 744 articles, 5 were included in the meta-analysis. A total of 303 patients presenting with primary or pure (50 patients) and secondary (253 patients) IVH, undergoing either NE (151) or EVD (152), were included in the metanalysis. The risk of ventriculoperitoneal (VP) shunt was higher in the EVD group (relative risk: 1.93, 95% confidence interval: 1.28-2.92, p = 0.0094). The risk of VP shunt was higher in the EVD group, but the overall outcome remains poor for patients with IVH, with a moderate-to-high disability. Large randomized controlled trials are needed to evaluate more deeper both advantages and effects on the outcome of NE over EVD.

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas.

OBJECTIVE: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. METHODS: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. RESULTS: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). CONCLUSIONS: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

A New Insight in Nonaneurysmal Subarachnoid Hemorrhage: The Potential Role of the Internal Jugular Veins.

BACKGROUND: Causes of the nonaneurysmal subarachnoid hemorrhage (na-SAH) are still debated. Many studies confirmed the possible involvement of the intracranial venous system, in particular variants of the basal vein of Rosenthal. STUDY OBJECT: The aim of this study is to investigate the role of extracranial venous system, in particular the jugular drainage, in the na-SAH pathophysiology. MATERIALS AND METHODS: This is a multicenter retrospective study including patients suffering from na-SAH who were radiologically screened to exclude vascular malformations. The course of the internal jugular veins was evaluated to reveal any stenosis (caliber reduction >80%). Particular attention was paid at the passage between the styloid process and the arch of C1 to detect possible compression. As a control group, we enrolled patients who underwent CT angiograms and/or cerebral DSAs in the past 2 years. RESULTS: We included 194 patients. The na-SAH group consisted of 94 patients, whereas the control group consisted of 100 patients. Fifty patients of the control group underwent a CT angiography for an ischemic cerebrovascular disease or trauma and 50 patients for an SAH due to a ruptured aneurysm. A significant jugular stenosis was found in 49 (52.1%) patients in the na-SAH group and in 18 (18%) patients in the control group. At univariate and multivariate analysis, the difference was statistically significant (p < 0.0001). CONCLUSIONS: This is the first study investigating the correlation between jugular stenosis and the occurrence of na-SAH. The impaired venous outflow due to reduced venous caliber could result in an engorgement of the upstream intracranial veins with transient hypertensive phases facilitating ruptures. Further larger prospective studies are necessary to confirm these data.

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Scientometric analysis of medical publications during COVID-19 pandemic: the twenty-twenty research boom.

INTRODUCTION: There was significant surge in the academic publications after the onset of COVID-19 outbreak. The aim of this study was to scientometrically analyze all the medical publications on COVID-19 in 2020 as well as the top 100 cited articles. EVIDENCE ACQUISITION: We performed a search of the "Web of Science" database using the keywords "COVID," and "corona" on December 20, 2020. EVIDENCE SYNTHESIS: Our search retrieved a total of 45,420 articles on the topic COVID-19 in the year 2020. Corresponding authors from 143 countries contributed to these articles. The highest number of articles were contributed by corresponding authors from the USA (N.=10299), whereas 50 articles in the top 100 cited articles had corresponding authors from China. Among the top 100 cited, the majority were published from Huazhong University of Science and Technology in China (N.=37). New England Journal of Medicine had the maximum impact (h-index of 57), closely followed by Lancet (h-index=55). CONCLUSIONS: Scientific publications amount on COVID-19 disease grew at an astonishing pace during 2020. We caution the readers that this rapidity of publication could have missed out on the rigorous review process and the scientific basis of the methods followed.

Do neurosurgeons follow the guidelines? A world-based survey on severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is going to be the third-leading cause of death worldwide, according to the WHO. Two European surveys suggested that adherence to brain trauma guidelines is poor. No study has compared compliance between low- (LMICs) and high-income (UHICs) countries. Hence, this study aimed to investigate differences in the management of severe TBI patients, comparing low- and high-income, and adherence to the BTF guidelines. METHODS: A web-based survey was spread through the Global Neuro Foundation, different neurosurgical societies, and social media. RESULTS: A total of 803 neurosurgeons participated: 70.4 from UHICs and 29.6% from LMICs. Hypertonic was administered as an early measure by the 73% and 65% of the responders in LMICs and UHICs, respectively (P=0.016). An invasive intracranial pressure monitoring was recommended by the 66% and 58% of the neurosurgeons in LMICs and UHICs, respectively (P<0.001). Antiseizure drugs (P<0.001) were given most frequently in LMICs as, against recommendations, steroids (87% vs. 61% and 86% vs. 81%, respectively). In the LMICs both the evacuation of the contusion and decompressive craniectomy were performed earlier than in UHICs (30% vs. 17% with P<0.001 and 44% vs. 28% with P=0.006, respectively). In the LMICs, the head CT control was performed mostly between 12 and 24 hours from the first imaging (38% vs. 23%, P<0.001). CONCLUSIONS: The current Guidelines on TBI do not always fit to both the resources and circumstances in different countries. Future research and clinical practice guidelines should reflect the greater relevance of TBI in low resource settings.

An international call for a new grading system for cerebral and cerebellar cavernomas.

Surgical indications for cerebral cavernous malformations remain significantly center- and surgeon-dependent. Available grading systems are potentially limited, as they do not include epileptological and radiological data. A novel grading system is proposed for supratentorial and cerebellar cavernomas: it considers neuroradiological features (bleeding, increase in size), neurological status (focal deficits and seizures), location of the lesion and age of the patient. The score ranges from -1 to 10; furthermore, surgery should be considered when a score of 4 or higher is present. Based on neuroradiological characteristics, 0 points are assigned if the CCM is stable in size at different neuroradiological controls, 1 point if there is an increase in volume during follow-up, 2 points if intra- or extra-lesional bleeding <1 cm is present and 3 points if the CCM produced a hematoma >1 cm. Regarding focal neurological deficits, 0 points are assigned if absent and 2 points if present. For seizures, 0 points are assigned if absent, 1 point if present, but controlled by medications, and 2 points if drug resistant. We considered the site of the CCM, and in case of deep-seated lesions in a critical area (basal ganglia, thalamus) 1 point (-1) is subtracted, while for subcortical or deep cerebellar lesions 0 points are assigned, for CCMs in a cortical critical area 1 point is assigned and in case of lesions in cortical not in critical area or superficial cerebellar area, 2 points are assigned. As far as age is concerned, 0 points are assigned for patients older than 50 years and 1 point for patients younger than 50. In conclusion, a novel grading for surgical decision making in cerebral cavernomas, based on the experience of selected neurosurgeons, basic scientists, and patients, is suggested with the aim of further improving and standardizing the treatment of CCMs. The aim of this paper was also to call for both retrospective and prospective multicenter studies with the aim of testing the efficacy of the grading system in different centers.

Cerebral cavernous malformation remnants after surgery: a single-center series with long-term bleeding risk analysis.

The aim of this work is to investigate the long-term bleeding risk of cerebral cavernous malformation (CCM) remnants. A review of clinical, radiological, operative, and post-operative data of a cerebral cavernous malformation (CCMs) prospective database was performed. Fisher's exact test and Mann-Whitney U-test were used to assess differences between non-hemorrhagic and hemorrhagic CCM remnants for 14 variables. Recursive partitioning analysis was performed to assess the order of variables most associated with CCM remnant bleeding. Twenty-four patients out of 126 had a CCM post-surgical remnant. Of these, 7 had at least one post-operative hemorrhagic event. The mean follow-up was 80.7 months (range 12-144). CCM post-surgical remnant bleeding presented mostly with acute headache (50%) and focal neurological deficit (25%); in the remaining cases, the hemorrhage was asymptomatic. Retreatment was performed in two patients, with surgery and radiosurgery, respectively; no treatment was performed in the majority of cases. All patients ranked as non-II, according to Zabramski classification, did not show any post-surgical bleeding. The presence of a pre-operative perilesional hemosiderin ring was highly significant in predicting post-surgical bleeding (sensitivity = 0.94, specificity = 0.88) and incorrectly predicted bleeding in only two of the 24 patients. This study provides an evaluation of clinical and radiological factors influencing the bleeding risk of a CCM post-surgical remnant in a homogeneous population. Perilesional hemosiderin ring and Zabramski Type II appear to strongly condition the bleeding risk of a CCM post-surgical remnant.

Anxiety in neurosurgical patients undergoing nonurgent surgery during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS: Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS: One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor associated with anxiety, even though none of the patients were infected. Neuro-oncological disease was associated with state anxiety and with worry about surgery and COVID-19. Increased bed distance and availability of hand sanitizer were associated with a feeling of safety. CONCLUSIONS: These data underline the importance of psychological support, especially for neuro-oncological patients, during a pandemic.

Determinants of the Choice of Job Search Channels by the Unemployed Using a Multivariate Probit Model.

We investigate factors affecting the job search channels (newspapers, agency, informal network, direct contact, internet) of unemployed individuals in Italy using a multivariate probit model. We separately analyse unemployed individuals who lost their job or who are entering the labour market for the first time (i.e., with or without previous job experience, respectively). We use cross-sectional microdata covering the 2014-2018 period. We do not find important differences in the determinants in common between unemployed individuals with and without previous job experience (such as, age, education, and citizenship). The main difference between the two samples is in the composition, with more young people in the latter group (mainly individuals in the school-to-work transition) than in the first one. We find that better-educated unemployed people have more of a multichannel attitude when searching for jobs than their counterparts. Moreover, for unemployed individuals with previous job experience, the characteristics of their last job play a crucial role in influencing the choice of search channel(s). For example, unemployed individuals from high-skilled professions (that typically require the employment of better-educated individuals) choose the internet with a higher probability than other channels, while those from low-skilled professions and with experience in manufacturing have a higher probability of considering employment agencies than those in qualified professions in commercial activities and services. We have assumed that the unobservable factors affecting the decision process of a multichannel job search (estimated through the pairwise correlation coefficients across the residuals of the models) are represented by personality features of an individual, such as motivation, self-control, and preferences. A strong, positive, and significant correlation is found between job searching through the internet and direct contact with firms, but with some spatial differences between macro-areas of the country.

Snake-Eye Myelopathy and Surgical Prognosis: Case Series and Systematic Literature Review.

The prognostic value of "snake-eyes" sign in spinal cord magnetic resonance imaging (MRI) is unclear and the correlation with different pathological conditions has not been completely elucidated. In addition, its influence on surgical outcome has not been investigated in depth. A literature review according to PRISMA (Preferred reporting items for systematic review and meta-analysis protocols) guidelines on the prognostic significance of "snake-eyes" sign in operated patients was performed. Clinical, neuroradiological, and surgical data of three institutional patients, were also retrospectively collected. The three patients, with radiological evidence of "snake-eyes" myelopathy, underwent appropriate surgical treatment for their condition, with no new post-operative neurological deficits and good outcome at follow-up. The literature review, however, reported conflicting results: the presence of "snake-eyes" sign seems a poor prognostic factor in degenerative cervical myelopathy, even if some cases can improve after surgery. "Snake-eyes" myelopathy represents a rare form of myelopathy; pathophysiology is still unclear. The frequency of this myelopathy may be greater than previously thought and according to our literature review it is mostly a negative prognostic factor. However, from our experience, prognosis might not be so dire, especially when tailored surgical intervention is performed; therefore, surgery should always be considered and based on the complete clinical, neurophysiological, and radiological data.