Management of Antithrombotic Drugs in Patients with Isolated Traumatic Brain Injury: An Intersociety Consensus Document.

BACKGROUND: All available recommendations about the management of antithrombotic therapies (ATs) in patients who experienced traumatic brain injury (TBI) are mainly based on expert opinion because of the lack of strength in the available evidence-based medicine. Currently, the withdrawal and the resumption of AT in these patients is empirical, widely variable, and based on the individual assessment of the attending physician. The main difficulty is to balance the thrombotic and hemorrhagic risks to improve patient outcome. METHODS: Under the endorsement of the Neurotraumatology Section of Italian Society of Neurosurgery, the Italian Society for the Study about Haemostasis and Thrombosis, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care, and the European Association of Neurosurgical Societies, a working group (WG) of clinicians completed two rounds of questionnaires, using the Delphi method, in a multidisciplinary setting. A table for thrombotic and bleeding risk, with a dichotomization in high risk and low risk, was established before questionnaire administration. In this table, the risk is calculated by matching different isolated TBI (iTBI) scenarios such as acute and chronic subdural hematomas, extradural hematoma, brain contusion (intracerebral hemorrhage), and traumatic subarachnoid hemorrhage with patients under active AT treatment. The registered indication could include AT primary prevention, cardiac valve prosthesis, vascular stents, venous thromboembolism, and atrial fibrillation. RESULTS: The WG proposed a total of 28 statements encompassing the most common clinical scenarios about the withdrawal of antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients who experienced blunt iTBI. The WG voted on the grade of appropriateness of seven recommended interventions. Overall, the panel reached an agreement for 20 of 28 (71%) questions, deeming 11 of 28 (39%) as appropriate and 9 of 28 (32%) as inappropriate interventions. The appropriateness of intervention was rated as uncertain for 8 of 28 (28%) questions. CONCLUSIONS: The initial establishment of a thrombotic and/or bleeding risk scoring system can provide a vital theoretical basis for the evaluation of effective management in individuals under AT who sustained an iTBI. The listed recommendations can be implemented into local protocols for a more homogeneous strategy. Validation using large cohorts of patients needs to be developed. This is the first part of a project to update the management of AT in patients with iTBI.

Ventilator-associated pneumonia in neurocritically ill patients: insights from the ENIO international prospective observational study.

BACKGROUND: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality. METHODS: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included. RESULTS: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001). CONCLUSIONS: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.

To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma.

OBJECTIVE: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease. METHODS: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear. CONCLUSIONS: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

De novo intracranial aneurysm formation in SARS-CoV-2 infection: first report of a yet unknown complication.

BACKGROUND AND IMPORTANCE: COVID-19 is a viral infection that mainly affects the respiratory tract, but can also cause multiple inflammatory reactions, including neurological and cerebrovascular manifestations. We report the case of a COVID-19 patient who developed 'de novo' multiple cerebral aneurysms with no risk factors for aneurysm formation. CLINICAL PRESENTATION: A 55-year-old man with SARS-CoV-2 infection came to our attention for left eye blindness accompanied by ptosis, palpebral chemosis and retro-orbital pain. Brain CT and CT-angiography were negative for hemorrhages and for vascular malformations. Repeated intracerebral hemorrhages and neurological deterioration then occurred, and a new CT-angiography showed multiple intracranial aneurysms that were not present before. CONCLUSION: Intracranial aneurysm formation as a complication of COVID-19 has not been previously reported. As other viral infections do, COVID-19 may be able to determine a vascular damage that can ultimately lead to development of an aneurysm. It is reasonable to hypothesize an involvement of the renin-angiotensin system as a pathogenic mechanism. A conservative therapy aiming at inflammatory modulation and vascular damage prevention may be warranted in these patients.

Effects of positive end-expiratory pressure on lung ultrasound patterns and their correlation with intracranial pressure in mechanically ventilated brain injured patients.

BACKGROUND: The effects of positive end-expiratory pressure (PEEP) on lung ultrasound (LUS) patterns, and their relationship with intracranial pressure (ICP) in brain injured patients have not been completely clarified. The primary aim of this study was to assess the effect of two levels of PEEP (5 and 15 cmH2O) on global (LUStot) and regional (anterior, lateral, and posterior areas) LUS scores and their correlation with changes of invasive ICP. Secondary aims included: the evaluation of the effect of PEEP on respiratory mechanics, arterial partial pressure of carbon dioxide (PaCO2) and hemodynamics; the correlation between changes in ICP and LUS as well as respiratory parameters; the identification of factors at baseline as potential predictors of ICP response to higher PEEP. METHODS: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP. Total and regional LUS scores, ICP, respiratory mechanics, and arterial blood gases values were analyzed at PEEP 5 and 15 cmH2O. RESULTS: Thirty patients were included; 19 of them (63.3%) were male, with median age of 65 years [interquartile range (IQR) = 66.7-76.0]. PEEP from 5 to 15 cmH2O reduced LUS score in the posterior regions (LUSp, median value from 7 [5-8] to 4.5 [3.7-6], p = 0.002). Changes in ICP were significantly correlated with changes in LUStot (rho = 0.631, p = 0.0002), LUSp (rho = 0.663, p < 0.0001), respiratory system compliance (rho = - 0.599, p < 0.0001), mean arterial pressure (rho = - 0.833, p < 0.0001) and PaCO2 (rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP. CONCLUSIONS: LUS-together with the evaluation of respiratory and clinical variables-can assist the clinicians in the bedside assessment and prediction of the effect of PEEP on ICP in patients with acute brain injury.

Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length.

PURPOSE: Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. METHODS: Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts. RESULTS: Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p = 1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019). CONCLUSIONS: Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome.

How do you manage ANTICOagulant therapy in neurosurgery? The ANTICO survey of the Italian Society of Neurosurgery (SINCH).

BACKGROUND: Anticoagulant assumption is a concern in neurosurgical patient that implies a delicate balance between the risk of thromboembolism versus the risk of peri- and postoperative hemorrhage. METHODS: We performed a survey among 129 different neurosurgical departments in Italy to evaluate practice patterns regarding the management of neurosurgical patients taking anticoagulant drugs. Furthermore, we reviewed the available literature, with the aim of providing a comprehensive but practical summary of current recommendations. RESULTS: Our survey revealed that there is a lack of knowledge, mostly regarding the indication and the strategies of anticoagulant reversal in neurosurgical clinical practice. This may be due a lack of national and international guidelines for the care of anticoagulated neurosurgical patients, along with the fact that coagulation and hemostasis are not simple topics for a neurosurgeon. CONCLUSIONS: To overcome this issue, establishment of hospital-wide policy concerning management of anticoagulated patients and developed in an interdisciplinary manner are strongly recommended.

Surgical challenges in posterior cervicothoracic junction instrumentation.

The cervicothoracic junction (CTJ) is a region of the spine submitted to significant mechanical stress. The peculiar anatomical and biomechanical characteristics make posterior surgical stabilization of this area particularly challenging. We present and discuss our surgical series highlighting the specific surgical challenges provided by this region of the spine. We have analyzed and reported retrospective data from patients who underwent a posterior cervicothoracic instrumentation between 2011 and 2019 at the Neurosurgical Department of the Geneva University Hospitals. We have discussed C7 and Th1 instrumentation techniques, rods design, extension of constructs, and spinal navigation. Thirty-six patients were enrolled. We have preferentially used lateral mass (LM) screws in the subaxial spine and pedicle screws (PS) in C7, Th1, and upper thoracic spine. We have found no superiority of 3D navigation techniques over 2D fluoroscopy guidance in PS placement accuracy, probably due to the relatively small case series. Surgical site infection was the most frequent complication, significantly associated with tumor as diagnosis. When technically feasible, PS represent the technique of choice for C7 and Th1 instrumentation although other safe techniques are available. Different rod constructs are described although significant differences in biomechanical stability still need to be clarified. Spinal navigation should be used whenever available even though 2D fluoroscopy is still a safe option. Posterior instrumentation of the CTJ is a challenging procedure, but with correct surgical planning and technique, it is safe and effective.

Clinical practice for antiplatelet and anticoagulant therapy in neurosurgery: data from an Italian survey and summary of current recommendations - part I, antiplatelet therapy.

The use of antiplatelet medication is widespread as reducing risk of death, myocardial infarction, and occlusive stroke. Currently, the management of neurosurgical patients receiving this type of therapy continues to be a problem of special importance. In this paper, we present the results of an Italian survey focused on the management neurosurgical patient under antiplatelet therapy and, for any item of the investigation, the relative advices coming from literature. This survey was conducted including 129 neurosurgery units in Italy. The present paper was designed by following each question posed in the survey by a brief discussion on literature data. There is a considerable lack of consensus regarding management of antiplatelet therapy in neurosurgery, with critical impact on patient's treatment. What is clearly evident from the present survey is the considerable variability in neurosurgical care for antiplatelet patients; it is reasonable to assume that this scenario reflects the paucity of evidence regarding this issue.

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review.

Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after tumour removal in 70-90% and 96%, respectively. New onset hydrocephalus is reported in about 2.1% of adult and 10-40% of paediatric patients after posterior fossa surgery. There is no consensus concerning prophylactic external ventricular drainage (EVD) placement that is frequently used before posterior fossa lesion removal, as well in those cases without clear evidence of hydrocephalus. The aim of the study was to define the most correct management for patients who undergo posterior fossa tumour surgery, thus identifying cohorts of patients who are at risk of persistent hydrocephalus prior to surgery. A systematic review of literature has been performed, following PRISMA guidelines. Most of the studies reported CSF shunt only in the presence of hydrocephalus, whereas only a few authors suggested its prophylactic use in the absence of signs of ventricular dilatation. Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocele, CSF leak and infection. The use of pre-resection CSF shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation.

Escalation therapy in severe traumatic brain injury: how long is intracranial pressure monitoring necessary?

Traumatic brain injury frequently causes an elevation of intracranial pressure (ICP) that could lead to reduction of cerebral perfusion pressure and cause brain ischemia. Invasive ICP monitoring is recommended by international guidelines, in order to reduce the incidence of secondary brain injury; although rare, the complications related to ICP probes could be dependent on the duration of monitoring. The aim of this manuscript is to clarify the appropriate timing for removal and management of invasive ICP monitoring, in order to reduce the risk of related complications and guarantee adequate cerebral autoregulatory control. There is no universal consensus concerning the duration of invasive ICP monitoring and its related complications, although the pertinent literature seems to show that the longer is the monitoring maintenance, the higher is the risk of technical issues. Besides, upon 72 h of normal ICP values or less than 72 h if the first computed tomography scan is normal (none or minimal signs of injury) and the neurological exam is available (allowing to observe variations and possible occurrence of new-onset pathological response), the removal of invasive ICP monitoring can be justified. The availability of non-invasive monitoring systems should be considered to follow up patients' clinical course after invasive ICP probe removal or for substituting the invasive monitoring in case of contraindication to its placement. Recently, optic nerve sheath diameter and straight sinus systolic flow velocity evaluation through ultrasound methods showed a good correlation with ICP values, demonstrating their potential role in place of invasive monitoring or in the early weaning phase from the invasive ICP monitoring.

Management of spinal aneurysms associated with arteriovenous malformations: systematic literature review and illustrative case.

PURPOSE: Spinal aneurysms are rare vascular malformations, commonly associated with spinal AVMs. AVM-associated spinal aneurysms are burdened by significant morbidity. The purpose of our study is to evaluate the best treatment strategy for these uncommon vascular lesions and to report an illustrative case. METHODS: We reviewed clinical and radiological data of a patient surgically treated at our institution for a spinal AVM with an associated prenidal aneurysm. According to PRISMA guidelines, a systematic literature review has been performed in order to discuss the best management AVM-associated prenidal aneurysms. RESULTS: In the reported case, the aneurysm showed spontaneous regression at follow-up after surgical removal of the AVM. Only 6 articles reported management of spinal prenidal AVM-associated aneurysms. Basing on our experience and data from literature, surgical treatment of the aneurysm may be indicated along with the resection of the AVM if the aneurysm is close to the nidus. Conversely, if the aneurysm is far away from the nidus or in an unfavorable position, resection of the nidus only may lead to aneurysm regression as in the reported case. CONCLUSIONS: The treatment strategy for AVM-associated spinal aneurysms should be tailored on the single patient. In presence of large aneurysms that cause mass-effect symptoms, when rupture of the aneurysm is suspected or when treatment of the AVM is not proposable, direct treatment of the aneurysm should be considered. Otherwise, when complete resection of the nidus is performed, the eventually associated unruptured aneurysms located in challenging positions can be safely managed conservatively.

Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly.

Acromegaly is a rare chronic, systemic disorder caused by excessive growth hormone (GH) secretion from a somatotroph pituitary adenoma. GH hypersecretion leads to overproduction of insulin-like growth factor-1 (IGF-1), which contributes to the somatic overgrowth, physical disfigurement, onset of multiple systemic comorbidities, reduced quality of life (QoL) and premature mortality of uncontrolled patients. Somatostatin receptor ligands, dopamine agonists and a GH receptor antagonist are currently available for medical therapy of acromegaly. The main aim of treatment is biochemical normalisation, defined as age-normalised serum IGF-1 values and random GH levels <1.0 µg/L. However, there is an increasing evidence suggesting that achieving biochemical control does not always decrease the burden of disease-related comorbidities and/or improve patients' QoL. This lack of correlation between biochemical and clinical control can be due to both disease duration (late diagnosis) or to the peculiarity of a given comorbidity. Herein we conducted ad hoc literature searches in order to find the most recent and relevant reports on biochemical and clinical disease control during medical treatment of acromegaly. Particularly, we analyse and describe the relationship between biochemical, as well as clinical disease control in patients with acromegaly receiving medical therapy, with a focus on comorbidities and QoL. In conclusion, we found that current literature data seem to indicate that clinical disease control (besides biochemical control), encompassing clinical signs and symptoms, comorbidities and QoL, emerge as a primary focus of acromegaly patient management.

Traumatic subarachnoid hemorrhage related to ophthalmic artery avulsion: a case report.

We present a case of ophthalmic artery (OA) traumatic avulsion, leading to a post-traumatic subarachnoid hemorrhage (SAH) with ventricular blood invasion and hydrocephalus, mimicking an internal carotid aneurysm rupture. This is the third case of such an event reported in literature and the first without orbital fractures and optic nerve avulsion. Conservative treatment was sufficient for the avulsion, but surgery was needed for the coexisting eye luxation. Traumatic OA avulsion is a rare but possible event and should be suspected in case of basal cisterns SAH, evidence of orbital trauma and CT angiogram or angiographic absence of opacification of the OA.

Pituitary image: pituicytoma.

INTRODUCTION: Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis. CASE REPORT: A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery. DISCUSSION/CONCLUSIONS: Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.

Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy?

PURPOSE: Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications. METHODS: We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27-61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2-4.2 mIU/L), with median fT4 2.52 ng/dL (0.9-1.7 ng/dL). RESULTS: Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease -72%), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach. CONCLUSIONS: Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50%). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.

Diagnosis of cerebral vasospasm and risk of delayed cerebral ischemia related to aneurysmal subarachnoid haemorrhage: an overview of available tools.

In the first weeks following aneurysmal subarachnoid haemorrhage, cerebrovascular alterations may impact the outcome significantly. Diagnosis of cerebral vasospasm and detection of alterations at risk of delayed cerebral ischemia are key targets to be monitored in the post-acute phase. Available tools include clinical monitoring, as well as studies that can detect possible arterial narrowing, alterations of perfusion, metabolism and neurophysiology. Each technique is able to investigate possible vascular impairment and has different advantages and limits. All available techniques have been described. Among these, the most practical have been selected and compared for their peculiar characteristics. Based on this analysis, a flowchart to monitor these patients is finally proposed.

Adiponectin as novel regulator of cell proliferation in human glioblastoma.

Adiponectin (Acrp30) is an adipocyte-secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co-expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87-MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches.

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction." Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain." Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.