Extracellular vesicles in glioblastoma: Biomarkers and therapeutic tools.

Glioblastoma (GBM) is the most aggressive tumor among the gliomas and intracranial tumors and to date prognosis for GBM patients remains poor, with a median survival typically measured in months to a few years depending on various factors. Although standardized therapies are routinely employed, it is clear that these strategies are unable to cope with heterogeneity and invasiveness of GBM. Furthermore, diagnosis and monitoring of responses to therapies are directly dependent on tissue biopsies or magnetic resonance imaging (MRI) techniques. From this point of view, liquid biopsies are arising as key sources of a variety of biomarkers with the advantage of being easily accessible and monitorable. In this context, extracellular vesicles (EVs), physiologically shed into body fluids by virtually all cells, are gaining increasing interest both as natural carriers of biomarkers and as specific signatures even for GBM. What makes these vesicles particularly attractive is they are also emerging as therapeutical vehicles to treat GBM given their native ability to cross the blood-brain barrier (BBB). Here, we reviewed recent advances on the use of EVs as biomarker for liquid biopsy and nanocarriers for targeted delivery of anticancer drugs in glioblastoma.

Clinical features, operative management and surgical results of first Draf III procedure, revision Draf III approach and the use of mucosal flaps and stents: a systematic review.

OBJECTIVES: Draf III procedure is a challenging endoscopic technique, which has gradually gained an increasing popularity in treating frontal sinus pathologies. The main aim of this systematic review is to offer a comprehensive overview on clinical indications, pre-operative evaluation, surgical techniques, post-operative management and complications of the Draf III procedure. As a step forward, such issues have been comparatively evaluated as referred to patients who underwent primary Draf III procedure and revision DRAF III one). Finally, surgical outcomes related to mucosal flaps and stents to prevent re-stenosis are analyzed. METHODS: A systematic literature review has been performed following PRISMA 2020 checklist statement. An automated search has been carried out by applying an extensive set of queries on the Embase/PubMed, Scopus and Cochrane databases, relating to papers published from 2000 to 2021. RESULTS: Frontal chronic refractory sinusitis is the most frequent indication to Draf III procedure (72%), followed by mucoceles (11%) and skull base or paranasal tumors (10%). The success rate of primary and revision Draf III are 83.5% and 71%, respectively. The re-stenosis phenomenon seems to depend on allergic mechanism and polyposis). The use of mucosal flaps could improve the Draf III efficacy, better than the use of stents (87 vs 72% of neo-ostium patency). CONCLUSION: Draf III is a safe and highly effective surgical technique. However, some limited clinical conditions require some careful technical features, such as the use of mucosal flap, in order to prevent re-stenosis.

Post-operative segmental cerebral venous sinus thrombosis: risk factors, clinical implications, and therapeutic considerations.

Cerebral venous sinus thromboses (CVSTs) are rare complications of neurosurgical interventions and their management remains controversial as most of cases appear clinically silent. Here, we analyzed our institutional series of patients with CVSTs evaluating clinical and neuroradiological characteristics, risk factors, and outcome. From the analysis of our institutional PACS, we collected a total of 59 patients showing postoperative CVSTs after supratentorial or infratentorial craniotomies. For every patient, we collected demographics and relevant clinical and laboratory data. Details on thrombosis trend were retrieved and compared along the serial radiological assessment. A supratentorial craniotomy was performed in 57.6% of cases, an infratentorial in 37.3%, while the remaining were a single cases of trans-sphenoidal and neck surgery (1.7%, respectively). A sinus infiltration was present in almost a quarter of patients, and in 52.5% of cases the thrombosed sinus was exposed during the craniotomy. Radiological signs of CVST were evident in 32.2% of patients, but only 8.5% of them developed a hemorrhagic infarct. CVST-related symptoms were complained by 13 patients (22%), but these were minor symptoms in about 90%, and only 10% experienced hemiparesis or impaired consciousness. The majority of patients (78%) remained completely asymptomatic along the follow-up. Risk factors for symptoms occurrence were interruption of preoperative anticoagulants, infratentorial sinuses involvement and evidence of vasogenic edema and venous infarction. Overall, a good outcome defined mRS 0-2 was observed in about 88% of patients at follow-up. CVST is a complication of surgical approaches in proximity of dural venous sinuses. CVST usually does not show progression and courses uneventfully in the vast majority of cases. The systematic use of post-operative anticoagulants seems to not significantly influence its clinical and radiological outcome.

Comparison Between Ventricular and Spinal Infusion Tests in Suspected Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12 mmHg and 23 a Rout <12 mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12 mmHg and 12 a Rout <12 mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.

Clipping versus coiling for treatment of middle cerebral artery aneurysms: a retrospective Italian multicenter experience.

Endovascular treatment has emerged as the predominant approach in intracranial aneurysms. However, surgical clipping is still considered the best treatment for middle cerebral artery (MCA) aneurysms in referral centers. Here we compared short- and long-term clinical and neuroradiological outcomes in patients with MCA aneurysms undergoing clipping or coiling in 5 Italian referral centers for cerebrovascular surgery. We retrospectively reviewed 411 consecutive patients admitted between 2015 and 2019 for ruptured and unruptured MCA aneurysm. Univariate and multivariate analyses of the association between demographic, clinical, and radiological parameters and ruptured status, type of surgical treatment, and clinical outcome at discharge and follow-up were performed. Clipping was performed in 340 (83%) cases, coiling in 71 (17%). Clipping was preferred in unruptured aneurysms and in those showing collateral branches originating from neck/dome. Surgery achieved a higher rate of complete occlusion at discharge and follow-up. Clipping and coiling showed no difference in clinical outcome in both ruptured and unruptured cases. In ruptured aneurysms age, presenting clinical status, intracerebral hematoma at onset, and treatment-related complications were significantly associated with outcome at both short- and long-term follow-up. The presence of collaterals/perforators originating from dome/neck of the aneurysms also worsened the short-term clinical outcome. In unruptured cases, only treatment-related complications such as ischemia and hydrocephalus were associated with poor outcome. Clipping still seems superior to coiling in providing better short- and long-term occlusion rates in MCA aneurysms, and at the same time, it appears as safe as coiling in terms of clinical outcome.

Machine learning model prediction of 6-month functional outcome in elderly patients with intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) has an increasing incidence and a worse outcome in elderly patients. The ability to predict the functional outcome in these patients can be helpful in supporting treatment decisions and establishing prognostic expectations. We evaluated the performance of a machine learning (ML) model to predict the 6-month functional status in elderly patients with ICH leveraging the predictive value of the clinical characteristics at hospital admission. Data were extracted by a retrospective multicentric database of patients ≥ 70 years of age consecutively admitted for the management of spontaneous ICH between January 1, 2014 and December 31, 2019. Relevant demographic, clinical, and radiological variables were selected by a feature selection algorithm (Boruta) and used to build a ML model. Outcome was determined according to the Glasgow Outcome Scale (GOS) at 6 months from ICH: dead (GOS 1), poor outcome (GOS 2-3: vegetative status/severe disability), and good outcome (GOS 4-5: moderate disability/good recovery). Ten features were selected by Boruta with the following relative importance order in the ML model: Glasgow Coma Scale, Charlson Comorbidity Index, ICH score, ICH volume, pupillary status, brainstem location, age, anticoagulant/antiplatelet agents, intraventricular hemorrhage, and cerebellar location. Random forest prediction model, evaluated on the hold-out test set, achieved an AUC of 0.96 (0.94-0.98), 0.89 (0.86-0.93), and 0.93 (0.90-0.95) for dead, poor, and good outcome classes, respectively, demonstrating high discriminative ability. A random forest classifier was successfully trained and internally validated to stratify elderly patients with spontaneous ICH into prognostic subclasses. The predictive value is enhanced by the ability of ML model to identify synergy among variables.

Retrospective application of risk scores to ruptured intracranial aneurysms: would they have predicted the risk of bleeding?

As the incidental diagnosis of unruptured intracranial aneurysms has been increasing, several scores were developed to predict risk of rupture and growth to guide the management choice. We retrospectively applied these scores to a multicenter series of patients with subarachnoid hemorrhage to test whether they would have predicted the risk of bleeding in the event of aneurysm discovery previous to its rupture. Demographical, clinical, and radiological information of 245 adults were retrieved from two neurovascular centers' database. Data were pooled and PHASES, UCAS, and ELAPSS scores were retrospectively calculated for the whole population and their performances in identifying aneurysms at risk of rupture were compared. Mean PHASES, UCAS, and ELAPSS scores were 5.12 ± 3.08, 5.09 ± 2.62, and 15.88 ± 8.07, respectively. Around half (46%) of patients would have been assigned to the low- or very low-risk class (5-year rupture risk < 1%) in PHASES. Around 28% of patients would have been in a low-risk class, with a probability of 3-year rupture risk < 1% according to UCAS. Finally, ELAPSS score application showed a wider distribution among the risk classes, but a significant proportion of patients (45.5%) lie in the low- or intermediate-risk class for aneurysm growth. A high percentage of patients with ruptured aneurysms in this multicenter cohort would have been assigned to the lower risk categories for aneurysm growth and rupture with all the tested scores if they had been discovered before the rupture. Based on these observations, physicians should be careful about drawing therapeutic conclusions solely based on application of these scores.

Intraventricular infusion test accuracy in predicting short- and long-term outcome of iNPH patients: a 10-year update of a three-decade experience at a single institution.

OBJECTIVE: In a previous work, we found that an Intracranial Elastance Index (IEI) ≥0.3 at ventricular infusion test had a high accuracy in predicting shunt response at 6 and 12 months in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to verify the accuracy of IEI to predict response to shunt at both short- and long-term follow-up. METHODS: Retrospective evaluation of 64 patients undergoing ventriculo-peritoneal shunting for iNPH between 2006 and 2015 based on a positive ventricular infusion test (IEI≥0.3). Patients were classified according to Krauss scale and mRS preoperatively, at 1-year and at last follow-up. An improvement of at least one point at Krauss score or at mRS was considered as a good outcome; unchanged or worsened patients were grouped as poor outcome. RESULTS: Mean follow-up was 6.6 years. Improvement at Krauss scale was seen in 62.5% and 64.3% of patients at 1-year and last follow-up, respectively. Patients in good functional status (mRS≤2) increased from 25 in the preoperative period to 57% at both 1-year and last follow-up. IEI was significantly associated with Krauss (p=0.041) and mRS (p=0.036) outcome at last follow-up. Patients with worse preoperative Krauss and mRS had higher chance to improve but higher overall scores after treatment. At ROC curves, IEI showed a good long-term prediction of change in mRS from first year to last follow-up. CONCLUSIONS: IEI≥0.3 predicts outcomes at both short- and long-term, with more than 50% of patients being able to look after themselves after 6 years from treatment.

Radiological outcomes for endovascular treatment of posterior communicating artery aneurysms: a retrospective multicenter study of the occlusion rate.

Although several innovations in techniques and implantable devices were reported over the last decades, a consensus on the best endovascular treatment for intracranial aneurysms originating from the posterior communicating artery is still missing. This work investigates radiological outcomes of different endovascular techniques for posterior communicating artery aneurysms treatment in a retrospective multi-centric cohort. We included patients endovascularly treated for posterior communicating artery aneurysms from 2015 through 2020 in six tertiary referral hospitals. We evaluated the relationship between patients and aneurysms characteristics, baseline neurological status, radiological outcomes, and the different endovascular techniques. Overall, 250 patients were included in this study. Simple coiling was the most frequent treatment in 171 patients (68%), followed by flow-diverter stenting in 32 cases (13%). Complete occlusion was reported in 163 patients (65%), near-complete occlusion in 43 (17%), and incomplete occlusion in 44 (18%). Radiological follow-up was available for 247 (98%) patients. The occlusion rate was stable in 149 (60%), improved in 49 (19%), and worsened in 51 (21%). No significant difference in exclusion rate was seen between ruptured and unruptured aneurysms at the last follow-up (p = 0.4). Posterior communicating artery thrombosis was reported in 25 patients (9%), transient ischemic attack in 6 (2%), and in 38 patients (15%), subsequent procedures were needed due to incomplete occlusion or reperfusion. Endovascular strategies for posterior communicating artery aneurysms represent effective and relatively safe treatments. Simple coiling provides a higher immediate occlusion rate, although recanalization has been frequently reported, conversely, flow-diversion devices provide good long-term radiological outcomes.

Reliability of intraoperative ultrasound in detecting tumor residual after brain diffuse glioma surgery: a systematic review and meta-analysis.

Intraoperative ultrasonography (iUS) is considered an accurate, safe, and cost-effective tool to estimate the extent of resection of both high-grade (HGG) and low-grade (DLGG) diffuse gliomas (DGs). However, it is currently missing an evidence-based assessment of iUS diagnostic accuracy in DGs surgery. The objective of review is to perform a systematic review and meta-analysis of the diagnostic performance of iUS in detecting tumor residue after DGs resection. A comprehensive literature search for studies published through October 2018 was performed according to PRISMA-DTA and STARD 2015 guidelines, using the following algorithm: ("ultrasound" OR "ultrasonography" OR "ultra-so*" OR "echo*" OR "eco*") AND ("brain" OR "nervous") AND ("tumor" OR "tumour" OR "lesion" OR "mass" OR "glio*" OR "GBM") AND ("surgery" OR "surgical" OR "microsurg*" OR "neurosurg*"). Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of iUS in DGs were calculated. A subgroup analysis for HGGs and DLGGs was also conducted. Thirteen studies were included in the systematic review (665 DGs). Ten articles (409 DGs) were selected for the meta-analysis with the following results: sensitivity 72.2%, specificity 93.5%, LR- 0.29, LR+ 3, and DOR 9.67. Heterogeneity among studies was non-significant. Subgroup analysis demonstrates a better diagnostic performance of iUS for DLGGs compared with HGGs. iUS is an effective technique in assessing DGs resection. No significant differences are seen regarding iUS modality and transducer characteristics. Its diagnostic performance is higher in DLGGs than HGGs and could be worsened by previous treatments, surgical artifacts, and small tumor residue volumes.

Acute subdural hematoma in the elderly: outcome analysis in a retrospective multicentric series of 213 patients.

OBJECTIVE: The objective of this study was to analyze the risk factors associated with the outcome of acute subdural hematoma (ASDH) in elderly patients treated either surgically or nonsurgically. METHODS: The authors performed a retrospective multicentric analysis of clinical and radiological data on patients aged ≥ 70 years who had been consecutively admitted to the neurosurgical department of 5 Italian hospitals for the management of posttraumatic ASDH in a 3-year period. Outcome was measured according to the Glasgow Outcome Scale (GOS) at discharge and at 6 months' follow-up. A GOS score of 1-3 was defined as a poor outcome and a GOS score of 4-5 as a good outcome. Univariate and multivariate statistics were used to determine outcome predictors in the entire study population and in the surgical group. RESULTS: Overall, 213 patients were admitted during the 3-year study period. Outcome was poor in 135 (63%) patients, as 65 (31%) died during their admission, 33 (15%) were in a vegetative state, and 37 (17%) had severe disability at discharge. Surgical patients had worse clinical and radiological findings on arrival or during their admission than the patients undergoing conservative treatment. Surgery was performed in 147 (69%) patients, and 114 (78%) of them had a poor outcome. In stratifying patients by their Glasgow Coma Scale (GCS) score, the authors found that surgery reduced mortality but not the frequency of a poor outcome in the patients with a moderate to severe GCS score. The GCS score and midline shift were the most significant predictors of outcome. Antiplatelet drugs were associated with better outcomes; however, patients taking such medications had a better GCS score and better radiological findings, which could have influenced the former finding. Patients with fixed pupils never had a good outcome. Age and Charlson Comorbidity Index were not associated with outcome. CONCLUSIONS: Traumatic ASDH in the elderly is a severe condition, with the GCS score and midline shift the stronger outcome predictors, while age per se and comorbidities were not associated with outcome. Antithrombotic drugs do not seem to negatively influence pretreatment status or posttreatment outcome. Surgery was performed in patients with a worse clinical and radiological status, reducing the rate of death but not the frequency of a poor outcome.

Usefulness of Brain Positron Emission Tomography with Different Tracers in the Evaluation of Patients with Idiopathic Normal Pressure Hydrocephalous.

Idiopathic normal pressure hydrocephalus (iNPH) is the only form of dementia that can be cured by surgery. Its diagnosis relies on clinical and radiological criteria. Identifying patients who can benefit from surgery is challenging, as other neurological diseases can be concomitant or mimic iNPH. We performed a systematic review on the role of positron emission tomography (PET) in iNPH. We retrieved 35 papers evaluating four main functional aspects with different PET radiotracers: (1) PET with amyloid tracers, revealing Alzheimer's disease (AD) pathology in 20-57% of suspected iNPH patients, could be useful in predictions of surgical outcome. (2) PET with radiolabeled water as perfusion tracer showed a global decreased cerebral blood flow (CBF) and regional reduction of CBF in basal ganglia in iNPH; preoperative perfusion parameters could predict surgical outcome. (3) PET with 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG ) showed a global reduction of glucose metabolism without a specific cortical pattern and a hypometabolism in basal ganglia; [18F]FDG PET may identify a coexisting neurodegenerative disease, helping in patient selection for surgery; postsurgery increase in glucose metabolism was associated with clinical improvement. (4) Dopaminergic PET imaging showed a postsynaptic D2 receptor reduction and striatal upregulation of D2 receptor after treatment, associated with clinical improvement. Overall, PET imaging could be a useful tool in iNPH diagnoses and treatment response.

One-stage frame-guided resection and reconstruction with PEEK custom-made prostheses for predominantly intraosseous meningiomas: technical notes and a case series.

Treatment of intraosseous meningiomas is a two-staged procedure including tumor resection and cranial reconstruction. Several are the potential pitfall of this kind of surgery such as the conspicuous dimensions usually reached by the tumor and the peculiar involvement of irregular and deep bony structures. For these reasons, a surgical accurate virtual planning and a careful removal followed by tailored reconstruction are mandatory to achieve satisfactory results. We analyzed six patients operated on for intraosseous meningiomas between September 2014 and June 2018. Resection strategy was planned beforehand and shared with the manufacturer who provided the PEEK cranioplasty used in the reconstructive phase. Between September 2014 and April 2018, six patients affected by intraosseous meningioma were operated on. Female/male ratio was 5:1 and mean age was 54 ± 10.8 years. Mean FU was 20.3 ± 16.4 months. Mean dimension was 73.9 ± 24.8 mm × 69.2 ± 16.2 mm. Mean surgical time was 5.1 ± 1.1 h. The resection of intraosseous meningiomas requires the earliest and finest reconstructive phase. Custom-made implants should be considered the gold-standard for cranioplasty, especially in large skull and in frontal or hairless areas of the skull. The described technique is simple, accurate, and effective in achieving good results in disease control as well as cosmetic and functional restoration.

Diagnostic Performance and Prognostic Value of PET/CT with Different Tracers for Brain Tumors: A Systematic Review of Published Meta-Analyses.

BACKGROUND: Several meta-analyses reporting data on the diagnostic performance or prognostic value of positron emission tomography (PET) with different tracers in detecting brain tumors have been published so far. This review article was written to summarize the evidence-based data in these settings. METHODS: We have performed a comprehensive literature search of meta-analyses published in the Cochrane library and PubMed/Medline databases (from inception through July 2019) about the diagnostic performance or prognostic value of PET with different tracers in patients with brain tumors. RESULTS: We have summarized the results of 24 retrieved meta-analyses on the use of PET or PET/computed tomography (CT) with different tracers in brain tumors. The tracers included were: fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 methionine (11C-methionine), fluorine-18 fluoroethyltyrosine (18F-FET), fluorine-18 dihydroxyphenylalanine (18F-FDOPA), fluorine-18 fluorothymidine (18F-FLT), and carbon-11 choline (11C-choline). Evidence-based data demonstrated good diagnostic performance of PET with different tracers in detecting brain tumors, in particular, radiolabelled amino acid tracers showed the highest diagnostic performance values. All the PET tracers evaluated had significant prognostic value in patients with glioma. CONCLUSIONS: Evidence-based data showed a good diagnostic performance for some PET tracers in specific indications and significant prognostic value in brain tumors.

Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations.

INTRODUCTION: Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. METHODS: In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. RESULTS: This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. CONCLUSIONS: Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery.

Odontoid process and clival regeneration with Chiari malformation worsening after transoral decompression: an unexpected and previously unreported cause of "accordion phenomenon".

PURPOSE: Transoral odontoidectomy followed by occipito-cervical fixation is a widely used approach to relieve ventral compressions at the craniovertebral junction (CVJ). Despite the large amount of literature on this approach and its complications, no previous reports of odontoid process and clival regeneration following transoral odontoidectomy are present in the English literature. METHODS: We report the case of odontoid process and clival regeneration following transoral odontoidectomy. RESULTS: A 7-year-old boy presented with symptoms of brainstem and upper cervical spinal cord compression due to a complex malformation at the CVJ including a basilar invagination with Chiari malformation. A successful transoral microsurgical endoscopic-assisted odontoidectomy extended to the clivus was performed along with occipito cervical instrumentation and fusion. Clinical and radiological resolution of the CVJ compression was evident up to 2 years post-op, when the child had a relapse of some of the presenting symptoms and the follow-up CT and MRI scans showed a quite complete regrowth of the odontoid process, clival partial regeneration and recurrence of preoperative Chiari malformation. CONCLUSIONS: Besides the need of an accurate complete resection of the periosteum, which apparently was incompletely performed in our case, our experience suggests the need of resection of the odontoid down to the dentocentral synchondrosis and an accurate lateral removal of the bone surrounding the anterior tubercle of the Clivus is advised when an anterior CVJ decompression is required in children presenting a still evident synchondrosis at neuroradiological investigation.

Idiopathic cerebrospinal fluid overproduction: case-based review of the pathophysiological mechanism implied in the cerebrospinal fluid production.

Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications.

Venous Sinus Thrombosis-Associated with Posterior Cranial Fossa Surgery. A Systematic Review and Meta-Analysis of Natural History, Risk Factors, Treatment, and Outcome.

BACKGROUND: Venous sinus thromboses (VSTs) are rare complications of neurosurgical procedures in the proximity of the dural sinuses. Surgery of the posterior cranial fossa (PCF) and particularly of the cerebellopontine angle (CPA) shows increased risk of VST. VST management is challenging because anticoagulant therapy must be balanced with the risk of postoperative bleeding. We performed a systematic review and meta-analysis to summarize the most important neuroradiologic and clinical aspects of VST after PCF/CPA surgery. METHODS: We performed a comprehensive literature search to identify articles reporting data on VST after PCF/CPA surgery. We selected only comparative studies providing adequate neuroimaging assessing VST and a control group. RESULTS: We included 13 articles reporting 1855 patients. VST occurred in 251/1855 cases (estimated incidence, 17.3%; 95% confidence interval [CI], 12.4%-22.2%). Only presigmoid approach (odds ratio [OR], 2.505; 95% CI, 1.161-5.404; P = 0.019) and intraoperative sinus injury (OR, 8.95; 95% CI, 3.43-23.34; P < 0.001) showed a significant association with VST. VST-related symptoms were reported in 12/251 patients with VST (pooled incidence, 3.1%; 95% CI, 1%-5.2%). In particular, we found a significantly increased OR of cerebrospinal fluid leak (OR, 3.197; 95% CI, 1.899-5.382; P < 0.001) and cerebrospinal fluid dynamic alterations in general (OR, 3.625; 95% CI, 2.370-5.543; P < 0.001). Indications for VST treatment were heterogeneous: 58/251 patients underwent antithrombotics, with 6 treatment-related bleedings. Recanalization overall occurred in 56.4% (95% CI, 40.6%-72.2%), with no significant difference between treated and untreated patients. However, untreated patients had a favorable outcome. CONCLUSIONS: VST is a relatively frequent complication after PCF/CPA surgery and a presigmoid approach and intraoperative sinus injury represent the most significant risk factors. However, the clinical course is generally benign, with no advantage of antithrombotic therapy.