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.

Geometry and Symmetry of Willis' Circle and Middle Cerebral Artery Aneurysms Development.

Background: A relationship between the geometry and symmetry of Willis' circle and intracranial aneurysms was reported for anterior communicating and posterior communicating (PCom) aneurysms. A similar association with the middle cerebral artery (MCA) aneurysms instead appeared weaker. Methods: We reviewed 432 patients from six Italian centers with unilateral MCA aneurysms, analyzing the relationship between the caliber and symmetry of Willis' circle and the presence of ruptured and unruptured presentation. CT-angiograms were evaluated to assess Willis' circle geometrical characteristics and the MCA aneurysm side, dimension and rupture status. Results: The hypoplasia of the first segment of the anterior cerebral artery (A1) was in approximately one-quarter of patients and PCom hypoplasia was in almost 40%. About 9% had a fetal PCom ipsilaterally to the aneurysm. By comparing the aneurysmal and healthy sides, only the PCom hypoplasia appeared significantly higher in the affected side. Finally, the caliber of the internal carotid artery (ICA) and the first segment of MCA (M1) caliber were significantly greater in patients with unruptured aneurysms, and PCom hypoplasia appeared related to the incidence of an ipsilateral MCA aneurysm and its risk of rupture. Conclusions: Although according to these findings asymmetries of Willis' circle are shown to be a risk factor for MCA aneurysm formation and rupture, the indifferent association with ipsilateral or contralateral hypoplasia remains a datum of difficult hemodynamic interpretation, thereby raising the concern that this association may be more casual than causal.

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.

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.

Combined 18F-FDG PET-CT markers in dementia with Lewy bodies.

INTRODUCTION: 18F-Fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG-PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis. METHODS: FDG-PET scans were visually and semi-quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi-quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features. RESULTS: At follow-up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi-quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%). DISCUSSION: FDG-PET is a valuable tool in DLB diagnosis, having visual and semi-quantitative analyses with the highest diagnostic accuracy at ML analyses.

Current Knowledge about the Peritumoral Microenvironment in Glioblastoma.

Glioblastoma is a deadly disease, with a mean overall survival of less than 2 years from diagnosis. Recurrence after gross total surgical resection and adjuvant chemo-radiotherapy almost invariably occurs within the so-called peritumoral brain zone (PBZ). The aim of this narrative review is to summarize the most relevant findings about the biological characteristics of the PBZ currently available in the medical literature. The PBZ presents several peculiar biological characteristics. The cellular landscape of this area is different from that of healthy brain tissue and is characterized by a mixture of cell types, including tumor cells (seen in about 30% of cases), angiogenesis-related endothelial cells, reactive astrocytes, glioma-associated microglia/macrophages (GAMs) with anti-inflammatory polarization, tumor-infiltrating lymphocytes (TILs) with an "exhausted" phenotype, and glioma-associated stromal cells (GASCs). From a genomic and transcriptomic point of view, compared with the tumor core and healthy brain tissue, the PBZ presents a "half-way" pattern with upregulation of genes related to angiogenesis, the extracellular matrix, and cellular senescence and with stemness features and downregulation in tumor suppressor genes. This review illustrates that the PBZ is a transition zone with a pre-malignant microenvironment that constitutes the base for GBM progression/recurrence. Understanding of the PBZ could be relevant to developing more effective treatments to prevent GBM development and recurrence.

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.

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody-drug conjugate therapy in glioblastoma.

Glioblastoma multiforme (GBM) is a lethal disease characterized by an overall survival of about 1 year, making it one of the most aggressive tumours, with very limited therapeutic possibilities. Specific biomarkers for early diagnosis as well as innovative therapeutic strategies are urgently needed to improve the management of this deadly disease. In this work, we demonstrated that vesicular galectin-3-binding protein (LGALS3BP), a glycosylated protein overexpressed in a variety of human malignancies, is a potential GBM disease marker and can be efficiently targeted by a specific antibody-drug conjugate (ADC). Immunohistochemical analysis on patient tissues showed that LGALS3BP is highly expressed in GBM and, compared with healthy donors, the amount of vesicular but not total circulating protein is increased. Moreover, analysis of plasma-derived extracellular vesicles from mice harbouring human GBM revealed that LGALS3BP can be used for liquid biopsy as a marker of disease. Finally, an ADC targeting LGALS3BP, named 1959-sss/DM4, specifically accumulates in tumour tissue, producing a potent and dose-dependent antitumor activity. In conclusion, our work provides evidence that vesicular LGALS3BP is a potential novel GBM diagnostic biomarker and therapeutic target deserving further preclinical and clinical validation.

Comparison Between Intrasylvian and Intracerebral Hematoma Associated with Ruptured Middle Cerebral Artery Aneurysms: Clinical Implications, Technical Considerations, and Outcome Evaluation.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to a middle cerebral artery (MCA) aneurysm rupture is often associated with an intracerebral hematoma (ICH) or intrasylvian hematoma (ISH). METHODS: We reviewed 163 patients with ruptured MCA aneurysms associated with pure SAH or SAH plus ICH or ISH. The patients were first dichotomized according to the presence of a hematoma (ICH or ISH). Next, we performed a subgroup analysis comparing ICH versus ISH to explore their relationship with the most relevant demographic, clinical, and angioarchitectural features. RESULTS: Overall, 85 patients (52%) had a pure SAH, and 78 (48%) had presented with an associated ICH or ISH. No significant differences were observed in the demographics or angioarchitectural features between the 2 groups. However, the Fisher grade and Hunt-Hess score were higher for the patients with hematomas. A good outcome was observed in a higher percentage of patients with pure SAH compared with those with an associated hematoma (76% vs. 44%), although the mortality rates were comparable. Age, Hunt-Hess score, and treatment-related complications were the main outcome predictors on multivariate analysis. Patients with ICH appeared worse clinically compared with those with ISH. We also found that older age, a higher Hunt-Hess score, larger aneurysms, decompressive craniectomy, and treatment-related complications were associated with poor outcomes among the patients with an ISH, but not an ICH, which appeared, per se, as a more severe clinical condition. CONCLUSIONS: Our study has confirmed that age, Hunt-Hess score, and treatment-related complications influence the outcome of patients with ruptured MCA aneurysms. However, in the subgroup analysis of patients with SAH associated with an ICH or ISH, only the Hunt-Hess score at onset appeared as an independent predictor of the outcome.

Intraoperative thermal infrared imaging in neurosurgery: machine learning approaches for advanced segmentation of tumors.

Surgical resection is one of the most relevant practices in neurosurgery. Finding the correct surgical extent of the tumor is a key question and so far several techniques have been employed to assist the neurosurgeon in preserving the maximum amount of healthy tissue. Some of these methods are invasive for patients, not always allowing high precision in the detection of the tumor area. The aim of this study is to overcome these limitations, developing machine learning based models, relying on features obtained from a contactless and non-invasive technique, the thermal infrared (IR) imaging. The thermal IR videos of thirteen patients with heterogeneous tumors were recorded in the intraoperative context. Time (TD)- and frequency (FD)-domain features were extracted and fed different machine learning models. Models relying on FD features have proven to be the best solutions for the optimal detection of the tumor area (Average Accuracy = 90.45%; Average Sensitivity = 84.64%; Average Specificity = 93,74%). The obtained results highlight the possibility to accurately detect the tumor lesion boundary with a completely non-invasive, contactless, and portable technology, revealing thermal IR imaging as a very promising tool for the neurosurgeon.

Glioblastoma stem cells express non-canonical proteins and exclusive mesenchymal-like or non-mesenchymal-like protein signatures.

Glioblastoma (GBM) cancer stem cells (GSCs) contribute to GBM's origin, recurrence, and resistance to treatment. However, the understanding of how mRNA expression patterns of GBM subtypes are reflected at global proteome level in GSCs is limited. To characterize protein expression in GSCs, we performed in-depth proteogenomic analysis of patient-derived GSCs by RNA-sequencing and mass-spectrometry. We quantified > 10 000 proteins in two independent GSC panels and propose a GSC-associated proteomic signature characterizing two distinct phenotypic conditions; one defined by proteins upregulated in proneural and classical GSCs (GPC-like), and another by proteins upregulated in mesenchymal GSCs (GM-like). The GM-like protein set in GBM tissue was associated with necrosis, recurrence, and worse overall survival. Through proteogenomics, we discovered 252 non-canonical peptides in the GSCs, i.e., protein sequences that are variant or derive from genome regions previously considered non-protein-coding, including variants of the heterogeneous ribonucleoproteins implicated in RNA splicing. In summary, GSCs express two protein sets that have an inverse association with clinical outcomes in GBM. The discovery of non-canonical protein sequences questions existing gene models and pinpoints new protein targets for research in GBM.

Does the Timing of the Surgery Have a Major Role in Influencing the Outcome in Elders with Acute Subdural Hematomas?

BACKGROUND: The incidence of traumatic acute subdural hematomas (ASDH) in the elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays no clear role as a predictor. We investigated whether the timing of surgery had a major role in influencing the outcome in these patients. METHODS: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 year period in five Italian hospitals. Patients were divided into three surgical timing groups from hospital arrival: ultra-early (within 6 h); early (6-24 h); and delayed (after 24 h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at the Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed. RESULTS: We included 136 patients. About 33% died as a result of the consequences of ASDH and among the survivors, only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting the Glasgow Outcome Scale (GCS), which was on average lower in the ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared to be neither associated with survival nor with functional outcome, also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. CONCLUSIONS: An earlier surgery was offered to patients with worse clinical-radiological findings. Additionally, after stratification for GCS, it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.

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.

Comparison between rupture/growth risk scores and treatment recommendation scores application to aneurysmal subarachnoid hemorrhage patients: A multicenter cross-reliability assessment study.

BACKGROUND: Two score families were introduced to help clinicians about the decision-making regarding intracranial aneurysms management. The first family estimates the growth/rupture risk (GRS), whereas the second provides straightforward recommendation (RS) for treatment decisions. However, both remain poorly validated and little is known about their agreement. In this paper, we performed a retrospective concordance analysis among the two scores families through their application to a multicenter cohort of SAH patients. METHODS: Demographical, clinical and radiological data were extracted in conformance with the variables included in PHASES, UCAS, ELAPSS, Juvela's growth score (JGS), UIATS and Juvela's treatment score (JTS). Individual patients' score were calculated for both score families, and pooled data were then analyzed. RESULTS: Overall, 146 patients were included. True positive rates were: 51.4% for PHASES; 71.9% for UCAS; between 60.3% and 90.4% for JTS; and between 27.4% and 68.5% for UIATS. In patients showing UIATS unclear recommendation and low JTS score (RS), UCAS outperformed PHASES (GRS) in identifying aneurysms at higher risk of rupture. Same results we found for patients with conservative UIATS recommendation and very low JTS score. Forty-to-sixty percent of aneurysms with unclear or conservative RS recommendation would have been identified as at high risk with GRS. CONCLUSIONS: Retrospectively applied, JTS appeared outperforming UIATS in correctly recommending treatment in a higher percentage of patients. UIATS and JTS appeared agreeing more with UCAS than PHASES predictions. Around 50% of patients with unclear or conservative UIATS/JTS recommendations were been classified as at higher growth risk by ELAPSS and JGS.

The role of the craniotomy size in the surgical evacuation of acute subdural hematomas in elderly patients: a retrospective multicentric study.

BACKGROUND: Elderly patients operated for an acute subdural hematoma (ASDH) frequently have a poor outcome, with a high frequency of death, vegetative status, or severe disability (Glasgow Outcome Score, GOS, 1-3). Minicraniotomy has been proposed as a minimally invasive surgical treatment to reduce the impact of surgery in the elderly population. The present study aimed to compare the influence of the size of the craniotomy on the functional outcome in patients undergoing surgical treatment for ASDH. METHODS: We selected patients ≥70 years old admitted to 5 Italian tertiary referral neurosurgical for the treatment of a post-traumatic ASDH between January 1st 2016 and December 31st 2019. We collected demographic data, clinical data (GCS, GOS, Charlson Comorbidity Index-CCI, antiplatelet/anticoagulant therapy, neurological deficits, seizure, pupillary size, length of stay), surgical data (craniotomy size, dividing the patients into 3 groups based on the corresponding tertile, and surgery duration), radiological data (ASDH side and thickness, midline shift, other post-traumatic lesions, extent of ASDH evacuation) and we assessed the functional outcome at hospital discharge and 6-month follow-up considering GOS=1-3 as a poor outcome. ANOVA and Chi-squared tests and logistic regression models were used to assess differences in and associations between clinicalradiological characteristics and functional outcomes. RESULTS: We included 136 patients (76 males) with a mean age of 78±6 years. Forty-five patients underwent a small craniotomy, 47 a medium size, and 44 a large craniotomy. Among the different craniotomy size groups, there were no differences in gender, anticoagulant/antithrombotic therapy, CCI, side of ASDH, ASDH thickness, preoperative GCS, focal deficits, seizures, and presence of other posttraumatic lesions. Patients undergoing small craniotomies were older than patients undergoing medium-large craniotomies; ASDH treated with medium size craniotomy were thinner than the others; patients undergoing large craniotomies showed greater midline shift and a higher rate of anisocoria. The three groups did not differ for functional outcome and postoperative midline shift, but the length of surgery and the rate of >50% of ASDH evacuation were lower in the small craniotomy group. CONCLUSIONS: A small craniotomy was not inferior to larger craniotomies in determining functional outcomes in the treatment of ASDH in the elderly.

Clinical and radiological outcomes following open door laminoplasty: a single center evolution of the technique.

BACKGROUND: The aim of the present study was to compare and describe clinical and radiological outcomes after two different variants of open door laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: Fifty-five patients underwent cervical laminoplasty for CSM. Between 2005 to 2009, 32 patients underwent open-door laminoplasty (Group A) performed with a monolateral exposure with contralateral "green stick" laminar fracture. A technical variant consisting in bilateral exposure, spinous process removal and symmetrical muscular closure was applied in the other 23 (Group B), from 2009 to 2016. A retrospective analysis of surgical results between the two groups was performed. RESULTS: In group B, the mean operative time was longer, and the mean volume of intraoperative blood loss was much higher than in group A. Both differences were not significant (P=0.1601 and P=0.0884, respectively). The average hospitalization was non-significantly longer in group B (7.3±1.8 vs. 6.5±1.6 d; P=0.0947). Postoperatively, axial neck pain was more severe in group A at last follow-up than preoperatively (P>0.05). mJOA scores and Nurick grades improved significantly in both groups at last follow-up; in group A, the mean recovery rates were 41.5% by mJOA scores and 29.4% by Nurick grades, whereas in group B they were 52.7% and 36.8%, respectively. CONCLUSIONS: Applying some few variations to a standard monolateral approach, although slightly more time and blood consuming, could reduce the incidence of long-term axial symptoms and, in our experience, are not burdened by worsening of outcomes. A prospective, multicentric study with a longer follow-up should be conducted in order to confirm our findings.

Dynamic 11C-Methionine PET-CT: Prognostic Factors for Disease Progression and Survival in Patients with Suspected Glioma Recurrence.

PURPOSE: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. METHODS: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression. RESULTS: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = 0.002) and T/B (p < 0.001); deceased patients (16/67) showed higher SUVmax (p = 0.03), SUVmean (p = 0.03) and T/B (p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS (p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmaxTTP (p = 0.02, p = 0.01, respectively). SUVmaxTTP was the only dynamic parameter associated with PFS (p = 0.02) and OS (p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmaxTTP were predictive for PFS (all p < 0.05); SUVmaxTTP was predictive for OS (p = 0.02). At multivariate analysis, SUVmaxTTP remained significant for PFS (p = 0.03). CONCLUSION: Semiquantitative parameters and SUVmaxTTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Styloidogenic-cervical spondylotic internal jugular venous compression, a vascular disease related to several clinical neurological manifestations: diagnosis and treatment-a comprehensive literature review.

Internal jugular vein (IJV) stenosis is associated with several central nervous system disorders such as Ménière or Alzheimer's disease. The extrinsic compression between the styloid process and the C1 transverse process, is an emerging biomarker related to several clinical manifestations. However, nowadays a limited number of cases are reported, and few information are available about treatment, outcome and complications. Our aim is to collect and identify clinical-radiological characteristics, diagnosis and treatment of the styloidogenic internal jugular venous compression. We performed a comprehensive literature review. Studies reporting patients suffering from extracranial jugular stenosis were searched. For every patient we collected: demography, clinical and radiological characteristics and outcome, type of treatment, complications. Thirteen articles reporting 149 patients were included. Clinical presentation was non-specific. Most frequent symptoms were headache (46.3%), tinnitus (43.6%), insomnia (39.6%). The stenosis was monolateral in 51 patients (45.9%) and bilateral in 60 (54.1%). Anticoagulants were the most common prescribed drug (57.4%). Endovascular treatment was performed in 50 patients (33.6%), surgery in 55 (36.9%), combined in 28 (18.8%). Improvement of general conditions was reported in 58/80 patients (72.5%). Complications were reported in 23% of cases. Jugular stenosis is a complex and often underestimated disease. Conservative medical treatment usually fails while surgical, endovascular or a combined treatment improves general conditions in more than 70% of patients.