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.

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.

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.

Decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A real-world study.

BACKGROUND: Malignant middle cerebral artery infarction (mMCA) is a devastating disease with rates of fatality as high as 80%. Decompressive hemicraniectomy (DHC) reduces mortality, but many survivors inevitably remain severely disabled. This study aimed to analyze patients with mMCA undergoing DHC or best medical treatment (BMT) baseline characteristics and factors linked to therapeutic choice and determinants of prognosis. METHODS: We recorded clinical and radiological features of patients undergoing BMT or DHC. The two groups were compared for epidemiology, clinical presentation, neuroimaging, and prognosis. Regression analysis was performed to identify predictors of surgical treatment and outcome. RESULTS: One hundred twenty-five patients were included (age 67.41 ± 1.39 yo; 65 M). Patients undergoing DHC (N = 57) were younger (DHC 55.71 ± 1.48 yo vs. BMT 77.22 ± 1.38) and had midline shift (DHC 96.5% (55/57) vs. BMT 35.3% (24/68), a larger volume of the affected hemisphere and reduced ventricles volume as compared to BMT. The chance of surgery depended on age (Exp(B) = 0.871, p < 0.001), clinical status at onset (NIHSS Exp(B) = 0.824, p = 0.030) and volume of the ventricle of the affected hemisphere (Exp(B) = 0.736, p = 0.006). Death rate during admission was significantly lower for DHC (DHC 15% (6/41) vs BMT 71.7% (38/53), Fisher's test = 30.234, p < 0.001). CONCLUSION: Although DHC may cause prolonged hospitalization and long-term disabled patients, it is a lifesaving therapy that should be considered for selected patients with mMCA but perioperative complications and cost-utility should be considered. Patients and families should be correctly counseled about this therapeutic choice and its short- and long-term consequences.

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.

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.

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.

Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma.

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients' survival suggests a prognostic role for this protein.

Retrospective Application of UIATS Recommendations to a Multicenter Cohort of Ruptured Intracranial Aneurysms: How It Would Have Oriented the Treatment Choices?

BACKGROUND: Decisions to treat unruptured intracranial aneurysms remain challenging, as the risk of rupture needs to be balanced with risk of intervention. In 2015, the Unruptured Intracranial Aneurysm Treatment Score (UIATS) was introduced to assist physicians in the decision making process. As its reliability is still debated, we retrospectively applied UIATS to a multicenter cohort of aneurysmal subarachnoid hemorrhage patients to test its performance in suggesting treatment in patients with known natural history. METHODS: Demographical, clinical, and radiological data of subarachnoid patients admitted in 2 referral cerebrovascular centers were collected. UIATS was individually calculated for each patient, and resulting recommendations were pooled in 3 groups (favor treatment, favor conservative management, unclear indication). RESULTS: One-hundred and forty-six patients were included in this study. In the event of aneurysm discovery previous to their rupture, UIATS calculation revealed that 40 (27.4%) patients would have received an indication-to-treat advice (mean score: 4.58 ± 1.32), 46 (31.5%) would have been suggested a conservative management (mean score: -7.07 ± 4.15), and 60 (41.1%) would have been included in an unclear recommendation group (mean score: 0.07 ± 1.42). UIATS sensitivity ranged between 27% and 68% depending on the inclusion of patients with unclear indication within the conservative or intervention group. CONCLUSIONS: In our study, UIATS would have failed to provide a clear recommendation to treat in up to 72.6% of patients whose aneurysm eventually ruptured. In agreement with previous reports, we provide additional evidence that some unruptured intracranial aneurysms may elude UIATS sensitivity. Further long-term prospective studies are necessary to assess UIATS reliability in real-world clinical practice.

Do antiplatelet and anticoagulant drugs modify outcome of patients treated for chronic subdural hematoma? Still a controversial issue.

BACKGROUND: Anticoagulants (ACs) and antiplatelet aggregation agents (AAAs) seem to be correlated to a higher incidence of chronic subdural hematoma (CSDH) but whether or not they contribute to its recurrence is debated. Few data are available on clinical outcomes and indications for the management of this therapy are not so well defined. We investigated the role of ACs and AAAs in modifying patients' clinical outcomes treated for CSDH, especially for re-bleedings. METHODS: This retrospective study, enrolled patients treated for CSDH. Patients characteristics were recorded including drugs used (antiplatelet/anticoagulant) and clinical conditions (Modified Rankin Scale [mRS]) upon admission. Patients underwent surgery (burrhole vs. minicraniectomy) with subdural drainage positioning. Clinical/radiological follow-ups were performed at one and six months. Chi-square/Fisher's Exact test were used to compare variables and stepwise backward logistic regression analysis was used for defining their impact on complications, risk of re-bleeding and reoperation. RESULTS: Overall, 230 patients (45 on ACs, 76 on AAAs and nine on both) were enrolled. Higher mRS scores were significantly associated with a higher risk of general complications (OR=3.78, 95% CI: 1.66-8.62, P=0.002), higher risk of rebleeding (OR =15.82, 95% CI: 4.33-57.90, P<0.001) and re-operation (OR=11.39, 95% CI: 3.35-37.56, P<0.0001). No statistically significant association was found between AAAs or ACs and complications or re-bleedings or risk of reoperation. CONCLUSIONS: AAAs and ACs alone do not seem to worsen the clinical outcome or increase re-bleedings. mRS may be a predicting factor, since patients with higher scores showed a worse outcome and an increased risk of re-bleeding, general complications and reoperation.

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.

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.

Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. METHODS: The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. RESULTS: CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. CONCLUSION: Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients.

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.