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BACKGROUND AND OBJECTIVES: The major clinical implication of brain arteriovenous malformations (bAVMs) is spontaneous intracranial hemorrhage. There is a growing body of experimental evidence proving that inflammation and blood-brain barrier (BBB) dysfunction are involved in both the clinical course of the disease and the risk of bleeding. However, how bAVM treatment affects perilesional BBB disturbances is yet unclear. METHODS: We assessed the permeability changes of the BBB using dynamic contrast-enhanced MRI (DCE-MRI) in a series of bAVMs (n = 35), before and at a mean of 5 (±2) days after treatment. A set of cerebral cavernous malformations (CCMs) (n = 16) was used as a control group for the assessment of the surgical-related collateral changes. The extended Tofts pharmacokinetic model was used to extract permeability (Ktrans) values in the lesional, perilesional, and normal brain tissues. RESULTS: In patients with bAVM, the permeability of BBB was higher in the perilesional of bAVM tissue compared with the rest of the brain parenchyma (mean Ktrans 0.145 ± 0.104 vs 0.084 ± 0.035, P = .004). Meanwhile, no significant changes were seen in the perilesional brain of CCM cases (mean Ktrans 0.055 ± 0.056 vs 0.061 ± 0.026, P = .96). A significant decrease in BBB permeability was evident in the perilesional area of bAVM after surgical resection (mean Ktrans 0.145 ± 0.104 vs 0.096 ± 0.059, P = .037). This benefit in BBB permeability reduction after surgery seemed to surpass the relative increase in permeability inherent to the surgical manipulation. CONCLUSION: In contrast to CCMs, BBB permeability in patients with bAVM is increased in the perilesional parenchyma, as assessed using DCE-MRI. However, bAVM surgical resection seems to reduce BBB permeability in the perilesional tissue. No evidence of the so-called breakthrough phenomenon was detected in our series. DCE-MRI could become a valuable tool to follow the longitudinal course of BBB damage throughout the natural history and clinical course of bAVMs.

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OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).

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BACKGROUND: Incidence, clinical course, and fatality of spontaneous subarachnoid hemorrhage (SAH) are evolving, with prevalence of risk factors diminishing, implementation of early detection programs and strategies for priority aneurysm exclusion, technical refinement with less invasive procedures, and improvements in neurocritical care. Modern epidemiological and prognostic data are lacking, especially in southern European and Mediterranean populations. METHODS: A prospective multicenter observational study on SAH was held in Catalonia, Northeast Spain, from 2020 to 2022 (HSACat project). All public tertiary hospitals participated in a common registry. Primary end points were functional outcomes (modified Rankin Scale) and mortality at 12 months. Secondary aims included epidemiological data, passage of patients between referral and tertiary hospitals, diagnostic and treatment delays, and in-hospital complications. RESULTS: Of 550 SAH cases reported in Catalonia (2020-2022), a complete registry for analysis was available for 474. Death rate was 20.6% during hospital admission and 26.9% at 1 year. Good functional outcome (modified Rankin Scale score 0-2) was observed in 63.4%, 70.1%, and 76.0% at 3, 6, and 12 months. Age at presentation was younger in men, patients who smoked, and patients with hypertension (P < 0.05). The female-to-male ratio was 3:2 except in the nonaneurysmal group. Time from onset to tertiary hospital admission was longer in rural than in metropolitan areas (7.0 hours vs. 4.7 hours, P < 0.01). Aneurysm occlusion in the first 72 hours was achieved in 83.3%; mainly endovascularly (77.5%) followed by microsurgically (19.3%). CONCLUSIONS: Even when most patients received timely aneurysm treatment, case fatality rates were considerably high. Data provided by the HSACat project may have public health effects and be used to guide prevention programs and screening strategies.

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Hyperglycemia during early brain injury (EBI) period after spontaneous subarachnoid hemorrhage (SAH) is associated with poor outcome, but the underlying physiopathology is unknown. This study assessed if hyperglycemia during EBI is associated with markers of neuroaxonal injury and whether these biomarkers partially account for the association between hyperglycemia and poor clinical outcome. Ninety-two SAH patients admitted within 24 h of bleeding onset were prospectively included. Glucose levels were measured at arrival and every 6 h for 72 h. Serum neurofilament light chain (NFL) levels were measured at 72 h. Functional outcome was assessed with the modified Rankin Scale (mRS) at 90 days (poor outcome, mRS > 2). The association between glucose metrics, NFL levels, and clinical outcome was assessed with univariate and multivariate analyses. Mediation analysis was performed to examine the potential chain in which NFL may mediate the relationship between glucose and functional outcome. Higher glucose and NFL levels during EBI were associated with poor clinical outcome in adjusted analysis. NFL levels were associated with older age, higher initial severity, and higher glucose levels during EBI period. In adjusted mediation analyses, the association between glucose and clinical outcome was significantly mediated by NFL levels. The mediator NFL explained 25% of the association between glucose during EBI period and poor functional outcome at 90 days. In SAH, the association between glucose levels during EBI and poor clinical outcome might be significantly mediated by NFL levels. The link between hyperglycemia and poor clinical outcome might be explained in part through secondary neuroaxonal injury.

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Introduction: Large and Giant intracranial aneurysms (LGIAs) have become the paradigm for which endovascular techniques do not provide satisfactory results. Yet, microsurgery is followed by non-negligible rates of morbimortality. This scenario may have changed since the introduction of flow-diversion devices. Research question: Contemporary and standardised revision on microsurgical and endovascular results, with emphasis on anterior circulation LGIAs. Materials and methods: A systematic literature search was conducted in two databases (PubMed and Embase) on treatment outcomes of LGIAs of the anterior circulation, after the introduction of flow-diverters 2008/01/01, till 2023/05/20. Small case series (<5 cases), series including >15% of posterior circulation aneurysms, and studies not reporting clinical and/or angiographic outcomes were excluded. Results: 44 relevant studies (observational cohorts) were identified, including 2923 LGIAs predominantly from anterior circulation. Mean follow-up 22 (±20) months. 1494 (51%) LGIAs were treated endovascularly and 1427 (49%) microsurgically. According to the random effects model, pooled rates of favourable clinical outcomes were 85.8% (CI 95% 82.6-88.4), complete occlusion 69.4% (CI 95% 63.7-7.46), complications 19.6% (CI 95%16-23.9) and mortality 5.6% (CI 95% 4.4-7.1). Focusing on type of treatment, occlusion rates are higher with microsurgical (842/993, 85% vs 874/1,299, 67%), although good outcomes are slightly more frequent with endovascular (1045/1,135, 92% vs 1120/1,294, 87%). Discussion and conclusions: According to contemporary data about occlusion rates, functional outcomes, and complications, primary or secondary treatment of LGIAs of the anterior circulation seems justified. Microsurgical occlusion rates are higher in LGIAs. An expert consensus on reporting complications and management strategies is warranted.

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BACKGROUND AND OBJECTIVES: Minimally invasive endoscopic approaches in cranial base surgery have been developing in the past decades. The transorbital (TO) route is one promising alternative, yet its adequacy for intracranial vascular lesions remains unclear. The present anatomic work aimed to test the feasibility and to provide a qualitative description of the endoscopic TO approach for the anterior circulation, namely the internal carotid artery and the middle cerebral artery. METHODS: Seven embalmed adult cadaveric specimens (12 sides) were used in the study. Each side was approached in 3 successive steps: (1) Superior-eyelid TO approach, with great and lesser sphenoid wing removal. (2) Removal of anterior clinoid process (ACP). (3) Removal of the lateral orbital rim. All the procedures were performed under endoscopic view. RESULTS: The TO approach without removing the ACP allowed to dissect the sphenoidal and lateral segments of the Sylvian fissure with an adequate identification of the middle cerebral artery bifurcation in all specimens. The removal of the ACP allowed further dissection toward the opticocarotid cistern, with the identification of the ophthalmic, posterior communicating, and the anterior choroidal arteries. The internal carotid artery bifurcation and A1 segment were also readily identified. Finally, removal of the lateral orbital rim provided a wider and more comfortable access to the above-mentioned vascular structures. CONCLUSION: According to our anatomic data, the TO approach can be used to reach the main vascular components of the anterior circulation. This opens the field for exploring its application in the treatment of vascular pathology, particularly aneurysms.

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INTRODUCTION: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. MATERIALS AND METHODS: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. RESULTS: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. DISCUSSION AND CONCLUSION: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.

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Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 27 patients with severe brain injury (10 traumatic brain injury and 17 subarachnoid hemorrhage patients) were included, with a total of 67 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 h pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Our results suggest that brain metabolism is altered after an IHT of neurocritical ill patients particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.

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BACKGROUND: In recent years, the endoscopic transorbital (TO) approach has gained increasing interest for the treatment of middle cranial fossa lesions. We propose a technical refinement to the conventional superior eyelid TO approach, which improves the surgical exposure and augments the working angles when targeting the opticocarotid region. METHODS: Four embalmed adult cadaveric specimens (8 sides) were dissected at the Laboratory of Surgical Neuroanatomy of our institution. A TO approach was performed, with removal of the anterior clinoid process and the lateral orbital rim. Subsequently, the MacCarty keyhole was drilled in the superolateral orbital wall. Given that the lesser sphenoid wing was already drilled in the conventional TO craniectomy, the opening of the keyhole was essentially a lateral extension of the craniectomy. RESULTS: The procedure was successfully conducted in all 4 orbits. Clinoidectomy was performed either before or after extending the craniectomy to the MacCarty point. Extending the craniectomy made anterior clinoidectomy easier, by increasing the surgical exposure, and allowing a more lateral entrance for the endoscope. The extension also facilitated frontal lobe retraction, and it facilitated the optic nerve and carotid artery manipulation. Postoperative computed tomography scans showed a minimal 10-mm craniectomy extension, which remained covered by the temporal muscle after reconstruction. CONCLUSIONS: The modified endoscopic TO approach with the extension of the craniectomy to MacCarty point improves surgical access and visualization of the opticocarotid region. This facilitates anterior clinoidectomy and optic nerve decompression. Although it implies judicious instrument manipulation and a larger incision size, further studies can define its potential benefits.

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INTRODUCTION: Stroke Units (SU) have been suggested as an alternative to Intensive Care units (ICU) for initial admission of low-grade non-aneurysmal spontaneous subarachnoid haemorrhage (naSAH). We hypothesised that the incidence of in-hospital complications and long-term clinical outcomes in low-grade naSAH patients would be comparable in both settings, and that a cost-minimisation analysis would favour the use of SU. PATIENTS AND METHODS: Retrospective, single-centre study at a third-level stroke-referral hospital, including low-grade spontaneous naSAH patients with WFNS 1-2. Primary outcomes were death and functional status at 3 months. Secondary outcomes were incidence of in-hospital major neurological and systemic complications. Additionally, a cost-minimisation analysis was conducted to estimate the average cost savings that could be achieved with the most efficient approach. RESULTS: Out of 96 naSAH patients, 30 (31%) were initially admitted to ICU and 66 (69%) to SU. Both groups had similar demographic and radiological features except for a higher proportion of WFNS 2 in ICU subgroup. There were no statistically significant differences between ICU and SU-managed subgroups in death rate (2 (7%) and 1 (2%), respectively), functional outcome at 90 days (28 (93%) and 61 (92%) modified Rankin Scale 0-2) or neurological and systemic in-hospital complications. Cost-minimisation analysis demonstrated significant monetary savings favouring the SU strategy. DISCUSSION AND CONCLUSION: Initial admission to the SU appears to be a safe and cost-effective alternative to the ICU for low-grade naSAH patients, with comparable clinical outcomes and a reduction of hospitalisation-related costs. Prospective multicenter randomised studies are encouraged to further evaluate this approach.

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BACKGROUND: In spontaneous subarachnoid haemorrhage (SAH) accurate determination of the bleeding source is paramount to guide treatment. Traditionally, the bleeding pattern has been used to predict the aneurysm location. Here, we have tested a software-based tool, which quantifies the volume of intracranial blood and stratifies it according to the regional distribution, to predict the location of the ruptured aneurysm. METHODS: A consecutive series of SAH patients admitted to a single tertiary centre between 2012-2018, within 72 h of onset, harbouring a single intracranial aneurysm. A semi-automatized method of blood quantification, based on the relative density increase, was applied to initial non-contrast CTs. Five regions were used to define the bleeding patterns and to correlate them with aneurysm location: perimesencephalic, interhemispheric, right/left hemisphere and intraventricular. RESULTS: 68 patients were included for analysis. There was a strong association between the distribution of blood and the aneurysm location (p < 0.001). In particular: ACom and interhemispheric fissure (p < 0.001), MCA and ipsilateral hemisphere (p < 0.001), ICA and ipsilateral hemisphere and perimesencephalic cisterns (p < 0.001), PCom and hemispheric, perimesencephalic and intraventricular (p = 0.019), and PICA and perimesencephalic and intraventricular (p < 0.001). The internal diagnostic value was high (AUROC ≥ 0.900) for these locations. CONCLUSION: Regional automatised volumetry seems a reliable and objective tool to quantify and describe the distribution of blood within the subarachnoid spaces. This tool accurately predicts the location of the ruptured aneurysm; its use may be prospectively considered in the emergency setting when speed and simplicity are attained.

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BACKGROUND: Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete samples. The focus of the machine learning researcher is to optimise the classifier's performance. METHODS: We utilise three simulated and three real-world clinical datasets with different feature types and missingness patterns. Initially, we evaluate how the downstream classifier performance depends on the choice of classifier and imputation methods. We employ ANOVA to quantitatively evaluate how the choice of missingness rate, imputation method, and classifier method influences the performance. Additionally, we compare commonly used methods for assessing imputation quality and introduce a class of discrepancy scores based on the sliced Wasserstein distance. We also assess the stability of the imputations and the interpretability of model built on the imputed data. RESULTS: The performance of the classifier is most affected by the percentage of missingness in the test data, with a considerable performance decline observed as the test missingness rate increases. We also show that the commonly used measures for assessing imputation quality tend to lead to imputed data which poorly matches the underlying data distribution, whereas our new class of discrepancy scores performs much better on this measure. Furthermore, we show that the interpretability of classifier models trained using poorly imputed data is compromised. CONCLUSIONS: It is imperative to consider the quality of the imputation when performing downstream classification as the effects on the classifier can be considerable.

Many artificial intelligence (AI) methods aim to classify samples of data into groups, e.g., patients with disease vs. those without. This often requires datasets to be complete, i.e., that all data has been collected for all samples. However, in clinical practice this is often not the case and some data can be missing. One solution is to 'complete' the dataset using a technique called imputation to replace those missing values. However, assessing how well the imputation method performs is challenging. In this work, we demonstrate why people should care about imputation, develop a new method for assessing imputation quality, and demonstrate that if we build AI models on poorly imputed data, the model can give different results to those we would hope for. Our findings may improve the utility and quality of AI models in the clinic.

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Hyperglycemia has been linked to worsening outcomes after subarachnoid hemorrhage (SAH). Nevertheless, the mechanisms involved in the pathogenesis of SAH have been scarcely evaluated so far. The role of hyperglycemia was assessed in an experimental model of SAH by T2 weighted, dynamic contrast-enhanced magnetic resonance imaging (T2W and DCE-MRI), [18F]BR-351 PET imaging and immunohistochemistry. Measures included the volume of bleeding, the extent of cerebral infarction and brain edema, blood brain barrier disruption (BBBd), neutrophil infiltration and matrix metalloprotease (MMP) activation. The neurofunctional outcome, neurodegeneration and myelinization were also investigated. The induction of hyperglycemia increased mortality, the size of the ischemic lesion, brain edema, neurodegeneration and worsened neurological outcome during the first 3 days after SAH in rats. In addition, these results show for the first time the exacerbating effect of hyperglycemia on in vivo MMP activation, Intercellular Adhesion Molecule 1 (ICAM-1) expression and neutrophil infiltration together with increased BBBd, bleeding volume and fibrinogen accumulation at days 1 and 3 after SAH. Notably, these data provide valuable insight into the detrimental effect of hyperglycemia on early BBB damage mediated by neutrophil infiltration and MMP activation that could explain the worse prognosis in SAH.

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OBJECTIVE: The endoscopic transorbital approach (ETOA) is a minimally invasive approach that could be particularly appropriate for management of spheno-orbital meningiomas. The aim of this study was to perform a systematic review of the literature on the management of spheno-orbital meningiomas via the minimally invasive ETOA, searching for clinical scenarios in which this approach could be best indicated. A secondary aim was to describe 4 illustrative cases. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data including patient demographics, tumor features, and surgical and postoperative outcomes were collected. Cases from our initial experience with ETOA were included in the data. RESULTS: Data of 58 patients from 9 selected records and from our surgical series were collected. Subtotal, near-total, and gross total resection rates were 44.8%, 10.3%, and 32.7%, respectively. Symptom improvement after surgery was 100% for proptosis, 93% for visual impairment, and 87% for ophthalmoplegia. The most common postoperative complications were transient ophthalmoplegia and maxillary nerve hypoesthesia. Cerebrospinal fluid leak was reported in 2 patients. CONCLUSIONS: Our findings support the use of the ETOA for management of spheno-orbital meningiomas, particularly in at least 3 clinical scenarios: 1) when predominant hyperostotic bone is present; 2) when a globular tumor not showing excessive medial or inferior infiltration is being treated; 3) as part of a multistage treatment for diffuse lesions.

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BACKGROUND: Completely extradural spinal schwannomas have a unique morphology (dumbbell tumors) with an intra- and extraspinal component. When they compromise two contiguous vertebral bodies or have an extraspinal extension >2.5 cm, they are classified as giant spinal schwannomas. The aim of this study is to present our experience in the surgical management of completely extradural giant spinal schwannomas with a minimally invasive approach. METHODS: This study is a case series of patients treated at the Neurosurgery Department of the University Clinical and Provincial Hospital of Barcelona, Spain, between January 2016 and December 2019. RESULTS: Fifteen patients met the inclusion criteria, with thoracic and lumbar spines being the most frequent locations. All patients underwent surgical treatment, with a mini-open interlaminar and far-lateral technique. Total gross resection was accomplished in all patients and spine instrumentation was not necessary. CONCLUSIONS: Microsurgery is the treatment of choice for spinal schwannomas, and gross total resection with low morbidity must be the surgical goal. Mini-open interlaminar and far-lateral access is a valid surgical option, with low morbidity in experienced hands, and there is no need for spinal instrumentation.

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BACKGROUND: Subarachnoid hemorrhage (SAH) entails high morbidity and mortality rates. Convolutional neural networks (CNN) are capable of generating highly accurate predictions from imaging data. Our objective was to predict mortality in SAH patients by processing initial CT scans using a CNN-based algorithm. METHODS: We conducted a retrospective multicentric study of a consecutive cohort of patients with SAH. Demographic, clinical and radiological variables were analyzed. Preprocessed baseline CT scan images were used as the input for training using the AUCMEDI framework. Our model's architecture leveraged a DenseNet121 structure, employing transfer learning principles. The output variable was mortality in the first three months. RESULTS: Images from 219 patients were processed; 175 for training and validation and 44 for the model's evaluation. Of the patients, 52% (115/219) were female and the median age was 58 (SD = 13.06) years. In total, 18.5% (39/219) had idiopathic SAH. The mortality rate was 28.5% (63/219). The model showed good accuracy at predicting mortality in SAH patients when exclusively using the images of the initial CT scan (accuracy = 74%, F1 = 75% and AUC = 82%). CONCLUSION: Modern image processing techniques based on AI and CNN make it possible to predict mortality in SAH patients with high accuracy using CT scan images as the only input. These models might be optimized by including more data and patients, resulting in better training, development and performance on tasks that are beyond the skills of conventional clinical knowledge.

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Introduction: Delayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs)-small non-coding RNAs involved in clue gene regulation at the post-transcriptional level-as biomarkers of neurological outcomes in SAH patients. Methods: We analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples. Results: We found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes. Conclusion: These observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-ß inflammatory pathway and blood-brain barrier disruption.

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Objective: Superior eyelid endoscopic transorbital approach (SETOA) is nowadays gaining progressive application in neurosurgical scenarios. Both anatomic and clinical reports have demonstrated the possibility of taking advantage of the orbital corridor as a minimally invasive route to reach anterior and middle cranial fossae and manage selected surgical lesions developing in these areas. The aim of this paper is to further shed light on other anatomic regions of the skull base as seen from a transorbital perspective, namely, the posterior cranial fossa and tentorial area, describing technical feasibility and steps in reaching this area through an extradural-transtentorial approach and providing quantitative evaluations of the "working area" obtained through this route. Material and methods: Four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise dissection of the transorbital approach to the tentorial area was described. Qualitative anatomical descriptions and quantitative analyses of working were evaluated by using pre- and postdissections CT and MRI scans, and three-dimensional reconstructions were made using Amira software. Results: With the endoscopic transorbital approach, posterior cranial fossa dura was reached by an extradural middle cranial fossa approach and drilling of the petrous apex. After clipping the superior petrosal sinus, the tentorium was divided and cut. An endoscope was then introduced in the posterior cranial fossa at the level of the tentorial incisura. Qualitative analysis provided a description of the tentorial and petrosal surfaces of the cerebellum, middle tentorial incisura, cerebellopontine fissures, and, after arachnoid dissection, by a 30° endoscopic visualization, the posterior aspect of the cerebellomesencephalic fissure. Quantitative analysis of the "working area" obtained after bone removal was also provided. Conclusions: This anatomic qualitative and quantitative study sheds light on the anatomy of the posterior cranial fossa contents, such as the tentorial area and incisura, as seen through a transorbital perspective. The first aim of the article is to enrich the anatomical knowledge as seen through this relatively new corridor and to provide quantitative details and insights into the technical feasibility of reaching these regions in a surgical scenario.

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Hyperglycaemia, hypoglycaemia and higher glucose variability during the Early Brain Injury (EBI) period of aneurysmal subarachnoid hemorrhage (aSAH) have been associated with poor clinical outcome. However, it is unclear whether these associations are due to direct glucose-driven injury or if hyperglycaemia simply acts as a marker of initial severity. Actually, strict glucose control with intensive insulin therapy has not been demonstrated as an effective strategy for improving clinical outcomes after aSAH. Currently published studies describing an association between hyperglycaemia and prognosis in aSAH patients have been based on isolated glucose measurements and did not incorporate comprehensive dynamic evaluations, such as those derived from subcutaneous continuous glucose monitoring devices (CMG). Arguably, a more accurate knowledge on glycaemic patterns during the acute phase of aSAH could increase our understanding of the relevance of glycaemia as a prognostic factor in this disease as well as to underpin its contribution to secondary focal and diffuse brain injury. Herein, we have summarized the available evidence on the diagnostic and prognostic relevance of glucose metrics during the acute phase of cerebrovascular diseases, focusing in the EBI period after aSAH. Overall, obtaining a more precise scope of acute longitudinal glucose profiles could eventually be useful for improving glucose management protocols in the setting of acute aSAH and to advance toward a more personalized management of aSAH patients during the EBI phase.

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BACKGROUND: Cervical spine balance and alignment targets after cervical spine surgery are poorly established in patients with cervical spine degenerative disease surgically treated by anterior cervical discectomy and fusion (ACDF). The objective of the study is to determine the correlation between radiological and clinical outcomes in patients surgically treated by ACDF with 2 different stand-alone cervical cages. METHODS: Clinical outcomes were evaluated using visual analog scale (VAS), Neck Disability Index (NDI), Nurick Scale, and Japanese Orthopedic Association score for myelopathy. Radiological evaluation included cervical and segmental Cobb angles, cervical sagittal vertical axis (cSVA), T1 slope (T1s), C0-C2 angle, fusion rates, adjacent segment degeneration, and cage subsidence. RESULTS: A total of 80 patients were included with an average age of 53 years. There was a statistically significant improvement in both clinical and radiological evaluations. There was a statistical significant correlation between cervical pain on cervical VAS and cSVA. There was a significant correlation between postoperative T1s and cSVA, related to the improvement in cervical angles. There was no significant difference in rates of fusion, adjacent segment changes, or reoperation between both cervical cages, and there was a higher rate of subsidence in the Aleutian group. There were significant differences between both groups on postoperative NDI and VAS, but this difference is not maintained during follow-up. CONCLUSIONS: Cervical sagittal balance is directly related to clinical outcome in patients with cervical spine degenerative disease. Both cervical implants analyzed were comparable in clinical and radiological outcomes. CLINICAL RELEVANCE: There are important clinical and radiological parameters that should be taken into account for the analysis of the surgical outcome of patients treated by ACDF; this is one of the few studies that report the results with 2 different cervical cage designs.