Brain metabolism response to intrahospital transfers in neurocritical ill patients and the impact of microdialysis probe location.

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.

Optimizing the Endoscopic Transorbital Approach: MacCarty Keyhole for Enhanced Surgical Exposure in the Opticocarotid Region.

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.

Stroke Unit as an alternative to Intensive Care Unit for initial hospital admission of low-grade non-aneurysmal subarachnoid haemorrhage: A safety and cost-minimisation analysis.

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.

Aneurysmal subarachnoid haemorrhage: Volumetric quantification of the blood distribution pattern to accurately predict the ruptured aneurysm location.

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.

The impact of imputation quality on machine learning classifiers for datasets with missing values.

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.

Multimodal imaging of the role of hyperglycemia following experimental subarachnoid hemorrhage.

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.

Endoscopic Transorbital Approach for the Management of Spheno-Orbital Meningiomas: Literature Review and Preliminary Experience.

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.

Minimally Invasive Surgical Technique for the Management of Giant Dumbbell Spinal Schwannoma.

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.

Mortality Prediction of Patients with Subarachnoid Hemorrhage Using a Deep Learning Model Based on an Initial Brain CT Scan.

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.

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients.

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.

Superior eyelid endoscopic transorbital approach to the tentorial area: A qualitative and quantitative anatomic study.

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.

Clinical relevance of glucose metrics during the early brain injury period after aneurysmal subarachnoid hemorrhage: An opportunity for continuous glucose monitoring.

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.

Clinical and Radiological Outcome in a Series of Patients Treated by Anterior Cervical Discectomy and Fusion: Retrospective Controlled Study With 2 Different Stand-Alone Cages.

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.

Minimally Invasive Surgery for Spontaneous Intracerebral Hematoma. Real-Life Implementation Model and Economic Estimation.

Objective: Spontaneous intracerebral hemorrhage is characterized by high fatality outcomes, even under best medical treatment. Recently, minimally invasive surgical (MIS) evacuation of the hematoma has shown promising results and may soon be implemented in the clinical practice. Hereby, we intended to foresee the logistic requirements for an early hematoma evacuation protocol, as well as to evaluate in a real-life implementation model the cost-utility of the two main MIS techniques for hemorrhagic stroke (catheter evacuation plus thrombolysis and neuroendoscopic aspiration). Methods: Data were obtained from the pool of hemorrhagic-stroke patients admitted to our institution during an annual period (2020-2021) and contrasted to the reported results in published trials of MIS techniques. Potential candidates for surgical treatment were identified according to the inclusion/exclusion criteria established in these trials. Then, a cost-utility analysis was performed, which explored the incremental cost per unit of health gained with a given treatment. The treatment effect was measured by differences in modified Rankin Score, and subsequently converted to quality-adjusted life years (QALY). Results: Of the 137 patients admitted to our center with supratentorial spontaneous intracerebral hemorrhage in a 1-year period, 17 (12.4%) were potential candidates for the catheter evacuation plus thrombolysis technique (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, MISTIE III criteria) and 59 (43.0%) for the neuroendoscopic aspiration technique (Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study, DIST criteria). The incremental cost-utility ratio was € 76,533.13 per QALY for the catheter-based evacuation and € 60,703.89 per QALY for the endoscopic-based technique. Conclusion: Around 12-43% of patients admitted to hospital with spontaneous hemorrhagic stroke could be potential candidates to MIS early evacuation of the cerebral hematoma. In our real-life implementation model, the cost-utility analysis favored the neuroendoscopic evacuation over the catheter aspiration technique. Further studies are advisable as new data from the ongoing randomized trials becomes available.

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score.

BACKGROUND: Risk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding. METHODS: A retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort. RESULTS: 68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 . CONCLUSIONS: Venous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

Graph Representation Forecasting of Patient's Medical Conditions: Toward a Digital Twin.

Objective: Modern medicine needs to shift from a wait and react, curative discipline to a preventative, interdisciplinary science aiming at providing personalized, systemic, and precise treatment plans to patients. To this purpose, we propose a "digital twin" of patients modeling the human body as a whole and providing a panoramic view over individuals' conditions. Methods: We propose a general framework that composes advanced artificial intelligence (AI) approaches and integrates mathematical modeling in order to provide a panoramic view over current and future pathophysiological conditions. Our modular architecture is based on a graph neural network (GNN) forecasting clinically relevant endpoints (such as blood pressure) and a generative adversarial network (GAN) providing a proof of concept of transcriptomic integrability. Results: We tested our digital twin model on two simulated clinical case studies combining information at organ, tissue, and cellular level. We provided a panoramic overview over current and future patient's conditions by monitoring and forecasting clinically relevant endpoints representing the evolution of patient's vital parameters using the GNN model. We showed how to use the GAN to generate multi-tissue expression data for blood and lung to find associations between cytokines conditioned on the expression of genes in the renin-angiotensin pathway. Our approach was to detect inflammatory cytokines, which are known to have effects on blood pressure and have previously been associated with SARS-CoV-2 infection (e.g., CXCR6, XCL1, and others). Significance: The graph representation of a computational patient has potential to solve important technological challenges in integrating multiscale computational modeling with AI. We believe that this work represents a step forward toward next-generation devices for precision and predictive medicine.

Intraoperative magnetic resonance imaging for cerebral cavernous malformations: When is it maybe worth it?

OBJECTIVE: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI. METHODS: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery -Timepoint 1- (Tp1) and at the 6-to-12-month follow-up -Timepoint2- (Tp2). RESULTS: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate post-surgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005). CONCLUSIONS: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs.

Women's role in neurosurgical research: is the gender gap improving?

OBJECTIVE: The percentage of women publishing high-impact neurosurgical research might be perceived as a representation of our specialty and may influence the perpetuation of the existing gender gap. This study investigated whether the trend in women taking lead roles in neurosurgical research has mirrored the increase in female neurosurgeons during the past decade and whether our most prestigious publications portray enough female role models to stimulate gender diversity among the new generation of neurosurgeons. METHODS: Two of the most prominent neurosurgical journals-Journal of Neurosurgery and Neurosurgery-were selected for this study, and every original article that was published in 2009 and 2019 in each of those journals was investigated according to the gender of the first and senior authors, their academic titles, their affiliations, and their institutions' region. RESULTS: A total of 1328 articles were analyzed. The percentage of female authors was significantly higher in Europe and Russia compared with the US and Canada (first authors: 60/302 [19.9%] vs 109/829 [13.1%], p = 0.005; and senior authors: 32/302 [10.6%] vs 57/829 [6.9%], p = 0.040). Significantly increased female authorship was observed from 2009 to 2019, and overall numbers of both first and senior female authors almost doubled. However, when analyzing by regions, female authorship increased significantly only in the US and Canada. Female authors of neurosurgical research articles were significantly less likely to hold an MD degree compared with men. Female neurosurgeons serving as senior authors were represented in only 3.6% (48/1328) of articles. Women serving as senior authors were more likely to have a female colleague listed as the first author of their research (29/97 [29.9%] vs 155/1231 [12.6%]; χ2 = 22.561, p = 0.001). CONCLUSIONS: Although this work showed an encouraging increase in the number of women publishing high-impact neurosurgical research, the stagnant trend in Europe may suggest that a glass ceiling has been reached and further advances in equity would require more aggressive measures. The differences in the researchers' profiles (academic title and affiliation) suggest an even wider gender gap. Cultural unconscious bias may explain why female senior authors have more than double the number of women serving as their junior authors compared with men. While changes in the workforce happen, strategies such as publishing specific issues on women, encouraging female editorials, and working toward more gender-balanced editorial boards may help our journals to portray a more equitable specialty that would not discourage bright female candidates.

Edema Resolution and Clinical Assessment in Poor-Grade Subarachnoid Hemorrhage: Useful Indicators to Predict Delayed Cerebral Infarctions?

BACKGROUND: The level of consciousness and cerebral edema are among the indicators that best define the intensity of early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Although these indicators are usually altered in patients with a poor neurological status, their usefulness for selecting patients at risk of cerebral infarction (CI) is not well established. Furthermore, little is known about the evolution of these indicators during the first week of post-ictal events. Our study focused on describing the association of the longitudinal course of these predictors with CI occurrence in patients with severe aSAH. METHODS: Out of 265 aSAH patients admitted consecutively to the same institution, 80 patients with initial poor neurological status (WFNS 4-5) were retrospectively identified. After excluding 25 patients with early mortality, a total of 47 patients who underwent early CT (<3 days) and late CT (<7 days) acquisitions were included in the study. Early cerebral edema and delayed cerebral edema were calculated using the SEBES score, and the level of consciousness was recorded daily during the first week using the Glasgow Coma Scale (GCS). RESULTS: There was a significant improvement in the SEBES (Early-SEBES median (IQR) = 3 (2-4) versus Delayed-SEBES = 2 (1-3); p = 0.001) and in GCS scores (B = 0.32; 95% CI 0.15-0.49; p = 0.001) during the first week. When comparing the ROC curves of Delayed-SEBES vs Early-SEBES as predictors of CI, no significant differences were found (Early-SEBES Area Under the Curve: 0.65; Delayed-SEBES: 0.62; p = 0.17). Additionally, no differences were observed in the relationship between the improvement in the GCS across the first week and the occurrence of CI (p = 0.536). CONCLUSIONS: Edema and consciousness level improvement did not seem to be associated with the occurrence of CI in a surviving cohort of patients with severe aSAH. Our results suggest that intensive monitoring should not be reduced in patients with a poor neurological status regardless of an improvement in cerebral edema and level of consciousness during the first week after bleeding.