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Background: Rete middle cerebral artery (MCA) is a rare anomaly of the intracranial circulation that mimics congenital Moyamoya disease (MMD). Similar to MMD, it is reported almost exclusively in East-Asian ethnicities. Here, we report 13 patients with rete MCA anomaly from a predominantly non-Asian background in the USA., Methods: Consecutive patients (≥18 years of age) with rete MCA seen in the neurovascular clinic at Columbia University Medical Center (2014-2024) were included. We retrieved demographics, clinical presentation, imaging findings, neurosurgical interventions, and clinical outcomes., Results: 13 patients were identified (mean age 42±21 years, 83.3% female): 7 were White (53.8%), 3 were multiracial Hispanic (23.1%), 2 were South-Asian (15.4%), and 1 was Black (7.7%). Rete MCA was unilateral in all (n=13) and collaterals typical of MMD were absent. MRI vessel wall imaging (n=6) did not show enhancement characteristic of MMD. With serial imaging (n=12), there was no progression or contralateral MCA involvement. Strokes occurred in 5 (38.5%): subarachnoid hemorrhage (n=2), intracerebral hemorrhage (n=2), and ischemic stroke (n=1) from cardioembolism (n=1). 5 (38.5%) underwent neurosurgical bypass (encephaloduroarteriosynangiosis) due to presumed initial diagnosis of MMD (n=4), or for hypoperfusion on imaging related to rete MCA (n=1). Over a 4±3-year mean follow-up, there were no acute neurovascular events., Conclusions: Rete MCA anomaly occurs in non-Asian populations, and is likely benign relative to MMD. The diagnosis should be considered with unilateral, non-progressive findings, and absent MMD-type collaterals. Neurosurgical bypass appears safe, but studies are required to assess the natural history and stroke risk in this condition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background/objective: Intracranial epidermoid tumors (ETs) are rare, benign lesions that present significant challenges in neurosurgical management due to their propensity to encase vital neurovascular structures. We aimed to evaluate the impact of clinical, demographic, and tumor-specific factors on surgical decisions (gross total resection [GTR] vs. subtotal resection [STR]) and outcomes and identify patient clusters with distinct profiles and outcomes post-resection., Methods: We retrospectively analyzed 72 patients with ET treated from 1998 to 2022, employing multivariable logistic regression for GTR versus STR predictors and Kaplan-Meier curves for progression-free survival (PFS). K-prototype clustering classified patients based on clinical data., Results: The mean age of our cohort was 39.8 ± 20.1 years. About 13.9% of patients had a recurrence, with a median PFS of 108 months (interquartile range: 57 -206). Seizures significantly predicted GTR (P < 0.05), whereas adherence to critical structures reduced GTR likelihood (P < 0.05). Initial surgeries more often achieved GTR, correlating with longer PFS (P < 0.0001) and reduced recurrence (P < 0.01) versus re-operations. Cluster analysis identified three distinct groups, with the initial GTR cluster showing superior PFS and the lowest recurrence (P < 0.0001 and P < 0.01, respectively). Statistically significant predictors of PFS included age and preoperative seizure presence, with older age favoring longer PFS (P < 0.01) and seizures associated with reduced PFS (P < 0.01). In addition, patients with previous surgeries showed a trend toward shorter PFS (P < 0.05)., Conclusions: This study emphasizes the importance of tailored surgical strategies in managing intracranial ETs, advocating for GTR to optimize long-term outcomes where possible. Future prospective studies are essential to further refine treatment approaches, enhancing survival for ET patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis., Methods: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis., Results: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant Kras G12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models., Conclusions: Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease., Competing Interests: Disclosures None.

This systematic review, meta-analysis, and novel time course analysis examines microvascular failure in the treatment of acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) and/or thrombolytic administration for stroke management. A systematic review and meta-analysis following PRIMSA-2020 guidelines was conducted along with a novel curve-of-best fit analysis to elucidate the time-course of microvascular failure. Scopus and PubMed were searched using relevant keywords to identify studies that examine recanalization and reperfusion assessment of AIS patients following large vessel occlusion. Meta-analysis was conducted using a random-effects model. Curve-of-best-fit analysis of microvascular failure rate was performed with a negative exponential model. Twenty-seven studies with 1151 patients were included. Fourteen studies evaluated patients within a standard stroke onset-to-treatment time window (≤6 hours after last known normal) and thirteen studies had an extended time window (>6 hours). Our analysis yields a 22% event rate of microvascular failure following successful recanalization (95% CI: 16-30%). A negative exponential curve modeled a microvascular failure rate asymptote of 28.5% for standard time window studies, with no convergence of the model for extended time window studies. Progressive microvascular failure is a phenomenon that is increasingly identified in clinical studies of AIS patients undergoing revascularization treatment.

Acute ischemic stroke remains the primary cause of disability worldwide. For patients with large vessel occlusions, intravenous thrombolysis followed by mechanical thrombectomy remains the standard of care. Revascularization of the large vessel is typically successful. However, despite reopening of the occluded vessel, many patients fail to return to independence. Functional failure, despite macrovascular recanalization, is often referred to as the no-reflow phenomenon. Even with an extensive characterization of reperfusion in animal models, numerous mechanisms may explain no-reflow. Further, uniform measurements of this microvascular dysfunction and prognostic markers associated with no-reflow are lacking. In this review, we highlight a number of mechanisms that may explain no-reflow, characterize current multimodal measurements, and assess its molecular markers., Competing Interests: Disclosures None.

Increased intracranial pressure (ICP) causes disability and mortality in the neurointensive care population. Current methods for monitoring ICP are invasive. We designed a deep learning framework using a domain adversarial neural network to estimate noninvasive ICP, from blood pressure, electrocardiogram, and cerebral blood flow velocity. Our model had a mean of median absolute error of 3.88 ± 3.26 mmHg for the domain adversarial neural network, and 3.94 ± 1.71 mmHg for the domain adversarial transformers. Compared with nonlinear approaches, such as support vector regression, this was 26.7% and 25.7% lower. Our proposed framework provides more accurate noninvasive ICP estimates than currently available. ANN NEUROL 2023;94:196-202., (© 2023 American Neurological Association.)

Ischemic stroke is a leading cause of death and disability worldwide. A serious risk of acute ischemic stroke (AIS) arises after the stroke event, due to inflammation and edema formation. Inflammation and edema in the brain are mediated by bradykinin, the formation of which is dependent upon a multi-ligand receptor protein called gC1qR. There are currently no preventive treatments for the secondary damage of AIS produced by inflammation and edema. This review aims to summarize recent research regarding the role of gC1qR in bradykinin formation, its role in inflammation and edema following ischemic injury, and potential therapeutic approaches to preventing post-stroke inflammation and edema formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Delgardo, Tang, Tudor, Pascual-Leone and Connolly.)

Background: Targeting a cerebral perfusion pressure optimal for cerebral autoregulation (CPPopt) has been gaining more attention to prevent secondary damage after acute neurological injury. Brain tissue oxygenation (PbtO 2 ) can identify insufficient cerebral blood flow and secondary brain injury. Defining the relationship between CPPopt and PbtO 2 after aneurysmal subarachnoid hemorrhage may result in (1) mechanistic insights into whether and how CPPopt-based strategies might be beneficial and (2) establishing support for the use of PbtO 2 as an adjunctive monitor for adequate or optimal local perfusion., Methods: We performed a retrospective analysis of a prospectively collected 2-center dataset of patients with aneurysmal subarachnoid hemorrhage with or without later diagnosis of delayed cerebral ischemia (DCI). CPPopt was calculated as the cerebral perfusion pressure (CPP) value corresponding to the lowest pressure reactivity index (moving correlation coefficient of mean arterial and intracranial pressure). The relationship of (hourly) deltaCPP (CPP-CPPopt) and PbtO 2 was investigated using natural spline regression analysis. Data after DCI diagnosis were excluded. Brain tissue hypoxia was defined as PbtO 2 <20 mmHg., Results: One hundred thirty-one patients were included with a median of 44.0 (interquartile range, 20.8-78.3) hourly CPPopt/PbtO2 datapoints. The regression plot revealed a nonlinear relationship between PbtO 2 and deltaCPP ( P <0.001) with PbtO 2 decrease with deltaCPP <0 mmHg and stable PbtO 2 with deltaCPP ≥0mmHg, although there was substantial individual variation. Brain tissue hypoxia (34.6% of all measurements) was more frequent with deltaCPP <0 mmHg. These dynamics were similar in patients with or without DCI., Conclusions: We found a nonlinear relationship between PbtO 2 and deviation of patients' CPP from CPPopt in aneurysmal subarachnoid hemorrhage patients in the pre-DCI period. CPP values below calculated CPPopt were associated with lower PbtO 2 . Nevertheless, the nature of PbtO 2 measurements is complex, and the variability is high. Combined multimodality monitoring with CPP/CPPopt and PbtO 2 should be recommended to redefine individual pressure targets (CPP/CPPopt) and retain the option to detect local perfusion deficits during DCI (PbtO 2 ), which cannot be fulfilled by both measurements interchangeably.

Background: Prolonged external ventricular drainage (EVD) in patients with subarachnoid hemorrhage (SAH) leads to morbidity, whereas early removal can have untoward effects related to recurrent hydrocephalus. A metric to help determine the optimal time for EVD removal or ventriculoperitoneal shunt (VPS) placement would be beneficial in preventing the prolonged, unnecessary use of EVD. This study aimed to identify whether dynamics of cerebrospinal fluid (CSF) biometrics can temporally predict VPS dependency after SAH., Methods: This was a retrospective analysis of a prospective, single-center, observational study of patients with aneurysmal SAH who required EVD placement for hydrocephalus. Patients were divided into VPS-dependent (VPS+) and non-VPS dependent groups. We measured the bicaudate index (BCI) on all available computed tomography scans and calculated the change over time (ΔBCI). We analyzed the relationship of ΔBCI with CSF output by using Pearson's correlation. A k-nearest neighbor model of the relationship between ΔBCI and CSF output was computed to classify VPS., Results: Fifty-eight patients met inclusion criteria. CSF output was significantly higher in the VPS+ group in the 7 days post EVD placement. There was a negative correlation between delta BCI and CSF output in the VPS+ group (negative delta BCI means ventricles become smaller) and a positive correlation in the VPS- group starting from days four to six after EVD placement (p < 0.05). A weighted k-nearest neighbor model for classification had a sensitivity of 0.75, a specificity of 0.70, and an area under the receiver operating characteristic curve of 0.80., Conclusions: The correlation of ΔBCI and CSF output is a reliable intraindividual biometric for VPS dependency after SAH as early as days four to six after EVD placement. Our machine learning model leverages this relationship between ΔBCI and cumulative CSF output to predict VPS dependency. Early knowledge of VPS dependency could be studied to reduce EVD duration in many centers (intensive care unit length of stay)., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: While clinical guidelines provide a framework for hospital management of spontaneous intracerebral hemorrhage (ICH), variation in the resource use and costs of these services exists. We sought to perform a systematic literature review to assess the evidence on hospital resource use and costs associated with management of adult patients with ICH, as well as identify factors that impact variation in such hospital resource use and costs, regarding clinical characteristics and delivery of services., Methods: A systematic literature review was performed using PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE(R) 1946 to present. Articles were assessed against inclusion and exclusion criteria. Study design, ICH sample size, population, setting, objective, hospital characteristics, hospital resource use and cost data, and main study findings were abstracted., Results: In total, 43 studies met the inclusion criteria. Pertinent clinical characteristics that increased hospital resource use included presence of comorbidities and baseline ICH severity. Aspects of service delivery that greatly impacted hospital resource consumption included intensive care unit length of stay and performance of surgical procedures and intensive care procedures., Conclusions: Hospital resource use and costs for patients with ICH were high and differed widely across studies. Making concrete conclusions on hospital resources and costs for ICH care was constrained, given methodologic and patient variation in the studies. Future research should evaluate the long-term cost-effectiveness of ICH treatment interventions and use specific economic evaluation guidelines and common data elements to mitigate study variation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Dysfunctional cerebral autoregulation often precedes delayed cerebral ischemia (DCI). Currently, there are no data-driven techniques that leverage this information to predict DCI in real time. Our hypothesis is that information using continuous updated analyses of multimodal neuromonitoring and cerebral autoregulation can be deployed to predict DCI., Methods: Time series values of intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure (CPP), optimal CPP (CPPOpt), ΔCPP (CPP - CPPOpt), mean arterial pressure, and pressure reactivity index were combined and summarized as vectors. A validated temporal signal angle measurement was modified into a classification algorithm that incorporates hourly data. The time-varying temporal signal angle measurement (TTSAM) algorithm classifies DCI at varying time points by vectorizing and computing the angle between the test and reference time signals. The patient is classified as DCI+ if the error between the time-varying test vector and DCI+ reference vector is smaller than that between the time-varying test vector and DCI- reference vector. Finally, prediction at time point t is calculated as the majority voting over all the available signals. The leave-one-patient-out cross-validation technique was used to train and report the performance of the algorithms. The TTSAM and classifier performance was determined by balanced accuracy, F1 score, true positive, true negative, false positive, and false negative over time., Results: One hundred thirty-one patients with aneurysmal subarachnoid hemorrhage who underwent multimodal neuromonitoring were identified from two centers (Columbia University: 52 [39.7%], Aachen University: 79 [60.3%]) and included in the analysis. Sixty-four (48.5%) patients had DCI, and DCI was diagnosed 7.2 ± 3.3 days after hemorrhage. The TTSAM algorithm achieved a balanced accuracy of 67.3% and an F1 score of 0.68 at 165 h (6.9 days) from bleed day with a true positive of 0.83, false positive of 0.16, true negative of 0.51, and false negative of 0.49., Conclusions: A TTSAM algorithm using multimodal neuromonitoring and cerebral autoregulation calculations shows promise to classify DCI in real time., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis., Methods: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported., Results: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert., Conclusions: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases. Ppil4 depletion in vertebrate models causes intracerebral hemorrhage, defects in cerebrovascular morphology and impaired Wnt signaling. Wild-type, but not IA-mutant, PPIL4 potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity and implicate PPIL4 gene mutations in the pathogenesis of IA., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction : For elderly adults in the United States, stroke is the fifth leading cause of death of which ischemic strokes comprise a vast majority. Optimal pharmacological management of elderly ischemic stroke patients involves both reperfusion and supportive care. Recent research into pharmacological management has focused on vascular, immunomodulatory, cytoprotective, and alternative agents, some of which have shown limited success in clinical trials. However, no treatments have been established as a reliable mode for management of cerebral ischemia for elderly adults beyond acute thrombolysis. Areas covered : The authors conducted a literature search for ischemic stroke management in the elderly and a search for human drug studies for managing ischemic stroke on clinicaltrials.gov. Here, they describe recent progress in the pharmacological management of cerebral ischemia in the elderly. Expert opinion : Many drug classes (antihypertensive, cytoprotective and immunomodulatory, and alternative agents) have been explored with limited success in managing ischemic stroke, though some have shown preventative benefits. We generally observed a broad gap in evidence on elderly patients from studies across all drug classes, necessitating further studies to gain an understanding of effective management of ischemic stroke in this large demographic of patients.

Background and Purpose: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage negatively impacts long-term recovery but is often detected too late to prevent damage. We aim to develop hourly risk scores using routinely collected clinical data to detect DCI., Methods: A DCI classification model was trained using vital sign measurements (heart rate, blood pressure, respiratory rate, and oxygen saturation) and demographics routinely collected for clinical care. Twenty-two time-varying physiological measures were computed including mean, SD, and cross-correlation of heart rate time series with each of the other vitals. Classification was achieved using an ensemble approach with L2-regularized logistic regression, random forest, and support vector machines models. Classifier performance was determined by area under the receiver operating characteristic curves and confusion matrices. Hourly DCI risk scores were generated as the posterior probability at time t using the Ensemble classifier on cohorts recruited at 2 external institutions (n=38 and 40)., Results: Three hundred ten patients were included in the training model (median, 54 years old [interquartile range, 45-65]; 80.2% women, 28.4% Hunt and Hess scale 4-5, 38.7% Modified Fisher Scale 3-4); 101 (33%) developed DCI with a median onset day 6 (interquartile range, 5-8). Classification accuracy before DCI onset was 0.83 (interquartile range, 0.76-0.83) area under the receiver operating characteristic curve. Risk scores applied to external institution datasets correctly predicted 64% and 91% of DCI events as early as 12 hours before clinical detection, with 2.7 and 1.6 true alerts for every false alert., Conclusions: An hourly risk score for DCI derived from routine vital signs may have the potential to alert clinicians to DCI, which could reduce neurological injury.

Background: Growing evidence suggests that chronic subdural hematoma (CSDH) may have long-term adverse effects even after surgical evacuation. Hematoma recurrence is commonly reported as a short-term, postoperative outcome measure for CSDH, but other measures such as hematoma resolution may provide better insight regarding mechanisms behind longer-term sequelae. This study aims to characterize postoperative resolution times and identify predictors for this relatively unexplored metric. Methods: Consecutive cases ( N = 122) of burr hole evacuation for CSDH by a single neurosurgeon at Columbia University Irving Medical Center from 2000 to 2019 were retrospectively identified. Patient characteristics, presenting factors, and date of hematoma resolution were abstracted from the electronic health record. Outcome measures included CSDH resolution at 6 months, surgery-to-resolution time, and inpatient mortality. Univariate and multivariate analyses were performed to determine predictors of outcome measures. Results: Hematoma resolution at 6 months was observed in 58 patients (47.5%), and median surgery-to-resolution time was 161 days (IQR: 85-367). Heavy drinking was predictive of non-resolution at 6 months and longer surgery-to-resolution time, while increased age was predictive of non-resolution at 6 months. Antiplatelet agent resumption was associated with non-resolution at 6 months and longer surgery-to-resolution time on univariate analysis but was not significant on multivariate analysis. Conclusion: Postoperative resolution times for most CSDHs are on the order of several months to a year, and delayed resolution is linked to heavy drinking and advanced age. Subsequent prospective studies are needed to directly assess the utility of hematoma resolution as a potential metric for long-term functional and cognitive outcomes of CSDH., (Copyright © 2020 Chang, Sim, Delgardo, Ruan and Connolly.)

Objectives: Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH., Patients and Methods: This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months., Results: The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p =  0.087). Gender did not affect PTSD symptom development, (t = 1.34, p =  0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01)., Conclusion: Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) remains a devastating diagnosis. While the ICH Score continues to be used in the clinical setting to prognosticate outcomes, contemporary improvements in management have reduced mortality rates for each scoring tier. The aims of this study were to examine mortality rates within ICH Score strata and examine if these findings are stable when major disability is included in categorizing poor outcomes., Methods: From a single-institution cohort built between 2009 and 2016, 582 patients were extracted based on the criteria for complete ICH Score, discharge mortality, and functional status for survivors. Mortality rates were stratified by ICH Score and compared with both historical and similar contemporary cohorts. Poor outcome was defined as severe disability (modified Rankin Scale score 5) in addition to death, stratified by ICH Score, and compared. A secondary analysis of patients with ICH Score of 2 was performed in light of the primary results., Results: Mortality rates stratified by ICH Score were notably lower than expected for low- and moderate-grade ICH compared with the original cohort. However, when defining a poor outcome as including severe disability (modified Rankin Scale score 5) in addition to death, the rates for poor outcomes were higher for patients with ICH Score of 2 (51.16% vs. 26%, P = 0.017) and no different for any other score group compared with the original cohort., Conclusions: Though the original ICH Score overestimates mortality for low-grade and moderate-grade hemorrhages, it may underpredict severe disability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to examine whether heart rate variability (HRV) measures can be used to detect neurocardiogenic injury (NCI)., Methods: Three hundred and twenty-six consecutive admissions with aneurysmal subarachnoid hemorrhage (SAH) met criteria for the study. Of 326 subjects, 56 (17.2%) developed NCI which we defined by wall motion abnormality with ventricular dysfunction on transthoracic echocardiogram or cardiac troponin-I > 0.3 ng/mL without electrocardiogram evidence of coronary artery insufficiency. HRV measures (in time and frequency domains, as well as nonlinear technique of detrended fluctuation analysis) were calculated over the first 48 h. We applied longitudinal multilevel linear regression to characterize the relationship of HRV measures with NCI and examine between-group differences at baseline and over time., Results: There was decreased vagal activity in NCI subjects with a between-group difference in low/high frequency ratio (β 3.42, SE 0.92, p = 0.0002), with sympathovagal balance in favor of sympathetic nervous activity. All time-domain measures were decreased in SAH subjects with NCI. An ensemble machine learning approach translated these measures into a classification tool that demonstrated good discrimination using the area under the receiver operating characteristic curve (AUROC 0.82), the area under precision recall curve (AUPRC 0.75), and a correct classification rate of 0.81., Conclusions: HRV measures are significantly associated with our label of NCI and a machine learning approach using features derived from HRV measures can classify SAH patients that develop NCI.

Background: Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has a multifactorial pathophysiology, with immune dysregulation being an important component. The neutrophil-lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, and sepsis., Objective: To determine whether there is a relationship between NLR and DCI in patients with aSAH., Methods: We evaluated 1067 patients with aSAH between 2006 and 2015 enrolled in a single-center, prospective, observational cohort study. Admission white blood cell differentials (NLR) were analyzed using a cut-off point of ≥5.9. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment, or a decrease in at least two points on the Glasgow Coma Scale, which was not apparent immediately after aneurysm occlusion, and could not be attributed to other causes. Cerebral infarct was defined as a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought to be vasospasm by the research team. Logistic regression models were generated., Results: We found that 768 (72%) patients had an admission NLR ≥5.9. In a multivariable model, elevated NLR was associated with poor admission Hunt-Hess grade (OR=1.6, 95% CI 1.2 to 2.6, p=0.005), Caucasian ethnicity (OR=2.6, 95% CI 1.9 to 3.7, p<0.001), anterior aneurysm location (OR=1.7, 95% CI 1.2 to 2.4, p=0.004), loss of consciousness at ictus (OR=1.4, 95% CI 1.0 to 2.0, p=0.055), and thick SAH (modified Fisher grade ≥3) (OR=1.8, 95% CI 1.3 to 2.4, p<0.001). Admission NLR predicted development of delayed cerebral ischemia (DCI) (OR=1.7; 95% CI 1.1 to 2.5, p=0.008) after controlling for known predictors such as age, poor admission clinical grade, thick SAH blood, and elevated admission mean arterial pressure., Conclusions: This study provides further evidence of the association between inflammation and DCI. Admission NLR is a readily available and convenient biomarker that may be a clinically useful tool for prognostication when evaluating aSAH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Stroke is a leading cause of death and disability worldwide and an increasing number of ischemic stroke patients are undergoing pharmacological and mechanical reperfusion. Both human and experimental models of reperfused ischemic stroke have implicated the complement cascade in secondary tissue injury. Most data point to the lectin and alternative pathways as key to activation, and C3a and C5a binding of their receptors as critical effectors of injury. During periods of thrombolysis use to treat stroke, acute experimental complement cascade blockade has been found to rescue tissue and improves functional outcome. Blockade of the complement cascade during the period of tissue reorganization, repair, and recovery is by contrast not helpful and in fact is likely to be deleterious with emerging data suggesting downstream upregulation of the cascade might even facilitate recovery. Successful clinical translation will require the right clinical setting and pharmacologic strategies that are capable of targeting the key effectors early while not inhibiting delayed repair. Early reports in a variety of disease states suggest that such pharmacologic strategies appear to have a favorable risk profile and offer substantial hope for patients.

To develop and validate a prediction model for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) using a temporal unsupervised feature engineering approach, demonstrating improved precision over standard features. 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Baseline information and standard grading scales were evaluated: age, sex, Hunt Hess grade, modified Fisher Scale (mFS), and Glasgow Coma Scale (GCS). An unsupervised approach applying random kernels was used to extract features from physiological time series (systolic and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (Partial Least Squares, linear and kernel Support Vector Machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.58. Combined demographics and grading scales: AUC 0.60. Random kernel derived physiologic features: AUC 0.74. Combined baseline and physiologic features with redundant feature reduction: AUC 0.77. Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that our models achieve higher classification accuracy.

Background: Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with carotid artery stenosis. We aimed to clarify the incidence and risk factors for early cognitive dysfunction (eCD) and early cognitive improvement (eCI), defined as change in cognitive performance ≤24 hours after surgery, using a battery of neuropsychometric tests., Methods: In total, 585 patients undergoing CEA were tested with neuropsychometric tests before and after surgery; 155 patients undergoing "simple" spine surgery were the reference group. Patient performance for each test was evaluated by z scores. Cognitive change was defined as eCD (or eCI) if: 1) patients had a z score ≤-2 (or ≥2) in ≥2 cognitive domains or 2) patients had mean z scores across all domains ≤-1.5 (or ≥1.5). Associations between the categorical cognitive outcomes and variables of interest were modeled using the proportional odds model., Results: Of the 585 subjects, 24% had eCD, 6% had eCI, and 70% had "no change." Patients who had eCD were more likely to be statin naïve (odds ratio [OR] 1.23 [1.03-1.48], P = 0.02) or women (OR 1.27 [1.06-1.53], P = 0.02). Those with eCI were less likely to have less formal education (OR 0.95 [0.90-1.00], P = 0.04) and less likely to have diabetes mellitus (OR 0.8 [0.65-0.99], P = 0.04)., Conclusions: Patients having CEA may develop eCD or eCI postoperatively. Medications likely to be associated with less eCD are statins and aspirin, which correlate most strongly in asymptomatic patients. In addition to confirming previous findings, we found that women were more likely than men to develop eCD. More sex-specific studies and analysis are needed to better explore these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Assuring clinical competence throughout the career of a neurosurgeon is of paramount importance for patient safety. We present the first comprehensive survey of all neurosurgeons board certified through the American Board of Neurological Surgery (ABNS) to evaluate perceptions of Maintenance of Certification (MOC). We administered a validated, online, confidential survey to 4899 neurosurgeons (2435 ABNS diplomates participating in MOC, 1440 diplomates certified prior to 1999 [time-unlimited certificates], and 1024 retired diplomates). We received 1449 responses overall (30% response rate). Our study found that most respondents believe that neurosurgeons should be required to participate in continuing professional improvement following initial board certification (75%). Most believe that specialty boards, working in conjunction with specialty societies, should require diplomates to participate in programs meant to promote continuous professional development (73%). The majority of respondents (76%) believed that self-assessment tests constituted a meaningful professional development activity, in addition to periodic case log reviews (33%) or quality improvement projects (32.6%). A plurality of respondents (44%) do not feel that the MOC process as currently structured provides them with value. There were no differences between those who were "grandfathered" and those who actively participate in MOC and no differences between those in private practice versus those in academics. The ABNS is cognizant of diplomate concerns and is actively developing new MOC paradigms to ensure that the process achieves both the goals of meeting the public interest and assuring that the quality of American neurosurgery remains exemplary.

Introduction: Cerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI)., Methods: We retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals., Results: Inter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not., Conclusions: The severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The epidemiology of acute renal dysfunction after stroke is routinely overlooked following stroke events. Our aim in this meta-analysis is to report the prevalence of acute kidney injury (AKI) following acute stroke and its impact on mortality., Methods: A systematic literature search was performed on PubMed, EMBASE and Google Scholar for observational studies examining the prevalence and mortality risk of stroke patients with AKI as a complication. The pooled prevalence rates and odds ratios for mortality risk were calculated using subgroup analyses between the stroke subtypes: acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH)., Results: A total of 12 studies (4,532,181 AIS and 615,636 ICH) were included. The pooled prevalence rate of AKI after all stroke types was 11.6% (95% CI 10.6-12.7). Subgroup analyses revealed that the pooled prevalence rate of AKI after AIS was greater but not statistically significantly different than ICH (19.0%; 95% CI 8.2-29.7 vs. 12.9%; 95% CI 10.3-15.5, p = 0.5). AKI was found to be a significant risk factor of mortality in AIS (adjusted OR [aOR] 2.23; 95% CI 1.28-3.89; I2 = 98.8%), whereas this relationship did not reach statistical significance in ICH (aOR 1.20; 95% CI 0.68-2.12; I2 = 74.2%)., Conclusions: This meta-analysis provides evidence that AKI is a common complication following both AIS and ICH and it is associated with increased mortality following AIS but not ICH. This highlights the need for early assessment of renal function in the acute phase of AIS, in particular, and avoidance of factors than may induce AKI in vulnerable patients., (© 2017 S. Karger AG, Basel.)

Three-dimensional (3D) printers are a developing technology penetrating a variety of markets, including the medical sector. Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics. With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well. Digital Imaging and Communication in Medicine (DICOM) can be translated into Stereolithography (STL) files, which are then read and methodically built by 3D Printers. Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients. Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research. In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, we outline the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery, their applications, and the limitations that need to be overcome if 3D printers are to become common practice in the neurosurgical field., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) is associated with neurological decline and poor prognosis. Although many etiologic models have been explored, secondary damage caused by continued inflammation and iron exposure from red blood cell lysis may explain poor outcomes at distant follow-up. Examining serum samples of patients with ICH for biomarkers of iron physiology may yield relationships between iron exposure and functional outcomes., Methods: The following study retrospectively evaluated 41 patient serum samples obtained 1 day and 7 days post-ictus for CD163, ferritin, and hepcidin concentrations. Functional outcomes, using the modified Rankin Scale, were dichotomized into good (0-3) and poor (4-6). Correlation analysis and logistic regression were used to explore relationships between biomarker values, clinical metrics (such as ICH Score), and functional outcomes at 3 and 12 months., Results: Clinical metrics (Acute Physiology and Chronic Health Evaluation II score, ICH Score, and National Institutes of Health Stroke Scale) were correlated with elevated ferritin levels 7 days post-ictus. Furthermore, it was found that mean CD163 levels on day 1 were significantly associated with functional outcomes at 3 and 12 months; mean serum ferritin concentrations on days 1 and 7 were elevated in those with poor outcomes at 3 months, and day 7 levels were independently correlated with 12-month outcomes., Conclusion: Although this study serves to contribute to a growing body of evidence that CD163 and ferritin are biomarkers of functional outcomes, prospective cohort studies may clarify the role of iron-related inflammatory biomarkers as they pertain to neurological decline in patients with ICH., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)