Higher Hospital Frailty Risk Score Is Associated With Increased Risk of Stroke: Observational and Genetic Analyses.

BACKGROUND: Frailty is a prevalent state associated with several aging-related traits and conditions. The relationship between frailty and stroke remains understudied. Here we aim to investigate whether the hospital frailty risk score (HFRS) is associated with the risk of stroke and determine whether a significant association between genetically determined frailty and stroke exists. DESIGN: Observational study using data from All of Us research program and Mendelian Randomization analyses. METHODS: Participants from All of Us with available electronic health records were selected for analysis. All of Us began national enrollment in 2018 and is expected to continue for at least 10 years. All of Us is recruiting members of groups that have traditionally been underrepresented in research. All participants provided informed consent at the time of enrollment, and the date of consent was recorded for each participant. Incident stroke was defined as stroke event happening on or after the date of consent to the All of Us study HFRS was measured with a 3-year look-back period before the date of consent for stroke risk. The HFRS was stratified into 4 categories: no-frailty (HFRS=0), low (HFRS ≥1 and <5), intermediate (≥5 and <15), and high (HFRS ≥15). Last, we implemented Mendelian Randomization analyses to evaluate whether genetically determined frailty is associated with stroke risk. RESULTS: Two hundred fifty-three thousand two hundred twenty-six participants were at risk of stroke. In multivariable analyses, frailty status was significantly associated with risk of any (ischemic or hemorrhagic) stroke following a dose-response way: not-frail versus low HFRS (HR, 4.9 [CI, 3.5-6.8]; P<0.001), not-frail versus intermediate HFRS (HR, 11.4 [CI, 8.3-15.7]; P<0.001) and not-frail versus high HFRS (HR, 42.8 [CI, 31.2-58.6]; P<0.001). We found similar associations when evaluating ischemic and hemorrhagic stroke separately (P value for all comparisons <0.05). Mendelian Randomization confirmed this association by indicating that genetically determined frailty was independently associated with risk of any stroke (OR, 1.45 [95% CI, 1.15-1.84]; P=0.002). CONCLUSIONS: Frailty, based on the HFRS was associated with higher risk of any stroke. Mendelian Randomization analyses confirmed this association providing evidence to support a causal relationship.

Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke.

BACKGROUND: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.064T portable MRI (pMRI) scanner using a methodology that provided clinical information to inform rater interpretations. As a secondary aim, we investigated whether the incorporation of a deep learning (DL) reconstruction algorithm affected ICH detection. METHODS: The pMRI device was deployed at Yale New Haven Hospital to examine patients presenting with stroke symptoms from October 26, 2020 to February 21, 2022. Three raters independently evaluated pMRI examinations. Raters were provided the images alongside the patient's clinical information to simulate real-world context of use. Ground truth was the closest conventional computed tomography or 1.5/3T MRI. Sensitivity and specificity results were grouped by DL and non-DL software to investigate the effects of software advances. RESULTS: A total of 189 exams (38 ICH, 89 acute ischemic stroke, 8 subarachnoid hemorrhage, 3 primary intraventricular hemorrhage, 51 no intracranial abnormality) were evaluated. Exams were correctly classified as positive or negative for ICH in 185 of 189 cases (97.9% overall accuracy). ICH was correctly detected in 35 of 38 cases (92.1% sensitivity). Ischemic stroke and no intracranial abnormality cases were correctly identified as blood-negative in 139 of 140 cases (99.3% specificity). Non-DL scans had a sensitivity and specificity for ICH of 77.8% and 97.1%, respectively. DL scans had a sensitivity and specificity for ICH of 96.6% and 99.3%, respectively. CONCLUSIONS: These results demonstrate improvements in ICH detection accuracy on pMRI that may be attributed to the integration of clinical information in rater review and the incorporation of a DL-based algorithm. The use of pMRI holds promise in providing diagnostic neuroimaging for patients with ICH.

The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

OBJECTIVE: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion. METHODS: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. RESULTS: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76). CONCLUSIONS: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications.

Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases.

PURPOSE: Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare pre-treatment patient characteristics and outcomes between the two treatment options. METHODS: Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018. Pre-treatment factors and treatment responses were compared between those treated with LITT versus bevacizumab. RESULTS: Twenty-five patients underwent LITT and 13 patients were treated with bevacizumab. The LITT cohort had a longer overall survival (median 24.8 vs. 15.2 months for bevacizumab, p = 0.003) and trended to have a longer time to local recurrence (median 12.1 months vs. 2.0 for bevacizumab), although the latter failed to achieve statistical significance (p = 0.091). LITT resulted in an initial increase in lesional volume compared to bevacizumab (p < 0.001). However, this trend reversed in the long term follow-up, with LITT resulting in a median volume decrease at 1 year post-treatment of - 64.7% (range - 96.0% to + > 100%), while bevacizumab patients saw a median volume increase of + > 100% (range - 63.0% to + > 100%), p = 0.010. CONCLUSIONS: Our study suggests that patients undergoing LITT for RN have longer overall survival and better long-term lesional volume reduction than those treated with bevacizumab. However, it remains unclear whether our findings are due only to a difference in efficacy of the treatments or the implications of selection bias.

Predictors of Extended Length of Stay Following Treatment of Unruptured Adult Cerebral Aneurysms: A Study of The National Inpatient Sample.

BACKGROUND: In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as a surrogate for operative success. One metric used is the length of hospital stay (LOS) during index admission. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay are relatively unknown. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS following treatment for unruptured cerebral aneurysms. METHODS: The National Inpatient Sample years 2010 - 2014 was queried. Adults (≥18 years) with unruptured aneurysms undergoing either clipping or coiling were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended LOS was defined as greater than 75th percentile for the entire cohort (>5 days). Weighted patient demographics, comorbidities, complications, LOS, disposition and total cost were recorded. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted extended LOS. The primary outcome was the degree which patient comorbidities or postoperative complications correlated with extended LOS. RESULTS: A total of 46,880 patients were identified for which 9,774 (20.8%) patients had extended LOS (Normal LOS: 37,106; Extended LOS: 9,774). Patients in the extended LOS cohort presented with a greater number of comorbidities compared to the normal LOS cohort. A greater proportion of the normal LOS cohort was coiled (Normal LOS: 63.0% vs. Extended LOS: 33.5%, P<0.001), while more patients in the extended LOS cohort were clipped (Normal LOS: 37.0% vs. Extended LOS: 66.5%, P<0.001). The overall complication rate was higher in the extended LOS cohort (Normal LOS: 7.3% vs. Extended LOS: 43.8%, P<0.001). On average, the extended LOS cohort incurred a total cost nearly twice as large (Normal LOS: $26,050 ± 13,430 vs. Extended LOS: $52,195 ± 37,252, P<0.001) and had more patients encounter non-routine discharges (Normal LOS: 8.5% vs. Extended LOS: 52.5%, P<0.001) compared to the normal LOS cohort. On weighted multivariate logistic regression, multiple patient-specific factors were associated with extended LOS. These included demographics, preadmission comorbidities, choice of procedure, and inpatient complications. The odds ratio for extended LOS was 5.14 (95% CI, 4.30 - 6.14) for patients with 1 complication and 19.58 (95% CI, 15.75 - 24.34) for patients with > 1 complication. CONCLUSIONS: Our study demonstrates that extended LOS after treatment of unruptured aneurysms is influenced by a number of patient-level factors including demographics, preadmission comorbidities, type of aneurysm treatment (open surgical versus endovascular), and, importantly, inpatient complications. A better understanding of these independent predictors of prolonged length of hospital stay may help to improve patient outcomes and decrease overall healthcare costs.

Knockdown of Autophagy Inhibits Infectious Hepatitis C Virus Release by the Exosomal Pathway.

UNLABELLED: Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. We showed previously that HCV induces autophagy for viral persistence by preventing the innate immune response. Knockdown of autophagy reduces extracellular HCV release, although the precise mechanism remains unknown. In this study, we observed that knockdown of autophagy genes enhances intracellular HCV RNA and accumulates infectious virus particles in cells. Since HCV release is linked with the exosomal pathway, we examined whether autophagy proteins associate with exosomes in HCV-infected cells. We observed an association between HCV and the exosomal marker CD63 in autophagy knockdown cells. Subsequently, we observed that levels of extracellular infectious HCV were significantly lower in exosomes released from autophagy knockdown cells. To understand the mechanism for reduced extracellular infectious HCV in the exosome, we observed that an interferon (IFN)-stimulated BST-2 gene is upregulated in autophagy knockdown cells and associated with the exosome marker CD63, which may inhibit HCV assembly or release. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated HCV release from infected hepatocytes. IMPORTANCE: Autophagy plays an important role in HCV pathogenesis. Autophagy suppresses the innate immune response and promotes survival of virus-infected hepatocytes. The present study examined the role of autophagy in secretion of infectious HCV from hepatocytes. Autophagy promoted HCV trafficking from late endosomes to lysosomes, thus providing a link with the exosome. Inhibition of HCV-induced autophagy could be used as a strategy to block exosome-mediated virus transmission.

Diagnostic accuracy of intraoperative neuromonitoring in transcarotid artery revascularization.

BACKGROUND: In recent years, transcarotid artery revascularization (TCAR) has emerged as a safe and effective alternative to carotid artery stenting. While intraoperative neuromonitoring (IONM) techniques such as electroencephalogram (EEG) and somatosensory evoked potentials (SSEPs) are often employed during TCAR, there is limited research on their diagnostic accuracy. METHODS: The authors retrospectively reviewed a multi-institutional IONM database of TCAR procedures performed with EEG and SSEP monitoring. A total of 516 TCAR procedures were included in this study. Significant changes in EEG and/or SSEPs, surgeon's interventions, resolution of significant changes, and immediate postoperative neurological outcome were documented. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: The incidence of intraoperative onset new neurologic deficit was 0.4%. Significant changes in EEG and/or SSEPs occurred in 5.4% of the cases. Of the cases with IONM alerts, 78.5% returned to baseline with a surgical or hemodynamic intervention. From the cases with unresolved IONM alerts, 33.3% woke up with a new neurological deficit. The overall sensitivity and specificity for IONM was 100% and 99.2%, respectively. The positive predictive value was 33.3% and the negative predictive value was 100%. CONCLUSIONS: IONM during TCAR offers high sensitivity and specificity in predicting postoperative outcome. Patients with resolved IONM alerts had immediate neurological outcomes that were comparable to those who had no IONM alerts.

Angiographic evidence of an inadvertent cannulation of the marginal sinus following central line migration: illustrative case.

BACKGROUND: Central venous catheters (CVCs) play an indispensable role in clinical practice. Catheter malposition and tip migration can lead to severe complications. The authors present a case illustrating the endovascular management of inadvertent marginal sinus cannulation after an internal jugular vein (IJV) catheter tip migration. OBSERVATIONS: A triple-lumen CVC was inserted without complications into the right IJV of a patient undergoing a repeat sternotomy for aortic valve replacement. Two weeks postinsertion, it was discovered that the tip had migrated superiorly, terminating below the torcula in the posterior fossa. In the interventional suite, a three-dimensional venogram confirmed the inadvertent marginal sinus cannulation. The catheter was carefully retracted to the sigmoid sinus to preserve the option of catheter exchange if embolization became necessary. After a subsequent venogram, which displayed an absence of contrast extravasation, the entire catheter was safely removed. The patient tolerated the procedure well. LESSONS: Clinicians must be vigilant of catheter tip migration and malposition risks. Relying solely on postinsertion radiographs is insufficient. Once identified, prompt management of the malpositioned catheter is paramount in reducing morbidity and mortality and improving patient outcomes. Removing a malpositioned catheter constitutes a critical step, best performed by a specialized team under angiographic visualization.

Use of a dedicated open transcarotid access system for neurovascular disease.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an increasingly popular technique for the management of extracranial carotid stenosis. Its off-label use in the treatment of intracranial neurovascular disease is poorly described. Our objective is to describe the use of a dedicated open transcarotid access system for the treatment of neurovascular pathologies other than extracranial carotid stenosis. METHODS: We conducted a retrospective review of a prospectively maintained database of consecutive patients who underwent treatment of neurovascular disease at a single academic center using the ENROUTE Transcarotid Arterial Sheath. Demographics, procedural characteristics, and patient outcomes were reported. RESULTS: Twenty patients were included in the study between September 2017 and March 2023. The following pathologies were treated: intracranial atherosclerotic disease (ICAD, nine patients), complex cervico-petrous carotid disease (five patients), intracranial aneurysms (three patients), and large vessel occlusion-acute ischemic stroke (three patients). Eighteen of the 20 cases were performed with active carotid flow reversal. All cases were successfully completed. There were no access-related complications. One periprocedural complication was incurred: a microguidewire perforation during an exchange maneuver for the treatment of ICAD. CONCLUSION: An open transcarotid approach using a dedicated transcarotid system may offer a safe alternative access strategy for the endovascular treatment of complex neurovascular pathologies when a traditional transfemoral or transradial approach is contraindicated or failed.

APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation.

Importance: Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. Objective: To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM. Design, Setting, and Participants: This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status. Main Outcomes and Measures: For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression. Results: The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03). Conclusions and Relevance: The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. METHODS: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. RESULTS: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). CONCLUSION: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

Higher Hospital Frailty Risk Score is associated with increased complications and healthcare resource utilization after endovascular treatment of ruptured intracranial aneurysms.

AIM: To use the Hospital Frailty Risk Score (HFRS) to investigate the impact of frailty on complication rates and healthcare resource utilization in patients who underwent endovascular treatment of ruptured intracranial aneurysms (IAs). METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. All adult patients (≥18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM codes. Patients were categorized into frailty cohorts: low (HFRS <5), intermediate (HFRS 5-15) and high (HFRS >15). Patient demographics, adverse events, length of stay (LOS), discharge disposition, and total cost of admission were assessed. Multivariate logistic regression analysis was used to identify independent predictors of prolonged LOS, increased cost, and non-routine discharge. RESULTS: Of the 33 840 patients identified, 7940 (23.5%) were found to be low, 20 075 (59.3%) intermediate and 5825 (17.2%) high frailty by HFRS criteria. The rate of encountering any adverse event was significantly greater in the higher frailty cohorts (low: 59.9%; intermediate: 92.4%; high: 99.2%, p<0.001). There was a stepwise increase in mean LOS (low: 11.7±8.2 days; intermediate: 18.7±14.1 days; high: 26.6±20.1 days, p<0.001), mean total hospital cost (low: $62 888±37 757; intermediate: $99 670±63 446; high: $134 937±80 331, p<0.001), and non-routine discharge (low: 17.3%; intermediate: 44.4%; high: 69.4%, p<0.001) with increasing frailty. On multivariate regression analysis, a similar stepwise impact was found in prolonged LOS (intermediate: OR 2.38, p<0.001; high: OR 4.49, p<0.001)], total hospital cost (intermediate: OR 2.15, p<0.001; high: OR 3.62, p<0.001), and non-routine discharge (intermediate: OR 2.13, p<0.001; high: OR 4.17, p<0.001). CONCLUSIONS: Our study found that greater frailty as defined by the HFRS was associated with increased complications, LOS, total costs, and non-routine discharge.

Triple therapy versus dual-antiplatelet therapy for dolichoectatic vertebrobasilar fusiform aneurysms treated with flow diverters.

BACKGROUND: Dolichoectatic vertebrobasilar fusiform aneurysms (DVBFAs) have poor natural history when left untreated and high morbimortality when treated with microsurgery. Flow diversion (FD) with dual-antiplatelet therapy (DAPT) is feasible but carries high risk of perforator occlusion and progression of brainstem compression. Elaborate antithrombotic strategies are needed to preserve perforator patency while vessel remodeling occurs. We compared triple therapy (TT (DAPT plus oral anticoagulation)) and DAPT alone in patients with DVBFAs treated with FD. METHODS: Retrospective comparison of DAPT and TT in patients with DVBFAs treated with FD at eight US centers. RESULTS: The groups (DAPT=13, TT=14) were similar in age, sex, clinical presentation, baseline disability, and aneurysm characteristics. Radial access use was significantly higher in the TT group (71.4% vs 15.3%; P=0.006). Median number of flow diverters and adjunctive coiling use were non-different between groups. Acute ischemic stroke rate during the oral anticoagulation period was lower in the TT group than the DAPT group (7.1% vs 30.8%; P=0.167). Modified Rankin Scale score decline was significantly lower in the TT group (7.1% vs 69.2%; P=0.001). Overall rates of hemorrhagic complications (TT, 28.6% vs DAPT, 7.7%; P=0.162) and complete occlusion (TT, 25% vs DAPT, 54.4%; P=0.213) were non-different between the groups. Rate of moderate-to-severe disability at last follow-up was significantly lower in the TT group (21.4% vs 76.9%; P=0.007). CONCLUSIONS: Patients with DVBFAs treated with FD in the TT group had fewer ischemic strokes, less symptom progression, and overall better outcomes at last follow-up than similar patients in the DAPT group.

Transcarotid artery revascularization (TCAR): a technical video.

Carotid revascularization is an important method of stroke prevention and includes carotid endarterectomy and transfemoral carotid angioplasty and stenting. More recently, a hybrid open-endovascular approach, termed transcarotid artery revascularization (TCAR), is garnering increased attention. Although fundamentally a 'stenting procedure', unlike transfemoral carotid angioplasty and stenting, TCAR allows for a proximal neuroprotection strategy based on flow reversal. In this technical video, we will review operative techniques and nuances of the TCAR procedure, with a particular focus on the neurovascular proceduralist looking to adopt this technique into routine clinical practice(video 1). neurintsurg;14/8/842/V1F1V1Video 1TCAR Technical Video.

Educational impact of early COVID-19 operating room restrictions on neurosurgery resident training in the United States: A multicenter study.

BACKGROUND: The coronavirus (COVID-19) pandemic has caused unprecedented suspensions of neurosurgical elective surgeries, a large proportion of which involve spine procedures. The goal of this study is to report granular data on the impact of early COVID-19 pandemic operating room restrictions upon neurosurgical case volume in academic institutions, with attention to its secondary impact upon neurosurgery resident training. This is the first multicenter quantitative study examining these early effects upon neurosurgery residents caseloads. METHODS: A retrospective review of neurosurgical caseloads among seven residency programs between March 2019 and April 2020 was conducted. Cases were grouped by ACGME Neurosurgery Case Categories, subspecialty, and urgency (elective vs. emergent). Residents caseloads were stratified into junior (PGY1-3) and senior (PGY4-7) levels. Descriptive statistics are reported for individual programs and pooled across institutions. RESULTS: When pooling across programs, the 2019 monthly mean (SD) case volume was 214 (123) cases compared to 217 (129) in January 2020, 210 (115) in February 2020, 157 (81), in March 2020 and 82 (39) cases April 2020. There was a 60% reduction in caseload between April 2019 (207 [101]) and April 2020 (82 [39]). Adult spine cases were impacted the most in the pooled analysis, with a 66% decrease in the mean number of cases between March 2020 and April 2020. Both junior and senior residents experienced a similar steady decrease in caseloads, with the largest decreases occurring between March and April 2020 (48% downtrend). CONCLUSIONS: Results from our multicenter study reveal considerable decreases in caseloads in the neurosurgical specialty with elective adult spine cases experiencing the most severe decline. Both junior and senior neurosurgical residents experienced dramatic decreases in case volumes during this period. With the steep decline in elective spine cases, it is possible that fellowship directors may see a disproportionate increase in spine fellowships in the coming years. In the face of the emerging Delta and Omicron variants, programs should pay attention toward identifying institution-specific deficiencies and developing plans to mitigate the negative educational effects secondary to such caseloads reduction.

Vessel wall MRI in ruptured cranial dural arteriovenous fistulas.

Intracranial high-resolution vessel wall MRI (VW-MRI) is an imaging paradigm that is useful in site-of-rupture identification in patients presenting with spontaneous subarachnoid hemorrhage and multiple intracranial aneurysms. Only a handful of case reports describe its potential utility in the evaluation of more complex brain vascular malformations. We report for the first time three patients with ruptured cranial dural arteriovenous fistulas (dAVFs) that were evaluated with high-resolution VW-MRI. The presumed site-of-rupture was identified based on contiguity of a venous ectasia with adjacent blood products and thick, concentric wall enhancement. This preliminary experience suggests a role for high-resolution VW-MRI in the evaluation of ruptured cranial dAVFs, in particular, site-of-rupture identification. It also supports an emerging hypothesis that all spontaneously ruptured, macrovascular lesions demonstrate avid vessel wall enhancement.

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals. Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk. Design, Setting, and Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort. Main Outcomes and Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue. Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways. Conclusions and Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.

Posterior Reversible Encephalopathy Syndrome Caused by Induced Hypertension to Treat Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The aim of the present study was to describe the case of a patient who had presented to a university hospital with induced-hypertension (IH) posterior reversible encephalopathy syndrome (PRES). We also reviewed all other reports of such patients. METHODS: We have described the clinical course of a patient who had presented to the university hospital neurosurgical department. We also performed a systematic review of studies related to the incidence of PRES caused by the use of IH in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. RESULTS: The patient had presented with an acute-onset headache and found to have a subarachnoid hemorrhage due to anterior communicating artery aneurysm rupture. She underwent coiling the next day. During the subsequent days, she demonstrated fluctuating clinical examination findings, aphasia, and decreased levels of arousal. Digital subtraction angiography was performed, and the findings were concerning for mild vasospasm of the anterior and middle cerebral arteries. The systolic blood pressure goal was increased to 180-220 mm Hg for an IH trial, which had initially resulted in some transient clinical improvements in her level of arousal. However, the improvement was not sustained. During the next 36 hours, the patient worsened, and she developed left middle cerebral artery syndrome. Given the concern for a possible ischemic event, magnetic resonance imaging was performed, which demonstrated interval development of multiple areas of cortical-based fluid-attenuated inversion recovery hyperintensity consistent with PRES. The systolic blood pressure goal was relaxed to normotension, and ~48 hours later, the patient's clinical status had significantly improved. CONCLUSION: IH-PRES is a rare complication that should be remembered in the differential diagnosis for at-risk patients.

Thirty- and 90-Day Readmissions After Treatment of Traumatic Subdural Hematoma: National Trend Analysis.

OBJECTIVE: Subdural hematoma (SDH), a form of traumatic brain injury, is a common disease that requires extensive patient management and resource utilization; however, there remains a paucity of national studies examining the likelihood of readmission in this patient population. The aim of this study is to investigate differences in 30- and 90-day readmissions for treatment of traumatic SDH using a nationwide readmission database. METHODS: The Nationwide Readmission Database years 2013-2015 were queried. Patients with a diagnosis of traumatic SDH and a primary procedure code for incision of cerebral meninges for drainage were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R). RESULTS: We identified a total of 14,355 patients, with 3106 (21.6%) patients encountering a readmission (30-R: n = 2193 [15.3%]; 90-R: n = 913 [6.3%]; Non-R: n = 11,249). The most prevalent 30- and 90-day diagnoses seen among the readmitted cohorts were postoperative infection (30-R: 10.5%, 90-R: 13.0%) and epilepsy (30-R: 3.7%, 90-R: 1.1%). On multivariate logistic regression analysis, Medicare, Medicaid, hypertension, diabetes, renal failure, congestive heart failure, and coagulopathy were independently associated with 30-day readmission; Medicare and rheumatoid arthritis/collagen vascular disease were independently associated with 90-day readmission. CONCLUSIONS: In this study, we determine the relationship between readmission rates and complications associated with surgical intervention for traumatic subdural hematoma.