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Objective: Despite having higher rates of failure and revision than other implant materials, autologous bone implants are the historical gold standard for restoring cranial defects after decompressive hemicraniectomy. More reliable synthetic implants have been developed, but they are significantly more expensive than autologous bone. The authors sought to compare the initial and long-term costs of custom synthetic implants and autologous cranioplasty grafts. Methods: The authors reviewed the hospital billing records over a 12-year period at their institution to identify patients who underwent cranioplasty after decompressive hemicraniectomy for trauma or stroke. The costs for imaging, hospital supplies, implants, pharmacy services, facility usage, and laboratory studies were captured for initial surgeries and for subsequent cranioplasty-related revision hospitalizations and surgeries. Clinical characteristics, long-term outcomes, and cost differences of autologous versus custom implants were compared by using univariate and multivariate analyses. These analyses were repeated after propensity-score matching adjusted for factors predictive of cranioplasty failure. Results: On unmatched analysis, 32 custom and 128 autologous implants were analyzed. Differences in initial cranioplasty failure rates between custom and autologous grafts were insignificant (12.5 % custom vs. 23.4 % autologous, p = 0.18). On univariate analysis, autologous implants cost 46.8 % of custom grafts during the initial hospitalization period (p

Background Multiple studies have highlighted the importance of carotid artery stenting (CAS) operator's experiences. However, fellowship‐trained neurointerventionalists remain an under‐represented specialty in the literature. We aim to report the complication rate of CAS performed exclusively by neurointerventionalists. Methods Retrospective cohort study regarding stenting symptomatic and asymptomatic carotid stenosis was collected at multiple comprehensive stroke centers. The primary outcome included a composite of the 30‐day periprocedural mortality, symptomatic ischemic stroke, symptomatic intracranial hemorrhage, and myocardial infarction. The secondary outcomes included other complications. Chi‐squared tests were performed for categorical variables, and Welch's t‐test was used for continuous variables. Cutoffs in continuous variables were estimated using grid search optimization. Sensitivity analyses were performed for missing data. Results Between 2018 and 2022, 1445 CAS procedures were performed by 38 neurointerventionalists. We have 30‐day outcome data on 1281 patients. Patients were predominantly symptomatic (93.01%), male (65.79%), White (70.36%), and had a median age of 69. The primary outcomes occurred in 26 (1.8%) cases, with 13 (0.9%) death, 8 (0.55%) symptomatic ischemic stroke, 4 (0.28%) symptomatic intracranial hemorrhage, and 1 (0.07%) myocardial infarction. A statistically significant increase in all outcomes correlated with advanced age (P = 0.001), women (P = 0.013), aortic arch type 3 (P = 0.01), and higher preprocedural modified Rankin score (P = 0.006). Secondary outcomes were higher in Hispanic and Black patients (P = 0.007) and those with low diastolic blood pressure at stenting (P = 0.04). Conclusion CAS, conducted by fellowship‐trained neurointerventionalist physicians in comprehensive stroke centers, demonstrates a lower complication rate than what was previously reported in CAS, carotid endarterectomy, and transcarotid artery revascularization literature. Physician training, higher frequency, and standardized stroke care in a comprehensive stroke center may contribute to this low complication rate.

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

Background Carotid artery disease, a major cause of strokes, often results from carotid atherosclerotic stenosis. Although carotid endarterectomy has long been the standard treatment, carotid artery stenting (CAS) emerged as an alternative for high‐risk surgical patients. Operator experience plays a crucial role in reducing complications, with neurointerventional specialists demonstrating proficiency in CAS. However, they are often underrepresented in CAS studies. The CASSH (Carotid Artery Stenting Outcomes in Comprehensive Stroke Hospitals) registry aims to provide comprehensive insights into CAS outcomes, particularly when performed by neurointerventionalists at comprehensive stroke centers. Methods The CASSH is a multicenter, prospective, observational study currently enrolling patients with carotid artery stenosis undergoing CAS performed by neurointerventional physicians. All the participating sites will screen and report cases that meet inclusion criteria, on a monthly basis. The decision of whether to use CAS is at the discretion of the interventionalist. Results We will collect patients’ baseline clinical, demographic, and radiographic data. In addition, we plan to collect procedure variables and postoperative clinical and imaging data. Outcomes include the rate of postoperative symptomatic stroke (hemorrhagic/ischemic), access site complications, in‐stent thrombosis, and mortality. Conclusion Current literature underrepresents neurointerventionalists in CAS studies, especially as it pertains to procedural expertise and outcomes. CASSH is a prospective observational study that will enhance our understanding of CAS management and outcomes, emphasizing the benefits of neurointerventional expertise within comprehensive stroke centers.

Summary: Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17–89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

Objective: In recent years, frailty has been reported to be an important predictive factor associated with worse outcomes in neurosurgical patients. The purpose of the present systematic review was to analyze the impact of frailty on outcomes of chronic subdural hematoma (cSDH) patients. Methods: We performed a systematic review of literature using the PubMed, Cochrane library, Wiley online library, and Web of Science databases following PRISMA guidelines of studies evaluating the effect of frailty on outcomes of cSDH published until January 31, 2023. Results: A comprehensive literature search of databases yielded a total of 471 studies. Six studies with 4085 patients were included in our final qualitative systematic review. We found that frailty was associated with inferior outcomes (including mortality, complications, recurrence, and discharge disposition) in cSDH patients. Despite varying frailty scales/indices used across studies, negative outcomes occurred more frequently in patients that were frail than those who were not. Conclusions: While the small number of available studies, and heterogenous methodology and reporting parameters precluded us from conducting a pooled analysis, the results of the present systematic review identify frailty as a robust predictor of worse outcomes in cSDH patients. Future studies with a larger sample size and consistent frailty scales/indices are warranted to strengthen the available evidence. The results of this work suggest a strong case for using frailty as a pre-operative risk stratification measure in cSDH patients.

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

Background The introduction of soft, large‐profile microwires has improved aspiration catheter delivery for intracranial large‐vessel occlusions. The Aristotle‐only direct aspiration first‐pass technique (AO‐ADAPT) uses the Aristotle 24 microwire to deliver a large‐bore aspiration catheter to the target occlusion without a microcatheter. We characterized rates of technical success achieved using this technique for mechanical aspiration thrombectomy. Methods A retrospective review of prospectively collected thrombectomy databases at 4 academic institutions identified patients undergoing procedures in which AO‐ADAPT was used. Patient demographics, clinical considerations, technical details, and radiographic outcomes were collected. Rates of successful aspiration catheter delivery without adjunctive devices and of successful reperfusion (Thrombolysis in Cerebral Infarction≥2B) were collected. Results Forty‐five patients met inclusion criteria (mean age 72.2±13.2 years, 62.2% female; 71.1% M1 occlusions). With a first‐line AO‐ADAPT approach, 42/45 (93.3%) patients achieved Thrombolysis in Cerebral Infarction≥2B reperfusion, with first‐pass recanalization in 26/45 (57.8%). We delivered the aspiration catheter to the target occlusion without adjunctive device in 35/45 (77.8%) patients. Of these, 29 (82.9%) underwent successful contact aspiration. This entire cohort (64.4% of the population) achieved Thrombolysis in Cerebral Infarction≥2B, with a mean time to reperfusion of 16 minutes and a first‐pass recanalization rate of 66%. Of the 16 patients who did not achieve successful AO‐ADAPT reperfusion, 6 needed a microcatheter for aspiration catheter delivery but underwent successful contact aspiration, 6 achieved microcatheter‐free delivery but needed a stentriever for final recanalization, and 4 required both microcatheter for delivery and stentriever for final recanalization. No intracranial vascular complications occurred during the procedures; 1 patient (2.2%) experienced symptomatic intracranial hemorrhage secondary to reperfusion injury. Conclusion The AO‐ADAPT approach to mechanical thrombectomy safely and effectively achieved reperfusion for patients with large‐vessel occlusions, with first‐pass success and successful recanalization rates comparable with other techniques. For most cases in this series, this technique obviated the need for a microcatheter and/or stentriever.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

Introduction Intracranial atherosclerotic disease (ICAD) is one of the most prevalent causes of stroke across the world, with a high morbidity and mortality rate. Endovascular treatment (ET) has gained prominence but remains a challenge with unfavorable results. Recent literature has demonstrated that the Resolute Onyx Zotarolimus‐Eluting stent (RO‐ZES) is a technically safe option with low complication rates. Preliminary data has also reported the 30‐day outcomes associated with intracranial stent placement for ICAD with RO‐ZES compared to results from the Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. Here, we aim to compare outcomes at 1 year with the SAMMPRIS trial to further evaluate the efficacy and outcomes of RO‐ZES in a multicenter study with long‐term follow up extending beyond 30 days. Methods Prospectively maintained databases across 7 stroke centers were reviewed to identify adult patients undergoing RO‐ZES placement for treatment of ICAD between January 2019 to May 2023. The primary endpoint was composite of 1‐year stroke, ICH, and/or death. This data was propensity score matched using age, sex, hypertension, diabetes mellitus, smoking status, and impacted vessel for comparison between RO‐ZES and the SAMMPRIS percutaneous angioplasty and stenting groups (S‐PTAS). Results A total of 104 patients met the inclusion criteria for analysis (mean age 62.6, 31.7% female). Impacted vessels included basilar artery (6.7%), internal carotid artery (26.9%), middle cerebral artery (29.8%), posterior cerebral artery (1.0%), and vertebral artery (35.6%). Propensity score match analysis of the 104 patients with S‐PTAS demonstrated 1‐year stroke, ICH, and/or death rate of 11.5% in the RO‐ZES group and 35.6% in the S‐PTAS group (OR 4.17, 95% CI 2.06‐8.96, p=0.001). Conclusion The RO‐ZES system provides a not only safe and effective alternative to other traditional stents, but also demonstrates strong potential to reduce long‐term complications at 1 year compared with the S‐PTAS group. Further prospective multicenter studies are needed to corroborate the findings and compare RO‐ZES directly with other stents.

Introduction Indications for flow diversion for the treatment of cerebral aneurysms have increased remarkably in recent years.1 This has been particularly useful for aneurysms that are difficult to treat via endosaccular or open approaches, such as pseudoaneurysms.2 Flow diversion, however, typically requires dual antiplatelet therapy (DAPT), which can contribute to greater morbidity particularly in patients with ruptured aneurysms or other comorbidities.3 The third‐generation iteration of the Pipeline Embolization Device (PED) incorporates Shield technology, a phosphorylcholine coating designed to reduce thrombogenicity via mimicry of native cell membranes.4 In light of this reduced thrombogenicity, there have been reports of early transition to single antiplatelet therapy (SAPT), or other variations on DAPT, in patients treated with PED Shield. We therefore aim to characterize the antiplatelet regimens, and associated thromboembolic/hemorrhagic outcomes, utilized in patients with aneurysms treated with PED Shield. Methods Factors including demographics, comorbidities, rupture status, devices placed, and antiplatelet regimen, among others, were collected. Follow‐up data including aneurysm thromboembolic complication, hemorrhagic complication, new neurological deficit, aneurysm occlusion, and in‐stent thrombosis were also recorded. Results One‐hundred and eighty patients were included in analysis, 18 of which were acutely ruptured. One hundred and sixty‐two patients had a single device placed, while the remaining had two devices placed. Three patients were maintained on SAPT post‐procedurally (aspirin or clopidogrel), with two additional patients treated with SAPT plus an anticoagulant for other purposes. One hundred and seventy‐two patients were maintained on DAPT, most commonly aspirin/clopidogrel (115), followed by aspirin/ticagrelor (40), and aspirin/prasugrel (16). Seven patients had strokes of any kind, three of which were unrelated to the treatment territory, and two of the remaining 4 were non‐compliant with antiplatelet therapy. One patient had a new intraparenchymal hemorrhage, but no appreciable deficit. Of the 135 patients with 6‐month follow‐up, 77 had complete aneurysm occlusion, and 116 demonstrated no in‐stent thrombosis. Conclusion We demonstrate herein the similar safety profile and efficacy of PED Shield with varying antiplatelet regimens, including SAPT in isolated cases.

Introduction Extracranial‐intracranial (EC‐IC) bypass is a niche procedure that has been selectively used for flow augmentation or flow restoration in patients with intracranial carotid insufficiency.1 The underlying etiology varies but is most commonly related to Moya Moya disease (MMD) or intracranial carotid atherosclerotic disease (ICAD).2 Patients are often managed non‐operatively until they begin to develop symptoms such as transient ischemic attacks (TIAs) or strokes that are recalcitrant to maximal medical management, at which point bypass is pursued.1 This lag period, however, could put patients at risk for long term deficit, not only in the form of focal neurological deficits but also in terms of overall neurocognitive capability.3 Several reports have previously demonstrated some level of association between EC‐IC bypass and neurocognitive outcomes, though in isolated populations of either MMD or ICAD.4,5 We therefore aim to further assess the relationship between EC‐IC bypass and neurocognitive outcomes in patients with intracranial carotid insufficiency. Methods Patients ages 18 years and up undergoing EC‐IC bypass were identified from a single institution database between January 2020 and December 2021. Patient records were reviewed for demographic data including age and sex, as well as preoperative clinical information including comorbidities, operative indication, anticoagulation/antiplatelet therapy usage, prior ischemic stroke, modified Rankin score (mRS), and Montreal Cognitive Assessment (MOCA) score. Radiographic data was also collected including Suzuki grade, collateralization, and perfusion. Post‐operative clinical information including complications, discharge mRS, and discharge MOCA scores were identified. Follow‐up duration, MOCA scores, and mRS were also identified and recorded. Results Of the forty‐four patients that underwent EC‐IC bypass during the specified period, ten had cognitive assessments before and after surgery available for review. The indications for bypass in these cases were ICA steno‐occlusive disease resulting in strokes despite maximal medical management in 9 cases, and MMD in one case. Suzuki grade was IV in the MMD case. Pial collaterals were present in 7 cases, and ECA collaterals were present in 5. Prior ischemic strokes were present in 8 cases, with a preoperative mRS range from 1‐4 (median 1), and average MOCA of 20. Perfusion imaging demonstrated a Tmax mismatch in eight cases, with an average volume of 73.6 cc at risk. All patients underwent direct superficial temporal artery to middle cerebral artery bypass, with additional encephaloduroarteriomyosynangiosis (EDAMS). Follow up MOCA score was improved in 8 cases, unchanged in one case, and worsened in one case (average MOCA increased from 20 to 23). Follow up mRS ranged from 0‐2. Additionally, CT perfusion demonstrated notable improvements in Tmax >4 seconds (decrease from 176 cc to 110 cc), Tmax >6 seconds (decrease from 59 cc to 29 cc), and mismatch (decrease from 59 cc to 17 cc) at 6 month follow up. Conclusion Patients with carotid insufficiency from MMD or ICAD undergoing EC‐IC bypass demonstrate well below normal preoperative MOCA scores. This is suggestive of ongoing neurocognitive decline, which is an often overlooked issue in patients with these pathologies. MOCA and mRS both appear to improve in patients after bypass at longer term follow‐up, suggesting that bypass may be an effective method of addressing the issue of neurocognitive decline in patients with carotid insufficiency.

OBJECTIVES:. We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN:. Retrospective cohort study. SETTING:. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS:. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of

Background Mechanical thrombectomy has been shown to be effective in patients with acute ischemic stroke secondary to large‐vessel occlusion and small to moderate infarct volume. However, there are no randomized clinical trials for large‐core infarct volume comparing mechanical thrombectomy to medical therapy in the population selected based solely on noncontrast computed tomography brain scan. The TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke) randomized clinical trial is designed to address this clinical question. Methods The TESLA trial aim is to demonstrate the efficacy (3‐month and 1‐year disability following stroke) and safety of intraarterial mechanical thrombectomy in patients with large‐volume infarction assessed with a noncontrast computed tomography scan. The TESLA trial design is a prospective, randomized controlled, multicenter, open‐label, assessor‐blinded anterior circulation acute ischemic stroke trial with adaptive enrichment design, enrolling up to 300 patients. Patients with anterior circulation large‐vessel occlusion who meet the imaging and clinical eligibility criteria with a large‐core infarction on the basis of noncontrast computed tomography Alberta Stroke Program Early CT Score (2–5) adjudicated by a site investigator will be randomized in a 1:1 ratio to undergo intraarterial thrombectomy or best medical management up to 24 hours from last known well. Results The primary efficacy outcome is utility‐weighted modified Rankin Scale (mRS) score distribution at 90 days between the groups. The results will be based on an intention‐to‐treat analysis that will examine the Bayesian posterior probability that, adjusted for Alberta Stroke Program Early CT Score, patients with large‐core infarct volume treated with intra‐arterial thrombectomy have higher expected utility‐weighted mRS than those treated with best medical management alone. The primary safety outcome is the 90‐day death rate. Key secondary outcomes are dichotomized mRS 0 to 2 and 0 to 3 outcomes, ordinal mRS scores, and quality of life (EuroQol 5 Dimension 5 Level survey) at 90 days and 1 year, utility‐weighted mRS at 1 year, hemicraniectomy rate, and rate of 24‐hour symptomatic intracranial hemorrhage in both groups. Conclusion TESLA is a pragmatic trial, designed to address the unanswered question of the efficacy and safety of intra‐arterial thrombectomy in patients with large infarcts diagnosed by the site investigator only on noncontrast computed tomography scan secondary to anterior circulation large‐vessel occlusion up to 24 hours from stroke symptoms onset.

Background Mechanical thrombectomy (MT) failure occurs in ≈10% to 20% of MTs. Among the common causes of failed MT is residual underlying intracranial stenosis (ICAS), typically attributable to atherosclerotic disease. ICAS large‐vessel occlusion (ICAS‐LVO) remains poorly understood, and management of ICAS‐LVO is unclear. The RESCUE‐ICAS (Registry of Emergent Large Vessel Occlusion Due to Intracranial Stenosis) aims at providing better understanding of the prevalence of ICAS‐LVO, and the overall safety and efficacy of various rescue therapies. Methods RESCUE‐ICAS is a multicenter, international, prospective registry that is currently enrolling patients with ICAS‐LVO who underwent MT. All sites are required to report monthly MT cases that meet inclusion criteria. The decision of whether to use rescue therapy is up to the interventionist. Results We will collect patients’ demographic, clinical, and radiographic data at baseline. Also, we will capture variables related to the MT procedure and rescue therapy (if performed), and postprocedural clinical and imaging variables. Outcomes include the rate of successful recanalization, defined by modified Thrombolysis in Cerebral Infarction score of ≥2b, the rate of symptomatic intracranial hemorrhage, the 90‐day modified Rankin scale score, and mortality. Conclusions No strong evidence is currently available to support an optimal treatment strategy for patients with ICAS‐LVO undergoing MT. RESCUE‐ICAS is a prospective cohort study that will provide important data to help design randomized controlled trials.

Introduction Coiling procedures for intracranial aneurysms (IAs) performed in the US have steadily increaseda, and volumetric efficiency may become an important consideration for hospitals. Coil volume depends on length and primary wind diameter (PWD), and volumetric efficiency can be achieved by either inserting more coils or using coils with larger volumetric filling. This scenario analysis evaluates the influence of PWD and length on total coil volume by comparing four similar Stryker and CEREPAK coils. Methods In this analysis, we test the influence of PWD (D2) and length (L) on the Coil Volume Formula: [Π(D2/2)2(L)]c. In two hypothetical scenarios, relative percent difference in total coil volume was calculated and compared between four Stryker Target 360 coils and four similar CEREPAK coils that were matched based on closest PWD and L. In scenario I, L remained constant and D2 varied. In scenario II, D2 and L were inversely varied. In both scenarios, coil volume achieved by CEREPAK and Stryker coils was calculated and descriptively compared. Results Scenario I: (a) Stryker Target XL 360 10mm x 40cm (D2 = 0.014”, length = 40cm) with volume of 39.726mm3 was matched to the CEREPAK Heliform XL 10mm x 40cm (D2 = 0.015”, length = 40cm) with 15% greater volume of 45.604mm3. (b)Stryker Target 360 3mm x 6cm (D2 = 0.010”, length = 6cm) with volume 3.040mm3 was matched to the CEREPAK Freeform 3mm x 6cm (D2 = 0.012”, length = 6cm) with 44% greater volume of 4.378mm3. Scenario II: (a) Stryker Target XL 360 12mm x 45cm (D2 = 0.014”, length = 45cm) with volume 44.692mm3 was matched to the CEREPAK Heliform XL 12mm x 42cm (D2 = 0.015”, length = 42cm) with 7% greater volume of 47.884mm3. (b)Stryker Target 360 5mm x 20cm (D2 = 0.010”, length = 20cm) with volume 10.134mm3 was matched to the CEREPAK Freeform 5mm x 15cm (D2 = 0.012”, length = 15cm) with 8% greater volume of 10.945mm3. Conclusions The four selected CEREPAK coils compared to four equivalent Stryker coils achieved higher total coil volume in all scenarios. An increase in PWD by as little as 0.001”‐0.002”, improved relative coil volume by 15%‐44% (with equivalent coil length) and 7–8% (with varied coil length by 3–5cm). Clinicians evaluate many coil characteristics when treating an IA, however, PWD might be given consideration over length due to its impact on total coil volume.

Blunt cerebrovascular injuries (BCVIs) are commonly encountered after blunt trauma. Given the increased risk of stroke incurred after BCVI, it is crucial that they are promptly identified, characterized, and treated appropriately. Current screening practices generally consist of computed tomography angiography (CTA), with escalation to digital subtraction angiography for higher-grade injuries. Although it is quick, cost-effective, and readily available, CTA suffers from poor sensitivity and positive predictive value. A review of the current literature was conducted to examine the current state of emergent imaging for BCVI. After excluding reviews, irrelevant articles, and articles exclusively available in non-English languages, 36 articles were reviewed and included in the analysis. In general, as CTA technology has advanced, so too has detection of BCVI. Magnetic resonance imaging (MRI) with sequences such as vessel wall imaging, double-inversion recovery with black blood imaging, and magnetization prepared rapid acquisition echo have notably improved the utility for MRI in characterizing BCVIs. Finally, transcranial Doppler with emboli detection has proven to be associated with strokes in anterior circulation injuries, further allowing for the identification of high-risk lesions. Overall, imaging for BCVI has benefited from a tremendous amount of innovation, resulting in better detection and characterization of this pathology.

Skull bone graft failure is a potential complication of autologous cranioplasty after decompressive craniectomy (DC). Our objective was to investigate the association of graft size with subsequent bone graft failure after autologous cranioplasty. This single-center retrospective cohort study included patients age ?18 years who underwent primary autologous cranioplasty between 2010 and 2017. The primary outcome was bone flap failure requiring graft removal. Demographic, clinical, and radiographic factors were recorded; three-dimensional (3D) reconstructive imaging was used to perform accurate measurements. Univariate and multi-variate regression analysis were performed to identify risk factors for the primary outcome. Of the 131 patients who underwent primary autologous cranioplasty, 25 (19.0%) underwent removal of the graft after identification of bone flap necrosis on computed tomography (CT); 16 (64%) of these were culture positive. The mean surface area of craniectomy defect was 128.5?cm2 for patients with bone necrosis and 114.9?cm2 for those without bone necrosis. Linear regression analysis demonstrated that size of craniectomy defect was independently associated with subsequent bone flap failure; logistic regression analysis demonstrated a defect area >125?cm2 was independently associated with failure (odds ratio [OR] 3.29; confidence interval [CI]: 0.249-2.135). Patient- and operation-specific variables were not significant predictors of bone necrosis. Our results showed that increased size of antecedent DC is an independent risk factor for bone flap failure after autologous cranioplasty. Given these findings, clinicians should consider the increased potential of bone flap failure after autologous cranioplasty among patients whose initial DC was >125?cm2.

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface–expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

Non-acute subdural hematomas (NASHs) are a cause of significant morbidity and mortality, particularly with recurrences. Although recurrence is believed to involve a disordered neuroinflammatory cascade involving vascular endothelial growth factor (VEGF), this pathway has yet to be completely elucidated. Neutrophil extracellular traps (NETs) are key factors that promote inflammation/apoptosis and can be induced by VEGF. We investigated whether NETs are present in NASH membranes, quantified NET concentrations, and examined whether NET and VEGF levels are correlated in NASHs. Samples from patients undergoing NASH evacuation were collected during surgery and postoperatively at 24 and 48 h. Fluid samples and NASH membranes were analyzed for levels of VEGF, NETs, and platelet activation. NASH samples contained numerous neutrophils positive for NET formation. Myeloperoxidase-DNA complexes (a marker of NETs) remained elevated 48 h postoperatively (1.06 ± 0.22 day 0, 0.72 ± 0.23 day 1, and 0.83 ± 0.33 day 2). VEGF was also elevated in NASHs (7.08 ± 0.98 ng/mL day 0, 3.40 ± 0.68 ng/mL day 1, and 6.05 ± 1.8 ng/mL day 2). VEGF levels were significantly correlated with myeloperoxidase-DNA levels. These results show that NETs are increasing in NASH, a finding that was previously unknown. The strong correlation between NET and VEGF levels indicates that VEGF may be an important mediator of NET-related inflammation in NASH.

ObjectiveTo examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort.MethodsWe performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes.ResultsThere were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge.ConclusionsPatients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.

Introduction: Treatments for acute stroke have significantly improved in the past decade, with emergent thrombectomy emerging as the standard of care. Despite these advancements, death after successful thrombectomy continues to pose a significant problem. Identifying patients least likely to benefit from thrombectomy would improve use of a limited resource and management of patient expectations.Method: We retrospectively reviewed the medical records of patients who underwent emergent thrombectomy of either anterior or posterior circulation strokes between January 2012 and January 2017. Relevant patient clinical data was collected and analyzed in a multivariable regression with a primary outcome of death at 90 days.Results: A total of 134 patients underwent emergent endovascular thrombectomy during the study period; sufficient clinical data was available in 111 of the them. Of these, 42 patients died during the 90 day post-procedural period and 69 patients survived this period. The mean NIHSS score at presentation was 14.9 in surviving patients and 19.6 in non-surviving patients (p < 0.002). Surviving patients were less likely to have a history of cancer (4.4% vs. 26.2%, p < 0.002), achieved higher rates of revascularization (78.3% vs. 50.0%, p < 0.003), had a lower rate of hemorrhagic conversion (21.7% vs. 47.6%, p < 0.004), and experienced fewer technical complications during their treatment (7.4% vs. 26.2%, p < 0.01). Overall, there were 16 intraprocedural complications and no procedural deaths.Conclusion: As emergent thrombectomy for the treatment of acute stroke becomes more prevalent, appropriate patient selection will be crucial in the utilization of a limited and costly intervention. Death within 90 days after thrombectomy appears to be more prevalent among patients with higher NIHSS at presentation, those with postprocedural hemorrhage or intraprocedural complications, and those with a history of cancer.

IntroductionThe use of endovascular treatments, including Pipeline embolization devices (PEDs) and coiling approaches (non-PEDs), has played an increasingly important role in the treatment of intracranial aneurysms. Despite multiple studies evaluating PEDs, a real-world evaluation of follow-up outcomes and costs remains to be completed.MethodsThe Premier Healthcare Database (PHD), 2010-2017, was queried to identify patients with unruptured intracranial aneurysms treated endovascularly. Rates of readmission, retreatment, and cost at the same hospital were compared between patients who underwent PED and non-PED endovascular treatments of their aneurysms. One-to-three (PED-to-non-PED) propensity score (PS) matching was performed to adjust for potential case selection bias into the PED cohort, with covariates including age group, sex, Charlson Comorbidity Index (CCI) group, payor, region, and randomized hospital identifier.ResultsA total of 679 patients underwent PED placement and 8432 had non-PED treatments. Prior to PS matching, there were significant but minor differences in age (56.7±12.8 vs. 58.2±12.6 years, p = 0.004) and sex (male 16.6% vs. 24.4%, pConclusionsThese results suggest that PEDs may potentially reduce downstream retreatment rates and costs. Further work is required to improve identification of patient subgroups that could benefit from PED over non-PED treatments both initially and during follow-up.

Magnetoencephalography (MEG) is a functional brain imaging technique with high temporal resolution compared with techniques that rely on metabolic coupling. MEG has an important role in traumatic brain injury (TBI) research, especially in mild TBI, which may not have detectable features in conventional, anatomical imaging techniques. This review addresses the original research articles to date that have reported on the use of MEG in TBI. Specifically, the included studies have demonstrated the utility of MEG in the detection of TBI, characterization of brain connectivity abnormalities associated with TBI, correlation of brain signals with post-concussive symptoms, differentiation of TBI from post-traumatic stress disorder, and monitoring the response to TBI treatments. Although presently the utility of MEG is mostly limited to research in TBI, a clinical role for MEG in TBI may become evident with further investigation.

Traumatic brain injury (TBI) is a widespread and expensive problem globally. The standard diagnostic workup for new TBI includes obtaining a noncontrast computed tomography image of the head, which provides quick information on operative pathologies. However, given the limited sensitivity of computed tomography for identifying subtle but meaningful changes in the brain, magnetic resonance imaging (MRI) has shown better utility for ongoing management and prognostication after TBI. In recent years, advanced applications of MRI have been further studied and are being implemented as clinical tools to help guide care. These include functional MRI, diffusion tensor imaging, MR perfusion, and MR spectroscopy. In this review, we discuss the scientific basis of each of the above techniques, the literature supporting their use in TBI, and how they may be clinically implemented to improve the care of TBI patients.

BACKGROUND:Coronal suture synostosis is a condition which can have deleterious physical and cognitive sequelae in humans if not corrected. A well-established animal model has previously demonstrated disruptions in intracranial pressure and developmental abnormalities in rabbits with congenital craniosynostosis compared to wild type rabbits. OBJECTIVE:The current study aimed to measure the cerebral blood flow (CBF) in developing rabbits with craniosynostosis who underwent suturectomy compared to those with no intervention and compared to wild type rabbits. METHODS:Rabbits with early onset coronal suture synostosis were assigned to have suturectomy at 10 days of age (EOCS-SU, n = 15) or no intervention (EOCS, n = 18). A subset of each group was randomly selected for measurement at 10 days of age, 25 days of age, and 42 days of age. Wild type rabbits (WT, n = 18) were also randomly assigned to measurement at each time point as controls. Cerebral blood flow at the bilateral hemispheres, cortices, thalami, and superficial cortices was measured in each group using arterial spin-labeling MRI. RESULTS:At 25 days of age, CBF at the superficial cortex was significantly higher in EOCS rabbits (192.6 ± 10.1 mL/100 mg/min on the left and 195 ± 9.5 mL/100 mg/min on the right) compared to WT rabbits (99.2 ± 29.1 mL/100 mg/min on the left and 96.2 ± 21.4 mL/100 mg/min on the right), but there was no significant difference in CBF between EOCS-SU (97.6 ± 11.3 mL/100 mg/min on the left and 99 ± 7.4 mL/100 mg/min on the right) and WT rabbits. By 42 days of age the CBF in EOCS rabbits was not significantly different than that of WT rabbits. CONCLUSION:Suturectomy eliminated the abnormally increased CBF at the superficial cortex seen in EOCS rabbits at 25 days of age. This finding contributes to the evidence that suturectomy limits abnormalities of ICP and CBF associated with craniosynostosis.

[This corrects the article DOI: 10.1371/journal.pone.0195827.].

Recent interest in the study of concussion and other neurological injuries has heightened awareness of the medical implications of American tackle football injuries amongst the public.Using the National Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS), the largest publicly available all-payer emergency department and inpatient healthcare databases in the United States, we sought to describe the impact of tackle football injuries on the American healthcare system by delineating injuries, specifically neurological in nature, suffered as a consequence of tackle football between 2010 and 2013.The NEDS and NIS databases were queried to collect data on all patients presented to the emergency department (ED) and/or were admitted to hospitals with an ICD code for injuries related to American tackle football between the years 2010 and 2013. Subsequently those with football-related neurological injuries were abstracted using ICD codes for concussion, skull/face injury, intracranial injury, spine injury, and spinal cord injury (SCI). Patient demographics, length of hospital stay (LOS), cost and charge data, neurosurgical interventions, hospital type, and disposition were collected and analyzed.A total of 819,000 patients presented to EDs for evaluation of injuries secondary to American tackle football between 2010 and 2013, with 1.13% having injuries requiring inpatient admission (average length of stay 2.4 days). 80.4% of the ED visits were from the pediatric population. Of note, a statistically significant increase in the number of pediatric concussions over time was demonstrated (OR = 1.1, 95% CI 1.1 to 1.2). Patients were more likely to be admitted to trauma centers, teaching hospitals, the south or west regions, or with private insurance. There were 471 spinal cord injuries and 1,908 total spine injuries. Ten patients died during the study time period. The combined ED and inpatient charges were $1.35 billion.Injuries related to tackle football are a frequent cause of emergency room visits, specifically in the pediatric population, but severe acute trauma requiring inpatient admission or operative interventions are rare. Continued investigation in the long-term health impact of football related concussion and other repetitive lower impact trauma is warranted.

The gut microbiome and its role in health and disease have recently been major focus areas of research. In this review, we summarize the different ways in which the gut microbiome interacts with the rest of the body, with focus areas on its relationships with immunity, the brain, and injury. The gut–brain axis, a communication network linking together the central and enteric nervous systems, represents a key bidirectional pathway with feed-forward and feedback mechanisms. The gut microbiota has a central role in this pathway and is significantly altered following injury, leading to a pro-inflammatory state within the central nervous system (CNS). Herein, we examine traumatic brain injury (TBI) in relation to this axis and explore potential interventions, which may serve as targets for improving clinical outcomes and preventing secondary brain injury.

Mild traumatic brain injury (mTBI) is commonly encountered in clinical practice. While the cognitive ramifications of mTBI are frequently described in the literature, the impact of mTBI on emotional, sensory, and motor function is not as commonly discussed. Chronic pain is a phenomenon more prevalent among patients with mTBI compared to those with moderate or severe traumatic brain injury. Chronic pain can become a primary disorder of the central nervous system (CNS) expressed as widespread pain, and cognitive, mood, and movement dysfunction. Shared mechanisms across chronic pain conditions can account for how pain is generated and maintained in the CNS, irrespective of the underlying structural pathology. Herein, we review the impact of mTBI on cognitive, emotional, sensory, and motor domains, and the role of pain as an important confounding variable in patient recovery and dysfunction following mTBI.