Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia.

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

P2Y12 inhibitor use predicts hematoma expansion in patients with intracerebral hemorrhage.

OBJECTIVE: Hematoma expansion (HE) predicts disability and death after acute intracerebral hemorrhage (ICH). Aspirin and anticoagulants have been associated with HE. We tested the hypothesis that P2Y12 inhibitors predict subsequent HE in patients. We explored laboratory measures of P2Y12 inhibition and dual antiplatelet therapy with aspirin (DAPT). METHODS: We prospectively identified patients with ICH. Platelet activity was measured with the VerifyNow-P2Y12 assay. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated technique. HE was defined as the difference between hematoma volumes on the initial and follow-up CT scans. Nonparametric statistics were performed with Kruskal-Wallis H, and correction for multiple comparisons performed with Dunn's test. RESULTS: In 194 patients, 15 (7.7%) were known to take a P2Y12 inhibitor (clopidogrel in all but one). Patients taking a P2Y12 inhibitor had more HE compared to patients not taking a P2Y12 inhibitor (3.5 [1.2-11.9] vs. 0.1 [-0.8-1.4] mL, p = 0.004). Patients taking DAPT experienced the most HE (7.2 [2.6-13.8] vs. 0.0 [-1.0-1.1] mL, p = 0.04). The use of P2Y12 inhibitors was associated with less P2Y12 activity (178 [149-203] vs. 288 [246-319] P2Y12 reaction units, p = 0.005). INTERPRETATION: Patients taking a P2Y12 inhibitor had more HE and less P2Y12 activity. The effect was most pronounced in patients on DAPT, suggesting a synergistic effect of P2Y12 inhibitors and aspirin with respect to HE. Acute reversal of P2Y12 inhibitors in acute ICH requires further study.

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

OBJECTIVES: Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. DATA SOURCES: A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. STUDY SELECTION: Abstracts and full texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS: The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. CONCLUSIONS: A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

Background Subtraction Angiography with Deep Learning Using Multi-frame Spatiotemporal Angiographic Input.

Catheter Digital Subtraction Angiography (DSA) is markedly degraded by all voluntary, respiratory, or cardiac motion artifact that occurs during the exam acquisition. Prior efforts directed toward improving DSA images with machine learning have focused on extracting vessels from individual, isolated 2D angiographic frames. In this work, we introduce improved 2D + t deep learning models that leverage the rich temporal information in angiographic timeseries. A total of 516 cerebral angiograms were collected with 8784 individual series. We utilized feature-based computer vision algorithms to separate the database into "motionless" and "motion-degraded" subsets. Motion measured from the "motion degraded" category was then used to create a realistic, but synthetic, motion-augmented dataset suitable for training 2D U-Net, 3D U-Net, SegResNet, and UNETR models. Quantitative results on a hold-out test set demonstrate that the 3D U-Net outperforms competing 2D U-Net architectures, with substantially reduced motion artifacts when compared to DSA. In comparison to single-frame 2D U-Net, the 3D U-Net utilizing 16 input frames achieves a reduced RMSE (35.77 ± 15.02 vs 23.14 ± 9.56, p < 0.0001; mean ± std dev) and an improved Multi-Scale SSIM (0.86 ± 0.08 vs 0.93 ± 0.05, p < 0.0001). The 3D U-Net also performs favorably in comparison to alternative convolutional and transformer-based architectures (U-Net RMSE 23.20 ± 7.55 vs SegResNet 23.99 ± 7.81, p < 0.0001, and UNETR 25.42 ± 7.79, p < 0.0001, mean ± std dev). These results demonstrate that multi-frame temporal information can boost performance of motion-resistant Background Subtraction Deep Learning algorithms, and we have presented a neuroangiography domain-specific synthetic affine motion augmentation pipeline that can be utilized to generate suitable datasets for supervised training of 3D (2d + t) architectures.

Charlson Comorbidity Index and Frailty as Predictors of Resolution Following Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

BACKGROUND: Research on variables associated with chronic subdural hematoma (cSDH) resolution following middle meningeal artery embolization (MMAE) is limited. This study investigated the clinical utility of age-adjusted Charlson Comorbidity Index (ACCI) and modified 5-item Frailty Index (mFI - 5) for predicting cSDH resolution following MMAE. METHODS: We identified patients who underwent MMAE at our institution between January 2018 and December 2022, with at least 20 days of follow-up and one radiographic follow-up study. Patient demographics, characteristics, and outcomes were collected. Complete resolution was defined as absence of subdural collections on CT-scan at last follow-up. Nonage adjusted CCI (CCI), ACCI, and mFI - 5 scores were calculated. Univariate and multivariable logistic regression analyzed the relationship between cSDH resolution and variables. A receiver operating characteristic (ROC) curve established the utility of ACCI and mFI - 5 in predicting hematoma resolution. RESULTS: The study included 85 MMAE procedures. In univariate analysis, patients without resolution were older, had higher CCI, higher ACCI, higher mFI - 5, and were more likely to have diabetes mellitus. In multivarible analysis, CCI (OR: 0.66, 95% CI: 0.48, 0.91) was independently associated with resolution controlling for age and antithrombotic resumption. The area under the ROC (AUROC) curve was 0.75 (95% CI: 0.65-0.85) for ACCI and 0.64 (95% CI: 0.52-0.76) for mFI - 5. The optimal cutoffs for predicting resolution were ACCI ≥5 (sensitivity = 0.63, specificity = 0.77), and mFI - 5 > 0 (sensitivity = 0.84, specificity = 0.43). CONCLUSIONS: ACCI and mFI - 5 moderately predict MMAE resolution and may aid in medical decision-making.

Clot composition and recanalization outcomes in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. METHODS: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. RESULTS: A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. CONCLUSIONS: Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Outpatient telemedicine in neurosurgery: 15,677 consecutive encounters in a comparative analysis of its effectiveness and impact on the surgical conversion rate.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has necessitated the use of telehealth visits (THVs). The effects on neurosurgical practice have not been well characterized, especially concerning new-patient THVs. Therefore, the authors of this study reviewed their institution's experience with outpatient clinic visits and THVs from before the COVID-19 pandemic to the present to focus on clinical metrics, rates of surgery, and the effects of implementing THVs in order to better understand their implications for clinical practice as more data emerge over time. METHODS: The authors reviewed 15,677 consecutive new outpatient in-person visits (IPVs), THVs, and neurosurgical procedures/cases proceeding from their institution between 2018 and 2022 for trends and associations related to THVs. RESULTS: Among spine patients, there was no difference in the proportion of encounters that led to surgery (surgical conversion rate) between THVs and IPVs (p = 0.49). Among cranial patients, THVs were negatively associated with conversion (OR 0.73, p = 0.03). On average, patients using THVs lived further from the hospital (p < 0.001); however, the patient catchment area appeared unchanged. The median distance to the hospital among THV patients was counterbalanced by a decreased distance for spine patients pursing IPVs (p < 0.001), with no significant change to case volume. There was no change in distance to the hospital among cranial patients. For both cranial and spine patients, surgical conversion was more likely among those who lived a great distance from the hospital if their initial encounter was an IPV (p = 0.007 and < 0.001, respectively). However, there was no relationship between distance from the hospital and surgical conversion among THV patients (p = 0.565). The availability of THVs did not significantly affect follow-up time (p = 0.837). For new patients at IPVs, there was no difference in time to the operating room between cranial and spine cases; for new patients at THVs, however, time to the operating room was significantly faster for cranial cases than for spine cases (p = 0.0018). CONCLUSIONS: Compared to IPVs, THVs lead to decreased surgical conversion for cranial patients but not spine patients. THVs do not appear to increase the catchment area. For patients who live far from the hospital, an IPV is associated with surgical conversion. Surgical conversion is faster following cranial THVs than after spine THVs. THVs did not increase the duration of follow-up.

Unplanned readmission after carotid stenting versus endarterectomy: analysis of the United States Nationwide Readmissions Database.

BACKGROUND: Hospital readmissions are costly and reflect negatively on care delivered. OBJECTIVE: To have a better understanding of unplanned readmissions after carotid revascularization, which might help to prevent them. METHODS: The Nationwide Readmissions Database was used to determine rates and reasons for unplanned readmission following carotid endarterectomy (CEA) and carotid artery stenting (CAS). Trends were assessed by annual percent change, modified Poisson regression was used to estimate risk ratios (RR) for readmission, and propensity scores were used to match cohorts. RESULTS: Analysis yielded 522 040 asymptomatic and 55 485 symptomatic admissions for carotid revascularization between 2010 and 2015. Higher 30-day readmission rates were noted after CAS versus CEA in both symptomatic (9.1% vs 7.7%, p<0.001) and asymptomatic (6.8% vs 5.7%, p<0.001) patients. Readmission rates trended lower over time, significantly so for 90-day readmissions in symptomatic patients undergoing CEA. The most common cause for 30-day readmission was stroke in both symptomatic (5.5%) and asymptomatic (3.9%) patients. Factors associated with a higher risk of readmission included age over 80; male gender; Medicaid health insurance; and increases in severity of illness, mortality risk, and comorbidity indices. Analysis of matched cohorts showed that CAS had higher readmission than CEA (RR=1.14 (95% CI 1.06 to 1.22); p<0.001) only in asymptomatic patients. Adverse events during initial admission which predicted 30-day readmission included acute renal failure and acute respiratory failure in asymptomatic patients; hematoma and cardiac events were additional predictive adverse events in symptomatic patients. CONCLUSIONS: Readmission is not uncommon after carotid revascularization, occurs more often after CAS, and is predicted by baseline factors and by preventable adverse events at initial admission.

Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study.

BACKGROUND: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters. METHODS: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ2 test were performed as appropriate. RESULTS: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively). CONCLUSIONS: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Low-molecular-weight Heparin (enoxaparin) versus unfractionated heparin for venous thromboembolism prophylaxis in patients undergoing craniotomy.

OBJECTIVE: To explore the difference in post-operative DVT, PE, and ICH complications following administration of prophylactic UFH or enoxaparin in patients undergoing craniotomy. METHODS: A retrospective chart review was conducted for 542 patients at our institution receiving either 5000units/0.5 mL UFH (BID or TID; 180 patients) or single daily 40 mg/0.4 mL enoxaparin (362 patients) following craniotomy. Multivariate linear regression models were developed comparing rates of postoperative DVT, PE, and reoperation for bleeding in patients given enoxaparin versus UFH prophylaxis while controlling for age at surgery, history of VTE, surgery duration, number of post-operative hospital days, reoperation, post-operative infections, and reason for surgery (tumor type, genetics, etc.). Mann Whitney U tests were subsequently performed comparing rates of postoperative DVT, PE, and ICH for each group. RESULTS: Patients receiving prophylactic enoxaparin, when compared to UFH, exhibited similar rates of postoperative DVT (22 % vs 20.6 %, p = 0.86), PE (9.7 % vs 8.9 %, p = 0.86), and reoperation for bleeding (0.4 % vs 0.2 %, p = 0.58), while controlling for the factors described above. CONCLUSION: In patients undergoing craniotomy, rates for DVT, PE, and ICH were similar between patients treated with either prophylactic enoxaparin or UFH. Further studies are needed to understand whether a certain subset of patients demonstrate improved benefit from either prophylactic anticoagulant.

Ethical Considerations in Surgical Decompression for Stroke.

Stroke is a major cause of morbidity and mortality. Neurosurgical decompression is often considered for the treatment of malignant infarcts and intraparenchymal hemorrhages, but this treatment can be frought with ethical dilemmas. In this article, the authors outline the primary principles of bioethics and their application to stroke care, provide an overview of key ethical issues and special situations in the neurosurgical management of stroke, and highlight methods to improve ethical decision-making for patients with stroke. Understanding these ethical principles is essential for stroke care teams to deliver appropriate, timely, and ethical care to patients with stroke.

Continued Dominance of Carotid Endarterectomy over Stenting in the United States: Volumes, Outcomes, and Complications from the National Inpatient Sample (1997-2015).

BACKGROUND: The introduction of carotid stenting (CAS) has led to numerous comparative trials with carotid endarterectomy (CEA). OBJECTIVE: The objective of the study was to review real-world volumes, outcomes, and complications following CEA versus CAS over an extended period to identify durable changes in practice. METHODS: Data were extracted from the National Inpatient Sample. Trends were assessed by annual percent change (APC), and adjusted risk ratios were calculated across the last 5 years of the study period. RESULTS: During 1997-2015, 199,330 symptomatic and 1,995,637 asymptomatic patients underwent carotid revascularization. In symptomatic patients, CEA declined (1997-2004; APC = -7.68%, P < 0.001) and CAS rose (1997-2008; APC = 15.48%, P < 0.001) during the first decade, subsequently becoming more muted. In asymptomatic patients, CEA decreased, whereas CAS initially increased (1997-2006; APC = 20.27%, P < 0.001) and then decreased (2007-2015; APC = -4.52%, P < 0.001). Routine discharge after symptomatic revascularization declined in CEA after 2003 and in CAS after 2006 (APC = -1.72% and -3.11%, respectively, P < 0.001 for both), corresponding to increasing patient comorbidity; similar trends were seen in asymptomatic patients. Death decreased after CEA (symptomatic and asymptomatic; APC = -4.85% and -3.53%, respectively, P < 0.001 for both) and CAS (asymptomatic only, APC = -2.53%, P = 0.04). CAS remained associated with a higher adjusted risk ratio for death, venous thromboembolism, and seizures in all patients and stroke and nonroutine discharge in symptomatic patients, during the last 5 years of the study period. CONCLUSIONS: Mortality has improved, but routine discharge has decreased following both CEA and CAS, congruent with increasing patient comorbidity. Trends in volumes, outcomes, and complication rates continue to favor CEA in real-world practice.

Holohemispheric Prostate Carcinoma Dural Metastasis Mimicking Subdural Hematoma: Case Report and Review of the Literature.

Prostate carcinomas are the most common malignancy to metastasize to the dura. These metastases can commonly mimic subdural hematomas and may similarly present with brain compression. The optimal management and outcomes after surgical management are not well characterized. We present a case of prostate carcinoma metastatic to the dura that was initially thought to be a large isodense subdural hematoma and was treated with surgical decompression. We also review the literature regarding prostate dural metastases mimicking subdural hematomas and discuss the relevant imaging findings, treatments, and outcomes. Dural metastasis should be considered when a patient with known metastatic prostate cancer presents with imaging evidence of a subdural mass.

Mass Deployment of Deep Neural Network: Real-Time Proof of Concept With Screening of Intracranial Hemorrhage Using an Open Data Set.

BACKGROUND: Intracranial hemorrhage (ICH) is considered an emergency that requires rapid medical or surgical management. Previous studies have used artificial intelligence to attempt to expedite the diagnosis of this pathology on neuroimaging. However, these studies have used local, institution-specific data for training of networks that limit deployment of across broader hospital networks or regions because of data biases. OBJECTIVE: To demonstrate the creation of a neural network based on an openly available imaging data tested on data from our institution demonstrating a high-efficacy, institution-agnostic network. METHODS: A data set was created from publicly available noncontrast computed tomography images of known ICH. These data were used to train a neural network using distinct windowing and augmentation. This network was then validated in 2 phases using cohort-based (phase 1) and longitudinal (phase 2) approaches. RESULTS: Our convolutional neural network was trained on 752 807 openly available slices, which included 112 762 slices containing intracranial hemorrhage. In phase 1, the final network performance for intracranial hemorrhage showed a receiver operating characteristic curve (AUC) of 0.99. At the inflection point, our model showed a sensitivity of 98% at a threshold specificity of 99%. In phase 2, we obtained an AUC of 0.98 after analysis of 726 scans with a negative predictive value of 99.70% (n = 726). CONCLUSION: We demonstrate an effective neural network trained on completely open data for screening ICH at an unrelated institution. This study demonstrates a proof of concept for screening networks for multiple sites while maintaining high efficacy.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

BACKGROUND: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. OBJECTIVE: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. METHODS: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). RESULTS: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. CONCLUSIONS: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Quantification of clot spatial heterogeneity and its impact on thrombectomy.

BACKGROUND: Compositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis. METHODS: We collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann-Whitney test and an artificial neural network (ANN) model. RESULTS: For cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration. CONCLUSIONS: Clot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

Concomitant cervical spine fractures are the primary driver of disability after traumatic vertebral artery dissection: A Case series of 123 patients.

Background: Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. Aims and Objectives: To characterize the tVAD population and identify factors associated with clinical outcomes. Materials and Methods: We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Results: Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p<0.0007), were more likely to smoke (OR 3.0 [1.2178, 7.4028], p=0.0202), be male (OR 7.125 [3.0181, 16.8236], p<0.0001), and have mRS≥3 at discharge (OR 3.0545 [1.0937, 8.5752], p=0.0449). On multivariable regression, only fracture independently predicted mRS≥3 at discharge (OR 5.6898 [1.5067, 21.4876], p=0.010). Conclusion: tVADs may be associated with stroke and/or cervical fracture. Presenting symptoms predict stroke, but baseline demographic and clinical characteristics do not. Comorbid cervical fractures, not stroke, drive negative outcomes.

Traumatic and Spontaneous Vertebral Artery Dissections: An Analysis of Tertiary-Center 310 Patient Cohort.

BACKGROUND: Vertebral artery dissections (VADs) are rare yet potentially devastating events. While the etiology of these events is either traumatic or spontaneous, there is a paucity of quantitative literature comparing the two. OBJECTIVE: To identify differences in predisposing factors, event characteristics, and clinical outcomes between traumatic VADs (tVADs) and spontaneous VADs (sVADs). METHODS: We retrospectively identified patients with VADs presenting to our institution at VAD onset with at least a 3-mo follow-up. Demographics, event characteristics, treatment details, and neurological outcomes as modified Rankin scale (mRS) scores were collected. RESULTS: Of the 310 patients sustaining 366 VADs total, 187 (60.3%) patients experienced a total of 221 (60.4%) sVADs and 123 (39.7%) patients experienced a total of 145 (39.6%) tVADs. sVADs were more likely to occur in the intracranial course of the artery (P = .042) and have a lower mRS at discharge, 3-month, and last clinical follow-up (P = 003, .002, and .001, respectively). tVADs were more likely associated with concomitant fractures (P < .001). CONCLUSION: Despite similar patient populations, tVADs are associated with higher mRS scores at all time points. Although further study is needed, this may suggest other concomitant trauma rather than the VAD itself is contributing to worse neurological status in patients with tVADs.

Clinical Characteristics, Course, and Outcomes of Vertebral Artery Dissections in the Postpartum Period.

BACKGROUND: Postpartum vertebral artery dissections (ppVADs) are rare but potentially morbid conditions that occur in otherwise healthy patients. OBJECTIVE: To evaluate clinical characteristics of ppVADs. METHODS: Demographic, clinical, treatment, and outcome data were collected on ppVADs and are presented in a case series of 12 patients and compared to the general cohort. RESULTS: In total, 12 patients had ppVADs in our cohort of 310 patients with vertebral artery dissections (VADs). They occurred 11.27 days (95% CI, -0.85 to 23.39) postdelivery. Of these, there were 5 (42%) with a hypertensive disorder of pregnancy, and 4 (33%) who had migraines. A total of 3 (25%) had ischemic strokes and 1 (8%) had a subarachnoid hemorrhage. In total, 2 patients (17%) had unfavorable modified Rankin Scale (mRS, 2-6) at discharge from hospital. Patients with ppVADs more often had bilateral VADs (42% vs 17%, P = .03), had pseudoaneurysms (50% vs 18%, P = .0068), were younger (33.83 years vs 44.32 years, P = .018), and had lower Charlson Comorbidity Index (CCI = 0 vs 0.99, P = .0038). Anticoagulant treatment was used in a similar percentage of patients. Multivariate analysis revealed 3 factors were predictive of change in mRS: CCI (OR = 1.09, 95% CI, 1.02-1.15), stroke (OR = 0.78, 95% CI, 0.65-0.95), and mRS at hospital discharge (OR = 0.80, 95% CI, 0.74-0.87). CONCLUSION: There are only 15 isolated ppVADs reported in the literature; this study adds 12 patients with 17 ppVADs. Postpartum VADs occur in younger, healthier patients than in the general cohort, raising questions about mechanism of injury. The majority of ppVADs have good neurological outcomes.