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.

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.

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.

Per pass analysis of thrombus composition retrieved by mechanical thrombectomy.

BACKGROUND AND AIM: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. METHODS: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. RESULTS: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). CONCLUSION: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology.

BACKGROUND: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology 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 scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2 test for categorical variables. RESULTS: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%). CONCLUSIONS: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.

Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source.

Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Platelet-rich clots as identified by Martius Scarlet Blue staining are isodense on NCCT.

BACKGROUND: Current studies on clot characterization in acute ischemic stroke focus on fibrin and red blood cell composition. Few studies have examined platelet composition in acute ischemic stroke clots. We characterize clot composition using the Martius Scarlet Blue stain and assess associations between platelet density and CT density. MATERIALS AND METHOD: Histopathological analysis of the clots collected as part of the multi-institutional STRIP registry was performed using Martius Scarlet Blue stain and the composition of the clots was quantified using Orbit Image Analysis (www.orbit.bio) machine learning software. Prior to endovascular treatment, each patient underwent non-contrast CT (NCCT) and the CT density of each clot was measured. Correlations between clot components and clinical information were assessed using the χ2 test. RESULTS: Eighty-five patients were included in the study. The mean platelet density of the clots was 15.7% (2.5-72.5%). There was a significant correlation between platelet-rich clots and the absence of hyperdensity on NCCT, (ρ=0.321, p=0.003*, n=85). Similarly, there was a significant inverse correlation between the percentage of platelets and the mean Hounsfield Units on NCCT (ρ=-0.243, p=0.025*, n=85). CONCLUSION: Martius Scarlet Blue stain can identify patients who have platelet-rich clots. Platelet-rich clots are isodense on NCCT.

Acute Oculomotor Nerve Palsy Caused by Compression from an Aberrant Posterior Communicating Artery.

Oculomotor nerve palsy (ONP) is a rare neurological deficit associated with numerous underlying pathologies. Of these, aneurysm of the posterior communicating artery (PCOM) has been described due to the intimate association with the third cranial nerve in the basal cistern. Less described are other vascular abnormalities and their contribution to ONP. We describe a case of ONP thought to result from a PCOM aneurysm, per the associated magnetic resonance imaging (MRI) scan, yet found intraoperatively to be caused by a congenital vascular aberrancy. This is the first case, to our knowledge, of this presentation.

Aggressive Endovascular Management of Massive Dural Venous Sinus Thrombosis in the Setting of Acute Myeloid Leukemia.

While hematologic malignancies are understood to be a risk factor for dural sinus thrombosis (DST), little data is available regarding the presentation and management of synchronous cases. In this case, a 40-year-old woman with newly diagnosed acute myeloid leukemia (AML) developed extensive DST with symptoms refractory to systemic anticoagulation. The decision was made to pursue aggressive endovascular intervention and the patient's symptoms significantly improved with minimal residual deficits. Here, we report the clinical course and complex management of this rare clinical scenario.

Successful reperfusion of bilateral middle cerebral artery embolic occlusions using stent retriever thrombectomy.

A 40-year-old woman presented to our stroke center for a left middle cerebral artery embolic occlusion. This was successfully treated with mechanical thrombectomy using a stent retriever and balloon guide catheter aspiration. The patient was discharged home in good condition on clopidogrel but returned 2 months later with a contralateral right middle cerebral artery embolic occlusion. This was also successfully treated, this time with a stent retriever and local aspiration (Sol-Arc technique). She was once again discharged in good condition but with warfarin and an implanted loop recorder. This case demonstrates the feasibility of short-term bilateral mechanical thrombectomy for embolic middle cerebral artery occlusions.

A Direct Aspiration First Pass Technique for Mechanical Thrombectomy in the Setting of a Suspected Cerebral Aneurysm.

There is little guidance in the literature on which thrombectomy technique is preferred in patients with acute ischemic stroke and concomitant aneurysms. Here, we present the case of a 58-year-old female with an acute ischemic stroke requiring emergent thrombectomy that was complicated by the presence of multiple, nonruptured intracranial aneurysms. Imaging confirmed an occlusion of the right middle cerebral artery and multiple nonruptured intracranial aneurysms. The patient was administered intravenous recombinant tissue plasminogen activator and the thrombus was aspirated via a direct aspiration first pass technique (ADAPT). Her symptoms improved significantly postoperatively with a consequent National Institutes of Health Stroke Scale (NIHSS) score of 0. The purpose of this case report is to give an overview and compare various techniques that can help guide the physician for safe, early revascularization while reducing recanalization time in patients having an ischemic stroke who also harbor intracranial aneurysms.

Preoperative Embolization in Tandem with Surgical Resection for Cerebral Arteriovenous Malformations.

A number of treatment options are available for cerebral arteriovenous malformations (AVMs) including surgical resection, stereotactic radiosurgery, and endovascular embolization. Endovascular embolization may be used pre-operatively to reduce the size of large AVMs and thus reduce surgical complications. Here we present two patients who successfully underwent preoperative embolization of their AVMs and subsequent surgery. Preoperative embolization is a viable option for AVMs to reduce complications and improve patient outcomes.

Angiographic and clinical outcomes of balloon remodeling versus unassisted coil embolization in the ruptured aneurysm cohort of the GEL THE NEC study.

BACKGROUND AND PURPOSE: GEL THE NEC (GTN) was a multicenter prospective registry developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We compared the angiographic and clinical outcomes of aneurysms treated with balloon assisted coil embolization (BACE) versus unassisted coil embolization (CE) in the ruptured aneurysm cohort. MATERIALS AND METHODS: GTN was performed at 27 centers in five countries. Patients aged 21-90 years with a ruptured aneurysm 3-15 mm in size were eligible for enrollment. We analyzed demographics/comorbidities, aneurysm location, and geometry, including maximum diameter, neck size, and dome to neck ratio, immediate and long term angiographic outcomes (graded by an independent core laboratory using the modified Raymond Scale), and procedure related adverse events. Angiographic and clinical outcomes were studied using χ2and t tests. RESULTS: Of the 599 patients in the GTN, 194 met the inclusion criteria. 84 were treated with BACE and 110 with CE. There were more prior smokers in the BACE group (p=0.01). The BACE group also had more vertebrobasilar aneurysms (p=0.006) and a larger mean neck size (p=0.02). More aneurysms were immediately completely occluded in the BACE group (p=0.02) Procedure- related major morbidity and mortality were no different between the techniques (p=0.4 and p=1, respectively). CONCLUSIONS: In this prospective ruptured aneurysm cohort from the GTN, BACE resulted in greater occlusion rates compared with unassisted CE with similar morbi-mortality.

Percutaneous Vertebral Artery Access for Embolization of Cerebrovascular Disease: Illustrative Case and Operative Technique.

Intracranial arteriovenous malformations can be further complicated by the development of aneurysms, which themselves carry the risk of rupture and hemorrhage. New endovascular techniques allow for more treatment options for these lesions in the setting of arteriovenous malformations. Here we present the case of a patient who developed an aneurysm in the setting of an arteriovenous malformation and subsequently underwent successful endovascular treatment via percutaneous access of the vertebral artery along with reviewing the literature on further treatment options and developments.

Mycotic Pseudoaneurysm Associated with Skull Base Osteomyelitis Treated with Endovascular Embolization.

Pseudoaneurysms occur due to malformations in arterial wall uniformity, leading to blood collection between the outer arterial layers and resultant outpouching of the vessel. Unlike true aneurysms, pseudoaneurysms do not involve all layers of the blood vessel. Mycotic pseudoaneurysms can occur after associated vessel adventitia infection, leading to transmural dissection. Here we present a case of a 78-year-old man with a history of chronic otitis externa and osteomyelitis who presented with increasing right ear pain with bloody discharge and associated headache. Catheter angiography demonstrated a large pseudoaneurysm in the right middle meningeal artery (MMA) at the base of the skull. Based on the clinical findings and the patient's history, the patient was ultimately diagnosed with mycotic pseudoaneurysms of the MMA. The patient was subsequently treated with antibiotics as well as endovascular embolization and recovered without any complications.

Intracranial Ischemic Infarct Due to Blunt Force Trauma in a High School Football Player.

Ischemic stroke is an uncommon cause of death among teenagers and young adults; however, the etiologies differ when compared to ischemic strokes in older individuals. Large-vessel atherosclerosis and small-vessel disease causing ischemic stroke are rare for the teenage population, while cervicocerebral arterial dissections account for up to 20% of ischemic strokes. Here, we present the case of a 16-year-old male who developed internal carotid artery dissection (ICAD) after a head injury and subsequently developed ischemic stroke and seizures.

Superior Ophthalmic Vein Access for Embolization of an Indirect Carotid Cavernous Fistula.

Carotid cavernous fistulae (CCF) are defined as abnormal connections between the carotid circulation and cavernous sinus. CCFs can be categorized as being direct or indirect. Direct CCFs are usually associated with trauma, whereas indirect CCFs are associated with revascularization following cavernous sinus thrombosis. We present a case of a 53-year-old male who presented with tinnitus, proptosis, conjunctivitis, and blurry vision. The patient had a recent endovascular transvenous embolization that was only partially successful, with a residual carotid cavernous fistula draining to the left superior ophthalmic vein and multiple cortical veins. A physical examination of the patient showed elevated intraocular pressures bilaterally. The patient had a high-flow indirect carotid cavernous fistula with bilateral superior ophthalmic vein (SOV) and retrograde cortical vein drainage. The SOV was punctured with a micropuncture needle and was used to successfully gain access to the cavernous sinus. Multiple coils were placed in the posterior aspect of the sinus until there was complete occlusion of venous flow. Coils were packed up to the posterior aspect of the orbit near the junction of the cavernous sinus with the SOV, and the embolization was successful. Indirect CCFs have gradual onset and are usually low-flow. Low-flow CCFs might improve with medical management.Some CCFs may cause ocular manifestations and can be symptomatically managed with prism therapy or ocular patching for diplopia, lubrication for keratopathy, or topical agents for elevated intraocular pressures. However, patients presenting with persistent ocular morbidity may require surgical or endovascular intervention.

To Stent or Not to Stent: A Tale of Two Occlusions.

Stenting and balloon angioplasty, along with mechanical thrombectomy, have gained notability as adjunctive treatment options to intravenous tissue plasminogen activator (IV-tPA) for tandem internal carotid artery (ICA) and middle cerebral artery (MCA) occlusions (TIM occlusions). Acute ischemic strokes (AISs) secondary to TIM occlusions are associated with poor patient outcomes primarily due to low recanalization rates following intravenous thrombolysis, consequently prompting the need for more invasive recanalization efforts. Often, the treatment algorithm is based on the success of the initial angioplasty, suspected volume of completed infarction, and whether or not thrombolytics are utilized. Here, we present two patients with AIS due to TIM occlusions where two different treatment modalities were implemented for recanalization efforts. Patient 1 did not receive IV-tPA and was successfully managed with balloon angioplasty and subsequent carotid stenting followed by direct oral anticoagulant (DOAC) administration. Patient 2 received IV-tPA and balloon angioplasty without carotid stenting followed by intracranial mechanical thrombectomy. Complete recanalization was attained in both cases. Administration of IV-tPA can make subsequent carotid stenting a potentially higher-risk treatment option for patients with TIM due to potential hemorrhagic complications in the setting of requisite antiplatelet agents. Each case of AIS resulting from a TIM must be considered unique, and the use of IV thrombolytics, balloon angioplasty, carotid stenting, and mechanical thrombectomy alone or in combination must be tailored to the individual clinical parameters.