Savastano, Luis

Objectives To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption. Materials and methods First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14). Results In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these ‘rupture’ phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption. Conclusions Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.

Background Although successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b–3) can be achieved in >80% of patients experiencing stroke attributable to large‐vessel occlusion, up to 50% of patients may develop poor clinical outcomes (modified Rankin scale score at 90 days of 3–6), termed as futile recanalization (FR). The meta‐analysis aims to determine various risk factors associated with FR. Methods In February 2021, a comprehensive literature search on risk factors associated with FR was performed with keywords, including “stroke,” “thrombectomy,” “treatment outcome,” and “risk factors.” Their correlations with FR were evaluated using the random effect size meta‐analysis model. Results Twenty studies with 3037 patients were included with an FR rate of 51.0%. Our meta‐analyses showed that age (mean difference [MD], 5.6; 95% CI, 4.7–6.6), National Institutes of Health Stroke Scale score (MD, 4.2; 95% CI, 3.2–5.1), Alberta Stroke Program Early Computed Tomography (CT) Score (MD, −0.5; 95% CI, 0.8–0.3), hypertension (odds ratio [OR], 1.5; 95% CI, 1.3–1.9), systolic blood pressure (MD, 6.9; 95% CI, 3.6–8.7), atrial fibrillation (OR, 1.5; 95% CI, 1.2–1.8), IV tPA (tissue‐type plasminogen activator) (OR, 0.7; 95% CI, 0.5–0.8), puncture to recanalization time (MD, 9.6; 95% CI, 5.3–13.8), and time of onset to recanalization (MD, 32.1; 95% CI, 6.5–47.7) were significantly associated with FR ( P <0.001). Conclusions Age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, comorbidities, including hypertension, systolic blood pressure, atrial fibrillation, and use of IV tPA, as well as time frames, including onset to recanalization and onset to arrival, were significant influencing factors for FR after mechanical thrombectomy. Future research on the mechanism underlying FR is warranted.

Stenting of the intracranial venous sinuses has shown promising results in patients who are refractory to medical treatment of idiopathic intracranial hypertension (IIH). Among the reported complications associated with this procedure, in-stent thrombosis is an unreported one. We present a case of cerebral sinus thrombosis during endovascular treatment of IIH. A 33-year-old man with multiple comorbidities was presented with non-specific vision changes and headaches. Initial workup revealed a diagnosis of idiopathic intracranial hypertension which was treated medically but with no improvement. Therefore, cerebral sinus stenting was pursued. During the procedure, an in-stent thrombus was identified which was retrieved mechanically and was sent for histological and immunohistochemical evaluation. The retrieved thrombus was predominantly composed of RBCs (57.8%) followed by fibrin (30.78%), platelet (6.4%), and WBCs (5.95%), with high expression of CitH3 (neutrophil extra cellular traps specific marker) (10.9%), and CD66 (11.35%).

In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)—the presence of blood components within an atheromatous plaque—has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.

A Carotid web (CaW) is defined as a focal shelf-like projection of non-atheromatous, fibrous tissue along the posterior wall of the carotid bulb. CaW are rare and commonly overlooked lesions increasingly recognized as a cause of stroke in otherwise healthy patients. Intravascular imaging modalities such as intravascular ultrasound and optical coherence tomography (OCT) have been proposed as an adjunct to digital subtraction angiography for the evaluation of CaW. However, the use of OCT in CaW has yet to be described. This report investigated the utility of OCT as an adjunct imaging modality in the evaluation of CaW morphology in a young patient with recurrent ischemic strokes.

Object We sought to determine the safety and efficacy in secondary stroke prevention of carotid endarterectomy (CEA) in patients with symptomatic non-stenotic carotid artery disease (SyNC). Methods This was a single-centre retrospective case series. All patients who underwent CEA for unilateral anterior circulation cerebrovascular events with ipsilateral <50% carotid stenosis from 2002 to 2020 were included. Imaging hallmarks including the degree of luminal stenosis and the presence of various vulnerable plaque characteristics (eg, intraplaque haemorrhage (IPH) on MR angiography, ulceration or low-density plaque on CT angiography) were assessed. The presence of vulnerable plaque characteristics was compared between arteries ipsilateral to the ischaemic event and contralateral arteries. The prevalence of perioperative/intraoperative complications, as well as recurrent ischaemic events at follow-up was determined. Results Thirty-two patients were included in the analysis, of which 25.0% were female. Carotid arteries ipsilateral to an ischaemic event had a significantly higher prevalence of IPH when compared with contralateral arteries (80.0% vs 0.0%; p<0.001). There were no intraoperative complications. One patient (3.1%) developed symptoms of transient ipsilateral ischaemia 1 day following CEA which resolved without treatment. In a median follow-up of 18.0 months (IQR 5.0–36.0), only one patient (3.1%) experienced a transient neurologic deficit with complete resolution (annualised rate of recurrent stroke after CEA of 1.5% for a total follow-up of 788 patient-months following CEA). All other patients (31/32, 96.9%) were free of recurrent ischaemic events. Conclusion CEA appears to be safe and well-tolerated in patients with SyNC. Additional studies with larger cohorts and longer follow-up intervals are needed in order to determine the role of CEA in this patient population.

Introduction: Mechanical thrombectomy (MT) has become the standard of care for acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). Clinical outcome of successful recanalization (mTICI 2b or higher) varies greatly and is associated with some baseline characteristics. Many studies have reported the relation of thrombus composition with MT outcomes however the association of thrombus composition with the prognosis of successful recanalization remains to be elucidated. Hypothesis: thrombi retrieved from patients with good clinical outcome may have different compositions compared to that of patients with poor clinical outcome. Methods: Thrombi retrieved from AIS-LVO patients with successful recanalization were included. Patients were divided according to modified Rankin Scale at 90 days (mRS-90days) into good clinical outcome (mRS-90days 0-2) and poor clinical outcome (mRS-90 days 3-6). Representative slide for each thrombus was stained with Martius Scarlet Blue (MSB) for red blood cells (RBCs), white blood cells (WBCs), fibrin (FIB), and platelet (PLT). Immunohistochemistry (IHC) was also performed for NETs (anti-citrullinated H3; CitH3) and vWF in thrombi. The overall mean value of each thrombus composition was calculated. Thrombus was considered rich in given composition if that composition was higher than its overall mean. We compared the thrombus composition and type between patients with good and poor clinical outcomes. Results: A total of 94 patients were included. Fifty-six patients had good clinical outcome. The overall average percentage of RBCs, WBCs, fibrin, platelet, NETs (CitH3), and vWF components in thrombi were 44.3%, 3.6%, 29.3%, 22.8%, 20.3% and 12.5% respectively. There was no association between thrombus type (including RBC-rich, FIB-rich, PLT-rich, vWF-rich, and NETs-rich) and clinical outcomes (P values>0.05). Multivariate logistic regression analysis showed no association between thrombus composition and clinical outcome (good vs poor) while adjusting for age, initial NIHSS score, ASPECT score, pre-MT IV-tPA, and MT technique and number of the device passes. Conclusion: we found no association between thrombus composition and clinical outcome after successful recanalization.

Introduction: Outcomes of mechanical thrombectomy (MT) are influenced by the composition of thrombi. Amongst the risk factors affecting clot composition, diabetes mellitus (DM) may be associated with more thrombus structural and mechanical alterations resulting in fibrinolysis-resistant thrombi. However, extensive analysis of the composition of thrombi obtained from patients is needed to elucidate this relationship. Hypothesis: Thrombi retrieved from patients with DM may have different compositions compared to that of patients with no history of DM. Methods: MT retrieved-thrombi from patients suffering from large vessel occlusion (LVO) stroke were included. Thrombi sections were stained with Martius Scarlet Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Additionally, immunohistochemistry (IHC) was performed to identify neutrophil extracellular traps (NETs) (anti-citrulinated H3; CitH3; NETs-specific marker) and von Willebrand Factor (vWF) in thrombi. Slides were then scanned and analyzed and the thrombus composition was compared between patients with or without a DM diagnosis at the time of stroke presentation. Results: A total of 140 patients were included of which 35 had a diagnosis of DM at stroke presentation. Baseline characteristics (excluding age), IV-tPA use prior to MT, and MT outcomes (number of device passes and final mTICI score) were similar between DM and non DM patients. The overall average percentage of RBCs, WBCs, fibrin, platelet, NETs (CitH3), and vWF components in thrombi were 47.4%, 3.2%, 27.4%, 21.8%, 25.9% and 17.6%, respectively. Thrombi from patients with DM were not statistically significant different from those of patients with no DM in terms of RBCs (44.3 vs 48.4 p=0.37), WBCs (2.7 vs 3.3 p=0.05), fibrin (29.5 vs 26.7 p=0.37), platelet (23.3 vs 21.3 p=0.57), NETs (25.6 vs 22.3 p=0.54), and vWF (17.5 vs 17.7 p=0.96). Conclusion: DM has no effect on the composition of thrombi as no significant difference was found in thrombi obtained from patients with and without DM.

Introduction: Ample evidence exists in support of the anti-inflammatory properties of statins which in turn could affect arterial thrombosis. Compositional analysis of thrombi retrieved by MT may provide us with knowledge useful for evaluating the effect of current Statin therapy on thrombus composition. Methods: Consecutive AIS-LVO patients were included. Histopathological evaluation of thrombi retrieved during MT was performed using Martius Scarlet Blue staining (MSB) and immunohistochemistry for von Willebrand Factor (vWF) and anti-citrulinated H3 (CitH3; NETs marker) and the composition of thrombi was determined using image analysis software. Thrombus was considered rich in a given composition if that composition was higher than its overall mean. We reviewed patient’s medication records and cataloged any statin therapy prior to MT. Results: 117 patients were included in this study. The mean density of red blood cells (RBCs), white blood cells (WBCs), platelets (PLT), fibrin (FIB), vWF and NETs (CitH3) in thrombi was 43.4%, 3.7%, 23.6%, 29.3%, 14.3% and 21.1% respectively. Twenty-seven patients were taking Statins at the time of MT. Statins were not associated with pre-thrombectomy IV-tPA, and stroke etiology (p values: >0.05). There was no association between Statins and thrombi composition and type (p values: >0.05 for all thrombus components and type). Additionally, Statins were not associated with MT outcomes including number of device passes and final mTICI score. Conclusion: Pre-stroke Statin therapy was not associated with differences in thrombus composition.