Savastano, Luis

Background The middle meningeal artery (MMA) has emerged as an endovascular route for treating chronic subdural hematoma (CSDH), meningioma, and refractory headaches. The third ARISE roundtable convened experts from neurology, neurosurgery, neuroradiology, industry, and regulatory agencies to develop consensus guidance on current evidence for MMA-based therapies Methods Over 50 experts participated in a multi-stakeholder discussion. Evidence from randomized and observational studies, early-phase interventional series, and preclinical work was reviewed. Breakout groups focused on four domains: (1) MMA embolization (MMAE) for CSDH, (2) preoperative embolization of meningiomas, (3) MMA-targeted therapies for headache, and (4) transvascular access for endovascular drainage of subdural hematomas. Consensus recommendations were developed by a writing committee Results Randomized trials support MMAE as an adjunct to surgery or medical management for selected patients with non-acute, symptomatic CSDH to reduce recurrence, progression, and reoperation. Evidence remains insufficient to support MMAE for acute or asymptomatic subdural hematomas. For meningioma, observational data suggest that preoperative embolization in experienced centers can reduce blood loss and operative time and may delay recurrence in large, hypervascular tumors with predominant dural or external carotid supply; primary embolization and intra-arterial oncologic therapies remain investigational. Early series of MMA-directed lidocaine infusion for refractory migraine, status migrainosus, and post-subarachnoid hemorrhage headache show short-term benefit, highlighting the need for controlled trials. Preclinical and first-in-human studies of combined MMAE and transvascular drainage for CSDH demonstrate high technical success, rapid radiographic and clinical improvement, and no early recurrences Conclusion The MMA represents a vascular pathway for an expanding spectrum of neurointerventional therapies.

Background Non-acute or chronic subdural hematoma (cSDH) is commonly treated with surgical evacuation followed by middle meningeal artery embolization (MMAe). This two step approach increases procedural complexity and redundancy, hospitalization duration, and patient risk. We hypothesized that cSDH could be managed through a single session endovascular procedure and conducted a multimodal preclinical study to evaluate feasibility. Methods We performed three-dimensional heat mapping of hematoma distribution from preoperative CT scans (n=69) and analyzed middle meningeal artery (MMA) and superior sagittal sinus (SSS) anatomy and perforation trajectories using imaging from 107 patients. Rheological properties of 41 SDH samples were assessed using hybrid rheometry and modeled with the Carreau equation. Aspiration feasibility was tested using a 0.027 inch microcatheter (n=16), and dura perforation forces were quantified with a 28 G needle in fresh cadaveric dura (n=10). Results Heat mapping localized cSDH to the parietal convexities (>80% probability) under the branches of the MMA, with limited midline involvement and proximity to the SSS (<10%). The posterior division of the MMA (diameter 1.23±0.23 mm) accommodated a 0.027 inch microcatheter in >90% of cases, with perforation trajectories targeting high probability hematoma zones in 105 of 107 cases. SDH samples exhibited shear thinning viscosity ( η ₀ =172 mPa×s, η ∞ =2.78 mPa×s), with mean aspiration times of 1.21±0.54 min per 10 mL. Perforation forces averaged 0.68±0.24 N in normal and 1.29±0.48 N in calcified dura (P=0.05). Conclusion Anatomical, rheological, and biomechanical data from this study support the feasibility of endovascular drainage of cSDH through the MMA.

Background: Little is known about the association between intraplaque hemorrhage (IPH) and other features of high-risk carotid atherosclerotic plaques, such as the presence of plaque ulceration, plaque enhancement, and lipid-rich necrotic core (LRNC). This study set out to assess the relationship between IPH and other vulnerable plaque features. Materials and Methods: A retrospective review was done of 102 patients with IPH in one or both of the internal carotid arteries (ICA) on neck MRA between 1/1/2016 and 3/31/2021. IPH was defined as a ≥200% signal intensity of the adjacent sternocleidomastoid muscle on MPRAGE images. All ICA plaques were assessed for the presence or absence of IPH, plaque ulceration, plaque enhancement, and LRNC, as well as IPH volume. IPH volume was measured manually by outlining the region of interest. Results: A total of 102 patients were included, with 88 (86.3%) being male. The average age was 73.5 years (SD = 9.0). Both IPH and LRNC were more commonly seen in the left carotid artery ( p = .018 and p = .047, respectively). For right-sided ICAs, there was a significant association between IPH and LRNC ( p < .0001). Lesions without IPH were more likely to have plaque enhancement than lesions with IPH ( p = .04). For left-sided ICAs, there was also a significant association between the presence of IPH and LRNC ( p < .0001). Conclusions: There is a significant association between the presence of IPH and LRNC. An inverse relationship was found between the presence of IPH and plaque enhancement for right-sided plaques. No associations were found between IPH and plaque ulceration.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Background Remarkable interest is rising around middle meningeal artery embolization (MMAE) as an emerging alternative therapy for chronic subdural hematoma (cSDH). The study aims to highlight a large center experience and the variables associated with treatment failure and build experimental machine learning (ML) models for outcome prediction. Material and Methods A 2-year experience in MMAE for managing patients with chronic subdural hematoma was analyzed. Descriptive statistical analysis was conducted using imaging and clinical features of the patients and cSDH, which were subsequently used to build predictive models for the procedure outcome. The modeling evaluation metrics were the area under the ROC curve and F1-score. Results A total of 100 cSDH of 76 patients who underwent MMAE were included with an average follow-up of 6 months. The intervention had a per procedure success rate of 92%. Thrombocytopenia had a highly significant association with treatment failure. Two patients suffered a complication related to the procedure. The best performing machine learning models in predicting MMAE failure achieved an ROC-AUC of 70%, and an F1-score of 67%, including all patients with or without surgical intervention prior to embolization, and an ROC-AUC of 82% and an F1-score of 69% when only patients who underwent upfront MMAE were included. Conclusion MMAE is a safe and minimally invasive procedure with great potential in transforming the management of cSDH and reducing the risk of surgical complications in selected patients. An ML approach with larger sample size might help better predict outcomes and highlight important predictors following MMAE in patients with cSDH.

Endovascular recanalization is increasingly being utilized in symptomatic patients with chronically occluded carotid arteries. 1 In carefully selected patients, endovascular recanalization has shown to lower the risk of ischemic events when compared to medical management alone.1 However, successful endovascular revascularization is technically challenging and not without risk. 1 , 2 In this video, we demonstrate a case of a 64-year-old woman who presented with recurrent transient ischemic attacks. On imaging she was found to have a chronic total occlusion of the common carotid artery from the arch. After obtaining informed consent, the patient underwent a successful endovascular recanalization and stenting of a chronically occluded left common carotid artery with aid from an intravascular guided re-entry catheter. Post operatively the patient developed a neck hematoma which improved and she returned to her neurological baseline. She reported no further symptoms on her three month follow up.

Objectives: The development and evaluation of percutaneous thrombectomy devices for pulmonary embolism (PE) pose a need for standardized large in vivo models with representative anatomical and physiological conditions and clots analogs. In this study, we present a swine model of PE model employing human-derived clot analogs. Material and Methods: Baseline angiographic and physiological pressure measurements were obtained in six adult Yorkshire pigs (45–65 kg) and results were benchmarked for interspecies comparison with published human data using fluoroscopic examinations, intra-arterial pressure measurements, and histologic studies. Then, clot analogs were created ex vivo employing banked human blood and a subset incubated in iodinated contrast for fluoroscopic visualization. Clot analogs were then embolized via a femoral venous access and angiographic/physiological consequences were evaluated. Results: The main, right, and left pulmonary artery diameters were 24 ± 1.1 mm, 16.5 ± 0.8 mm, and 12.6 ± 1.2 mm, respectively. The angle between the main pulmonary artery at the bifurcation point was approximately 90–95°. The clot analogs were heterogeneous and had increased fibrin content along the clot length. The overall composition was 96.63% red blood cell (RBC)/3.37% fibrin in the initial section, 48.85% RBC/51.15% fibrin in the intermediate section, and 3.44% RBC/96.56% fibrin in the final section. Embolization of the clot analogs resulted in distal occlusion of the right and left pulmonary arteries. Conclusions: This swine model coupled with clot analog is able to accurately mimic human anatomical and physiological conditions in PE making it feasible for the evaluation of pulmonary thrombectomy devices.

Background: Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT. 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 and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes. Results: A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,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 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 compared to RBC-rich and mixed clots (median, 2 and 1.5 vs.1, respectively, P=0.02). CA displayed 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. Conclusion: Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.

Michelangelo’s unparalleled frescoes in the Sistine Chapel have been traditionally construed to represent the traditional, Roman Catholic interpretation of the Seven Days of Creation in the Book of Genesis and the Last Judgement. Indeed, in September 2018, Pope Francis I offered a benediction for the Vatican’s art treasures and for “those who contributed to the Church’s history through art.” A number of studies have suggested that Michelangelo concealed anatomic information about the human brain in his renderings of God and biblical prophets and saints. Was the anatomic content of these images purposeful or coincidental? Was the anatomy intentionally concealed? Is there a common pattern with symbolic connotations in the anatomic representations? Was Michelangelo sending an encoded message? In this study, we analyze the imagery in the Sistine frescoes in light of the literature surrounding Michelangelo’s artistry with a particular interest in the relationship between the certain purported anatomic depictions and details demonstrable using scientific and anatomic techniques available during the High Renaissance.