Carotid Stenosis and Stroke: Historical Perspectives Leading to Current Challenges.

The carotid artery is unique; it is the only vessel to bifurcate into a bulb larger than itself. The history of its anatomic description, understanding of its pathophysiology and evolution of its imaging are relevant to current controversies regarding measurement of stenosis, surgical/endovascular therapies and medical management of carotid stenosis in stroke prevention. Treatment decisions on millions of symptomatic and asymptomatic patients are routinely based on information from clinical trials from over 30 years ago. This article briefly summarizes the highlights of past research in key areas and discuss how they led to current challenges of diagnosis and treatment.

Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke.

Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.

Safety Evaluation of Primary Carotid Stenting: Transcranial Doppler and MRI.

BACKGROUND AND PURPOSE: Cerebral emboli are generated by every step of standard carotid angioplasty and stenting. Primary carotid stenting (PCS) is a technique in which the use of balloon angioplasty (BA) is minimized to decrease the embolic load. The primary aim of this study is to establish the number of emboli generated by each step of primary stenting and determine the relationship to new diffusion (DWI) lesions on subsequent magnetic resonance imaging (MRI). METHODS: Eighty-five patients with severe, symptomatic carotid stenosis were prospectively recruited and underwent carotid stenting. Intraoperative transcranial Doppler was performed in 77 patients. The number and size of microemboli for each of seven procedural steps were recorded. Correlation was made with the number and location of new DWI lesions. RESULTS: PCS was performed in 73 patients. BA was required in 12 patients. The mean number of microemboli was 114, and most microemboli were generated by stent deployment, followed by BA. Balloon techniques generated significantly more emboli than primary stenting (p = 0.017). There was a significant relationship between total microemboli and new DWI lesions (p = 0.009), and between new DWI lesions in multiple territories and the severity of pretreatment stenosis (p = 0.002). CONCLUSIONS: During PCS, more emboli are generated by stent deployment than during any other stage of the procedure. When BA is necessary, more malignant emboli are generated but total emboli are unchanged and there is no difference in new diffusion lesions on MRI. PCS is safe and is not inferior to historical controls for the generation of new DWI lesions.

Neuroprotection in Acute Ischemic Stroke: A Brief Review.

The goal of effective neuroprotection in acute ischemic stroke remains elusive. Despite decades of experimental preclinical and clinical experience with innumerable agents, no strategy has proven to be beneficial in humans. As endovascular therapies mature and approach the limits of speed and efficacy, neuroprotection will become the next frontier of acute stroke care. This review will briefly summarize the history, preclinical and clinical triumphs and failures, and future directions of cerebral neuroprotection.

A Protocol for Carotid Artery Stenting in COVID Times. A Single Canadian Centre Experience.

OBJECTIVES: The COVID-19 pandemic has resulted in huge disruption to healthcare delivery worldwide. There is a need to balance the urgent needs of the neurovascular patient population with the desire to preserve critical inpatient hospital capacity. It is incumbent on neurointerventionalists to advocate for their patients to minimise future disability. Patients still require semiurgent carotid revascularisation after ischaemic embolic events. We present a review of a novel protocol for expediting patient flow through the carotid stenting process, in accordance with government directives to minimise nonessential inpatient admissions, ensure its efficacy, and evaluate its safety. We also evaluate the literature regarding complications with attention to the timing of these related to the procedure. METHODS: A retrospective review of 45 consecutive carotid stenting cases performed at London Health Sciences Centre between March 2020 and March 2021 for symptomatic extracranial internal carotid artery stenosis utilising a default same-day discharge policy was performed. Complications were plotted as a function of time. RESULTS: Twenty-four patients underwent carotid artery stenting with same-day discharge and 21 patients underwent stenting with an overnight inpatient stay. A single stent occlusion occurred 27 h post stenting. CONCLUSION: Simple modification of protocol for symptomatic carotid artery stenting during the COVID-19 outbreak with radial access as first approach appears to provide safe, efficacious care.

Investigating the Association between Aortic Arch Variants and Intracranial Aneurysms.

BACKGROUND: There is an association between anterior cerebral artery vessel asymmetry and anterior communicating artery aneurysm, presumably based on flow dynamics. The purpose of this study is to investigate the potential relationship between aortic arch branching patterns and incidence of intracranial aneurysm. METHODS: This study included patients scanned over 1 year at our tertiary care center who underwent high-resolution imaging (computed tomography angiography or digital subtracted angiogram) of the head and neck arteries, aortic arch, and superior mediastinum. Exclusion criteria included patients with suboptimal images. Patient age, gender, aortic arch branching pattern, and the presence, location, and number of aneurysms were documented. RESULTS: Among the 1082 patients analyzed, 250 (23%) patients had a variant aortic arch branching pattern, 22 (8.8%) of whom had aneurysms. There were 104 patients with 126 aneurysms, with majority of patients with normal aortic arch branching pattern (n = 82, 79%). The most common variant was a common origin of the left common carotid artery and brachiocephalic trunk with or without direct origin of the left vertebral artery. Twenty-two patients with aneurysms had an aberrant aortic arch (21%), compared to 232 patients without an aneurysm (24%). Fischer exact test showed no statistically significant difference between the incidence of aneurysm with different aortic arch variant groups (two-tailed p-value = 0.715). CONCLUSION: To our knowledge, this is the first study to examine the association between aortic arch branching patterns and incidence of intracranial aneurysm. No significant association was found between aortic arch branching pattern and the incidence of intracranial aneurysm.

Interventional Neuroradiology: A Review.

Interventional neuroradiology (INR) has evolved from a hybrid mixture of daring radiologists and iconoclastic neurosurgeons into a multidisciplinary specialty, which has become indispensable for cerebrovascular and neurological centers worldwide. This manuscript traces the origins of INR and describes its evolution to the present day. The focus will be on cerebrovascular disorders including aneurysms, stroke, brain arteriovenous malformations, dural arteriovenous fistulae, and atherosclerotic disease, both intra- and extracranial. Also discussed are cerebral vasospasm, venolymphatic malformations of the head and neck, tumor embolization, idiopathic intracranial hypertension, inferior petrosal venous sinus sampling for Cushing's disease, and spinal interventions. Pediatric INR has not been included and deserves a separate, dedicated review.

Embolized cerebral arteriovenous malformations: a multivariate analysis of 101 excised specimens.

OBJECTIVE: Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens. METHODS: The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980-2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision. RESULTS: A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates. CONCLUSIONS: Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body-type granulomatous inflammation are more common at 1 week and beyond.

A systematic characterization of the factors influencing polymerization and dynamic behavior of n-butyl cyanoacrylate.

INTRODUCTION: Brain arteriovenous malformations are abnormal connections between arteries and veins without an intervening capillary bed. Endovascular glue embolization with N-butyl cyanoacrylate (NBCA) is an accepted form of treatment. The reported complication rates vary widely from 2% to 15%, and timing of polymerization appears to play a major role. Additionally, the interaction between NBCA and vessel surface as well as the presence of biological catalysts are poorly understood. METHODS: Polymerization time was measured for mixtures of Lipiodol/NBCA of 50/50, 70/30, and 60/40. The influence of pH, temperature, and the presence of biological catalysts on polymerization time was investigated. Contact angles were measured on polyvinyl alcohol cryogel (PVA-C), silicone, and endothelial surfaces in a submerged aqueous environment to assess physical surface interactions. High speed video analysis of glue injection through a microcatheter was performed to characterize simulated coaxial flow. RESULTS: NBCA polymerization rate increased with pH and temperature. A hydrophilic surface such as PVA-C was better than silicone at mimicking the physical properties of endothelium. Live endothelium provided a catalytic surface that at least doubled the rate of polymerization. Blood products further increased the polymerization rate in the following order (slowest to fastest): plasma, platelets, red blood cells (RBCs), and lysed RBCs. These factors could explain the discrepancy between in vitro and in vivo results reported in the current literature. High speed video analysis of NBCA injection showed dripping to jetting transition with significant wall effect which deviated from previous ideal assumptions. CONCLUSIONS: The determinants of NBCA polymerization rate are multifactorial and dependent mainly on the presence of biological catalysts coupled with flow related wall interaction.

De novo giant posterior cerebral artery aneurysm developing 25 years after basilar bifurcation aneurysm treatment using a Drake tourniquet: case report and implications for aneurysm follow-up.

The objective of this paper was to report a rare complication of basilar artery (BA) tourniquet treatment of a giant basilar tip aneurysm, and to discuss possible causes for the formation of a de novo giant posterior cerebral artery (PCA) aneurysm. A 34-year-old woman underwent satisfactory treatment of a ruptured giant basilar bifurcation aneurysm by BA ligation (Drake tourniquet) in 1985. She presented 25 years later with a new aneurysm in the left PCA, successfully treated by coil embolization. To the authors' knowledge, this is the first case of de novo aneurysm formation on a PCA, and the first de novo aneurysm reported as a complication of BA ligation therapy by Drake tourniquet. Long-term follow-up is necessary in patients with treated cerebral aneurysms, particularly those occurring in young patients, those with multiple aneurysms, those with complex posterior circulation aneurysms, and those undergoing flow diversion or flow-altering therapies.

Multilevel, ultra-large-volume epidural blood patch for the treatment of neurocognitive decline associated with spontaneous intracranial hypotension: case report.

Spontaneous intracranial hypotension (SIH) is a progressive clinical syndrome characterized by orthostatic headaches, nausea, emesis, and occasionally focal neurological deficits. Rarely, SIH is associated with neurocognitive changes. An epidural blood patch (EBP) is commonly used to treat SIH when conservative measures are inadequate, although some patients require multiple EBP procedures or do not respond at all. Recently, the use of a large-volume (LV) EBP has been described to treat occult leak sites in treatment-refractory SIH. This article describes the management of a patient with profound neurocognitive decline associated with SIH, who was refractory to conservative management and multiple interventions. The authors describe the successful use of an ultra-LV-EBP of 120 ml across multiple levels, the largest volume reported in the literature, and describe the technical aspects of the procedure. This procedure has resulted in dramatic and sustained symptom resolution.

The Uniform Cortex Sign: A Diagnostic Sign of Diffuse Cortical Injury on MR Imaging of the Brain at 1.5 T.

BACKGROUND: To introduce the "uniform cortex sign" (UCS) and evaluate its performance as a diagnostic test for the presence of diffuse cortical injury (DCI). METHODS: The study was approved by our institutional review board. Three experienced neuroradiologists were given a tutorial on the UCS. They were subsequently presented with 14 cases (7 control patients and 7 DCI patients with the UCS) in random order and asked to determine whether the UCS was present. Each case consisted of selected DWI, T2-weighted, and FLAIR images from unenhanced 1.5T MRI examinations. A consensus result for each case was determined by unanimity or majority rule. RESULTS: All control patients were correctly identified as normal by all neuroradiologists (7/7). The UCS was correctly identified in 86% of DCI patients (6/7). UCS interrater agreement was high (multirater κ=0.81). CONCLUSIONS: This small study shows that the UCS can identify DCI, especially in patients with hypoxic-ischemic encephalopathy. The UCS can be subtle, hence the reader must be vigilant for this finding. The accuracy of the UCS may depend on the extent of cortical injury and time between injury and MRI. Also, a UCS may be reversible, as in our case of viral meningoencephalitis.

Effect of Self-Expanding Carotid Stents on Plaque Thickness and Vessel Diameter.

BACKGROUND: In vitro models have suggested that stents affect atherosclerotic plaques symmetrically because of their outward radial forces. We evaluated the effects of stents on carotid plaque and the arterial wall using carotid ultrasound in carotid stenting patients to see whether these effects were borne out in vivo. METHODS: From a carotid stent database, 30 consecutive patients were selected. All had carotid Doppler ultrasound performed pre- and poststenting. The diameters of the lumen at the level of stenotic plaque pre- and poststenting, the dorsal and ventral plaque thickness, and of the outer arterial wall diameter were measured. Plaque thickness was measured at the level of maximal stenosis. Nonparametric tests were used to determine whether the stent effect and luminal enlargement were based on wall remodeling or on total arterial expansion. RESULTS: The patients were followed for an average of 22 months. Eighteen patients were male, with an average age of 70 years. A total of 87% of patients were symptomatic ipsilateral to the side of stenosis. Nine patients had angioplasty intraprocedurally. The luminal diameter increased poststenting in the region of severe stenosis. Plaque thickness, both ventrally and dorsally, decreased poststenting, with no significant difference between the ventral and dorsal plaque effects. The outer arterial wall diameters did not change. The measured lumen in the stent increased over time poststenting. CONCLUSIONS: Self-expanding nitinol stents alter the baseline ventral and dorsal plaque to a significant degree and do not significantly affect the native arterial wall and the overall arterial diameter.

Intra-Arterial Use of Abciximab in Thromboembolic Complications Associated with Cerebral Aneurysm Coiling: The London Ontario Experience.

BACKGROUND: Experience with intra-arterial infusion of abciximab for the treatment of endovascular thrombotic complications is limited to short case series. Our objective is to evaluate the safety and effectiveness of this drug for the treatment of thromboembolic complications during aneurysm coiling and to determine the risk factors. METHODS: From an aneurysm coiling database, patients treated with intra-arterial abciximab after having thrombotic complications during the coiling procedure were selected for analysis. Complications after using abciximab were categorized as hemorrhage, distal migration of the thrombus, and aneurysm recanalization. RESULTS: Fourteen coiling patients sustained a thromboembolic complication and were treated using intra-arterial infusion of abciximab and were subjected to further analysis. The age range was 48-76 years. Three patients were male. Seven patients had subarachnoid hemorrhage. Only complete recanalization was associated with clinical improvement, but this occurred in only 4 patients (28.5%). Partial or complete recanalization occurred in 13 patients (93%). Eight patients (57%) had complications derived from the infusion. Three patients had aneurysm recanalization, 3 patients had distal migration of the thrombus and 1 patient had a hemorrhagic complication. Eight patients demonstrated acute infarcts related to the occluded vessel, whereas 7 patients made a good functional recovery. CONCLUSION: Successful recanalization of a vessel occluded by thrombus formation during aneurysm coiling using abciximab (Reopro) infusion is less than optimal. There are risks related to abciximab, including bleeding and aneurysm recanalization.