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.

Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. METHODS: We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods. RESULTS: The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. CONCLUSION: DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

Hemodynamic and Anatomical Factors in Arteriovenous Malformation Clinical Presentation: 45 Case Studies.

BACKGROUND: Hemodynamic factors have been implicated in hemorrhage from cerebral arteriovenous malformations (AVMs). The goal of this endovascular study is to analyze the hemodynamic variability in AVM feeders in a balanced group of ruptured and unruptured AVMs of various sizes and at both superficial and deep locations. METHODS: We monitored feeder artery pressure (FP) using microcatheters in 45 patients with AVMs (16 with hemorrhage, 29 without) during superselective angiography and AVM embolization. RESULTS: Mean FP was 49 mm Hg. Significant determinants of FP were the systemic pressure (p < 0.001), AVM size (p = 0.03), and the distance of the microcatheter tip from the Circle of Willis (p = 0.06), but not the presence of hemorrhage, patient age, or feeder artery diameter. The FP in ruptured AVMs was 7 mm Hg higher than in unruptured ones (53.8 mm Hg vs. 47.1 mm Hg, p = 0.032). The presence or absence of venous outflow stenosis and the position of the AVM nidus (superficial or deep to the cortical surface) were important anatomical predictors of AVM presentation. CONCLUSION: The pressure in the feeding artery supplying an AVM is the result of factors which include the systemic arterial pressure, the size of the AVM nidus, and the distance of the AVM from the Circle of Willis. The correlation between these variables makes it difficult to study the risk of hemorrhage as a function of a single factor, which may account for the variation in the conclusions of previous studies.

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.

High-fidelity, simulation-based microsurgical training for neurosurgical residents.

OBJECTIVE: Simulation is increasingly recognized as an important supplement to operative training. The live rat femoral artery model is a well-established model for microsurgical skills simulation. In this study, the authors present an 11-year experience incorporating a comprehensive, longitudinal microsurgical training curriculum into a Canadian neurosurgery program. The first goal was to evaluate training effectiveness, using a well-studied rating scale with strong validity. The second goal was to assess the impact of the curriculum on objective measures of subsequent operating room performance during postgraduate year (PGY)-5 and PGY-6 training. METHODS: PGY-2 neurosurgery residents completed a 1-year curriculum spanning 17 training sessions divided into 5 modules of increasing fidelity. Both perfused duck wing and live rat vessel training models were used. Three modules comprised live microvascular anastomosis. Trainee performance was video recorded and blindly graded using the Objective Structured Assessment of Technical Skills Global Rating Scale. Eleven participants who completed the training curriculum and 3 subjects who had not participated had their subsequent operative performances evaluated when they were at the PGY-5 and PGY-6 levels. RESULTS: Eighteen participants completed 106 microvascular anastomoses during the study. There was significant improvement in 6 measurable skills during the curriculum. The mean overall score was significantly higher on the fifth attempt compared with the first attempt for all 3 live anastomotic modules (p < 0.001). Each module had a different improvement profile across the skills assessed. Those who completed the microvascular skills curriculum demonstrated a greater number of independent evaluations during superficial surgical exposure, deep exposure, and primary maneuvers at the PGY-5 and PGY-6 levels. CONCLUSIONS: High-fidelity microsurgical simulation training leads to significant improvement in microneurosurgical skills. Transfer of acquired skills to the operative environment and durability for at least 3 to 4 years show encouraging preliminary results and are subject to ongoing investigation.

The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia.

Background: Hypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume. Methods: A cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology. Results: Between group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm3 smaller in hypothermia-treated pigs (P = 0.04) and showed a similar, but non-significant reduction in MRI (P = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's r = 0.48 (p = 0.05) and r = -0.59 (p = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C. Conclusions: In a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.

Endovascular selective hypothermia facilitates giant aneurysm clipping: illustrative case.

BACKGROUND: The authors present a case of selective hypothermia used for neuroprotection during clipping of a giant partially thrombosed middle cerebral artery (MCA) aneurysm. Although these cases have traditionally required deep hypothermic cardiac arrest, this case illustrates a novel and entirely endovascular solution that avoids cardiac standstill and whole-body cooling. OBSERVATIONS: This is, to the authors' knowledge, the first case in human surgery of a catheter-based selective hypothermic circuit used to facilitate MCA trapping for almost 30 minutes. Core temperatures never dropped below 34°C, and the patient recovered uneventfully and has been well for over 5 years. LESSONS: The technical nuances and physiological changes unique to selective hypothermia are discussed.

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.

Emergent Carotid Endarterectomy with Open Thrombectomy for Acute Carotid Stent Occlusion.

Acute occlusion of a carotid stent is a rare complication that necessitates rapid diagnosis and treatment to prevent devastating neurologic injury. Management options may include thrombolysis, mechanical thrombectomy, or open surgical revascularization; however, the optimal treatment is unclear due to the low reported incidence of this complication. Video 1 illustrates the surgical technique for open revascularization with carotid stent removal, thrombectomy, and endarterectomy. We present the case of a 64-year-old woman who presented with expressive speech and right-sided motor deficits and was identified to have complete occlusion of the distal left M1 and proximal M2 branches, as well as near-occlusion of the left internal carotid artery. She underwent successful mechanical thrombectomy of the intracranial occlusion with complete reperfusion and also angioplasty and stenting of the carotid stenosis. She deteriorated overnight and was identified to have complete carotid stent occlusion but no large infarct, suggestive of collateral flow impairment. Cerebral reperfusion was established by emergent open stent removal and endarterectomy. An extended exposure of the carotid was required, as the stent extended beyond the typical sites of clamping both proximally and distally. Intraoperatively, the clot from the internal carotid artery was manually aspirated via a 5-French catheter. Postoperative imaging demonstrated appropriate vessel patency. In follow-up, the patient made a full neurologic recovery.

Neuroprotection by selective endovascular brain cooling - the TwinFlo™ Catheter.

The neuroprotective effects of hypothermia have been demonstrated in experimental models and clinical trials. Experimental studies indicate that improved efficacy and broadened indications can be achieved with moderate to deep hypothermia. The TwinFlo catheter was designed to provide very rapid, deep and selective brain cooling with faster cooling rates, and temperatures much lower than those which can be achieved by any other hypothermia device and technique. This report describes the experimental in vivo studies and initial clinical experience with the TwinFlo catheter.

Iatrogenic pseudoaneurysms associated with cerebrospinal fluid diversion procedures.

BACKGROUND: Cerebrospinal fluid diversion procedures, including ventriculoperitoneal (VP) shunt and external ventricular drain insertion, are common treatments for hydrocephalus. Common complications include obstruction, infection, and hemorrhage. Pseudoaneurysm formation secondary to catheter insertion is a distinctly rare complication, and usually involves the anterior cerebral artery or branches of the external carotid artery (superficial temporal artery or middle meningeal artery). CASE DESCRIPTION: We present the case of a fusiform pseudoaneurysm in a 36-year-old female, which arose from a branch of the middle cerebral artery following VP shunt insertion. Parenchymal and intraventricular hemorrhage at the catheter insertion site developed 15 days postoperatively. The VP shunt was removed, and the aneurysmal segment was coagulated and occluded. Use of a limited dural opening during ventricular catheter placement may have been a factor in pseudoaneurysm formation. CONCLUSIONS: The literature regarding this rare complication is reviewed. Careful consideration should be given to vascular anatomy when planning shunt insertions, and a cruciate dural opening for cortical visualization and coagulation may help avoid this complication. Prompt identification and management of iatrogenic pseudoaneurysms is essential to avoid re-bleeding and associated hemorrhagic complications.

Recent Trends in Neurosurgery Career Outcomes in Canada.

BACKGROUND: As with other specialties, Royal College of Physicians and Surgeons of Canada (RCPSC) trainees in Neurosurgery have anecdotally had challenges securing full-time employment. This study presents the employment status, research pursuits, and fellowship choices of neurosurgery trainees in Canadian programs. METHODS: RCPSC neurosurgery trainees (n = 143) who began their residency training between 1998 and 2008 were included in this study. Associations between year of residency completion, research pursuits, and fellowship choice with career outcomes were determined by Fisher's exact test (p < 0.05, statistical significance). RESULTS: In 2015, 60% and 26% of neurosurgery trainees had permanent positions in Canada and the USA, respectively. Underemployment, defined as locum and clinical associate positions, pursuit of multiple unrelated fellowships, unemployment, and career change to non-surgical career, was 12% in 2015. The proportion of neurosurgery trainees who had been underemployed at some point within 5 years since residency completion was 20%. Pursuit of in-folded research (MSc, PhD, or non-degree research greater than 1 year) was significantly associated with obtaining full employment (94% vs. 73%, p = 0.011). However, fellowship training was not significantly associated with obtaining full employment (78% vs. 75%, p = 1.000). CONCLUSIONS: Underemployment in neurosurgery has become a significant issue in Canada for various reasons. Pursuit of in-folded research, but not fellowship training, was associated with obtaining full employment.

Tendances récentes au Canada en ce qui regarde les possibilités d'emploi en neurochirurgie.Contexte: À l'instar d'autres stagiaires de la médecine spécialisée, des stagiaires en neurochirurgie membres du Collège royal des médecins et des chirurgiens du Canada (CRMCC) ont dit éprouver, selon des données empiriques, des difficultés à obtenir un emploi à plein temps. Cette étude entend présenter la situation professionnelle des stagiaires inscrits dans des programmes canadiens en neurochirurgie ainsi que leurs activités de recherche et leurs choix en matière de bourses de recherche postdoctorale. Méthodes : Des stagiaires membres du CRMCC ayant entrepris leur résidence entre 1998 et 2008 (n = 143) ont été inclus dans cette étude. Les liens pouvant exister entre l'année de résidence complétée, les activités de recherche, les choix en matière de bourses de recherche postdoctorale et les possibilités d'emploi ont été déterminés au moyen du test exact de Fisher (p < 0,05 ; signification statistique). Résultats : En 2015, 60 % des stagiaires en neurochirurgie du Canada disaient compter sur un poste permanent alors qu'ils étaient 26 % à affirmer la même chose aux États-Unis. Le sous-emploi, défini comme par des postes de suppléant (locum) et de clinicien adjoint, par l'obtention de plusieurs bourses de recherche postdoctorale sans liens apparents, par le chômage et par un changement d'orientation excluant la chirurgie, atteignait 12 % la même année. La proportion de stagiaires disant avoir été sous-employés à un moment ou un autre au cours des 5 années de leur résidence était par ailleurs de 20 %. Le fait de mener un projet de recherche dans le cadre de sa résidence (M.Sc., Ph.D. ou en dehors des cycles supérieurs pendant au moins 12 mois) était clairement associé à l'obtention d'un emploi à temps plein (94 % contre 73 % ; p = 0,011). Cela dit, une formation offerte à la suite de l'obtention d'une bourse de recherche postdoctorale n'a pas été associée de manière notable à l'obtention d'un emploi à temps plein (78 % contre 75 % ; p = 1,000). Conclusions : Le sous-emploi en neurochirurgie est désormais un enjeu important au Canada, et ce, pour toutes sortes de raisons. Contrairement aux formations liées à l'obtention d'une bourse de recherche postdoctorale, le fait de mener un projet de recherche régulier a été associé à l'obtention d'un emploi à temps plein.

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.

Diagnosis and management of carotid free-floating thrombus: A systematic literature review.

BACKGROUND: There is no consensus regarding the management of carotid free-floating thrombi in patients with acute ischemic stroke and transient ischemic attack. AIMS: This systematic review aims to (1) describe the current imaging methods for diagnosis of carotid free-floating thrombi and its associated risk factors, (2) estimate the proportion of carotid free-floating thrombi diagnosed in stroke patients, (3) estimate the proportion of carotid free-floating thrombi patients treated medically and surgically, and (4) evaluate 30-day outcomes. METHODS: We searched MEDLINE, EMBASE, and manually for references reporting carotid free-floating thrombi from 1960 until June 2017. We estimated the frequency of carotid free-floating thrombi and evaluated 30-day outcomes using Cox regression. We defined the timing of surgical intervention as early (less than 72 h) and delayed (more or equal to 72 h). SUMMARY OF REVIEW: We retrieved 525 carotid free-floating thrombi cases from 58 case series and 83 case reports. Carotid free-floating thrombi were present in 1.53% of stroke patients. Carotid free-floating thrombi diagnosis was made by digital subtraction angiography (38.1%), carotid duplex ultrasound (29.5%), and computed tomography angiography (29.5%). The 30-day risk of transient ischemic attack, silent brain ischemia, any stroke or death was 17.1%. In multivariate analyses, there were no differences in outcome for any anticoagulation regime or timing of revascularization procedure. CONCLUSIONS: The diagnosis of carotid free-floating thrombi is more common due to the increased use of early noninvasive vascular imaging in transient ischemic attack and stroke. It poses a high short-term risk of stroke and death, but there is as yet no established treatment. The low quality of evidence in the carotid free-floating thrombi literature limits the interpretation of our results and warrants a large-scale prospective cohort study in carotid free-floating thrombi.

Cold blood perfusion for selective hypothermia in acute ischemic stroke.

Hypothermia is the most reliably effective neuroprotectant, and yet systemic complications limit application. A large body of animal data suggests that hypothermia is effective for focal cerebral ischemia, namely acute ischemic stroke. In order to apply hypothermia effectively, a selective approach is required to maximize the effect on the brain while minimizing systemic side effects. Due to poor transferability of promising findings in rodent models to human clinical trials for neuroprotection, the focus of this review is large animal gyrencephalic models. Unlike rodent data which favor mild hypothermia, the majority of large animal studies on selective hypothermia support moderate-to-deep hypothermia (<30°C). Cold blood perfusion produces the rapid rate of temperature reduction and depth of hypothermia required to produce meaningful neuroprotection. Further studies of selective hypothermia in acute ischemic stroke require attention to duration and rate of cooling to optimize the neuroprotection offered by this technique.

Determining blood flow direction from short neurovascular surgical microscope videos.

Neurovascular surgery aims to repair diseased or damaged blood vessels in the brain or spine. There are numerous procedures that fall under this category, and in all of them, the direction of blood flow through these vessels is crucial information. Current methods to determine this information intraoperatively include static pre-operative images combined with augmented reality, Doppler ultrasound, and injectable fluorescent dyes. Each of these systems has inherent limitations. This study includes the proposal and preliminary validation of a technique to identify the direction of blood flow through vessels using only video segments of a few seconds acquired from routinely used surgical microscopes. The video is enhanced to reveal subtle colour fluctuations related to blood pulsation, and these rhythmic signals are further analysed in Fourier space to reveal the direction of blood flow. The proposed method was validated using a novel physical phantom and retrospective analysis of surgical videos and demonstrated high accuracy in identifying the direction of blood flow.