Microvascular reperfusion during endovascular therapy: the balance of supply and demand.

BACKGROUND: Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post-EVT outcomes. METHODS: Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre-EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS-derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit - microvascular reperfusion. A good functional outcome was defined as 90-day modified Rankin Scale score ≤2. RESULTS: Thirty-six of 40 patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median 1% (IQR -11%-16%)) than patients with poor outcomes (median 28% (IQR 2-50%)) (p=0.02). Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. CONCLUSIONS: CBF augmentation alone does not predict post-EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post-EVT care aimed at CBF optimization.

Early neurologic deterioration with symptomatic isolated internal carotid artery occlusion: a cohort study, systematic review, and meta-analysis.

Background: Acute endovascular revascularization for isolated internal carotid occlusion without tandem intracranial occlusion has been proposed to prevent early neurologic deterioration (END) and improve outcome, but has not been shown to be more effective than medical therapy. We aimed to evaluate prognosis with initial medical therapy alone, and also performed a systematic review to put these results in a broader context. Methods: We performed a retrospective cohort study of patients admitted over a 2-year period with acute stroke/TIA due to isolated internal carotid artery occlusion. Subjects with tandem intracranial occlusion or ASPECTS≤5 were excluded. The primary outcome was END within 48 hours (NIHSS increase ≥4 persisting for ≥24 hours). Secondary outcomes included discharge NIHSS and disposition. We also performed a systematic review and meta-analysis of published studies along with the data from our cohort. Results: Twenty-three patients met our inclusion criteria. Median age was 69 years, initial ASPECTS 10, and NIHSS score 3. END attributed to recurrent ischemia occurred in 5/23 patients (22%, 95%CI: 7-44%). At discharge, 78% had a favorable outcome with a median NIHSS of 2 (IQR 1-3). END appeared more frequent in those with higher baseline NIHSS. In our systematic review, 7 prior studies met our inclusion criteria. END occurred in 17% (95%CI:12-23%) of patients, 18% with medical therapy versus 13% with endovascular therapy, with substantial heterogeneity among studies. Conclusions: In patients with acute stroke or TIA due to isolated internal carotid occlusion, END is relatively common (occurring in about 1 out of 6 patients). Further research is needed to evaluate the roles of maximal medical management or acute endovascular thrombectomy in these patients.

A Case Report of Herpes Simplex-1 Viral Encephalitis Complicated by Hemorrhagic Conversion.

Herpes simplex virus (HSV) encephalitis is the most common cause of nonendemic sporadic encephalitis in the United States. Treatment with acyclovir has been proven to reduce mortality by 50%. Antiviral therapy should be initiated immediately in patients with clinical suspicion of viral encephalitis and should not be delayed by serological confirmation of the diagnosis. The most common central nervous system complication of HSV encephalitis is seizures (38%), while intracranial hemorrhage is very rare (2.7%). We describe a case of a 59-year-old African American male who presented to the hospital after being found unresponsive for a day and was found to have HSV-1 encephalitis that was complicated by hemorrhagic conversion. Our patient's neurological status did not improve even with appropriate antiviral treatment with a 28-day course of intravenous (IV) acyclovir. Intracranial hemorrhage is a rare complication in patients with HSV encephalitis. Close monitoring of neurological status is recommended for signs of deterioration or lack of improvement, and further imagings are needed (as in our patient) to evaluate for neurological complications such as intracranial hemorrhage.

Highly Visible Wall-Timer to Reduce Endovascular Treatment Time for Stroke.

BACKGROUND: Endovascular therapy for acute ischemic stroke has revolutionized clinical care for patients with stroke and large vessel occlusion, but treatment remains time sensitive. At our stroke center, up to half of the door-to-groin time is accounted for after the patient arrives in the angio-suite. Here, we apply the concept of a highly visible timer in the angio-suite to quantify the impact on endovascular treatment time. METHODS: This was a single-center prospective pseudorandomized study conducted over a 32-week period. Pseudorandomization was achieved by turning the timer on and off in 2-week intervals. The primary outcome was angio-suite-to-groin time, and secondary outcomes were angio-suite-to-intubation time, groin-to-recanalization time, and 90-day modified Rankin scale. A stratified analysis was performed based on type of anesthesia (ie, endotracheal intubation versus not). RESULTS: During the 32-week study period, 97 mechanical thrombectomies were performed. The timer was on and off for 38 and 59 cases, respectively. The timer resulted in faster angio-suite-to-groin time (28 versus 33 minutes; P=0.02). The 5-minute reduction in angio-suite-to-groin was maintained after adjusting for intubation status in a multivariate regression (P=0.02). There was no difference in the 90-day modified Rankin scale between groups. The timer impact was consistent across the 32-week study period. CONCLUSIONS: A highly visible timer in the angio-suite achieved a meaningful, albeit modest, reduction in endovascular treatment time for patients with stroke. Given the lack of risk and low cost, it is reasonable for stroke centers to consider a highly visible timer in the angio-suite to improve treatment times.

Aortic arch anomalies, embryology and their relevance in neuro-interventional surgery and stroke: A review.

BACKGROUND: Congenital aortic arch anomalies are commonly encountered during neurointerventional procedures. While some anomalies are identified at an early age, many are incidentally discovered later in adulthood during endovascular evaluations or interventions. Proper understanding of the normal arch anatomy and its variants is pivotal to safely navigate normal aortic arch branches and to negotiate the catheter through anomalies during neurointerventional procedures. This is particularly relevant in the increasingly "transradial first" culture of neurointerventional surgery. Moreover, some of these anomalies have a peculiar predilection for complications including aneurysm formation, dissection, and rupture during the procedure. Therefore, an understanding of these anomalies, their underlying embryological basis and associations, and pattern of circulation will help endovascular neurosurgeons and interventional radiologists navigate with confidence and consider relevant pathologic associations that may inform risk of cerebrovascular disease. METHODS: Here, we present a brief review of the basic embryology of the common anomalies of the aortic arch along with their neurological significances and discuss, through illustrative cases, the association of aortic arch anomalies with cerebral vascular pathology. CONCLUSIONS: Understanding the aortic arch anomalies and its embryological basis is essential to safely navigate the cerebral vascular system during neurointerventional surgeries.

Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes.

BACKGROUND: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results. OBJECTIVE: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs. METHODS: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee. RESULTS: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively. CONCLUSIONS: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585.

Artery of Davidoff and Schechter: A Large Angiographic Case Series of Dural AV Fistulas.

The artery of Davidoff and Schechter (ADS) is the only meningeal branch of the posterior cerebral artery (PCA), supplying the medial tentorial margin and posterior portions of the falx. Given its small size, it is rarely identified on angiographic studies, unless enlarged in pathologies such as dural arteriovenous fistulas (DAVFs) or vascularized masses. This artery was first described by Wollschlaeger and Wollschlaeger in 1965, and to date, only a few reports have described its significance. The objective of this study is to report our experience with the ADS in dural fistulas from 2 tertiary medical centers and to emphasize the importance of recognizing this artery during angiographic examination of vascular tentorial and posterior fossa lesions. To our knowledge, this report demonstrates the largest angiographic case series published to date, recognizing a total of 7 patients with ADS arising secondary to a posterior fossa or tentorial DAVF and one of the largest reported series of DAVFs supplied by the ADS treated by endovascular and surgical techniques. Our cases validate the importance of prompt identification of the ADS for the diagnosis as well as endovascular treatment of vascular malformations in the posterior fossa and tentorial region.

Intra-arterial Bevacizumab for Posterior Fossa Hemangioblastoma.

Hemangioblastoma (HB) is a rare, highly vascularized, and benign central nervous system (CNS) tumor. This vascularity is due to a high degree of signaling by vascular endothelial growth factor (VEGF). Consequently, anti-VEGF agents, such as bevacizumab, have been postulated and shown in a few cases to be effective in treating these tumors when surgical therapy is not feasible. Additionally, selective intra-arterial (IA) administration of bevacizumab has shown promise in treating other cancers such as glioblastoma (GBM). Here, we present the case of a 60-year-old female with a symptomatic posterior fossa HB where embolization and surgery were not feasible due to tumor location. She underwent selective IA treatment with bevacizumab, which led to tumor stability and symptomatic improvement. Bevacizumab has been used intravenously (IV) as a treatment for HB, however, its efficacy has not been well-established. This case demonstrates the potential viability of selective bevacizumab in HB, as demonstrated by symptomatic improvement and decreased tumor size on MRI. Further research is needed to demonstrate the specific efficacy of IA bevacizumab for CNS HB when surgery or other treatment modalities are not viable options.

Severe peripartum cardiomyopathy complicated by COVID-19 infection and small intestinal obstruction.

COVID-19 infection can be a possible trigger for peripartum cardiomyopathy. Multidisciplinary teamwork was crucial for the favorable outcome in our patient. Small bowel strangulation is a rare complication post-cesarean section.

Encephalopathy at admission predicts adverse outcomes in patients with SARS-CoV-2 infection.

AIMS: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered. RESULTS: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001). CONCLUSIONS: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.

Detection of Angiographically Occult Ruptured Basilar Sidewall Perforator Aneurysm by Vessel Wall MR Imaging.

Basilar artery perforator aneurysms are rare with a prevalence of less than 1%. These are particularly challenging to detect given their small size and tendency to intermittently thrombose. We describe a case of a ruptured basilar artery sidewall perforator aneurysm that was angiographically occult on computed tomographic angiogram and cerebral catheter angiogram. One day after the initial diagnostic work-up, intracranial vessel wall MR imaging (VWI) was performed which revealed a small outpouching along the right posterolateral basilar arterial wall with a punctate enhancing focus suggestive of a thrombosed basilar perforator artery aneurysm. Thrombus within the small aneurysm sac likely contributed to the poor opacification of the aneurysm sac on conventional lumen-based imaging techniques. Ruptured aneurysms have high morbidity and mortality due to their tendency to rebleed, making their expedient detection and treatment imperative. This case highlights the role VWI can play in detecting small ruptured aneurysms that intermittently thrombose and are otherwise challenging to diagnose with conventional vessel imaging.

Differentiating Dynamic Cerebral Autoregulation Across Vascular Territories.

Objective: Transcranial Doppler is commonly used to calculate cerebral autoregulation, but measurements are typically restricted to a single cerebral artery. In exploring topographic heterogeneity, this study reports the first thorough comparison of autoregulation in all major cerebral vessels. Methods: In forty healthy adults, flow velocity was monitored in the anterior, middle, and posterior cerebral arteries, and synchronized with arterial blood pressure. A transfer function analysis provided characteristics of autoregulation by quantifying the relationship between blood pressure and cerebral blood flow velocity. Results: Phase, which quantifies the time course of autoregulation, was similar in all vessels. Gain, which quantifies the magnitude of hemodynamic regulation, was lower in posterior cerebral artery, indicative of tighter regulation. However, after adjusting for baseline flow differences in each vascular territory, normalized gain was similar in all vessels. Conclusions: Discriminating dynamic cerebral autoregulation between cerebrovascular territories is feasible with a transcranial doppler based approach. In the posterior cerebral artery of healthy volunteers, absolute flow is more tightly regulated, but relative flow regulation is consistent across cerebrovascular territories. Significance: The methodology can be applied to focal disease states such as stroke or posterior reversible encephalopathy syndrome, in which the topographic distribution of autoregulation may be particularly critical.

Impact of carotid tortuosity on outcome after endovascular thrombectomy.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is efficacious in patients with large vessel occlusion stroke (LVO). We explored whether internal carotid (ICA) tortuosity increases the technical difficulty of EVT thereby lowering the chances of successful recanalization and favorable outcomes. PATIENTS AND METHODS: Consecutive patients with LVO and patent ICAs who underwent EVT were included. Carotid tortuosity was determined on pre-EVT CTA and classified by raters blinded to outcomes into: type 1-straight ICA trunk and type 2-severe tortuosity potentially impeding adequate catheter placement. Thrombolysis in cerebral infarction (TICI) 2b-3 was considered successful recanalization, and 90-day-modified Rankin Scale ≤ 2 was considered favorable functional outcome. RESULTS: Among 302 patients (mean age 70 ± 15, median NIHSS 17), 53% had type 1, and 47% type 2 tortuosity. Overall, 85% had successful recanalization. Patients with type 2 tortuosity were significantly older (p < 0.0001) and less frequently achieved successful recanalization (80% vs. 90%; p = 0.019) but had similar outcomes compared with those without tortuosity. On regression analysis, marked tortuosity was associated with lower chances of successful recanalization (OR 0.43 95% CI 0.20-0.92) but had no effect on clinical outcomes. CONCLUSIONS: Carotid tortuosity does not appear to impact the likelihood of favorable functional outcome but may influence recanalization.

Cell Therapy for Stroke: A Mechanistic Analysis.

Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts. In the present work, we review the major clinical trials of cell therapy for stroke and highlight a mechanistic shift between the earliest studies, which aimed to replace dead and damaged neurons, and later ones that focused on exploiting the various neuromodulatory effects afforded by stem cells. We discuss why both mechanisms are worth pursuing and emphasize the means through which cell replacement can still be achieved.

Chronic back pain in first-degree relatives (FDRs) of patients with ankylosing spondylitis: predictive value of HLA-B27 and persistence of inflammatory back pain over time.

BACKGROUND/PURPOSE: First-degree relatives (FDRs) of patients with ankylosing spondylitis (AS) may be at high risk of spondyloarthritis. We examined the frequency, characteristics of chronic back pain (CBP), associated features, persistence of symptoms, and HLA-B27 allele frequency in FDRs of AS patients, also comparing those FDRs with participants in NHANES 2009-2010 with CBP. METHODS: 399 FDRs of AS probands were divided into: (1) No CBP (subjects >40 years old at study visit without CBP) (n=162); (2) NICBP (non-inflammatory CBP) (n=82), and (3) CIBP (inflammatory CBP) (n=155). White FDRs with CBP were compared with 772 participants in NHANES 2009-2010 with CBP. FDRs were invited to return for reassessment. RESULTS: FDRs with CIBP had earlier onset of CBP than those with NICBP (p<0.001) and had higher frequency of heel pain than those without CBP (p=0.002). HLA-B27 occurred in 57% of FDRs with CIBP vs 39.6% of those without CBP (p=0.005, OR=1.9). Of 23 patients with CIBP at baseline re-evaluated 67.04±31.02 months later, 16 (73%) still had CIBP, whereas 4 (31%) of 13 NICBP patients seen 61.23±31.84 months later remained symptomatic. CONCLUSION: CIBP in FDRs of AS patients is HLA-B27-associated, has earlier onset and tends to persist compared to NICBP.

Neuroendovascular Treatment of Acute Stroke During COVID-19: A Guide From the Frontlines.

Since the initial reports surfaced of a novel coronavirus causing illness and loss of life in Wuhan, China, COVID-19 has rapidly spread across the globe, infecting millions and leaving hundreds and thousands dead. As hospitals cope with the influx of patients with COVID-19, new challenges have arisen as health-care systems care for patients with COVID-19 while still providing essential emergency care for patients with acute strokes and acute myocardial infarction. Adding to this complex scenario are new reports that patients with COVID-19 are at increased risk of thromboembolic complications including strokes. In this article, we detail our experience caring for acute stroke patients and provide some insight into neurointerventional workflow modifications that have helped us adapt to the COVID-19 era.

Impact of the COVID-19 Epidemic on Stroke Care and Potential Solutions.

BACKGROUND AND PURPOSE: When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted. In this study, we investigated the impact of the COVID-19 outbreak on stroke care across China. METHODS: Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy. We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes. The survey was distributed to the leaders of stroke centers in these 280 hospitals. RESULTS: From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% (P<0.0001) and 25.3% (P<0.0001), respectively, in February 2020 as compared with February 2019. We retrieved 227 valid complete datasets from the 280 stroke centers. Nearly 50% of these hospitals were designated hospitals for COVID-19. The capacity for stroke care was reduced in the majority of the hospitals. Most of the stroke centers stopped or reduced their efforts in stroke education for the public. Hospital admissions related to stroke dropped ≈40%; thrombolysis and thrombectomy cases dropped ≈25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019. Many factors contributed to the reduced admissions and prehospital delays; lack of stroke knowledge and proper transportation were significant limiting factors. Patients not coming to the hospital for fear of virus infection was also a likely key factor. CONCLUSIONS: The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy. Although many factors contributed, patients not coming to the hospital was probably the major limiting factor. Recommendations based on the data are provided.

Decreased contrast enhancement on high-resolution vessel wall imaging of unruptured intracranial aneurysms in patients taking aspirin.

OBJECTIVE: Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms (UIAs). Animal and human studies have suggested that, due to its antiinflammatory effect, aspirin (ASA) may decrease the risks of growth and rupture of UIAs. High-resolution vessel wall imaging (HR-VWI) has emerged as a noninvasive method to assess vessel wall inflammation and UIA instability. To the authors' knowledge, to date no studies have found a significant correlation between patient use of ASA and contrast enhancement of UIAs on HR-VWI. METHODS: The University of Iowa HR-VWI Project database was analyzed. This database is a compilation of data on patients with UIAs who prospectively underwent HR-VWI on a 3T Siemens MRI scanner. The presence of aneurysmal wall enhancement was objectively defined using the aneurysm-to-pituitary stalk contrast ratio (CRstalk). This ratio was calculated by measuring the maximal signal intensity in the aneurysmal wall and the pituitary stalk on postcontrast T1-weighted images. Data on aneurysm size, morphology, and location and patient demographics and comorbidities were collected. Use of ASA was defined as daily intake of ≥ 81 mg during the previous 6 months or longer. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with increased contrast enhancement of UIAs on HR-VWI. RESULTS: In total, 74 patients harboring 96 UIAs were included in the study. The mean patient age was 64.7 ± 12.4 years, and 60 patients (81%) were women. Multivariate analysis showed that age (OR 1.12, 95% CI 1.05-1.19), aneurysm size ≥ 7 mm (OR 21.3, 95% CI 4.88-92.8), and location in the anterior communicating, posterior communicating, and basilar arteries (OR 10.7, 95% CI 2.45-46.5) were significantly associated with increased wall enhancement on HR-VWI. On the other hand, use of ASA was significantly associated with decreased aneurysmal wall enhancement on HR-VWI (OR 0.22, 95% CI 0.06-0.83, p = 0.026). CONCLUSIONS: The study results establish a correlation between use of ASA daily for ≥ 6 months and significant decreases in wall enhancement of UIAs on HR-VWI. The findings also demonstrate that detection of wall enhancement using HR-MRI may be a valuable noninvasive method for assessing aneurysmal wall inflammation and UIA instability.