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Background and Purpose: The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic. Early data suggest higher rate of ischemic stroke in severe COVID-19 infection. We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak., Methods: This is a retrospective, observational case series. Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19. Patients' demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record. Comparison was made between COVID-19 positive and negative cohorts. The incidence of ELVO stroke was compared with the pre-COVID period., Results: Forty-five consecutive ELVO patients presented during the observation period. Fifty-three percent of patients tested positive for COVID-19. Total patients' mean (±SD) age was 66 (±17). Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P =0.004). Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P =0.032). Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P =0.027]). In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P ≤0.0001)., Conclusions: More than half of the ELVO stroke patients during the peak time of the New York City's COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White. Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Stroke is a leading cause of morbidity, mortality, and disability in patients undergoing cardiac surgery. Identifying modifiable perioperative stroke risk factors may lead to improved patient outcomes. The association between the severity and duration of intraoperative hypotension and postoperative stroke in patients undergoing cardiac surgery was evaluated., Methods: A retrospective cohort study was conducted of adult patients who underwent cardiac surgery requiring cardiopulmonary bypass at a tertiary center between November 1, 2009, and March 31, 2015. The primary outcome was postoperative ischemic stroke. Intraoperative hypotension was defined as the number of minutes spent within mean arterial pressure bands of less than 55, 55 to 64, and 65 to 74 mmHg before, during, and after cardiopulmonary bypass. The association between stroke and hypotension was examined by using logistic regression with propensity score adjustment., Results: Among the 7,457 patients included in this analysis, 111 (1.5%) had a confirmed postoperative diagnosis of stroke. Stroke was strongly associated with sustained mean arterial pressure of less than 64 mmHg during cardiopulmonary bypass (adjusted odds ratio 1.13; 95% CI, 1.05 to 1.21 for every 10 min of mean arterial pressure between 55 and 64 mmHg; adjusted odds ratio 1.16; 95% CI, 1.08 to 1.23 for every 10 min of mean arterial pressure less than 55 mmHg). Other factors that were independently associated with stroke were older age, hypertension, combined coronary artery bypass graft/valve surgery, emergent operative status, prolonged cardiopulmonary bypass duration, and postoperative new-onset atrial fibrillation., Conclusions: Hypotension is a potentially modifiable risk factor for perioperative stroke. The study's findings suggest that mean arterial pressure may be an important intraoperative therapeutic hemodynamic target to reduce the incidence of stroke in patients undergoing cardiopulmonary bypass.

The current study examined how techniques in a psychodynamic model of therapy (Blagys and Hilsenroth, Clin Psychol Sci Pract. 7, 167-188, 2000) were related to changes in anxiety symptoms across early treatment process among a transdiagnostic sample of patients with primary anxiety disorder, subclinical anxiety disorder, and no anxiety disorder. Secondary analyses examined the use of specific psychodynamic techniques in relation to symptom change. Results revealed that therapists' use of psychodynamic-interpersonal (PI) techniques were significantly and directly related to changes in anxiety symptoms, in line with previous findings (Pitman, Slavin-Mulford, and Hilsenroth, J Nerv Ment Dis. 202, 391-396, 2014). In addition, patients with co-occurring axis I and II disorders demonstrated positive changes in anxiety symptoms regardless of level of PI technique used, whereas patients without co-occurring disorders experienced greater improvement with more PI. Implications for transdiagnostic treatment protocols for anxiety, notably Leichsenring and Salzer's (Psychotherapy 51, 224, 2104) Unified Psychodynamic Protocol for Anxiety Disorders, are discussed in relation to the current findings.

Coronary drug-eluting stents are commonplace in clinical practice with acceptable safety and efficacy. Preclinical evaluation of novel drug-eluting stent technologies has great importance for understanding safety and possibly efficacy of these technologies, and well-defined preclinical testing methods clearly benefit multiple communities within the developmental, testing, and clinical evaluation chain. An earlier consensus publication enjoyed widespread adoption but is in need of updating. This publication is an update, presenting an integrated view for testing drug-eluting technologies in preclinical models, including novel devices such as bioabsorbable coatings, totally bioabsorbable stents, bifurcation stents, and stent-free balloon-based drug delivery. This consensus document was produced by preclinical and translational scientists and investigators engaged in interventional technology community. The United States Food and Drug Administration (USFDA) recently issued a Draft Guidance for Industry Document for Drug-Eluting Stents. This expert consensus document is consistent with the Food and Drug Administration guidance. The dynamic nature of this field mandates future modifications and additions that will be added over time.

Background and Purpose: The most common presentation of ischemic stroke related to pregnancy is arterial occlusion, occurring during the third trimester or postpartum. The authors present the first successful administration of intra-arterial cerebral tissue plasminogen activator to treat an embolic cerebral vascular accident in a 37-week parturient resulting in complete recovery of neurological function., Methods: The patient presented with left hemiplegia, left-sided neglect, and aphasia. Right internal carotid artery cerebral angiogram showed occlusion of the mid-M1 segment of the middle cerebral artery (MCA). After 15 mg of tissue plasminogen activator was administered via intra-arterial route, there was greatly improved retrograde flow through the posterior communication artery and the MCA territory., Results: A reduction in size of the MCA occlusion was noted with improvement of antegrade flow through the MCA. Three days after the procedure, the patient was induced successfully and delivered a healthy infant vaginally., Conclusions: This report describes the use of intra-arterial tissue plasminogen activator in the setting of stroke in late pregnancy.

Recent advances in the prevention and pharmacotherapy of cerebrovascular disease have provided more favorable clinical outcomes. For the treatment of an acute ischemic stroke, the early use of thrombolytic agents can reduce the degree of brain damage while improving functional outcomes. However, trials evaluating various classes of other neuroprotective agents have not shown benefit to date. For the prevention of second stroke, the use of antiplatelet drugs, HMG-CoA reductase inhibitors, and angiotensin-converting enzyme inhibitors with a diuretic have shown benefit in reducing new events. In patients with underlying heart disease or atrial fibrillation, warfarin appears to be the drug of choice in preventing stroke. Early treatment of hemorrhagic stroke with calcium channel blockers can improve the functional outcome. Innovative therapies are now available for the treatment of migraine and vascular dementia. Primary prevention of stroke remains the optimal therapeutic strategy and includes treatment of systemic hypertension and hypercholesterolemia.

To define the natural history of aortic arch plaque, we used B-mode ultrasonography to perform sequential study of the aortic arch. Eighty-nine patients were studied for up to 18 months. There was no change in 67% of total plaques; 77% of simple plaque (<4 mm) and 48% of complex plaque (> or =4 mm) did not progress. Atherosclerosis of the aortic arch can be sequentially studied with B-mode ultrasonography, and most of these lesions remain unchanged after up to 18 months of observation.

Objective: To determine whether elevated titers of antiphosphatidyl serine antibodies (aPS) are associated with an increased risk of ischemic stroke in a general stroke population., Background: aPS are members of the family of antiphospholipid antibodies that has been associated with increased stroke risk. Although aPS have been demonstrated to occur in 18% of a group of young patients with cerebrovascular symptoms, their prevalence in the general stroke population is unknown, and no controlled study to assess the strength of their association with ischemic stroke has been undertaken previously., Methods: A case-control study comparing 267 acute ischemic stroke patients and 653 community controls. Sera were obtained immediately after acute stroke in patients. Titers of IgG aPS >16 IgG phospholipid units or IgM aPS >22 IgM phospholipid units were considered positive. Odds ratios (ORs) were obtained by logistic regression, adjusting for age, gender, race/ethnicity, history of hypertension, diabetes mellitus, cardiovascular disease, and cigarette smoking., Results: The adjusted OR was 5.6 (95% confidence interval [CI] 1.8, 18.0) for IgG aPS and 2.9 (95% CI 1.6, 5.3) for IgM aPS. The adjusted OR for either an elevated IgG or IgM aPS was 3.2 (95% CI 1.8, 5.5)., Conclusions: This study demonstrates that elevated IgG and IgM antiphosphatidyl serine antibodies titers are associated with increased risk of ischemic stroke. The prevalence of these antibodies is lower, but the associated stroke risk is comparable with that of anticardiolipin antibodies.

The goal of therapy for acute stroke is immediate treatment to reduce the risk of permanent neurologic disability and death. For ischemic stroke, it is imperative to reestablish brain perfusion while at the same time trying to preserve neuronal function. Early treatment of hemorrhagic stroke, particularly subarachnoid hemorrhage, also may improve clinical outcome. Prevention of stroke still remains the most important treatment strategy. In this review, pharmacologic strategies to both prevent and treat thrombotic, embolic, and hemorrhagic strokes are discussed. Treatment modalities for other cerebrovascular disease entities, migraine syndrome, and vascular dementia also are reviewed.

Background: Intravascular irradiation with beta-emitters has been proposed for inhibition of restenosis in coronary arteries after balloon angioplasty or stent implantation. Previous studies have shown the effectiveness of gamma-radiation to prevent recurrent restenosis, even in the presence of an implanted stent. The limited range of beta-particles compared with gamma-radiation, however, opens the question of whether absorption and scattering of beta-particles by stent struts will cause significant perturbations in the uniformity and magnitude of the radiation dose, which may in turn compromise treatment., Methods and Results: Nine different stents were deployed with a balloon filled with a beta-emitting radioactive liquid. Dose distributions were measured with Gafchromic film. Stents varied significantly in their absorption of beta-particles. Some stents, constructed of fine meshed wires, produced minimal dose perturbations. Others, with thicker, high-atomic-number struts, induced cold spots in the dose distribution adjacent to the wires of

Nitric oxide release during cerebral ischemia is the result of both neuronal and endothelial subclasses of nitric oxide synthase (NOS). In this study, we examined the role of specific neuronal NOS inhibition (nNOSI) on excitatory neurotransmitter and gamma-aminobutyric acid (GABA) release during global cerebral ischemia. Microdialysis probes were placed into the striatum of 24 rats. After probe stabilization, rats were randomized to receive 7-nitroindazole (7-NI), a selective nNOSI, in doses of 0, 5, 10, or 20 mg/kg. Temporary global forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion. nNOSI administration did not produce detectable changes in neurotransmitter recovery prior to ischemia. There were significant increases in aspartate (ASP), glutamate (GLU), glycine (GLY), and GABA recovery during ischemia in the absence of nNOSI. 7-NI resulted in an attenuation in GLU, GLY, and GABA recovery during ischemia and reperfusion. No differences in ASP recovery were detected with nNOSI. Differences between the present study and other studies that examine the role of nonspecific constitutive NOSI during cerebral ischemia demonstrate the contribution of neuronal NOS on the modulation of ischemic excitatory neurotransmitter and GABA release.

Systemic nitric oxide synthase inhibition (NOSI) decreases cerebral blood flow, which may worsen ischemic insults. To examine the local effects of NOSI without this confounding effect, we examined the role of a locally administered NOSI, NG-nitro-L-arginine-methyl-ester (L-NAME), on neurotransmitter recovery during cerebral ischemia. Rats were assigned to one of three groups: locally administered L-NAME via a striatal microdialysis probe (n = 11), systemic L-NAME (n = 5), or control (n = 11). Temporary global forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion. L-NAME resulted in decreases of basal aspartate (ASP; 74% of basal) and glutamate (GLU; 60% of basal) recovery. While systemic L-NAME caused significant increases in ischemic ASP and GLU recovery (by 224% and 110%, respectively, compared with ischemic controls), local NOSI administration resulted in a significant attenuation of peak ASP, GLU, glycine, and gamma-aminobutyric acid recovery (43%, 38%, 53%, and 72%, respectively, compared with ischemic controls). We conclude that local NOSI attenuated ischemic neurotransmitter recovery during ischemia/reperfusion. Our results emphasize the importance of the systemic effects of NOSI and suggest both deleterious and beneficial effects of NOSI during ischemia/reperfusion.

Background: Basic fibroblast growth factor (bFGF) is a mitogenic polypeptide that demonstrates enhanced expression and promotes angiogenesis in animal models of myocardial ischemia and infarction. Elevated levels of bFGF are present in the urine of humans with metastatic tumors, but its expression in human myocardial ischemia is unknown. Thus, we sought to determine whether urine levels of bFGF are altered by exercise-induced ischemia in humans., Methods and Results: Eighty-six patients underwent exercise thallium studies for evaluation of anginal symptoms. Urine levels of bFGF (corrected for urine creatinine) were determined by ELISA immediately before and between 2 and 4 hours after exercise. The change in urine bFGF level was compared between 43 patients with and 43 patients without exercise-induced ischemia. Patients with ischemia had an increase in urine bFGF compared with nonischemic patients (1052 +/- 245 versus -278 +/- 130 pg/g creatinine, P < .0001). Exercise, demographic, and clinical variables were assessed and analyzed for possible effect on bFGF response to exercise. By univariate analysis, a history of hypertension was negatively associated with a change in bFGF level (P < .05). No other variables were associated. By multivariate analysis, only bFGF response (P < .001) and age (P < .05) were independently related to exercise-induced ischemia., Conclusions: Significantly increased levels of bFGF are detected in the urine within hours of exercise-induced ischemia. Further studies are warranted to determine whether bFGF might serve as a useful circulating marker of myocardial ischemia in humans.

The development of accelerated transplant-related coronary artery disease (T-CAD) is the major obstacle to long-term survival of cardiac allografts. We have investigated the role of various demographic and immunologic parameters as prognostic indicators of T-CAD in a population of 274 heart allograft recipients. Our data demonstrate that patients who experience more than 1 episode of acute rejection per year and/or develop antidonor HLA antibodies are at increased risk of developing T-CAD. Using HLA-A2 as a marker for the release of soluble HLA antigens from the donor, we established that recipients displaying circulating donor alloantigens for more than 26 weeks following transplantation are at increased risk of developing T-CAD (P=0.008). This association suggests that the release of alloantigens from the allograft is indicative of chronic injury and/or that it stimulates chronic rejection via the indirect allorecognition pathway. Our findings indicate that patients at risk of developing T-CAD can be identified by monitoring the release of donor alloantigens and production of antidonor HLA antibodies following transplantation.

Dopamine (DA) is released in large quantities from the striatum during cerebral ischemia. Along with excitatory neurotransmitters, DA plays a role in cellular neuronal ischemic injury. In this study we examined the role of nitric oxide (NO) in the ischemia-induced release of DA. A microdialysis probe was stereotactically placed into the corpus striatum of 16 Sprague-Dawley rats for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) level determinations. After probe stabilization, the animals received either NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, or vehicle through the microdialysis probe. Temporary global forebrain ischemia was induced using bilateral carotid artery ligature tightening and controlled hemorrhagic hypotension for 15 min. L-NAME administration caused a reduction in ischemic estimated extraneuronal DA concentration by 60% (P < 0.005) compared with control. There was an increase in both DOPAC and HVA concentrations during the recovery period compared to baseline values in the control group (P < 0.05). L-NAME also caused a reduction in HVA concentration compared to vehicle administration during the latter part of recovery (P < 0.05). These data support the concept that ischemic dopamine release may be mediated by NO. This NO-modulated DA release may contribute to the previously reported deleterious neurotoxic effects of NO during ischemia.

Dopamine (DA) is released in large quantities into the corpus striatum during cerebral ischemia and may exacerbate tissue damage. Using cerebral microdialysis, we studied the effect of etomidate on in vivo ischemia-induced DA release in rat corpus striatum. Reversible cerebral ischemia was induced by using carotid ligatures and hypovolemic hypotension, and monitored with laser Doppler flowmetry. After baseline measurements, 20 normothermic, anesthetized rats were subjected to three separate periods of cerebral ischemia, interrupted by 45- to 75-min periods of reperfusion. The rats were randomized into two groups. All rats received 400 mg/kg of intraperitoneal chloral hydrate for induction of anesthesia. In Group I (n = 10) anesthesia was maintained using additional intraperitoneal chloral hydrate 100 mg/kg every 2 h. Group II received etomidate 0.6 mg/kg 10 min before the first episode of cerebral ischemia, followed by an infusion of 60 micrograms.kg-1 x min-1. Before each subsequent period of induced ischemia, an additional dose of etomidate (0.6 mg/kg) was administered. DA levels were approximately 350 times above baseline in Group I during the three ischemic episodes (IS1, IS2, and IS3). In Group II, ischemia-induced DA release was significantly attenuated (by 79%) during IS1, IS2, and IS3 compared to Group I (P < 0.01). DA levels did not significantly change in magnitude during the three ischemic episodes in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Dopamine is released in large quantities into the corpus striatum during cerebral ischemia and may exacerbate tissue damage., Methods: Using cerebral microdialysis, the effect of isoflurane on in vivo ischemia-induced dopamine release was studied in rat corpus striatum. Reversible cerebral ischemia was induced using carotid ligatures and induced hypovolemia and was monitored with laser-Doppler flowmetry. Following baseline measurements, 28 normothermic, anesthetized rats were subjected to cerebral ischemia followed by reperfusion. The rats were divided into four groups. Group 1 (n = 10) was anesthetized using chloral hydrate. Groups 2 and 3 received 1.5% end-tidal isoflurane. In group 2 (n = 6), hypotension was left untreated during the reperfusion period, and in group 3 (n = 6), mean arterial pressure was maintained using phenylephrine. Group 4 (n = 6) received 1-1.2% end-tidal halothane., Results: Compared with pre-ischemic levels, large quantities of dopamine (350 x baseline levels) were released in group 1 animals during cerebral ischemia. Compared with group 1, ischemia-induced dopamine release was significantly reduced in group 2 (by 58%) and in group 3 (by 56%), but not in group 4. Group 2 animals were uniformly hypotensive during reperfusion and continued to release substantial amounts of dopamine (8 x baseline levels). In groups 1, 3, and 4, dopamine release decreased to near baseline levels during reperfusion. In group 3, dopamine metabolite production was significantly increased during ischemia, suggesting that enzymatic function and neuronal reuptake of dopamine was preserved., Conclusions: Isoflurane, compared with chloral hydrate and halothane, inhibits the release of the neurotransmitter dopamine during cerebral ischemia.

Non-invasive carotid artery testing was performed on 500 consecutive patients with visual disturbances not related to local ophthalmic pathology to determine the extent of carotid artery disease, particularly in patients with symptoms not typical of amaurosis fugax. Three hundred eighty six patients (77.2%) had an abnormal study. However, the incidence of hemodynamically significant lesions was only 16%. The patients could be divided into three groups: Patients with symptoms that could be explained on an ocular basis, including amaurosis fugax, had a 79% incidence of ipsilateral carotid plaques. Patients with symptoms which could not be easily explained on an ocular basis, such as bilateral blurred vision, bilateral visual loss (both transient and permanent), and homonymous hemianopsia had an incidence of carotid artery plaques similar to patients with amaurosis fugax. Patients with unilateral blurred vision and bilateral scintillations had a lower incidence (57%) of carotid plaques than the other groups. Younger symptomatic patients had less carotid plaques than the overall series. Twenty-one percent of patients under age 50 had the Doppler finding of early systolic flutter turbulence, which is usually of mitral valve origin. Women predominated in the under 50 age group by about 2:1. In view of the prevalence of carotid plaques in the population of patients with visual symptoms other than amaurosis fugax, evaluation of these patients with non-invasive testing is indicated to determine which of these patients has hemodynamically significant obstruction to flow at the carotid artery bifurcation.

Mongolian gerbils were treated with alpha-methyl-para-tyrosine methyl ester (AMPT, a tyrosine hydroxylase inhibitor), in order to decrease brain levels of catecholamines. Six hours later, unilateral ischemic stroke was induced by ligation of the left common carotid artery. The delayed degeneration of nerve terminals was studied sixteen hours later by measuring the high-affinity uptake of radiolabeled transmitters by isolated synaptosomes. Dopamine, serotonin and glutamate terminals were studied. AMPT-treated gerbils were compared to untreated (no AMPT) animals; 220 gerbils were studied. AMPT pretreatment (100, 250 and 400 mg/kg) produced a dose-dependent protection of all three types of nerve terminals. In the absence of AMPT pretreatment, the uptake of radiolabeled transmitters by the ischemic hemisphere, expressed as a percentage of that seen in the contralateral (unaffected) side of the brain, was as follows (mean +/- SEM): 27.3 +/- 5.2% for dopamine terminals, 49.5 +/- 6.2% for serotonin terminals, and 42.7 +/- 5.3% for glutamate terminals. Protection was essentially complete at a dose of 400 mg AMPT per kg. The number of animals with significant damage to nerve terminals was reduced from 38.5% in untreated animals to 11.1% in animals treated with AMPT 400 mg/kg. Although the nerve terminals were protected, gerbils still showed the behavioral signs of unilateral stroke due to the permanent occlusion of the left carotid. These results indicate that endogenous dopamine may play a significant role in ischemic damage to nerve terminals in the cerebrum.

Two cases of acute meningoencephalitis, presumably viral in origin, with brainstem involvement are reported. Common to both patients during the course of their illness was coma, downbeat nystagmus, and ataxia. Although both reached what appeared to be a terminal state, recovery began following treatment with corticosteroids. The significance of the neurologic signs, particularly the unusual occurrence of downbeat nystagmus, is discussed, as is the appropriate management of the disorder.