Ipsilateral Common Carotid Artery Research Articles

Usefulness of “AcT ratio” in diagnosis of internal carotid artery stenosis: a multicenter, retrospective, observational study

PurposeThe ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the “AcT ratio,” which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates.MethodsThis study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve.ResultsA significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50% had a sensitivity, specificity, and negative predictive value (NPV) of 70.2%, 71.6%, and 91.5%, respectively, when the cut-off value of the AcT ratio was 1.17. NASCET stenosis of ≥ 70% had a sensitivity, specificity, and NPV of 70.5%, 72.1%, and 95.9%, respectively, when the cut-off value of the AcT ratio was 1.22.ConclusionsThe findings of this multicenter, retrospective, cross-sectional study suggest that the AcT ratio is useful for diagnosing ICA-origin stenosis, especially for diagnosis by exclusion. NASCET stenosis of ≥ 50% was considered unlikely if the Act ratio was ≤ 1.17, whereas NASCET stenosis of ≥ 70% was considered unlikely if it was ≤ 1.22.

Abstract TP178: Impact of Fetal PCA on Ipsilateral Carotid Artery Stiffness: Results From Northern Manhattan Stroke Study (NOMAS)

Introduction: The wall stress is the major contributor of arterial stiffness, which is well-known risk factor for cardiovascular diseases. The interindividual variability of the Circle of Willis affects blood flow redistribution intracranially. The fetal posterior cerebral artery (fPCA) is associated with larger carotid arteries due to increased brain territory supplied by the anterior circulation. Thus, an fPCA increases blood flow in the ipsilateral carotid artery and could plausibly increase ipsilateral carotid artery stiffness. Methods: We included participants from the multi-ethnic community-based Northern Manhattan Stroke Study (NOMAS) cohort with available time-of-flight MRA. High-resolution B-mode ultrasound of the right common carotid artery (CCA) evaluated markers of arterial stiffness, including diastolic diameter (DD), strain (systolic diameter - DD/DD), cIMT (carotid intima-media thickness), and stiffness (systolic blood pressure - diastolic blood pressure/strain). We used multivariable regression analyses to calculate odds ratios and beta values, examining the association of fPCA and markers of stiffness. Results: Among 1,210 NOMAS (mean age 70 ± 9 years, 61% women, 66% Hispanic) participants with available MRA, 151 (12.5%) participants had a right fPCA, and 129 (10.7%) had a left fPCA. In models adjusted for demographics, vascular risk factors, and height, right fPCA was associated with a higher ipsilateral CCA diastolic diameter (B = 0.31, p=0.001) and strain (B=0.04, p=0.02). Notably, no similar association was found between the left fPCA and contralateral carotid measures (Table 1). Conclusion: A fetal PCA associated with ipsilateral markers of cervical carotid stiffness. This research provides valuable insight into the changes in demands resulting from the variability of the circle of Willis and the extracranial correspondence of such demand.

The accumulated oxygen deficit as an indicator of the ischemic retinal insult

We here attempt to improve quantification of the ischemic retinal insult, that is, what is imposed on the retinal tissue by ischemia, especially in experimental models of ischemia. The ischemic retinal insult initiates the ischemic retinal injury (or outcome). Accordingly, it is reasonable to assume that the better the quantification of the insult, the better the correlation with, and thereby estimation of, the injury. The insult seldom has been quantified in terms of the relevant physiological factors, especially in connection with the rate of oxygen delivery (DO2). We here propose the accumulated oxygen deficit (AO2D) as an indicator of the ischemic retinal insult. We hypothesized that AO2D is correlated with the rate of oxygen metabolism measured 1 h after reperfusion following an episode of ischemia (MO2_1_Hr). Previously, we showed that MO2_1_Hr is related to the electroretinogram amplitude and the retinal thickness when they are measured seven days after reperfusion. We studied 27 rats, as well as 26 rats from our published data on retinal ischemia in which we had measurements of DO2 and duration of ischemia (T) of various levels and durations. We also measured DO2 in 29 rats treated with sham surgery. Ischemia was induced by either ipsilateral or bilateral common carotid artery occlusion or by ophthalmic artery occlusion, which gave a wide range of DO2. DO2 and MO2_1_Hr were evaluated based on three types of images: 1) red-free images to measure vessel diameters, 2) fluorescence images to estimate blood velocities by the displacement of intravascular fluorescent microspheres over time, and 3) phosphorescence images to quantify vascular oxygen tension from the phosphorescence lifetime of an intravascular oxygen sensitive phosphor. Loss of oxygen delivery (DO2L) was calculated as the difference between DO2 under normal/sham condition and DO2 during ischemia. AO2D, a volume of oxygen, was calculated as the product DO2L and T. Including all data, the linear relationship between AO2D and MO2_1_Hr was significant (R2 = 0.261, P = 0.0003). Limiting data to that in which T or DO2L was maximal also yielded significant relationships, and revealed that DO2L at a long duration of ischemia contributed disproportionately more than T to MO2_1_Hr. We discuss the potential of AO2D for quantifying the ischemic retinal insult, predicting the ischemic retinal injury and evaluating the likelihood of infarction.

Subclavian to carotid artery bypass for a case of ocular ischemic syndrome.

Ocular Ischemic Syndrome (OIS) is a rare, vision threatening condition associated with severe carotid artery disease. There are few cases of OIS reported in the literature. We present the case of a 54-year-old male with history of multiple previous carotid interventions including a right carotid stent, who presented with right-sided OIS. CTA and angiogram showed a severe calcific plaque causing restenosis of the right carotid stent, with a patent right internal carotid artery (ICA) in the very distal neck. The right common carotid artery (CCA) was patent but diseased with ulcerated plaque extending proximally to below the level of the clavicle. The left CCA was chronically occluded from its origin all the way to the bifurcation. Given our patient's surgical history, the imperative to revascularize the ipsilateral carotid, and a diffusely diseased ipsilateral CCA, he was successfully treated with an ipsilateral subclavian to internal carotid bypass. There is paucity of data regarding the best approach for carotid revascularization in OIS. This case report discusses our unique perioperative decision making as well as relevant literature.

Abstract WMP112: Type 2 Diabetes Dampens Neuroprotection Against Ischemic Injury By Lipopolysaccharide-Induced Preconditioning

Introduction: Evidence suggests that lipopolysaccharide ( LPS ) preconditioning (PC) provides neuroprotection by inducing tolerance to subsequent lethal ischemia. Ischemic tolerance (IT) declines with age, yet it is unclear whether metabolic disease like type 2 diabetes (T2DM) also interfere with IT. The current study sought to determine whether T2DM reduces neuroprotection induced by LPS PC, and the molecular mechanisms underlying the dampened IT. Methods: Male and female diabetic db/db and control db/+ mice (8-10 months of age) were i.p. injected with Toll-like receptor (TLR)4 ligand LPS at 0.2 mg/kg or saline. Stroke was induced 3 days later by permanent distal occlusion of middle cerebral artery and temporary occlusion of ipsilateral common carotid artery for 60 min. Sensory and motor function was evaluated 1 day after stroke by a combination of tests. Infarct size was determined 3 days after stroke following TTC staining. The effect of LPS PC on the phenotypes of leukocytes in the brain parenchyma after stroke was quantified by Fluorescent activated cell sorter (FACS) 2 days after stroke with a panel of markers for subsets of myeloid cells. Transcriptome was determined by RNAseq of isolated monocytes from peripheral blood mononuclear cells. Differentially expressed genes were examined for distinct biological pathways via enrichment analysis. Results: LPS PC significantly reduced infarct in db/+ mice by one third and improved neurological scores, but it did not protect the db/db mice from stroke. FACS data showed that LPS PC reduced the number of Ly6G+ cells in db/+ but not db/db brains, suggesting that LPS PC curbed stroke-induced infiltration of neutrophils in the brain parenchyma. Pathway analysis suggests that diabetic mice exhibited down-regulated pathways in interferon signaling. The expression of Jak-Stat signaling (such as Stat1), MHC antigen presentation (H2A family), and Toll-like receptor (TLR) signaling (such as Irf7) were also reduced in diabetic mice after stroke. Conclusions: The dampened IT in the diabetic mice induced by LPS-PC is associated with increased neutrophil infiltration after stroke compared to control mice. Ongoing studies will seek toovercome the underlying defective molecular mechanisms in T2DM.

Determination of the Unilaterally Damaged Region May Depend on the Asymmetry of Carotid Blood Flow Velocity in Hemiparkinsonian Monkey: A Pilot Study.

The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson's disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.

Laser Speckle Flowmetry for the Prognostic Estimation Study of Permanent Focal Ischemia in Mice

The distal middle cerebral artery occlusion (dMCAO) model that mainly targets the cortex and causes low mortality is developed for the study of permanent focal ischemia, and it is highly appropriate for the study in the aged population. The two most common methods used to establish dMCAO models are dMCAO alone and dMCAO plus ipsilateral common carotid artery occlusion (CCAO). Up to now, studies on the prognosis of the two types of dMCAO models and the accuracy of cerebral blood flow (CBF) in predicting prognosis have not yet been reported. In the present study, we established permanent focal ischemia models in two groups of aged mice by dMCAO alone or by dMCAO plus ipsilateral common carotid artery occlusion (CCAO). CBF was evaluated by laser speckle flowmetry (LSF) before and after surgery. Cerebral infarction was assessed by TTC staining at day 2 after surgery and MAP2 staining at day 21 after surgery. In addition, behavioral outcomes were evaluated using the modified Garcia scoring system, adhesive removal test, and foot-fault test. Our results showed that compared with those in the dMCAO alone group, the mice in the dMCAO plus CCAO group had a larger cerebral infarct size and more severe neurological deficits. According to the results of the correlation analysis, the area of the ischemic core region on CBF imaging in the dMCAO group was helpful in predicting the infarct volume. In addition, the total CBF of the ischemic area in the dMCAO plus CCAO group showed a significant correlation with Garcia scores 3 days after surgery, but there was no significant correlation of CBF imaging with the foot-fault test 7 days after surgery. These results suggest that the total CBF of the ischemic area might be helpful to predict the severity of neurological damage at the acute stage.

Right Vertebral Artery Arising From Ipsilateral Common Carotid Artery With Severe Stenosis of Ostio-proximal Segment of Aberrant Right Subclavian Artery: A Rare Life-Saving Variant

Anomalous origins of vertebral arteries are rare vascular anomalies that are incidentally identified during computed tomography, magnetic resonance imaging, or digital subtraction angiograms. We present the case of a 45-year-old male who had gangrene of the right ring finger associated with absent radial, ulnar, and brachial artery pulses. A computed tomography angiogram of the upper limb including the arch of aorta showed an aberrant right subclavian artery having near-total stenosis at the origin. An anomalous origin of the right vertebral artery from the right common carotid artery was also noted. This incidental variant anomaly of the vertebral artery was vital in this case as it spared the posterior cerebral circulation from vascular insufficiency complications. It is also important for future head and neck endovascular interventions to avoid inadvertent arterial injury.

Abstract WP255: Cyfip2 Genotype Contributes To Variation In Stroke Vulnerability Among C57BL/6 Mouse Substrains

C57BL/6 mouse substrains of the N lineage derived from the NIH colony later than the separation of the Bailey line in the early 1960s show increased stroke vulnerability relative to C57BL/6J. A missense mutation in Cyfip2 , encoding cytoplasmic FMR1 interacting protein 2, is one of several known variants with a corresponding substrain distribution. This study evaluated reciprocal mouse lines in which the N Cyfip2 variant had been either introduced into C57BL/6J (J- Cyfip2 <N>) or corrected in C57BL/6NJ (NJ- Cyfip2 <J>) by CRISPR-Cas9 editing. Stroke was produced by permanent surgical occlusion of the middle cerebral and ipsilateral common carotid arteries under isoflurane anesthesia, and infarct volume was measured as the region of pallor in brain slices incubated with triphenyltetrazolium chloride at 24 hours. Figure illustrates mean ± SEM (group sizes in parentheses) for mice of the current study, along with prior data for parent substrains. Introduction of the N-lineage mutation markedly increased infarct size in both males and females (†) while maintaining the sex difference seen in J mice (*). Correction of the mutation in NJ had no significant effect. At face value these results establish Cyfip2 genotype as an important determinant of stroke vulnerability since the variant alone is sufficient to increase infarct volume in the J background. However, it is not the sole basis for differing stroke outcome among substrains, and at least one other variant must underlie the heterogeneity in sex difference. Cyfip2 encodes a protein with recognized functional roles in brain and the immune system, but the precise intersection with stroke pathology remains to be established.

ORIGIN OF THE LEFT VERTEBRAL ARTERY FROM IPSILATERAL COMMON CAROTID ARTERY IN A HUMAN FETUS: CASE REPORT AND BRIEF REVIEW OF THE LITERATURE

Although the vertebral artery (VA) is a type of artery with a lot of variations, its origin from the common carotid artery (CCA) is one of the rarities that deserves to be presented.Microdissection of injected arteries in the thorax and neck of human fetuses under the operating microscope was used and documented in the workbook and photos. The origin of the left VA from ipsilateral CCA, and its entry into the transverse foramen of the fourth cervical vertebra (C IV), associated with the normal vascular arrangement of branches of the aortic arch were the main features of this case. Simultaneously, the right VA of normal (subclavian) origin entered the C V transverse foramen. A present case of the left VA−CCA variant is the only one discovered in human fetuses, respectively, in total it is the tenth human case in the literature. However, the future findings could show whether the right aortic arch and the carotid stenosis discovered in half of known adult cases can be possible causal and/or consequent abnormalities of the left VA−CCA variant.

A Case of Symptomatic Internal Carotid Artery Stenosis and Concomitant Ipsilateral Chronic Common Carotid Artery Occlusion Treated with Carotid Endarterectomy

A Case of Symptomatic Internal Carotid Artery Stenosis and Concomitant Ipsilateral Chronic Common Carotid Artery Occlusion Treated with Carotid Endarterectomy

Carotid webs produce greater hemodynamic disturbances than atherosclerotic disease: a DSA time–density curve study

BackgroundCarotid webs (CaWs) are associated with ischemic strokes in younger patients without degrees of stenosis that are traditionally considered clinically significant.ObjectiveTo compare the hemodynamic parameters in the internal carotid artery...

Vasoreactivity of the Murine External Jugular Vein and Carotid Artery

Introduction: Impaired venous reactivity has potential to contribute to clinically significant pathologies such as arteriovenous fistula (AVF) maturation failure. Vascular segments commonly used in murine preclinical models of AVF include the carotid artery and external jugular vein. Detailed descriptions of isometric procedures to evaluate function of murine external jugular vein ex vivo have not been previously published. Objective: To establish isometric procedures to measure naive murine external jugular vein reactivity ex vivo. Methods: Vasomotor responses of external jugular veins and ipsilateral common carotid arteries from C57BL/6 mice were evaluated using isometric tension procedures. Results: External jugular veins developed tension (p < 0.05) to potassium chloride and U-46619, but not to phenylephrine, whereas common carotid arteries responded to all 3 agents (p < 0.05). While maximal responses to acetylcholine (ACh) were similar between the venous and arterial segments, the dose required to achieve this value was lower (p < 0.05) in the artery versus vein. Nitric oxide synthase inhibition attenuated (p < 0.05) but did not abolish ACh-evoked vasorelaxation in both vascular segments, whereas cyclooxygenase blockade had no effect. Endothelium-independent vasorelaxation to sodium nitroprusside was similar in the artery and vein. Conclusion: Vasorelaxation and vasocontraction can be reliably assessed in the external jugular vein in C57BL/6 mice using isometric procedures.

Vasoreactivity of the Murine External Jugular Vein and Carotid Artery

Few studies have characterized vasoreactivity of the murine external jugular vein. This segment often is used in preclinical models to evaluate vascular remodeling in response to arteriovenous fistula (AVF) maturation. When an AVF is established, the venous segment is exposed to arterial pressures and disturbed flow patterns that have strong potential to impact vasoreactivity. Before testing this hypothesis in the context of AVF, we sought to establish procedures to comprehensively characterize endothelium‐dependent and vascular smooth muscle function of the carotid artery and external jugular vein from healthy mice. External jugular veins and ipsilateral common carotid arteries were isolated from five‐month‐old male C57BL/6 mice and vasomotor responses were evaluated using isometric tension procedures. External jugular veins developed tension (p&lt;0.05) to the voltage‐gated Ca2+ channel opener potassium chloride (KCl) and the thromboxane A2 receptor agonist U‐46619, but not to the α‐1 receptor agonist phenylephrine (PE), whereas common carotid arteries responded to all three vasocontractile agents in a more robust (p&lt;0.05) manner. While maximal responses (~70%) to the endothelium‐dependent vasodilator acetylcholine (ACh) were similar between the venous and arterial segments, the dose required to achieve this value was lower (p&lt;0.05) in the artery versus the vein. Nitric oxide synthase (NOS) inhibition using L‐NMMA attenuated (p&lt;0.05) but did not abolish ACh‐evoked vasorelaxation in both vascular segments. Endothelium‐independent vasorelaxation to sodium nitroprusside (SNP) was similar in the artery and the vein. Endothelium‐dependent and vascular smooth muscle function can be reliably assessed in the murine external jugular vein of healthy male C57Bl/6 mice. Compared to common carotid arteries, external jugular veins are resistant to PE‐evoked vasocontraction, less responsive to KCl and U‐46619‐evoked vasocontraction, less sensitive to ACh‐evoked vasorelaxation, and equally responsive to NOS inhibition and guanylate cyclase activation via SNP. Ongoing studies will determine if and how external jugular vein function is altered by arterial pressures and disturbed flow patterns that are encountered subsequent to establishing an AVF.Support or Funding InformationJMC (University of Utah Graduate Research Fellowship); YTS (R01DK100505; I01BX004133); JDS (AHA16GRNT31050004, NIH RO3AGO52848, RO1HL141540); TL (R44DK109789, R01HL139692, I01BX003387).

Abstract 114: Diverse Patients Show Physiologic Benefit From Refined Sphenopalatine Ganglion Electrode Placement and Stimulation Level Selection to Augment Blood Flow and Neurologic Function in Acute Ischemic Stroke (The IMPACT-24M Trial)

Background: Two large RCTs have indicated sphenopalatine ganglion (SPG) stimulation reduces 3m disability in acute ischemic stroke patients with confirmed cortical involvement. The current trial evaluated two refinements in SPG stimulation technique: 1) SPG electrode placement with real-time optical tracking guidance; and 2) stimulation intensity comfortable tolerance level (CTL) selection using non-noxious facial physiologic markers. Methods: Single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke &lt;24h, NIHSS 1-6, not receiving recanalization therapies. Stimulation level was based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by volumetric blood flow in the ipsilateral common carotid artery (ultrasound) and affected hand grasp and pinch strength before and during stimulation, and by NIHSS change by day 7. Results: Among 50 enrolled patients, age was median 66y (IQR 60-74), 44% female, NIHSS median 5 (IQR 4-5), and median onset-to-screening time 18h (IQR 9-20). Median implantation skin-to-skin time was 4 minutes (IQR 3-7) and all 50 implants were placed correctly. CTL was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end diastolic blood flow (up 44%, p&lt;0.0001; and up 52%, p&lt;0.0001) and improved pinch strength (up 42%, p&lt;0.0001) and grasp strength (up 26%, p&lt;0.0001). Degree of NIHSS recovery by day 7 was greater than in matched historic controls, median 75% vs 50%, p=0.0003. Forest plot analysis showed benefits were homogenous across the subgroups of: sex, age, time from onset, stroke side, NIHSS, and ASPECTS score. Conclusion: SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of optimal stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG activation led to cranial blood flow augmentation and improved hand motor function during stimulation, and neurologic deficit reduction at 1 week, consistently across broad patient subsets of age, sex, side, severity, and time to treatment.

Abstract WMP40: Cervical Internal Carotid Artery Tortuosity as a Marker of Non-Atherosclerotic Aging: Results From the Northern Manhattan Study (NOMAS)

Background: Cervical internal carotid artery (ICA) tortuosity has been associated with vascular risk and stroke as well as genetic disorders related to abnormal extracellular matrix remodeling. It is plausible that dystrophic or aberrant arterial remodeling may therefore relate to cervical ICA tortuosity. We hypothesized that cervical ICA tortuosity relates to carotid dilatation, but not to traditional ultrasound (US) markers of atherosclerosis. Methods: Subjects of the NOMAS with available time-of-flight MRA were included in our study. Cervical ICA tortuosity was defined as a bend in the distal cervical ICA of &gt; 90° as seen on MRA. We excluded subjects with &lt; 5 cm of the cervical ICA visualized. Distensibility was calculated as the percentage excursion of the right CCA diastolic diameter during systole, which was assessed by high-resolution B-mode US of the right common carotid artery (CCA). We used multivariable logistic regression analyses to estimate odds ratios for the association of cervical ICA tortuosity and Doppler measures of carotid wall aging. Results: We visualized cervical ICA tortuosity in 468 NOMAS participants (mean age 64±8 years, 70% women, 70% Hispanic). It was present in 23% of subjects. In unadjusted models, cervical ICA tortuosity was more common in women (OR 2.34, 95% CI 1.34-4.11), Hispanics (OR 1.85, 95%CI 1.06-3.25) and those with higher diastolic blood pressures (OR per mm Hg 1.04, 95%CI 1.01-1.06), and less common among smokers (OR 0.23, 95%CI 0.07-0.78). In models adjusted for demographic and vascular risks, right CCA tortuosity was associated with ipsilateral larger CCA DD (OR 1.42, 95%CI 1.02-1.96) and borderline associated with lower distensibility (OR 0.94, 95%CI 0.87-1.01, P=0.06) but not with ipsilateral ICA IMT (OR 0.26, 95%CI 0.14-4.77), number of plaques (OR 1.08, 95%CI 0.76-1.53), maximum plaque thickness (OR 0.96, 95%CI 0.73-1.27), or plaque area (1.00, 95%CI 0.97-1.05). Conclusions: Cervical ICA tortuosity associates with ipsilateral cervical ICA dilatation and lower distensibility, but not with traditional US markers of atherosclerosis. The association with diastolic blood pressure suggests a role of steady, rather than pulsatile, hemodynamics in aberrant cervical ICA remodeling.

Suitable methods of measuring acceleration time in the diagnosis of internal carotid artery stenosis

PurposeTo enhance the utility of acceleration time (AcT) in the diagnosis of internal carotid artery (ICA) stenosis, we assessed the value of AcT measurements with different waveform patterns.MethodsNinety-three patients with acute atherothrombotic cerebral infarction were enrolled, and they underwent both carotid ultrasonography and digital subtraction angiography (DSA). AcT was determined by a conventional procedure (using the first peak point or the bending point) and the peak systolic velocity (PSV) procedure. The AcT ratio was calculated as (AcT of ICA)/(AcT of the ipsilateral common carotid artery). We evaluated the correlation of stenosis rate as assessed by the North American Symptomatic Carotid Endarterectomy Trial method using DSA (DSA-NASCET) with the AcT of ICA (ICA-AcT), the AcT ratio measured by the conventional procedure (conventional AcT ratio), and the AcT ratio measured by the PSV procedure (PSV AcT ratio). The area under receiver operating characteristic curves (AUC) for DSA-NASCET was calculated based on the ICA-AcT and AcT ratio.ResultsForty-five vessels had 50% or greater ICA stenosis. DSA-NASCET was positively correlated with the conventional AcT ratio (r = 0.723), conventional ICA-AcT (r = 0.638), and PSV AcT ratio (r = 0.245). The corresponding AUCs for ICA stenosis ≥ 50% were 0.971, 0.886, and 0.572, respectively.ConclusionWe demonstrated the usefulness of the conventional procedure for diagnosing stenosis of ICA origin using AcT and showed that the AcT ratio was a more beneficial parameter than AcT.

Refined Sphenopalatine Ganglion Stimulator Placement and Intensity Setting to Augment Blood Flow and Neurologic Function.

Background and Purpose- Two large, randomized trials indicated that sphenopalatine ganglion (SPG) stimulation improves final disability outcome in acute anterior circulation patients with ischemic stroke with confirmed cortical involvement. This study evaluated 2 refinements in SPG stimulation treatment technique: (1) SPG electrode placement with real-time optical tracking guidance; and (2) stimulation intensity comfortable tolerance level selection using non-noxious facial physiological markers. Methods- This study was a single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke, National Institutes of Health Stroke Scale 1 to 6 including arm weakness subitem score ≥1, not receiving recanalization therapies, and within 24 hours of onset. Stimulation level was set based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by measuring volumetric blood flow in the ipsilateral common carotid artery by ultrasound and grasp and pinch strength in the affected hand before and during stimulation, and by change in National Institutes of Health Stroke Scale from day 1 to 7. Results- Among 50 enrolled patients, age was median 66 years (interquartile range, 60-74), 44% were female, National Institutes of Health Stroke Scale median was 5 (interquartile range, 4-5), and median onset-to-screening time was 18 hours (interquartile range, 9-20). Median implantation skin-to-skin time was 4 minutes (interquartile range, 3-7), and all 50 implants were placed correctly. Comfortable tolerance level was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end-diastolic blood flow (44%, P<0.0001; and 52%, P<0.0001) and improved pinch strength (42%, P<0.0001) and grasp strength (26%, P<0.0001). Degree of National Institutes of Health Stroke Scale recovery by day 7 was greater than in matched historic controls, median 75% versus 50%, P=0.0003. Conclusions- SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG stimulation led to cervico-cranial blood flow augmentation and improved hand motor function. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03551093.

Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke

BackgroundStroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016).MethodsTransient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses.ResultsWe now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair.ConclusionsTaken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.

Concomitant ipsilateral carotid endarterectomy and stenting is an effective treatment for tandem carotid artery lesions

ObjectiveData regarding the treatment of tandem carotid artery lesions at the bifurcation and ipsilateral, proximal common carotid artery (CCA) are limited. It has been suggested that concomitant treatment with carotid endarterectomy (CEA) and proximal ipsilateral carotid artery stenting confers a high risk of stroke and death. The objective of this study was to evaluate the technique and outcomes of this hybrid procedure at a single institution. MethodsA retrospective chart review was performed including patients who underwent CEA + ipsilateral carotid artery stenting for treatment of atherosclerotic carotid artery disease between December 2007 and April 2017. Primary endpoints were postoperative myocardial infarction, neurologic event, and perioperative mortality. ResultsTwenty-two patients (15 male [68%]) underwent CEA + ipsilateral carotid artery stenting with a mean follow-up of 67 ± 77 months. The mean age was 70.0 ± 6.1 years old, all with a prior smoking history (eight current smokers [64%]). Twelve patients (55%) were treated for symptomatic disease and three had a prior ipsilateral CEA (one also with CAS). Computed tomographic angiography imaging was performed preoperatively in 21 patients (95%). CEA was performed first in 18 patients (82%) followed by ipsilateral carotid artery stenting. CEA was performed with a patch in 20 and eversion endarterectomy in two patients. Ipsilateral CCA was stented in 21 patients (96%) and one innominate was stented in a patient with a right CEA. Additional endovascular interventions were performed in three patients: 1 innominate stent, 1 distal ipsilateral internal carotid artery stent, and 1 right subclavian artery stent. All proximal stents were placed with sheath access through the endarterectomy patch in 12 (55%), CCA in 7 (32%), and through the arteriotomy before patching in 3 (14%). Distal internal carotid artery clamping was performed in 18 (90%, available 20) of patients before ipsilateral carotid artery stenting. All proximal lesions were successfully treated endovascularly with no open conversion. One dissection was created and treated effectively with stenting. One perioperative stroke (4.5%) occurred in a patient treated for symptomatic disease, 1 postoperative myocardial infarction (4.5%), and 2 patients (9.1%) with cranial nerve injuries. There was one patient who expired within 30 days, shortly after discharge for unknown reasons. The mean length of stay was 2.6 ± 2.0 days. ConclusionsIn appropriately selected patients, concomitant CEA and ipsilateral carotid artery stenting can be safely performed in high-risk patients with a low risk of myocardial infarction, neurologic events, and perioperative mortality when careful surgical technique is used, using direct carotid access, and distal carotid clamping for cerebral protection before stenting.