Cerebral Collateral Flow Research Articles

Association between heart failure and cerebral collateral flow in large vessel occlusive ischemic stroke

BackgroundCerebral collateral circulation plays a crucial role in determining the extent of brain ischemia in large vessel occlusive (LVO) stroke. Heart failure (HF) is known to cause cerebral hypoperfusion, yet the relationship between HF and robustness of collateral flow has not been well described. MethodsConsecutive patients with middle cerebral and/or internal carotid LVO who underwent endovascular thrombectomy (EVT) between 2012 and 2020 were included. Single-phase head CTA prior to EVT was used to assess collateral status (poor <50 % filling; good ≥50 %). Classification of HF by left ventricular ejection fraction (LVEF) on echocardiogram was used where HF with reduced ejection fraction (HFrEF) had LVEF ≤40 %, HF with preserved EF (HFpEF) had LVEF ≥50 % with evidence of structural heart disease, and no HF had LVEF≥50 % without structural heart disease. Multivariable logistic regression analyses were performed to evaluate the association between HF and poor collaterals. ResultsWe identified 235 patients, mean age was 69 ± 15 years; initial NIHSS was 18 ± 7. Of these, 107 (45.5 %) had HF and 105 (44.7 %) had poor collaterals. Those with HF were likely to have poor collaterals compared to those without HF (56.1 % vs 35.2 %, P = 0.001). There was a dose-dependent relationship between EF and poor collaterals: adjusted odds of poor collaterals were 1.63 and 2.45 in HFpEF and HFrEF, compared to those without HF (trend P = .018). ConclusionPatients with HFrEF are more likely to have poor cerebral collaterals. Further study is needed to explore the pathomechanisms. Optimization of HF may improve cerebral collaterals and enhance EVT outcomes.

Factors affecting functional independence and recanalization in acute stroke patients undergoing mechanical thrombectomy and the importance of cerebral collateral flow

Factors affecting functional independence and recanalization in acute stroke patients undergoing mechanical thrombectomy and the importance of cerebral collateral flow

Drug-induced arterial hypertension in a patient with ischemic stroke

Progressive ischemic stroke is the most frequent form of stroke with neurologic deterioration. The pathogenesis of progressive ischemic stroke is based on the expansion of the brain infarction zone and reduction of the "penumbra" zone in the area of focal ischemia. The leading role in maintaining the balance between irreversible and reversible ischemia belongs to cerebral collateral blood flow. Being a multifactorial phenomenon, collateral blood flow is caused by both morphological and functional characteristics of the collateral arterial channel and systemic factors, among which hemodynamics is of great importance. The tactic of purposeful increase in blood pressure to improve cerebral perfusion is called drug-induced arterial hypertension. A number of experimental studies have demonstrated the safety and efficacy of this method, but the small number and heterogeneity of data in the studies do not allow us to conduct a meta-analysis and form an optimal protocol for drug-induced arterial hypertension. In this article we want to describe the clinical observation of a patient with ischemic stroke on the background of critical stenosis of stroke-related internal carotid artery and atrial fibrillation, in the treatment of which we applied drug-induced arterial hypertension.

Impact of cerebral collateral flow on stroke outcomes after carotid stenting.

Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; − 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Worsened Stroke Outcome in a Model of Preeclampsia is Associated With Poor Collateral Flow and Oxidative Stress.

Preeclampsia increases the incidence of maternal stroke, a devastating condition that is on the rise. We investigated stroke outcome in a model of experimental preeclampsia with and without treatment with clinically relevant doses of magnesium sulfate (experimental preeclampsia+MgSO4) compared to normal late-pregnant and nonpregnant rats. Transient middle cerebral artery occlusion was used to induce focal stroke for either 1.5 or 3 hours. Infarct volume and hemorrhagic transformation were determined as measures of stroke outcome. Changes in core middle cerebral artery and collateral flow were measured by dual laser Doppler. The relationship between middle cerebral artery perfusion deficit and infarction was used as a measure of ischemic tolerance. Oxidative stress and endothelial dysfunction were measured by 3-nitrotyrosine and 8-isoprostane, in brain and serum, respectively. Late-pregnant animals had robust collateral flow and greater ischemic tolerance of brain tissue, whereas experimental preeclampsia had greater infarction that was related to poor collateral flow, endothelial dysfunction, and oxidative stress. Importantly, pregnancy appeared preventative of hemorrhagic transformation as it occurred only in nonpregnant animals. MgSO4 did not provide benefit to experimental preeclampsia animals for infarction. Stroke outcome was worse in a model of preeclampsia. As preeclampsia increases the risk of future stroke and cardiovascular disease, it is worth understanding the influence of preeclampsia on the material brain and factors that might potentiate injury both during the index pregnancy and years postpartum.

Abstract WMP67: Cerebral Collateral Flow State Correlates With Stroke Severity And Functional Outcomes

Introduction: Hypoperfusion index ratio (HIR) measured by computerized tomography perfusion (CTP) has been shown to predict collateral flow state in acute ischemic stroke (AIS). Low HIR (&lt;0.4) is indicative of good collateral flow state. Hypothesis: Good collateral flow state correlates with lower stroke severity and better clinical outcome at discharge. Methods: Data from AIS patients who underwent CTP during initial stroke evaluation were linked with Get With the Guideline database in a comprehensive stroke center between 2018 and 2020. Patients with good collateral flow (HIR&lt;0.4) were compared to those with poor collateral flow (≥0.4) group. They were stratified based on modified Rankin Score (mRS) at discharge into good outcome (mRS 0-2) or poor outcome (mRS 3-6). In addition to demographics, and risk factors data was collected on the initial stroke severity using the NIH stroke scale (NIHSS). Continuous variables were compared using t-test (parametric) and Mann-Whitney U test (non-parametric). Univariate and multivariable analyses (multiple logistic regression) were used to test the association between good collateral flow state and good discharge outcome. Results: CT perfusion data was obtained in 1442 patients, after excluding patients who underwent thrombectomy and all non-vascular etiologies of stroke like presentation, there was 890 patients (age 68±14, 52% male, 50% white, 50% black/others), of who 756 (85%) demonstrated good collateral flow and 134 (15%) showed poor collateral flow. Those with good collateral flow were younger (68±14 vs. 70±15, p=0.07) and lower median NIHSS (6 IQR 3-10 vs. 13 IQR 6-18, p&lt;0.001). Good collateral flow was associated with good outcome on discharge (OR 2.2, 95% CI 1.5-3.3). The association remained significant after adjustment for age, gender, race, hypertension, diabetes, coronary artery disease, congestive heart failure and atrial fibrillation (adjusted OR 2.2 (1.4-3.3). Conclusions: In patients presenting with AIS, good collateral flow state was associated with lower stroke severity. It was independently associated with good outcome after adjustment for several comorbidities. Based on our study results, CT perfusion imaging may have utility in predicting stroke severity and discharge outcome.

Correlation between Serum Erythropoietin and Cerebral Collateral Flow in Acute Ischemic Stroke Patient.

Erythropoietin (EPO), which is associated with anemia, exerts neuroprotective effects in ischemic stroke. In cases of stenosis or narrowing of the main cerebral blood vessel, the prognosis is favorable if collateral blood circulation is well developed in acute stroke. Several studies have investigated the relationship between EPO administration and stroke outcomes. The present study investigated the correlation between serum EPO level and cerebral collateral circulation, which could result in favorable clinical outcomes. The study subjects were patients diagnosed with acute ischemic stroke who underwent initial brain magnetic resonance imaging between January 2020 and March 2022. Following brain computed tomography perfusion for collateral flow, serum EPO levels were measured. Collaterals were assessed according to the Mass system and divided into good collateral (GC) or poor collateral (PC) groups. Serum EPO levels were determined using a chemiluminescence immunoassay method. A correlation coefficient analysis was conducted to determine the correlation between serum EPO levels and GC. A receiver operating characteristic curve analysis determined the cutoff value of EPO for GC. Serum EPO levels were significantly higher in the GC than that in the PC group (P<0.05). The cut-off level of serum EPO for a good outcome was 9.1 mIU/mL. A high serum EPO (>9.1 mIU/mL) could be a marker of GC in patients with acute ischemic stroke that predicts good clinical outcomes.

The determinants of collateral circulation status in patients with chronic cerebral arterial circle occlusion: A STROBE Study.

The condition of collateral pathways is an important predictor of stroke prognoses; however the major determinants of collaterals are still unknown. The purpose of this study is to identify potentially determinants for collateral circulation status in patients with chronic occlusion of cerebral arterial circle.All patients with chronic occlusion of either unilateral internal carotid artery or middle cerebral artery M1 or M2 segment, diagnosed by digital subtraction angiography at the neurology department of the First Medical Centre of Chinese PLA General Hospital from January 2015 to December 2017, were retrospectively collected in our sample. After screening according to inclusion and exclusion criteria, the patients’ relevant clinical data were collected and analyzed. Collateral circulations were assessed by 2 independent raters using the American society of interventional and therapeutic neuroradiology/society of interventional radiology flow-grading system.Baseline characteristics (n = 163): our sample consists of 116 (71.2%) male and 47 (28.8%) female patients with an average age of 57.5 ± 11.9 years. Cerebral collateral flow was poor in 59 (36.2%) patients. Our univariate analyses showed that poor collateral circulation was associated with lower high-density lipoproteins cholesterol (HDL), elevated homocysteine levels, aging and hyperlipidemia. A multivariate analysis identified HDL, homocysteine levels and ageing as major predictors for collateral circulation status. In the subgroup analysis, the HDL contributed to collateral angiogenesis internal carotid artery occlusion group. In the middle cerebral artery occlusion group, the homocysteine and ageing were related to the poor collateral status.Low HDL, high levels of homocysteine and ageing are identified as possible risk factors for a poor collateral vessel blood flow in patients with chronic anterior circulation occlusion.

Association of Systolic Blood Pressure and Cerebral Collateral Flow in Acute Ischemic Stroke by Stroke Subtype.

Background and PurposeCollateral flow in acute ischemic stroke is known as a predictor of treatment outcome and long-term prognosis. However, factors determining the initial collateral flow remain unclear. We investigated factors related to collateral flow in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke etiology.MethodsThis was a retrospective study using prospective stroke registry data from a single university hospital from October 2014 to May 2021. AIS-LVO with middle cerebral artery M1 occlusion identified by pre-treatment multiphasic computed tomography angiography was included. Collateral flow score was graded on a 6-point ordinal scale according to pial arterial filling.ResultsA total of 74 patients [cardioembolism (CE): 57; large artery atherosclerosis (LAA): 17] was included. The mean age of all patients was 72.2 ± 11.7 years, and 37.8 % (n = 28) were men. Multivariate regression analysis showed that initial SBP [odds ratio (OR): 0.994; 95% confidence interval (CI): 0.990–0.998; p = 0.002] and stroke etiology (OR: 0.718; 95% CI: 0.548–0.940; p = 0.019) were independent factors of the collateral flow grade. Collateral flow grade was independently associated with initial SBP in the CE group (OR: 0.993; 95% CI: 0.989–0.998; p = 0.004) but not in the LAA group (OR: 0.992; 95% CI: 0.980–1.004; p = 0.218). Initial SBP was significantly correlated with NIHSS score in the CE group but not in the LAA group (r2= 0.091, p = 0.023; r2 = 0.043, p = 0.426, respectively).ConclusionsElevated initial SBP was associated with poor cerebral collateral flow and more severe symptoms in the CE group, but not in the LAA group in patients with AIS-LVO. These findings suggest differential effects of initial SBP elevation on collateral flow by stroke subtypes.

Extremely low frequency electromagnetic stimulation reduces ischemic stroke volume by improving cerebral collateral blood flow

Extremely low frequency electromagnetic stimulation (ELF-EMS) has been considered as a neuroprotective therapy for ischemic stroke based on its capacity to induce nitric oxide (NO) signaling. Here, we examined whether ELF-EMS reduces ischemic stroke volume by stimulating cerebral collateral perfusion. Moreover, the pathway responsible for ELF-EMS-induced NO production was investigated. ELF-EMS diminished infarct growth following experimental stroke in collateral-rich C57BL/6 mice, but not in collateral-scarce BALB/c mice, suggesting that decreased lesion sizes after ELF-EMS results from improved collateral blood flow. In vitro analysis demonstrated that ELF-EMS increased endothelial NO levels by stimulating the Akt-/eNOS pathway. Furthermore, ELF-EMS augmented perfusion in the hind limb of healthy mice, which was mediated by enhanced Akt-/eNOS signaling. In healthy C57BL/6 mouse brains, ELF-EMS treatment increased cerebral blood flow in a NOS-dependent manner, whereas no improvement in cerebrovascular perfusion was observed in collateral-sparse BALB/c mice. In addition, ELF-EMS enhanced cerebral blood flow in both the contra- and ipsilateral hemispheres of C57BL/6 mice subjected to experimental ischemic stroke. In conclusion, we showed that ELF-EMS enhances (cerebro)vascular perfusion by stimulating NO production, indicating that ELF-EMS could be an attractive therapeutic strategy for acute ischemic stroke by improving cerebral collateral blood flow.

Abstract 1122‐000181: Collateral Circulation in Ischemic Stroke is Not Determined by Anatomical Variants of the Cerebral Arteries

Introduction : In acute ischemic stroke, collateral circulation determines tissue fate and treatment results. The aim of this study was to evaluate the role of anatomical variations of the Circle of Willis (CoW) in formation of cerebral collateral blood flow in patients with acute M1 occlusion. Methods : This study was a retrospective assessment of radiological examinations of patients with stroke due to middle cerebral artery M1 segment occlusion. All patients underwent mechanical thrombectomy from January 2015 until March 2021. The anatomy of the CoW was assessed on initial CT‐angiography and DSA. CTA was utilized to grade cranial collateral vasculature status and cortical vein opacification score (COVES). Non‐contrast CT scans and ASPECTS scores (using RAPID software) were used to determine the ischemic area. Results : A total of 100 patients were included in the analysis (58 females and 42 males, mean age: 71.6 +/‐ 13.9). We classified the anatomy of the CoW according to its continuity as a full circle. Patients with fully continuous CoW (n = 19) had worse COVES scores than those with CoW incomplete at both anterior and posterior portion (n = 9) (89% vs 68% with COVES 0–2, p = 0.179). No statistically significant results were found when comparing the enhancement of collaterals between these two groups (p = 0.390). The COVES scores were similar for patients with complete and incomplete anterior portions of CoW (77% vs 80% with COVES 0–2, p = 0.812). Patients with incomplete posterior portions of CoW had lower COVES scores than those with complete (80% vs 67% with COVES 0–2, p = 0.206). No statistically significant differences were discovered when comparing different types of the posterior communicating artery (adult, transitional and fetal). Analysis of ischemic areas determined as ASPECTS scores pre‐ and post‐thrombectomy yielded no significant differences between any of the groups. Conclusions : Although certain variants of the CoW have been reported to increase the risk of ischemic stroke, our results show that the anatomy of CoW has no large effect on collateral blood flow during acute M1 occlusion. We presume that the greater role is played by pial arterioles than anatomical variants of major cerebral arteries in cerebral collateral circulation formation. Detailed knowledge about the factors that influence collateral blood flow is crucial as it may aid in identification of patients prone to worse outcomes of ischemic stroke. Anatomical variants of CoW do not play a major role in formation of cerebral collaterals.

Cerebral Collateral Flow State in Acute Ischemic Stroke Correlates with Clinical Functional Outcome (4481)

Cerebral Collateral Flow State in Acute Ischemic Stroke Correlates with Clinical Functional Outcome (4481)

Progress towards optimizing blood pressure control after reperfusion therapy for acute ischemic stroke.

Managing hypertension after acute stroke has been a longstanding, and still ongoing, controversy. On the one hand, clinical studies are near consistent in showing positive relations between increasing blood pressure (BP) and adverse outcomes in both acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH), which supports pathophysiological mechanisms of hypertension-induced endothelial stress and blood-brain barrier disruption.1 Conversely, randomized controlled trials of BP lowering have shown variable results in mixed and pathologically distinct stroke subtypes,2-4 which has fuelled debate over the potential for adverse effects of such treatment when cerebral autoregulation and collateral blood flow are disrupted by ischemia.

Right watershed cerebral infarction following neck cannulation for veno-arterial extracorporeal membrane oxygenation in pediatric septic shock: a case series.

Children supported by extracorporeal membrane oxygenation present a high risk of neurological complications. Although carotid cannulation is known to be associated with neurologic injury, conflicting data exist with regard to the predominance of right- or left-sided lesions. We describe here two infants requiring veno-arterial extracorporeal membrane oxygenation for septic shock who encountered right watershed infarction ipsilateral to carotid artery cannulation. Hemodynamic failure seems to be the most probable underlying mechanism. The asymmetry of transcranial Doppler metrics in one case and the low right regional cerebral oxygen saturation value observed soon after right cannulation in both cases suggest an insufficient cerebral collateral flow compensation. The risk of ipsilateral watershed injury should be considered before cervical cannulation, notably in the context of sepsis and an evaluation of the cerebral collateral blood flow before and just after cannulation may be interesting in order to identify infants with higher risk of ipsilateral ischemic lesions.

The Value of ADAMTS13 in Predicting Clinical Outcomes in Patients With Acute Ischemic Stroke Receiving Thrombolysis.

Objective: To determine the association between baseline ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) antigen level and 90-days clinical outcome in patients with acute ischemic stroke (AIS) receiving recombinant tissue plasminogen activator (rt-PA) thrombolysis.Methods: AIS patients receiving rt-PA thrombolytic therapy from Huashan Hospital and Fifth People's Hospital of Shanghai, China in 2014–2017 were consecutively enrolled. Blood samples for ADAMTS13 tests were drawn before intravenous rt-PA administration. The primary outcome was defined as the poor functional outcome of modified Rankin Scale (mRS) >2 at 90-days follow-up. Secondary outcome was hemorrhagic transformation after rt-PA therapy. Moreover, for AIS patients with large vessel occlusion from Huashan Hospital, the association between baseline ADAMTS13 level and cerebral collateral flow was also assessed.Results: A total of 163 AIS patients (median age 66.2 years, 63.8% male) were included. Baseline ADAMTS13 level was marginally decreased in patients with 90-days mRS >2 than in those with mRS ≤ 2 (mean ± SD, 1458.4 ± 323.3 vs. 1578.3 ± 395.4 ng/mL, p = 0.046). However, no difference of ADAMTS13 level was found after adjusting for age, history of atrial fibrillation, glycemia, baseline NIHSS score and TOAST classification (p = 0.43). We found no difference in ADAMTS13 level between patients with parenchymal hemorrhage after rt-PA therapy and those without (p = 0.44). Among 66 patients with large vessel occlusion, there was also no association between ADAMTS13 level and cerebral collateral flow in multivariable analyses.Conclusion: In our cohort, blood ADAMTS13 antigen level before rt-PA therapy could not be used as an independent biomarker in predicting clinical outcomes of AIS patients at 90 days.

Assessment of Cerebral Collateral Flow With Single-Phase Computed Tomography Angiography-Based Multimodal Scales in Patients With Acute Ischemic Stroke.

Assessing collateral status is important in acute ischemic stroke (AIS). The purpose of this study was to establish an easy and rapid method for evaluating collateral flow. A total of 60 patients with AIS were enrolled. The patients were aged 18 to 85 years with endovascular therapy treatment within 10 hours after the appearance of stroke symptoms, prestroke modified Rankin Scale ≤1, Alberta Stroke Program Early CT Score ≥6, and the occlusion of large vessels in anterior circulation. We reformed imaging strategies by conducting a small-dose group-injection test before normal computed tomography angiography (CTA) scanning and selected the visual collateral score and the regional leptomeningeal score scales as the single-phase CTA collateral flow assessment scales with the replacement of the parasagittal anterior cerebral artery territory by anterior cerebral artery regions adjacent to the longitudinal fissure and then verified, respectively, the consistencies between the 2 single-phase CTA-based collateral scales and the digital subtraction angiography (DSA)-based American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale and compared the prognosis of endovascular therapy between the AIS patients in the poor-collateral-flow group and the other patients' group assessed by 2 single-phase CTA-based collateral scales. There was a high consistency between the 2 single-phase CTA-based collateral flow scales with DSA-based American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale. The assessment by using CTA-based collateral flow assessment methods generated consistent results. The single-phase CTA-based visual collateral score scale and regional leptomeningeal score scale can be used as the imaging evidence for the evaluation of collateral flow in AIS patients in the majority of grassroots hospitals where DSA is difficult to carry out.

An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial

Sphenopalatine ganglion stimulation increased cerebral collateral blood flow, stabilised the blood-brain barrier, and reduced infarct size, in preclinical models of acute ischaemic stroke, and showed potential benefit in a pilot randomised trial in humans. The pivotal ImpACT-24B trial aimed to determine whether sphenopalatine ganglion stimulation 8-24 h after acute ischaemic stroke improved functional outcome. ImpACT-24B is a randomised, double-blind, sham-controlled, pivotal trial done at 73 centres in 18 countries. It included patients (men aged 40-80 years and women aged 40-85 years) with anterior-circulation acute ischaemic stroke, not undergoing reperfusion therapy. Enrolled patients were randomly assigned via web-based randomisation to receive active sphenopalatine ganglion stimulation (intervention group) or sham stimulation (sham-control group) 8-24 h after stroke onset. Patients, clinical care providers, and all outcome assessors were masked to treatment allocation. The primary efficacy endpoint was the difference between active and sham groups in the proportion of patients whose 3-month level of disability improved above expectations. This endpoint was evaluated in the modified intention-to-treat (mITT) population (defined as all patients who received one active or sham treatment session) and the population with confirmed cortical involvement (CCI) and was analysed using the Hochberg multi-step procedure (significance in both populations if p<0·05 in both, and in one population if p<0·025 in that one). Safety endpoints at 3 months were all serious adverse events (SAEs), SAEs related to implant placement or removal, SAEs related to stimulation, neurological deterioration, and mortality. All patients who underwent an attempted sphenopalatine ganglion stimulator or sham stimulator placement procedure were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00826059. Between June 10, 2011, and March 7, 2018, 1078 patients were enrolled and randomly assigned to either the intervention or the sham-control group. 1000 patients received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the mITT population (481 [48%] received sphenopalatine ganglion stimulation, 519 [52%] were sham controls), among whom 520 (52%) patients had CCI on imaging. The proportion of patients in the mITT population whose 3-month disability level was better than expected was 49% (234/481) in the intervention group versus 45% (236/519) in the sham-control group (odds ratio 1·14, 95% CI 0·89-1·46; p=0·31). In the CCI population, the proportion was 50% (121/244) in the intervention group versus 40% (110/276) in the sham-control group (1·48, 1·05-2·10; p=0·0258). There was an inverse U-shaped dose-response relationship between attained sphenopalatine ganglion stimulation intensity and the primary outcome in the CCI population: the proportion with favourable outcome increased from 40% to 70% at low-midrange intensity and decreased back to 40% at high intensity stimulation (p=0·0034). There were no differences in mortality or SAEs between the intervention group (n=536) and the sham-control group (n=519) in the safety population. Sphenopalatine ganglion stimulation is safe for patients with acute ischaemic stroke 8-24 h after onset, who are ineligible for thrombolytic therapy. Although not reaching significance, the trial's results support that, among patients with imaging evidence of cortical involvement at presentation, sphenopalatine ganglion stimulation is likely to improve functional outcome. BrainsGate Ltd.

The blood pressure paradox in acute ischemic stroke.

To explore the association of poststroke baseline blood pressure with cerebral collateral flow and functional outcome in acute ischemic patients with large vessel occlusion/stenosis. Patients identified with large vessel occlusion/stenosis with baseline multimodal computed tomography, follow-up imaging, and complete clinical profiles were included. A 90-day modified Rankin Scale of 0-1 was defined as an excellent functional outcome. Cerebral collateral flow was quantified by the volume ratio of tissue within the delay time >3 seconds perfusion lesion with severely delayed contrast transit (delay time >3 seconds/delay time >6 seconds). There were 306 patients included in this study. With every increase of 10 mmHg in baseline systolic blood pressure, the odds of achieving an excellent functional outcome decreased by 12% in multivariate analysis (odds ratio = 0.88, p = 0.048). Conversely, increased baseline blood pressure was associated with better collateral flow. In subgroup analysis of patients with major reperfusion, higher blood pressure was associated with decreased infarct growth and a better clinical outcome, and vice versa in patients without reperfusion. Higher baseline blood pressure in acute ischemic stroke patients with large vessel occlusion/stenosis was associated with better collateral flow. However, for patients without reperfusion, higher baseline blood pressure was associated with increased infarct growth, leading to an unfavorable clinical outcome. The relationship between blood pressure and outcomes is highly dependent on reperfusion, and active blood pressure-lowering treatment may be inappropriate in acute ischemic stroke patients prior to reperfusion treatment. ANN NEUROL 2019;85:331-339.

Abstract WP88: Relationship Between Small Vessel Ischemic White Matter Disease and Collateral Recruitment in Patients With Acute Embolic Ischemic Stroke

Introduction: White matter hyperintensities (WMH) is the most prominent neuroimaging feature of small vessel disease (SVD). SVD is thought to be a result of arteriolosclerosis, chronic hypoperfusion of white matter, selective oligodendrocyte death and degeneration of myelinated fibers. The risk of ischemic stroke is significantly increased with the presence of WMH. The presence of intracranial collaterals is a strong predictor of salvageable neurological function in acute stroke; however, the factors affecting the ability to recruit collaterals are poorly understood. We wanted to study if the presence and severity of small vessel white matter disease had an adverse effect on cerebral collateral flow in acute embolic large vessel stroke. Methods: We identified a consecutive series of adult subjects with acute embolic large vessel strokes confirmed on CT angiography (CTA) from a 10-year institutional database. Patients without a brain MRI within six months of CTA were excluded. Collateral scores of the affected hemisphere were calculated on CTA using the modified Tan scale (0-4) by two independent trained reviewers and confirmed by a neuroradiologist. The WMH was quantified using the Fazekas scale (0-3) incorporating both deep and periventricular components. Areas of restricted diffusion on brain MRI in the peri-stroke period were eliminated from the assessment of Fazekas score. Spearman’s correlation tests were performed for the association between collateral scores and WMH. Results: A total of 234 patients (mean age 70±14 years, 47% [110/234] women) satisfied the inclusion criteria. The prevalence of periventricular and deep WMH was 83% and 87% respectively. Aging had a significant impact on periventricular WMH (r=0.48, p &lt;0.001) and deep WMH (r=0.47, p &lt;0.001). However, collateral scores exhibited no statistically significant relationship with the presence or severity of periventricular scores (r=0.08, p=0.17) or deep WMH scores (r=0.01, p=0.77). Conclusions: Our results indicate that the presence of SVD does not affect cerebral collateral flow. The vascular niche and risk factors of SVD appear to be distinct from that of intracranial vessels responsible for collateral reperfusion of ischemic territory in acute large vessel embolic stroke.