Leptomeningeal Collateral Flow Research Articles

Collateral status, hyperglycemia, and functional outcome after acute ischemic stroke

BackgroundMixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial.MethodsIn this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05.ResultsAmong the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37–16.0).ConclusionsIn a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke.Trial registrationClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

Role of Head Position in Stroke Outcome: An Observational Study from Tertiary Care Hospital in Pakistan

Background and Aim: Acute ischemic stroke patients mainly rely on cerebral blood flow (CBF) to sustain penumbral tissue perfusion in turn depend on arterial blood pressure in affected cerebral autoregulation. Head positioning either sitting-up or lying flat allows gravitational force to enhance leptomeningeal circulation and collateral blood flow. The present study aimed to determine the role of head position in acute ischemic stroke patients. Methodology: This prospective observational study was conducted on 500 stroke patients in the Department of Neurology and Medical department of Fauji Foundation Hospital, Rawalpindi from January 2020 to December 2021. Patients with acute ischemic stroke receive care in either a lying flat on bed or sitting-up position with elevated head position at 30 to 45 degrees. The designated position was established shortly after hospital admission and was held for 24 hours. Outcomes such as pneumonia, aspiration pneumonia, and increased hospital stay, disability, and mortality were associated with flat head position and elevated head position. Modified Rankine scale (0-6) was used for assessing the degree of disability as a primary outcome in three months. Rankine scale higher score indicates the greater disability and maximum score 6 indicate mortality. Results: The average time from initiation of assigned position and onset of ischemic stroke symptoms was 14 hours (IQR 5-35). Patients in the sitting position group (93%, p&lt;0.001) were more likely than the lying-flat group (82%, p&lt;0.001) in maintaining their position for 24 hours. Based on a modified Rankine scale, both lying flat and sitting-up position groups had no significant differences in a proportional-odds model in terms of 90-days disability outcomes distribution. The mortality rate in lying flat and sitting-up position was 6.8% and 6.9% (p=0.79). Also, both groups had no significant differences in terms of severe outcomes including pneumonia. Conclusion: The present study found that disability outcomes in acute stroke patients were similar irrespective of their position either flat or sitting position with head elevated at 30 to 45 degree for 24 hours. The prevalence of AIS was 95.6%. Keywords: Head position, Acute ischemic stroke, Outcomes

Association of distal hyperintense vessel sign and recurrent stroke in patients with symptomatic intracranial stenosis

ObjectiveThe distal hyperintense vessel sign (DHV) on fluid-attenuated inversion recovery magnetic resonance image (MRI) is an imaging biomarker of slow leptomeningeal collateral flow in the presence of large artery stenosis or occlusion reflecting impaired cerebral hemodynamics. In this study, we aim to investigate the significance of the DHV sign in patients with symptomatic ≥ 70% intracranial atherosclerotic stenosis. MethodsWe retrospectively reviewed patients with ischemic stroke or transient ischemic attack admitted to a single center from January 2010 to December 2017. Patients were included if they had symptomatic ≥ 70% atherosclerotic stenosis of the intracranial internal carotid artery or middle cerebral artery. The presence of the DHV sign was evaluated by blinded neuroradiologist and vascular neurologists. Recurrent ischemic stroke in the vascular territory of symptomatic intracranial artery was defined as new neurological deficits with associated neuroimaging findings during the follow up period. ResultsA total of 109 patients were included in the study, of which 55 had DHV sign. Average duration of follow up was 297 ± 326 days. Four patients were lost during follow up. Patients with the DHV sign had a higher rate of recurrent ischemic stroke (38%), compared to patients without the DHV sign (17%; p=0.018). In multivariate regression analysis, the presence of DHV sign was an independent predictor of recurrent ischemic stroke. A DHV score of ≥ 2 had a 63% sensitivity and 69% specificity for recurrent ischemic stroke. InterpretationIn patients with severe symptomatic intracranial atherosclerotic stenosis, those with a DHV sign on MRI are at higher risk of recurrent ischemic stroke.

Transcranial Doppler After Endovascular Treatment to Evaluate Collateral Status and Outcomes in Patients With Large‐Vessel Occlusion

Background Recent advances in endovascular therapy (EVT) have led to significant improvements in functional outcomes of patients with stroke. However, early neurological deterioration after EVT has remained a concerning issue. This cohort study was designed to assess the feasibility of early transcranial Doppler (TCD) after EVT and to identify associations between TCD findings and early neurological deterioration. Methods Between October 16, 2020, and March 28, 2021, we recruited 20 patients with acute ischemic stroke with large‐vessel occlusion who underwent EVT. Five patients were excluded because of a poor temporal window; 2 had an unsuccessful intervention. Using TCD, we measured peak systolic velocity, end‐diastolic velocity, mean flow velocity, and pulsatility index for all selected arteries before and within 60 minutes after EVT. We also examined the association between active leptomeningeal collateral flow after EVT and early neurological deterioration. Patients were followed for 3 months, and disability was measured using the modified Rankin scale. Results Two patients had early neurological deterioration with elevated blood pressure and active leptomeningeal flow despite successful EVT. Most patients with poststroke disability (modified Rankin scale&gt;2) had either flow diversion or active leptomeningeal collateral flow in the presence of elevated blood pressure (≥170/93 mm Hg). In cases without early neurological deterioration and in those with a modified Rankin scale&lt;2, we did not observe any flow diversion or active leptomeningeal collateral. They also had a blood pressure of ≤155/85 mm Hg after EVT. All patients with hemorrhagic transformation had evidence of hyperemia on TCD. Conclusions Early TCD is a feasible and safe approach to evaluate cerebral blood flow before and after EVT and identify those at risk of early neurological deterioration. For the next phase of this study, we plan to manage blood pressures based on individualized cerebral flow and the presence of active collateral arteries after EVT.

Abstract 81: Shear-activated Nanoparticle Aggregates Containing Nitroglycerin Selectively Increase Collateral Perfusion During Experimental Ischemic Stroke

Introduction: Leptomeningeal collateral flow is a strong predictor of stroke outcome. Enhancing collateral flow is an appealing therapeutic approach. However, previous attempts to enhance collateral flow with vasodilators have failed, due to systemic hypotension and cerebrovascular steal from the penumbra. We have shown that during experimental stroke collaterals have fluid shear stress that is 3-7 times higher (100 dyne/cm 2 ) than other blood vessels. This unique feature of collateral vessels provides a way to selectively enhance flow, using nanoparticle aggregates loaded with nitroglycerin (NG-NPAs), that only release drug in areas of high shear stress (≥ 100 dyne/cm 2 ). Hypothesis: Shear-activated NG-NPAs will selectively enhance collateral perfusion and improve stroke outcome. Methods: Proximal occlusion of the middle cerebral artery (MCAo) was induced for 70 min in male Spontaneously Hypertensive Rats. Changes in cerebral blood flow in the collateral-supplied ischemic MCA territory, and in the contralateral homotypic region were measured by laser speckle contrast imaging. Animals were randomized to receive I.V. infusion of blank-NPA (B-NPA, control, 4mg in 2ml of saline, n=7) or NG-NPA (50μg NG in 4 mg NPA = 4μg/kg/min of NG, n=7), commencing 25 minutes after MCAo, until reperfusion. Infarct volume was measured at 24 h. Results: NG-NPA significantly increased collateral perfusion by 44% vs. 11% for B-NPA at 40 minutes post-infusion (p=0.026), without altering perfusion in the contralateral region (NG-NPA: +19%, B-NPA: +13% of pre-infusion baseline, p=0.99) and without reducing blood pressure (NG-NPA: 161 mmHg, B-NPA: 163 mmHg, p=0.99). NG-NPA significantly reduced infarct volume at 24 h (NG-NPA: 70 mm 3 , B-NPA: 121 mm 3 , p=0.005). Better collateral perfusion was correlated with smaller infarct volume (R 2 = 0.44, p=0.012). Conclusion: Shear-activated NG-NPA selectively enhanced collateral perfusion to penumbral tissue without inducing systemic side effects, which resulted in smaller infarcts in this model. Given the known importance of collateral flow, shear-activated NG-NPA show great promise as a potential therapy for ischemic stroke patients, both pre-reperfusion therapy and in those unsuitable for such therapies.

Abstract WP120: Can Early Transcranial Doppler Ultrasound Predict Early Neurological Deterioration And Risk Of Hemorrhagic Transformation After Endovascular Treatment?

Background: Recent advances in endovascular therapy (EVT) have led to a significant improvement in functional outcomes of patients with stroke. However, early neurological deterioration (END) after EVT has still remained a concerning issue. Reasons for END include reocclusion, hyperperfusion after recanalization, and hemorrhagic transformation. The current study was designed to assess the feasibility of early transcranial Doppler (TCD) after EVT, to identify association between TCD findings and END. Methods: This is a pilot study to assess the feasibility of TCD prior and early (within 60 minutes) after EVT. For all selected arteries, we measured peak systolic velocity, end diastolic velocity, mean flow velocity and pulsatility index. Patients were followed for three months after the intervention and disability was measured using modified Rankin scale (mRS). We examined the possible association between active leptomeningeal collateral flow after EVT and END. Results: Between October 16, 2020, and March 28, 2021, we recruited 20 acute ischemic stroke patients with large vessel occlusion who underwent EVT. Five patients were excluded because of a poor temporal window; two had an unsuccessful intervention. Four patients had END and all of them had active leptomeningeal flow with elevated blood pressure after EVT. In cases without END, we did not observe any flow diversion or active leptomeningeal collateral after EVT.In those without significant post-stroke disability (mRS&lt;2), we did not observe any active leptomeningeal flow or flow diversion with blood pressure of ≤ 155/85. Most patients with post-stroke disability (mRS ≥ 2) had either flow diversion or active leptomeningeal flow in the presence of blood pressure ≥ 170/93. Hyperemia was associated with hemorrhagic transformation, particularly in the presence of elevated blood pressure. All cases with symptomatic hemorrhagic transformation had hyperemia. Conclusion: TCD is a feasible approach early after EVT. It has clinical implications in identifying those with END and risk for sICH. Early TCD after EVT may provide personalized BP management based on individualized cerebral flow and the presence of active collateral flow after EVT. Studies with larger sample size are warranted.

Reduced Leukoaraiosis, Noncardiac Embolic Stroke Etiology, and Shorter Thrombus Length Indicate Good Leptomeningeal Collateral Flow in Embolic Large-Vessel Occlusion.

Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status. Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

Leptomeningeal collateral flow in patients with middle cerebral artery occlusion assessed by transcranial Doppler.

To explore the application value and clinical significance of transcranial Doppler(TCD)in assessing leptomeningeal collateral flow (LMF) status in patients with unilateral middle cerebral artery (MCA) occlusion. Medical records of patients with unilateral MCA occlusion confirmed by digital subtraction angiography (DSA) were analyzed retrospectively. The patients were divided into three groups according to LMF status, and the laboratory and imaging results were collected. Cerebral blood flow velocity (CBFV) of MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) on the affected side (ipsilateral, i) and the healthy side (contralateral, c) were measured and recorded by TCD. The results of CBFV changes detected by TCD were compared with those of DSA, and the correlation between CBFV changes and LMF status was analyzed. Eighty-four patients with unilateral MCA occlusion were included. CBFViACA and CBFViPCA were significantly faster than CBFVcACA and CBFVcPCA in patients with good LMF status (p<.05). There was a significant positive correlation between CBFViACA and LMF status (r = 0.697, p<.001). There was statistical significance in receiver operating characteristic curve analysis of CBFViACA and CBFViPCA (p<.05). The area under the curve of CBFViACA and CBFViPCA, respectively, was 0.879 and 0.678, and the best cutoff value was 82 and 60.5 cm/s. TCD can assess LMF status by detecting the changes of flow velocity of intracranial vessels. CBFV of ACA and PCA in patients with MCA occlusion is significantly correlated with LMF status by DSA. Assessing LMF status, CBFViACA, CBFViACA/CBFVcACA, and CBFViACA/CBFViMCA has the great diagnostic value, which is of great significance in guiding MCA occlusion patients to choose individualized treatment.

The diagnostic reliability and validity of noninvasive imaging modalities to assess leptomeningeal collateral flow for ischemic stroke patients: A systematic review and meta-analysis.

Leptomeningeal collateral flow (LMF) is associated with infarct area and clinical outcome for ischemic stroke patients. Although LMF can be detected by multiple imaging methods, but their diagnostic performance is uncertain.The aim of this study was to evaluate the diagnostic validity or reliability of noninvasive image methods in assessing LMF.Databases included PubMed, Web of Science, Embase, and Cochrane Library.Original observational cohort studies.Ischemic stroke patients.Different noninvasive image methods to assess LMF.Newcastle–Ottawa Scale to evaluate the quality of the studies; forest plot to show pooled results; I2 and Egger test to evaluate the heterogeneity and publication bias.Thirty of the 126 selected studies were eligible. For CT angiography, the interobserver agreement ranged from 0.494 to 0.93 and weighted kappa was 0.888; for patients receiving thrombolysis or endovascular treatment, 0.68 to 0.91; 0.494 to 0.89 for the 2-point system, 0.60 to 0.93 for the 3-point system, 0.68 to 0.87 for the system of >4 points; area under the curve (AUC) was 0.78. For perfusion computed tomography (CTP), the interobserver agreement ranged from 0.724 to 0.872; for patients receiving thrombolysis or endovascular treatment, 0.74 to 0.872; 0.724 for the 2-point system, 0.783 to 0.953 for the 3-point system; the intraobserver agreement was 0.884; AUC was 0.826. For MRI-fluid attenuated inversion recovery (FLAIR), the interobserver agreement ranged from 0.58 to 0.86; for patients receiving thrombolysis or endovascular treatment, 0.75 to 0.86; 0.86 for the two-point system, 0.77 to 0.87 for the system of more than 5 points; AUC was 0.82.No pooled data of CTP and FLAIR. The difference cohort study had difference bias. The unpublished data were not included.CT angiography is a good tool for assessing LMF. CTP shows a good validity and reliability, but its diagnostic value needs more evidence. FLAIR is a good modality to assess LMF. These image methods had better validity and reliability to evaluate LMF of patients receiving thrombolysis or endovascular treatment than all ischemic stroke patients.

Abstract P340: Chronic Cerebrovascular Damage and Acute Embolic Mechanisms Associated With Acute Leptomeningeal Collateral Flow in Embolic Large Vessel Occlusion

Background and Purpose: Acute leptomeningeal collateral flow is vital to maintain blood perfusion to penumbral tissue in acute ischemic stroke due to large vessel occlusion (LVO). However, the degree of this collateral flow differs among patients. Patient premorbid factors as well as factors caused by the mechanisms of stroke are expected to be associated with this collateral flow. We aimed to investigate the clinical determinants of acute leptomeningeal collateral flow in embolic LVO. Methods: Among consecutive stroke patients caused by acute embolic anterior circulation LVO, we retrospectively reviewed 108 patients who underwent evaluation of acute leptomeningeal collateral status (CS) on pretreatment CTA admitted from January 2015 to December 2019. Both premorbid information including cerebrovascular risk factors and leukoaraiosis evaluated by the total white matter (WM) Fazekas score on MRI, which was calculated as periventricular plus deep WM scores, and stroke related information including stroke subtypes, severity, time course, and occlusive thrombus characteristics were collected. Among thrombus characteristics, thrombus length was measured by tracing the filling defect of contrast on CTA. The clinical determinants of good leptomeningeal CS (&gt; 50% collateral filling of the occluded territory) were analyzed. Results: CS was good in 67 patients (62%). On multivariate logistic regression analysis, cardioembolic stroke subtype was negatively related (OR, 0.170; 95% CI, 0.022-0.868), and mild leukoaraiosis (total WM Fazekas scores of 0-2) was positively related (OR, 9.57; 95% CI, 2.49-47.75) to good CS. On subgroup analysis limited to 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.913 per mm increase; 95% CI, 0.819-0.999) as well as mild leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good CS. Conclusions: Premorbid leukoaraiosis and cardioembolic etiology are determinants of acute leptomeningeal collateral flow in embolic LVO. In addition, thrombus length is also a determinant of collateral flow in cardioembolic LVO. These findings indicate that a combination of chronic cerebrovascular damage and acute embolic mechanisms could determine the degree of leptomeningeal collateral flow.

The impact of native leptomeningeal collateralization on rapid blood flow recruitment following ischemic stroke

The leptomeningeal collateral status is an independent predictor of stroke outcome. By means of optical coherent tomography angiography to compare two mouse strains with different extent of native leptomeningeal collateralization, we determined the spatiotemporal dynamics of collateral flow and downstream hemodynamics following ischemic stroke. A robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, with continued expansion over the course of seven days. In contrast, little collateral recruitment was seen in Balb/C mice during- and one day after MCAO, which coincided with a greater infarct size and worse functional outcome compared to C57BL/6, despite a slight improvement of cortical perfusion seven days after MCAO. Both strains of mice experienced a reduction of blood flow in the penetrating arterioles (PA) by more than 90% 30-min after dMCAO, although the decrease of PA flow was greater and the recovery was less in the Balb/C mice. Further, Balb/C mice also displayed a prolonged greater heterogeneity of capillary transit time after dMCAO in the MCA territory compared to C57BL/6 mice. Our data suggest that the extent of native leptomeningeal collaterals affects downstream hemodynamics with a long lasting impact in the microvascular bed after cortical stroke.

Classification of Intracranial Stenoses: Discrepancies between Transcranial Duplex Sonography and Computed Tomography Angiography

Transcranial color-coded duplex sonography (TCCS) and computed tomography angiography (CTA) are widely used to identify intracranial stenoses (ISs). We assessed concordance of IS grading between TCCS and CTA and proposed new TCCS criteria for severe IS ≥70%. One hundred two stroke patients (70 ± 13 y) with TCCS-identified IS were included. TCCS and CTA were performed within 24 h after admission. TCCS peak systolic velocity cutoffs for <50%/50%–69% stenoses were ≥155/≥220 cm/s (middle cerebral artery [MCA]-M1), ≥100/≥140 cm/s (MCA-M2), ≥120/≥155 cm/s (anterior cerebral artery [ACA]-A1), ≥100/≥145 cm/s (posterior cerebral artery [PCA]-P1 and PCA-P2), ≥90/≥120 cm/s (vertebral artery [VA]-V4) and ≥100/≥140 cm/s (basilar artery [BA]). Criteria for ≥70% stenoses were, despite variable flow velocities, post-stenotic flow alterations and/or leptomeningeal collateral flow. One hundred seventy-seven ISs were detected by TCCS. The number and grade (<50%/50%–69%/≥70%) of ISs were MCA 70 (39/19/12), BA 24 (9/11/4), ACA 21 (14/7/0), PCA 49 (29/15/5) and VA 13 (2/6/5). IS localization was confirmed by CTA in 84 of 177 cases (48%): MCA, 41/70 (59%); BA, 16/24 (67%); ACA 2/21, (10%); PCA, 17/49 (35%); VA, 8/13 (62%). Concordance between TCCS and CTA grading was (<50%/50%–69%/≥70%) 17%/19%/77%. TCCS and CTA exhibited substantial differences in the detection and grading of IS. Higher concordance rates for severe stenosis support our proposed TCCS criteria.

Asymmetric Deep Medullary Veins in Patients With Occlusion of a Large Cerebral Artery: Association With Cortical Veins, Leptomeningeal Collaterals, and Prognosis.

Objective: To explore the relationships of asymmetric deep medullary veins (ADMV) to asymmetric cortical veins (ACV), leptomeningeal collaterals and prognosis in patients with occlusion of a large cerebral artery.Methods: Clinical and imaging data of 56 patients with occlusion of a large cerebral artery were collected and reviewed. We assessed the time delayed between stroke onset and MR imaging (within 24 h of stroke onset), extension of cerebral infarction using the Alberta stroke program early CT score based on diffusion-weighted imaging (ASPECTs). ADMV and ACV were assessed using susceptibility-weighted imaging. The presence of ADMV (ACV) was defined as deep medullary veins (cortical veins) of the affected hemisphere that were greater in number and diameter than in the contralateral hemisphere. To evaluate leptomeningeal collaterals, the hyperintense vessel sign (HVS) was detected using T2 weighted fluid attenuated inversion recovery images. At 90 days, a modified Rankin scale score (mRS) was assessed to evaluate the clinical outcome.Results: Of 56 patients, 27 presented with ADMV. Those patients who presented with and without ADMV differed significantly in HVS and ACV (P < 0.05) but not in time delayed between stroke onset and MR imaging, age, gender, stroke risk factors, baseline NIHSS score, or modified Rankin scale score at 3 months (P > 0.05). Logistic regression analysis found that the presence of ADMV was independently related to HVS and ACV (ACV: OR 95% C.I., 1.287–4.368; HVS: OR 95% C.I., 1.132–4.887).Conclusions: The presence of ADMV on SWI was associated with prominent ACV and good leptomeningeal collateral flow but was not related to prognosis in patients with occlusion of a large cerebral artery.

Correction to: Detrimental Effect of Chronic Hypertension on Leptomeningeal Collateral Flow in Acute Ischemic Stroke.

Correction to: Detrimental Effect of Chronic Hypertension on Leptomeningeal Collateral Flow in Acute Ischemic Stroke.

Abstract TP145: Admission Hyperglycemia Predicts Poor Cerebral Collateral Flow in Acute Ischemic Stroke

Introduction: Poor leptomeningeal collateral flow is related to worse neurological outcome in acute ischemic stroke. The increased release of stress hormones during the first hours of acute stroke leads to inhibition of insulin secretion and increase insulin resistance, thus inducing stress hyperglycemia, which is often evident on blood glucose levels at admission. While admission hyperglycemia, independent of diabetes mellitus (DM) is associated with poor clinical outcome in ischemic stroke, studies on its effect on collateral circulation after acute cerebral embolism are largely inconclusive. Methods: We identified a consecutive series of patients aged 18 years and older from 2008 to 2018 with acute embolic large vessel stroke confirmed on CT angiography (CTA) using an institutional database. Individual CTAs were over-read, and collateral scores of the affected hemisphere were calculated using a modification of the Tan scale (0-4), by two trained readers. We reviewed the electronic medical records for presenting NIHSS, admission glucose and HbA1C levels, and prior history of DM. Spearman’s ρ, odds ratios (OR), and their 95% confidence intervals (CI) were analyzed. All tests were considered significant when P&lt;0.05. Results: Of the 405 patients identified through the database (mean age 70 years [range, 55-85], 45% [183/405] women), 35% (142/405) had a prior history of DM. Mean admission glucose was 134±51 mg/dL, and median NIHSS at presentation was 17. Blood glucose level at admission was negatively correlated with collateral scores (ρ= -0.23, P=0.008). Specifically, glucose levels above 120 mg/dL were significantly associated (OR 1.68 CI 1.13-2.5) with poor collateral scores (≤1). However, collateral scores exhibited no statistically significant relationship with HbA1c (ρ=-0.08, P=0.15) or prior history of DM (P=0.73). Conclusions: Patients with higher admission glucose levels have poor collateral scores, while HbA1c and prior DM do not have a similar effect on collateral flow. Our results suggest that poor collateral flow may explain adverse outcomes associated with hyperglycemia in acute ischemic stroke. Determining if there is a benefit of aggressive glycemic control within the first few hours of embolic stroke warrants further study.

Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation

Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony‐stimulating factor (G‐CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G‐CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5‐fluorouracil (5‐FU) significantly limited the neuroprotection of RIPC or G‐CSF treatment. The protein expression of proangiogenic factors such as Ang‐2 was increased by ischemia, but treatment with either RIPC or G‐CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke.

Sustaining cerebral perfusion in intracranial atherosclerotic stenosis: The roles of antegrade residual flow and leptomeningeal collateral flow

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50–69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70–99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

Posterior circulation involvement and collateral flow pattern in moyamoya disease with the RNF213 polymorphism.

Moyamoya disease is a chronic cerebrovascular disorder characterized by progressive stenosis of the circle of Willis with a compensatory collateral vessel network. Recent studies have identified the ring finger protein 213 gene (RNF213) as the unique susceptibility gene for moyamoya disease. The purpose of this study was to compare clinical features of moyamoya disease, especially angiographic findings, between patients with and without the RNF213 mutation. Blood samples from 35 patients with moyamoya disease were obtained between May 2016 and May 2017. Information on age at the time of diagnosis, sex, and initial symptom were obtained via retrospective chart review. Angiographic records were evaluated. RNF213 variants were detected in the 28 of 35 patients (80%), including all pediatric patients (100%) and 18 of 25 adult patients (72%) in our cohort. Leptomeningeal collateral flow from posterior to anterior circulation was more frequent in the RNF213-negative group than in the RNF213-positive group (100% versus 38.9%; p = 0.020). Posterior cerebral arterial territorial involvement was more frequently observed in RNF213-positive patients than in RNF213-negative patients (50% versus 0%; p = 0.027). RNF213 may play a significant role in the development of collateral anastomoses.

Inter- and intraobserver reliability for angiographic leptomeningeal collateral flow assessment by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale

BackgroundThe adequacy of leptomeningeal collateral flow has a pivotal role in determining clinical outcome in acute ischemic stroke. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR)...

Clinical Imaging Factors Associated With Infarct Progression in Patients With Ischemic Stroke During Transfer for Mechanical Thrombectomy

When transferred from a referring hospital (RH) to a thrombectomy-capable stroke center (TCSC), patients with initially favorable imaging profiles (Alberta Stroke Program Early CT Score [ASPECTS] ≥6) often demonstrate infarct progression significant enough to make them ineligible for mechanical thrombectomy at arrival. In rapidly evolving stroke care networks, the question of the need for vascular imaging at the RHs remains unsolved, resulting in an important amount of futile transfers for thrombectomy. To examine the clinical imaging factors associated with unfavorable imaging profile evolution for thrombectomy in patients with ischemic stroke initially transferred to non-TCSCs. Data from patients transferred from 1 of 30 RHs in our regional stroke network and presenting at our TCSC from January 1, 2010, to January 1, 2016, were retrospectively analyzed. Consecutive patients with acute ischemic stroke initially admitted to a non-thrombectomy-capable RH and transferred to our center for which a RH computed tomography (CT) and a CT angiography (CTA) at arrival were available for review. ASPECTS were evaluated. The adequacy of leptomeningeal collateral blood flow was rated as no or poor, decreased, adequate, or augmented per the adapted Maas scale. The main outcome was an ASPECTS decay, defined as an initial ASPECTS of 6 or higher worsening between RH and TCSC CTs to a score of less than 6 (making the patient less likely to derive clinical benefit from thrombectomy at arrival). A total of 316 patients were included in the analysis (mean [SD] age, 70.3 [14.2] years; 137 [43.4%] female). In multivariable models, higher National Institutes of Health Stroke Score, lower baseline ASPECTSs, and no or poor collateral blood vessel status were associated with ASPECTS decay, with collateral blood vessel status demonstrating the highest adjusted odds ratio of 5.14 (95% CI, 2.20-12.70; P < .001). Similar results were found after stratification by vessel occlusion level. In patients with ischemic stroke transferred for thrombectomy, poor collateral blood flow and stroke clinical severity are the main determinants of ASPECTS decay. Our findings suggest that in certain subgroups vascular imaging, including collateral assessment, can play a crucial role in determining the benefits of transfer for thrombectomy.