Leptomeningeal Collateral Circulation Research Articles

Modeling cerebrovascular responses to assess the impact of the collateral circulation following middle cerebral artery occlusion.

An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.

Radiological predictors of final infarct volume in patients with proximal vascular occlusion

IntroductionVarious clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. Materials and methodsThis retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. ResultsWe included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%). Final infarct volume correlated with the grade of leptomeningeal collateral circulation (p=0.03) and with the clot burden score (p=0.01). Neither the length nor the density of the thrombus correlated with final infarct volume. ConclusionThe final infarct volume can be estimated on the initial CT angiogram. Nevertheless, we found no useful predictive factors in unenhanced CT images. The best independent radiologic predictors of the final infarct volume are the grade of collateral circulation and the clot burden score, especially in patients who did not undergo mechanical thrombectomy, because mechanical thrombectomy improves outcomes. These factors are important for decision making in the management of patients with ischemic cerebrovascular accidents due to proximal occlusion.

Fetal posterior cerebral artery in pediatric and adult moyamoya disease: A single-center experience of 480 patients

PurposeIn past pediatric and adult cohort studies of moyamoya disease, the fetal posterior cerebral artery has received less attention. Its relationship with the clinical manifestations and collateral circulation of moyamoya disease or ipsilateral cerebral hemispheres remains unclear. MethodWe summarize the clinical features of patients with and without fetal posterior cerebral artery moyamoya disease from consecutive cases.We explored the relationship between fetal posterior cerebral arteries and collateral circulation in the ipsilateral cerebral hemispheres, as well as differences among different subgroups of patients.According to the morphology, the fetal posterior cerebral artery is divided into complete fetal posterior cerebral artery and partial fetal posterior cerebral artery. Clinical features were classified as: infarction,hemorrhage,and non-stroke in unilateral/bilateral cerebral hemispheres. Collateral circulation is divided into extracranial vascular compensation and leptomeningeal collateral circulation. Digital subtraction angiography and CT/MR were used to evaluate the blood flow status and clinical characteristics of patients with moyamoya disease. ResultA total of 960 cerebral hemispheres from 142 pediatric patients and 338 adult patients were included in the study. A total of 273 (56.9%) patients had 399 cerebral hemispheres (41.6%) with fetal posterior cerebral arteries. Adults with fetal posterior cerebral arteries had lower rates of infarction (24.6%vs37.3%, P =0.005) and were less likely to have bilateral stroke (8.4%vs11.5%, P =0.038). Cerebral hemispheres with fetal posterior cerebral artery were more likely to have anterior cerebral artery and middle cerebral artery stenosis and less likely to have occlusion (P =0.002, 0.001), and less likely to involve the posterior circulation (P < 0.001). The cerebral hemispheres of the fetal posterior cerebral artery had higher leptomeningeal collateral circulation scores. There are significant differences in extracranial vascular compensation between cerebral hemispheres with and without fetal posterior cerebral artery. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage (P =0.017). ConclusionsOur results suggest that fetal posterior cerebral artery is associated with infarct manifestations in pediatric and adult moyamoya disease. In the cerebral hemispheres, the fetal posterior cerebral artery is associated with ipsilateral hemispheric anterior and posterior circulation artery injury, extracranial vascular compensation, leptomeningeal collateral circulation compensation, and infarction. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage.

Modelling collateral flow and thrombus permeability during acute ischaemic stroke.

The presence of collaterals and high thrombus permeability are associated with good functional outcomes after an acute ischaemic stroke. We aim to understand the combined effect of the collaterals and thrombus permeability on cerebral blood flow during an acute ischaemic stroke. A cerebral blood flow model including the leptomeningeal collateral circulation is used to simulate cerebral blood flow during an acute ischaemic stroke. The collateral circulation is varied to capture the collateral scores: absent, poor, moderate and good. Measurements of the transit time, void fraction and thrombus length in acute ischaemic stroke patients are used to estimate thrombus permeability. Estimated thrombus permeability ranges between 10^-7 and 10^-4 mm². Measured flow rates through the thrombus are small and the effect of a permeable thrombus on brain perfusion during stroke is small compared with the effect of collaterals. Our simulations suggest that the collaterals are a dominant factor in the resulting infarct volume after a stroke.

Predictores radiológicos del volumen final del infarto cerebral en pacientes con obstrucción vascular proximal

IntroductionVarious clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. Materials and methodsThis retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. ResultsWe included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%). Final infarct volume correlated with the grade of leptomeningeal collateral circulation (p=0.03) and with the clot burden score (p=0.01). Neither the length nor the density of the thrombus correlated with final infarct volume. ConclusionThe final infarct volume can be estimated on the initial CT angiogram. Nevertheless, we found no useful predictive factors in unenhanced CT images. The best independent radiologic predictors of the final infarct volume are the grade of collateral circulation and the clot burden score, especially in patients who did not undergo mechanical thrombectomy, because mechanical thrombectomy improves outcomes. These factors are important for decision making in the management of patients with ischemic cerebrovascular accidents due to proximal occlusion.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensity in Cerebrovascular Disease: A Review for Radiologists and Clinicians.

Neuroradiological methods play important roles in neurology, especially in cerebrovascular diseases. Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is frequently encountered in patients with acute ischemic stroke and significant intracranial arterial stenosis or occlusion. The mechanisms underlying this phenomenon and the clinical implications of FVH have been a matter of debate. FVH is associated with large-vessel occlusion or severe stenosis, as well as impaired hemodynamics. Possible explanations suggested for its appearance include stationary blood and slow antegrade or retrograde filling of the leptomeningeal collateral circulation. However, the prognostic value of the presence of FVH has been controversial. FVH can also be observed in patients with transient ischemic attack (TIA), which may have different pathomechanisms. Its presence can help clinicians to identify patients who have a higher risk of stroke after TIA. In this review article, we aim to describe the mechanism and influencing factors of FVH, as well as its clinical significance in patients with cerebrovascular disease.

Modelling the leptomeningeal collateral circulation during acute ischaemic stroke

A novel model of the leptomeningeal collateral circulation is created by combining data from multiple sources with statistical scaling laws. The extent of the collateral circulation is varied by defining a collateral vessel probability. Blood flow and pressure are simulated using a one-dimensional steady state blood flow model. The leptomeningeal collateral vessels provide significant flow during a stroke. The pressure drop over an occlusion predicted by the model ranges between 60 and 85 mmHg depending on the extent of the collateral circulation. The linear transport of contrast material was simulated in the circulatory network. The time delay of peak contrast over an occlusion is 3.3 s in the model, and 2.1 s (IQR 0.8–4.0 s) when measured in dynamic CTA data of acute ischaemic stroke patients. Modelling the leptomeningeal collateral circulation could lead to better estimates of infarct volume and patient outcome.

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients

Introduction: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. Patients and Methods: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. Results: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = −0.47, P < .001 for 3-month modified Rankin Scale; rho = −0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. Conclusions: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

Effect of direct angioplasty therapy on acute middle cerebral artery occlusion with good leptomeningeal collateral

ObjectiveThe objective of this study was to investigate and discuss the effect of direct angioplasty therapy on acute middle cerebral artery occlusion (MCAO) patients with good leptomeningeal collateral circulation in 4.5 h. Patients and MethodsWe retrospectively reviewed our acute ischemic stroke database from January 2017 to January 2019, then selected consecutive patients with evidence of the proximal M1 segments of MCAO and good leptomeningeal collateral who have received angioplasty or mechanical thrombectomy (MT). The baseline characteristics and outcome of patients was statistical analysis, included age, gender and risk factors, baseline national institutes of health stroke scale (NIHSS) scores, preoperative alberta stroke programme early CT (ASPECT) score, time from door to needle, time of door to puncture, endovascular procedure time, 7d NIHSS score and the modified treatment in cerebral infarction (m-TICI) 2b or 3, symptomatic hemorrhage, average hospital stays, modified rankin scale (mRS) score 0–2 at 3-month and mortality. All the thrombi were analyzed by histopathology. All statistical analysis was done with t-test for continuous data and χ2 test for binary data. ResultsA total of 93 patients were included (direct angioplasty = 41 (44.1 %), MT = 52 (55.9 %)). There was no significant difference in baseline data between the two groups. The difference in the time of door to recanalization, the time of puncture to recanalization, symptomatic hemorrhage, and average hospital stays were significantly different between groups (P < 0.05). The other agents were not significantly different between groups (P > 0.05 each). Histopathological analysis showed all thrombi contained different amounts of platelets, fibrinogen, white blood cell, and red blood cell. ConclusionDirect angioplasty therapy on acute MCAO with good leptomeningeal collateral may help to shorten the time of surgery, reduce symptomatic hemorrhage, and hospital stay.

Abstract WP69: Does CBF Below 30% Actually Represent Infarct Core in Acute Ischemic Stroke? Proof of Mis-Concept

On CT perfusion (CTP), cerebral blood flow &lt; 30% than the contralateral hemisphere (CBF&lt;30) is considered a marker of infarct core. Our hypothesis is that CBF&lt;30 defines a reversible poor hemodynamic area rather than core and aimed to study CBF&lt;30 evolution over time, its relationship with leptomeningeal collateral circulation (CC) and outcome parameters. Methods: Retrospective analysis of a prospective database of acute ischemic strokes who underwent CTP on admission and immediately after endovascular thrombectomy (EVT). CC was graded on CT angiography (CTA) by the modified Tan scale (good CC: 2-3 grades). Complete recanalization was defined by modified Thrombolysis in Cerebral Ischemia ≥ 2B. Final infarct volume (FIV) was semi-automatically measured on 48-72h CT; ghost core was defined as: admission CBF&lt;30 - FIV &gt; 10cc. Results: We included 494 patients; median time from onset to CT: 137 min (IQR 68-238). Median CBF&lt;30 volume on admission: 8 cc (0-28). With longer onset-to-CT times ischemic changes progressively increased on non-contrast CT (ASPECTS decay r=-0.21, p&lt;0.01), however CBF&lt;30 progressively decreased (r=-0.13, p&lt;0.01). 294 patients (60.6%) presented good CC. Good CC was associated with lower admission CBF&lt;30 (median CBF&lt;30 on good CC: 0 cc (0-12) vs 28.5 (7-57) on poor CC, p&lt;0.01). In recanalized patients (419, 84.8%), CBF&lt;30 virtually disappeared in CTP post-EVT (n=103) (median CBF&lt;30: 0ml (IQR 0) (88%= 0 cc) despite that most patients developed established infarcts (median FIV 16 (4-50), 59% FIV&gt;10cc)). Even in recanalized patients, baseline CBF&lt;30 only moderately correlates with FIV (r=0.55, p&lt;0.01). A ghost core was identified in 13.7% (34.5% if CT was performed &lt;90min from onset). 46.6% patients had good functional outcome (mRS&lt;3 at 3 months). A multivariate analysis of recanalized patients showed that CC (OR 0.43, CI 0.27-0.69, p&lt;0.01) but not CBF&lt;30 was an independent predictor of functional outcome. Conclusion: CBF&lt;30 represents an hemodynamic state rather than established infarct core, evolving over time inversely as it should physiologically (increase of infarct core over time). CBF&lt;30 should be considered as an outcome predictor but not used as exclusion criterion for EVT, especially in early time-windows.

24-Hour Near-Infrared Spectroscopy Monitoring of Acute Ischaemic Stroke Patients Undergoing Thrombolysis or Thrombectomy: A Pilot Study

IntroductionMonitoring of acute ischaemic stroke patients during thrombolysis or thrombectomy is based mostly on frequent physical examinations, since no objective measurement of cerebrovascular haemodynamics is available in routine clinical practice. Near-infrared spectroscopy (NIRS) is a bed-side, noninvasive assessment tool that could help monitor these patients and potentially guide therapeutic interventions. Our goal in this pilot study was to investigate whether NIRS is a suitable method to monitor leptomeningeal collateral circulation via changes in cortical oxygen saturation in the first 24 hours of acute ischaemic stroke. Patients and methodsOur study included 5 patients with acute anterior circulation infarcts. All patients received thrombolytic therapy and 1 had thrombectomy. 24-hour continuous NIRS monitoring was performed on all participants. ResultsWe aimed to give a detailed description of each NIRS recording and explain how the observed findings could correlate with changes in anterior watershed territory collateral circulation and clinical outcome. ConclusionOur pilot study supports the use of NIRS monitoring in acute ischaemic stroke. We believe that this technique could provide real-time information on the dynamic changes of leptomeningeal collateral circulation and help monitor the effects of thrombolysis and thrombectomy.

Posterior communicating and anterior communicating arteries on pre-thrombectomy computed tomography scans are associated with good outcomes irrespective of leptomeningeal collateral status.

Collateral blood flow is known to be an important factor that sustains the penumbra during acute stroke. We looked at both the leptomeningeal collateral circulation and the presence of anterior and posterior communicating arteries to determine the factors associated with good outcomes and mortality. We included all patients with acute ischaemic stroke in the anterior circulation, who underwent thrombectomy with the same thrombectomy device from 2013 to 2016. We assessed the leptomeningeal circulation by the Tan, Miteff and Maas validated scoring systems on pre-treatment computed tomographic angiography scans and looked at collateral flow through anterior and posterior communicating arteries. The results were good functional outcomes at 3 months (modified Rankin scale 0-2) and mortality. A total of 147 consecutive acute stroke patients treated with the Embotrap device were included with a median National Institutes of Health stroke scale of 15 (range 2-26). On multivariate analysis only younger age (odds ratio (OR) 0.96/year, 95% confidence interval (CI) 0.94-0.99, P = 0.026), lower National Institutes of Health stroke scale score (OR 0.87/point, 95% CI 0.80-0.93, P < 0.001), number of attempts (OR 0.80/attempt, 95% CI 0.65-0.99, P = 0.043) and the presence of a patent anterior communicating artery (OR 14.03, 95% CI 1.42-139.07, P = 0.024) were associated with good functional outcomes. The number of attempts (OR 1.66/attempt, 95% CI 1.21-2.29, P = 0.002) was significantly associated with mortality and the presence of a patent posterior communicating artery (OR 0.098, 95% CI 0.016-0.59, P = 0.011) was inversely associated with mortality. Our study shows that the presence of anterior and posterior communicating arteries is significantly associated with good functional outcomes and reduced mortality, respectively, independent of the leptomeningeal circulation status.

Abstract WP338: Penetrating Arteriole Flow Dynamics and Capillary Transient Time Heterogeneity Following Experimental Stroke in Two Mouse Strains With Distinct Pial Collateral Circulation

Introduction: In the pathophysiology of ischemic stroke, Leptomeningeal collateral circulation plays a key role on the severity of infarction. Balb/C mice have impaired leptomeningeal collateral due to variants of Rabep2 on chromosome 7 ( Candq1 ), causing sever stroke compared to C57BL/6 mice with rich collateral anastomosis. However, it still remains unclear whether and how poor collateral circulation specifically affects hemodynamic adaptation of microvessels during cerebral ischemia. Method: Male C57BL/6 and Balb/C mice were subjected to distal middle cerebral artery occlusion (dMCAO) combined with 90 minutes-occlusion of the ipsilateral common carotid artery. A 4x4 mm 2 cranial window was created on the parietal cortex 2 mm lateral and 1 mm posterior from the bregma 3 weeks prior to imaging. Spatial and temporal changes of the total flow and axial velocity of the penetrating arterioles (PA), as well as mean transit time (MTT) and capillary transit time heterogeneity (CTTH) in the capillaries bordering the distal MCA and ACA branches were determined by optical coherent tomography-based microangiography and capillary velocimetry at baseline, during dMCAO, 1 hour, 1 day and 7 days after reperfusion in each strain. Results: Stroke-induced increase in CTTH in the region of middle cerebral artery was significantly greater in Balb/C compared to C57BL/6 mice, leading to significantly increased microvascular resistance and reduced oxygen extraction during MCAO and 1 hour after reperfusion in the former (P&lt;0.05). The total blood flow in PA reduced immediately after dMCAO in both strains of mice but it remained reduced in Balb/C mice after reperfusion in contrast to a sustainable recovery at 50% of prestroke level 7 days after stroke. Conclusion: Poor collateral anastomosis and impaired flow of penetrating arterioles is an additional risk factor for hemodynamic compromise during cerebral ischemia caused by reduced oxygen extraction, which may increase the severity of stroke.

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.

Therapeutic effects of long-term continuous positive airway pressure treatment on improving leptomeningeal collateral circulation in obstructive sleep apnea syndrome patients.

This study aims to use methods of scoring collaterals on CT angiography to analyze changes in collateral circulation in untreated patients with moderate and severe OSAS before and after nasal continuous positive airway pressure (CPAP) treatment. Ninety-eight moderate and severe OSAS patients treated with nasal CPAP and seventy-four controls that weren't treated with CPAP, were involved in this study. Two independent neuroradiologists evaluated intracranial collaterals by using Miteff scale, modified Tan scale. Intracranial collaterals differences were compared between OSAS group (before and after treated) and control group. Correlations between intracranial collaterals and clinical parameters were analyzed. Compared with pre-therapy of moderate and severe groups, apnea-hypopnea index (AHI), oxygen desaturation index (ODI), epworth sleepness scale (ESS) were lower after treatment. The lowest oxygen saturation, average blood oxygen saturation, Miterff scale, modified Tan scale in moderate and severe groups were significantly increased after treatment. We documented significant decrease of Miterff scale after two years in moderate and severe OSAS group without CPAP therapy (n = 32, p < 0.01). Conversely, mild OSAS group without CPAP therapy did not change Miterff scale after two years (n = 32, p > 0.05). Multivariate Logistic regression analysis showed that AHI had significant impact on Miterff scale and modified Tan scale. Severe OSAS were independently related with Miterff scale (odds ratio 0.343, 95% confidence interval 0.301-0.391, p < 0.01) and modified Tan scale (odds ratio 0.267, 95% confidence interval 0.095-0.754, p = 0.013). Long-term CPAP treatment is a viable therapeutic choice for improving leptomeningeal collateral circulation in OSAS patients.

Sphingosine-1-Phosphate Receptor 1 Activation Enhances Leptomeningeal Collateral Development and Improves Outcome after Stroke in Mice

Development of collateral circulation after acute ischemic stroke is triggered by shear stress that occurs in pre-existing arterioles. Recently, sphingosine-1-phosphate receptor 1 (S1P1) on endothelial cells was reported to sense shear stress and transduce its signaling pathways. BALB/c mice (n = 118) were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham operation. We investigated the effect of an S1P1-selective agonist SEW2871 on leptomeningeal collateral arteries and neurological outcome after pMCAO. Immunohistochemistry showed that without treatment, the expression of S1P1 on endothelial cells of leptomeningeal arteries and capillaries increased early after pMCAO, peaking at 6 hours, whereas a significant increase in the expression of S1P1 in neurons was seen from 24 hours later. After intraperitoneal administration of SEW2871 for 7 days after pMCAO, the number of leptomeningeal collateral arteries was significantly increased, cerebral blood flow improved, infarct volume was decreased, and neurological outcome improved compared with the controls. Significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS) as early as 6 hours after pMCAO and higher expression of tight junction proteins at postoperative day 3 were observed with SEW2871 treatment as assessed by Western blot. Daily administration of SEW2871 also increased capillary density in peri-infarct regions and promoted monocyte/macrophage mobilization to the surface of ischemic cortex at 7 days after pMCAO. An S1P1-selective agonist enhanced leptomeningeal collateral circulation via eNOS phosphorylation and promoted postischemic angiogenesis with reinforced blood-brain barrier integrity in a mouse model of acute ischemic stroke, leading to smaller infarct volume and better neurological outcome.

Predictors of short-term outcome in patients with acute middle cerebral artery occlusion: unsuitability of fluid-attenuated inversion recovery vascular hyperintensity scores.

Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days (National Institutes of Health Stroke Scale) and 90 days (modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.

FLAIR vascular hyperintensities and 4D MR angiograms for the estimation of collateral blood flow in anterior cerebral artery ischemia.

PurposeTo assess FLAIR vascular hyperintensities (FVH) and dynamic (4D) angiograms derived from perfusion raw data as proposed magnetic resonance (MR) imaging markers of leptomeningeal collateral circulation in patients with ischemia in the territory of the anterior cerebral artery (ACA).MethodsForty patients from two tertiary care university hospitals were included. Infarct volumes and perfusion deficits were manually measured on DWI images and TTP maps, respectively. FVH and collateral flow on 4D MR angiograms were assessed and graded as previously specified.ResultsForty-one hemispheres were affected. Mean DWI lesion volume was 8.2 (± 13.9; range 0–76.9) ml, mean TTP lesion volume was 24.5 (± 17.2, range 0–76.7) ml. FVH were observed in 26/41 (63.4%) hemispheres. Significant correlations were detected between FVH and TTP lesion volume (ρ = 0.4; P<0.01) absolute (ρ = 0.37; P<0.05) and relative mismatch volume (ρ = 0.35; P<0.05). The modified ASITN/SIR score correlated inversely with DWI lesion volume (ρ = -0.58; P<0.01) and positively with relative mismatch (ρ = 0.29; P< 0.05). ANOVA of the ASITN/SIR score revealed significant inter-group differences for DWI (P<0.001) and TTP lesion volumes (P<0.05). No correlation was observed between FVH scores and modified ASITH/SIR scores (ρ = -0.16; P = 0.32).ConclusionsFVH and flow patterns on 4D MR angiograms are markers of perfusion deficits and tissue at risk. As both methods did not show a correlation between each other, they seem to provide complimentary instead of redundant information. Previously shown evidence for the meaning of these specific MR signs in internal carotid and middle cerebral artery stroke seems to be transferrable to ischemic stroke in the ACA territory.

Analysis of the Outcome and Prognostic Factors of Decompressive Craniectomy between Young and Elderly Patients for Acute Middle Cerebral Artery Infarction.

ObjectiveWe compared the effect of decompressive craniectomy between patients < 65 and ≥ 65 years age and investigated prognostics factors that may help predict favorable outcome in acute stroke patients undergoing decompressive surgery.Materials and Methods52 patients diagnosed with acute middle cerebral artery (MCA) territory infarction that underwent decompressive craniectomy were retrospectively reviewed. The outcome of all patients were evaluated by assessing the Glasgow coma scale, Glasgow outcome scale (GOS), and Modified Rankin scale (mRS) six months after the onset of the disease. 21 patients were preoperatively evaluated with a computed tomography angiography (CTA). Leptomeningeal collateral (LMC) circulation was graded using CTA by experienced neurosurgeons to assess its prognostic value.ResultsThe thirty day mortality for patients ≥ 65 was 35.0% compared to 37.5% in patients < 65. There was no significant difference in the clinical and function outcome between the two groups (4.8 ± 1.2 vs. 4.5 ± 1.5, p = 0.474). Mortality was lower with early surgery (within 24 hours) group for both age groups (25% vs. 37.5% in ≥ 65, 20% vs. 40.7% in < 65). Longer intensive care units stay time and good collateral supply score were correlated with favorable outcome (p = 0.028, p = 0.018).ConclusionDecompressive craniectomy within 24 hours of stroke symptom onset improved survival in both the < 65 and ≥ 65 age groups. There was no significant difference in the functional outcome of both age groups. Unlike previous reports, old age, delayed operation, and multiple of infarct territories were not predictive of poor functional outcome. The presence of good collateral circulation may be a predictor of positive clinical outcome in acute ischemic stroke patients undergoing decompressive craniectomy.

Abstract 186: Poor Leptomeningeal Collateral Circulation Baseline Status Is a Predictor of Malignant Infarction in Patients Treated With tPA

Background and Purpose: Malignant infarction (MI) is a life-threatening complication in patients with hemispheric stroke. Although few biochemical and neuroimaging markers have been published to be useful for the prediction of MI development, information about predictors of this complication is scarce. Leptomeningeal collateral circulation (LMC) has been associated in few studies with poor clinical outcome and infarct growth in patients with acute ischemic stroke, but no data have been reported about the possible association about LMC and MI. In this study, we investigated wether LMC baseline status can be a predictor of MI in patients treated with tissue plasminogen activator (tPA). Methods: One hundred and thirty-six patients with hemispheric stroke treated with tPA and angio-CT perfusion before tPA administration were evaluated. MI was diagnosed following Schwab et al. criteria (complete space-occupying MCA infarction with midline shift and compression of the basal cisterns on follow-up CT and further neurological deterioration consisting of a decrease in the level of consciousness to somnolence or stupor compared with baseline clinical status at admission). ASPECTS score was evaluated on CT at admission. LMC baseline status was also scored on CT angiography maps before tPA and classified as good or poor according to Tan et al. criteria and Lima et al. criteria Results: Sixty-six patients (48.2%) had good LMC and 70 patients (51.1%) had poor LMC, regardless of the classification used. Patients with poor LMC had a significantly higher NIHSS at admission and ASPECTS score &lt; 7 was also found more frequently in this group. With regards to LMC, 14 patients (93%) developed MI in the group with poor LMC whereas just 1 patient (6.7%) had MI in the group with good LMC (p&lt;0.001). In the multivariate analysis, only poor LMC at admission remained as an independent predictor of this complication (OR 12.8; CI 95%, 1.58-104.13; p=0.017). Conclusions: Poor LMC at admission is a predictor of MI in patients treated with tPA and, so this neuroimaging finding might be useful to identify those patients at higher risk to develop this fatal complication.