Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Predictores radiológicos del volumen final del infarto cerebral en pacientes con obstrucción vascular proximal / Radiological predictors of final infarct volume in patients with proximal vascular occlusion

Introducción: Múltiples variables clínicas y radiológicas están involucradas en el pronóstico neurológico de los pacientes con accidente cerebrovascular (ACV) isquémico. Alrededor del 30% de los ACV isquémicos son causados por la obstrucción vascular proximal del circuito anterior; en estos casos, la utilidad de la trombólisis sistémica es limitada. La angiotomografía está indicada en los pacientes que pueden ser candidatos a tratamiento endovascular. Diferentes factores radiológicos como el grado de colaterales leptomeníngeas, o el largo, la densidad o la extensión del trombo, fueron descritos como predictores del pronóstico neurológico tras un ACV isquémico con compromiso vascular proximal. El volumen final del infarto cerebral se correlaciona con la mortalidad y el grado funcional a largo plazo de estos pacientes. El propósito de este estudio es determinar los mejores predictores radiológicos del volumen final del infarto cerebral en pacientes con ACV isquémico con compromiso proximal, utilizando angiotomografía. Materiales y métodos: Realizamos un estudio observacional retrospectivo. Incluimos pacientes adultos con ACV isquémico causado por la obstrucción de un vaso proximal, diagnosticados mediante angiotomografía en el período de junio de 2009 a diciembre de 2019. Medimos la densidad y el largo del trombo en la adquisición sin contraste, registramos el grado de colaterales leptomeníngeas y la extensión del trombo utilizando el clot burden score. Luego medimos el volumen final del infarto en una tomografía de control y analizamos el grado de correlación entre estos factores radiológicos en el volumen infartado. Resultados: Incluimos 54 pacientes con ACV isquémico por compromiso vascular proximal; 41 (75%) fueron mujeres. La mediana de edad fue de 82 años. Alrededor del 60% de los ACV comprometieron el hemisferio derecho y el vaso más afectado fue el segmento M1 de la arteria cerebral media (40,7%)...(AU)

Introduction: Various 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 methods: This 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. Results: We 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%)...(AU)

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

INTRODUCTION: Various 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 METHODS: This 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. RESULTS: We 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. CONCLUSION: The 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.

[Variants of collateral cerebral circulation in moyamoya disease]. / Varianty kollateral'nogo krovoobrashcheniya golovnogo mozga pri bolezni moya-moya.

BACKGROUND: Moyamoya disease is a chronic progressive cerebrovascular disease with a complex pathophysiology and unique features of neoangiogenesis. These features are still known only to a few specialists, although they determine clinical course and outcomes of disease. OBJECTIVE: To determine the nature and degree of neoangiogenesis in restructuring the natural collateral circulation in patients with moyamoya disease and its effect on cerebral blood flow. The influence of collateral circulation on postoperative results and factors of its effectiveness will be analyzed in the 2nd part of the study. MATERIAL AND METHODS: The study included 65 patients with moyamoya disease who underwent preoperative selective direct angiography with separate contrast enhancement of both internal, external and vertebral arteries. We analyzed 130 hemispheres. Suzuki stage of disease, pathways of collateral circulation and their relationship with reduction of cerebral blood flow and clinical manifestations were assessed. Distal vessels of the middle cerebral artery (MCA) were additionally studied. RESULTS: Suzuki stage 3 was the most common (36 hemispheres, 38%). Leptomeningeal collaterals were the most common among intracranial collateral tracts (82 hemispheres, 66.1%). Extra-intracranial transdural collaterals were found in half of the cases (56 hemispheres). We observed certain changes in distal vessels of the MCA (hypoplasia of M3 branches) in 28 (20.9%) hemispheres. Suzuki stage of disease significantly determined degree of cerebral blood flow insufficiency, i.e. more severe perfusion deficit was observed at the later stages of disease. A well-developed system of leptomeningeal collaterals significantly reflected stages of compensation and subcompensation of cerebral blood flow according to perfusion data (χ2=20.394, p<0.001). CONCLUSION: Neoangiogenesis is a natural compensatory mechanism in moyamoya disease designed to maintain brain perfusion under reduced cerebral blood flow. Predominant intra-intracranial collaterals are associated with ischemic and hemorrhagic events. Timely restructuring on extra-intracranial ways of collateral circulation prevents adverse manifestations of disease. Assessment and understanding of collateral circulation in patients with moyamoya disease create the prerequisites for substantiating the method of surgical treatment.

Clinical and radiological factors predicting stroke outcome after successful mechanical intervention in anterior circulation.

The recanalization effect of large-vessel occlusion (LVO) in anterior circulation is well documented but only some patients benefit from endovascular treatment. We analysed clinical and radiological factors determining clinical outcome after successful mechanical intervention. We included 146 patients from the Prague 16 study enrolled from September 2012 to December 2020, who had initial CT/CTA examination and achieved good recanalization status after mechanical intervention (TICI 2b-3). One hundred and six (73%) patients achieved a good clinical outcome (modified Rankin Scale 0-2 in 3 months). It was associated with age, leptomeningeal collaterals (LC), onset to intervention time, ASPECTS, initial NIHSS, and leukoaraiosis (LA) in univariate analysis. The regression model identified good collateral status [odds ratio (OR) 5.00, 95% confidence interval (CI) 1.91-13.08], late thrombectomy (OR 0.24, 95% CI 0.09-0.65), LA (OR 0.44, 95% CI 0.19-1.00), ASPECTS (OR 1.45, 95% CI 1.08-1.95), and NIHSS score (OR 0.86, 95% CI 0.78-0.95) as independent outcome determinants. In the late thrombectomy subgroup, 14 out of 33 patients (42%) achieved a favourable clinical outcome, none of whom with poor collateral status. The presence of LC and absence of LA predicts a good outcome in acute stroke patients after successful recanalization of LVO in anterior circulation. Late thrombectomy was associated with higher rate of unfavourable clinical outcome. Nevertheless, collateral status in this subgroup was validated as a reliable selection criterion.

Clinical Implications of Prominent Cortical Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke Patients Treated with Recanalization Therapy.

Prominent cortical vessels on susceptibility-weighted imaging (PCV-SWI) correlate with poor leptomeningeal collaterals. However, little is known about PCV-SWI in recanalization therapy-treated patients with anterior circulation large vessel occlusions (LVO). We investigated PCV-SWI-based assessment of leptomeningeal collaterals and outcome predictions in 100 such patients in an observational study. We assessed PCV-SWI using the Alberta Stroke Program Early CT Score and evaluated leptomeningeal collaterals on multiphase CT angiography (mCTA). Predictive abilities were analyzed using multivariable logistic regression and area of receiver operating curves (AUCs). The extent of PCV-SWI correlated with leptomeningeal collaterals on mCTA (Spearman test, r = 0.77; p < 0.001); their presence was associated with worse functional outcomes and a lower successful recanalization rate (adjusted odds ratios = 0.24 and 0.23, 95% CIs = 0.08-0.65 and 0.08-0.65, respectively). The presence of PCV-SWI predicted outcomes better than good collaterals on mCTA did (C-statistic = 0.84 vs. 0.80; 3-month modified Rankin Scale (mRS) 0-2 = 0.75 vs. 0.67 for successful recanalization). Comparison of AUCs showed that they had similar abilities for predicting outcomes (p = 0.68 for 3-month mRS 0-2; p = 0.23 for successful recanalization). These results suggest that PCV-SWI is a useful feature for assessing leptomeningeal collaterals in acute ischemic stroke patients with anterior circulation LVO and predicting outcomes after recanalization therapy.

The Hyperdense middle cerebral artery sign is associated with poor leptomeningeal collaterals in acute ischemic stroke: a retrospective study.

BACKGROUND: The hyperdense middle cerebral artery sign (HMCAS) is an early radiological marker to provide an early diagnosis and to identify ischemia. As reported, HMCAS is associated with heavy clot burden. Moreover, a heavy clot burden may cause obstruction of the orifices of arteries for leptomeningeal collateral flows and can lead to severe clinical conditions. However, the direct relationship between HMCAS and collateral flows remains unclear. Therefore, we explored the association between HMCAS and leptomeningeal collaterals in patients with acute ischemic stroke. METHODS: Consecutive ischemic stroke patients were enrolled from January 2015 to April 2021. HMCAS appearance and collateral status were detected by multimodal computed tomography at admission. Logistic regression analyses helped to identify the association between HMCAS, collateral flows and stroke severity. RESULTS: In 494 included patients, 180 (36.4%) presented with HMCAS. Ipsilateral collaterals were not seen or less prominent in patients with HMCAS (P < 0.001). The HMCAS appearance was significantly associated with less collaterals (odds ratio 5.17, 95% confidence interval 3.27-8.18, P < 0.001), internal carotid artery + M1/M1 occlusion, the initial stroke severity and follow-up outcomes. Subgroup analyses further confirmed HMCAS as an indicator of poor collaterals in ischemic stroke (all P values < 0.05). CONCLUSIONS: HMCAS is associated with poor leptomeningeal collaterals, the stroke severity and a poor neurological outcome. Therefore, the HMCAS appearance can act as an early warning sign for healthcare professionals to be alert for poor collateral flows and poor neurological outcomes in ischemic stroke patients with middle cerebral artery occlusion.

ColorViz, a New and Rapid Tool for Assessing Collateral Circulation during Stroke.

Prognosis of patients with acute ischemic stroke is strictly related to the patency and prominence of the collateral leptomeningeal pathways distal to the arterial occlusion. The gold standard for assessment of collateral circulation is conventional angiography, but it is invasive and used in selected cases. To date, the most reliable technique is multiphase CTA; currently, the available classifications of collateral circles are often complex, time-consuming, and require a trained observer. The purpose of our work is to establish the effectiveness of a new semi-automatic post-processing software (ColorViz FastStroke, GE Healthcare, Milwaukee, Wisconsin) in evaluation of collateral circulation compared to the six-point classifications of multiphase CTA already validated in literature. We selected 86 patients with anterior ischemic stroke symptoms who underwent multiphasic CTA in our emergency department. Two radiologists separately evaluated the collateral leptomeningeal vessels, analyzing respectively, the multiphase CTA (using the six-point scale and its trichotomized form) and ColorViz (using a three-point scale). Then the results were matched. We found a good correlation between the two different analyses; the main advantage of ColorViz is that, while maintaining fast diagnostic times, it allows a simpler and more immediate evaluation of collateral circulation, especially for less experienced radiologists.

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

BACKGROUND: In the event of acute ischemic stroke (AIS) due to anterior large vessel occlusion (aLVO), leptomeningeal collaterals (LMCs) status is a key factor to define the severity and functional prognosis of this disease. However, the extent of LMCs exhibits substantial variability among the patients, which is genetic determined. Long non-coding RNAs (lncRNAs) expression profiles in human peripheral blood have been found to be altered after AIS. But whether there are specific lncRNAs correlated with LMC status in aLVO has not yet been investigated. METHODS: Differential lncRNA expression panels in peripheral blood mononuclear cells (PBMCs) were assessed by microarray analysis and individual quantitative real-time polymerase chain reaction (RT-PCR) in three independent sets consist of 134 patients with aLVO and 73 healthy controls (HCs). LMCs Status in those patients was assessed based on baseline computed tomographic angiography (CTA). RESULTS: Microarray analysis showed 23 differentially expressed lncRNAs in patients with poor LMCs status. After independent validations by RT-PCR, lncRNA ENST00000422956 was found to be significantly downregulated in patients with poor LMCs status. Receiver-operating characteristic (ROC) analysis revealed the area under the ROC curve (AUC) for ENST00000422956 to predict poor LMCs status was 0.749. Moreover, ENST00000422956 expression level and baseline National Institutes of Health Stroke Scale (NIHSS) score were identified as independent predictors for impaired LMCs, and a significantly positive correlation was observed between ENST00000422956 expression level and LMCs status. Via cis-regulatory analysis, paired box 8 (Pax8) was identified as the target gene for ENST00000422956. CONCLUSIONS: The dysregulated lncRNA ENST00000422956 in PBMCs was associated with impairment of LMCs in patients with aLVO, suggesting that measurement of circulatory lncRNAs might be included as possible biomarkers for evaluation of LMCs status in AIS. More importantly, this might be the foundation for understand the potential roles of lncRNAs in LMCs formation after ischemic stroke.

Spatiotemporal dynamics of pial collateral blood flow following permanent middle cerebral artery occlusion in a rat model of sensory-based protection: a Doppler optical coherence tomography study.

There is a growing recognition regarding the importance of pial collateral flow in the protection from impending ischemic stroke both in preclinical and clinical studies. Collateral flow is also a major player in sensory stimulation-based protection from impending ischemic stroke. Doppler optical coherence tomography has been employed to image spatiotemporal patterns of collateral flow within the dorsal branches of the middle cerebral artery (MCA) as it provides a powerful tool for quantitative in vivo flow parameters imaging (velocity, flux, direction of flow, and radius of imaged branches). It was employed prior to and following dorsal permanent MCA occlusion (pMCAo) in rat models of treatment by protective sensory stimulation, untreated controls, or sham surgery controls. Unexpectedly, following pMCAo in the majority of subjects, some MCA branches continued to show anterograde blood flow patterns over time despite severing of the MCA. Further, in the presence of protective sensory stimulation, the anterograde velocity and flux were stronger and lasted longer than in retrograde flow branches, even within different branches of single subjects, but stimulated retrograde branches showed stronger flow parameters at 24 h. Our study suggests that the spatiotemporal patterns of collateral-based dorsal MCA flow are dynamic and provide a detailed description on the differential effects of protective sensory stimulation.

The Prognostic Value of CT-Angiographic Parameters After Reperfusion Therapy in Acute Ischemic Stroke Patients With Internal Carotid Artery Terminus Occlusion: Leptomeningeal Collateral Status and Clot Burden Score.

BACKGROUND: The objective of this study was to investigate the prognostic value of computed tomographic angiography (CTA) based on leptomeningeal collateral (LMC) status and other parameters in acute ischemic stroke (AIS) patients with internal carotid artery (ICA) terminus occlusion treated with endovascular treatment (EVT). METHODS: All eligible patients from January 2013 to December 2017 undergoing EVT were retrospectively reviewed. The regional leptomeningeal score was used to assess the LMCs on baseline CTA. The collateral status measured by the LMC score (0-20) was trichotomized into 3 groups: good (17-20), intermediate (11-16), and poor (0-10). RESULTS: Our sample included a total of 119 eligible patients (60 males; mean age, 73 years) with a median baseline National Institute of Health Stroke Scale (NIHSS) score of 14. Patients with a good LMC score had a lower baseline mean NIHSS score, a higher mean Alberta Stroke Program Early CT score, and a higher mean clot burden score (CBS). Baseline NIHSS score <15 (odds ratio [OR] 3.69 95% confidence ratio [CI]: 1.32-10.29, P = .013), CBS ≥ 6 (OR 3.97 95%CI: 1.05-14.99, P = .042), good LMC score (OR 5.14 95%CI: 1.62-16.26, P = .005) and successful recanalization (OR 11.55 95%CI: 2.72-48.99 P = .001) were independent predictors of good clinical outcomes. CONCLUSIONS: CTA-based LMC status and CBS are powerful predictors of clinical outcomes in patients with an acute ICA terminus occlusion treated with EVT.

Intracranial artery to artery spontaneous revascularization in a child.

INTRODUCTION: Intracranial artery-to-artery antegrade revascularization is a poorly recognized entity, more so when it involves main stem arteries. The etiology, appearance, and significance of this condition are not described in the literature. CASE PRESENTATION: We describe a case of spontaneous revascularization of a chronically occluded middle cerebral arterial branch by collaterals from the proximal segment reconstituting distal flow, mimicking a brain arteriovenous malformation in a 9-year old boy. We discuss the nature of these channels, presumed to be related to artery to artery collaterals that are either dilated adventitial vasa vasorum, or, more likely, leptomeningeal collaterals that are hypertrophied in response to cerebral demand. We review the literature regarding intracerebral vasa vasorum and leptomeningeal collaterals including their imaging. CONCLUSION: Recognizing the tortuous channels associated with this type of vascular abnormality as normal vessels reconsituting distal flow may prevent unnecessary and potentially dangerous treatments.

Sex Differences in the Cerebral Collateral Circulation.

Premenopausal women and intact female rodents sustain smaller cerebral infarctions than males. Several sex-dependent differences have been identified as potential contributors, but many questions remain unanswered. Mice exhibit wide variation in native collateral number and diameter (collateral extent) that is dependent on differences in genetic background, aging, and other comorbidities and that contributes to their also-wide differences in infarct volume. Likewise, variation in infarct volume correlates with differences in collateral-dependent blood flow in patients with acute ischemic stroke. We examined whether extent of pial collateral arterioles and posterior communicating collateral arteries (PComAs) differ depending on sex in young, aged, obese, hypertensive, and genetically different mice. We combined new data with meta-analysis of our previously published data. Females of C57BL/6J (B6) and BALB/cByJ (BC) strains sustained smaller infarctions than males after permanent MCA occlusion. This protection was unchanged in BC mice after introgression of the B6 allele of Dce1, the major genetic determinant of variation in pial collaterals among mouse strains. Consistent with this, collateral extent in these and other strains did not differ with sex. Extent of PComAs and primary cerebral arteries also did not vary with sex. No dimorphism was evident for loss of pial collateral number and/or diameter (collateral rarefaction) caused by aging, obesity, and hypertension, nor for collateral remodeling after pMCAO. However, rarefaction was greater in females with long-standing hypertension. We conclude that smaller infarct volume in female mice is not due to greater collateral extent, greater remodeling, or less rarefaction caused by aging, obesity, or hypertension.

Collateral state and the effect of endovascular reperfusion therapy on clinical outcome in ischemic stroke patients.

PURPOSE: Clinically successful endovascular therapy (EVT) in ischemic stroke requires reliable noninvasive pretherapeutic selection criteria. We investigated the association of imaging parameters including CT angiographic collaterals and degree of reperfusion with clinical outcome after EVT. METHODS: In our database, we identified 93 patients with large vessel occlusion in the anterior circulation treated with EVT. Besides clinical data, we assessed the baseline Alberta Stroke Program Early CT score (ASPECTS) on noncontrast CT (NCCT) and CT angiography (CTA) source images, collaterals (CT-CS) and clot burden score (CBS) on CTA and the degree of reperfusion after EVT on angiography. Three readers, blinded to clinical information, evaluated the images in consensus. Data-driven multivariable ordinal regression analysis identified predictors of good outcome after 90 days as measured with the modified Rankin Scale. RESULTS: Successful angiographic reperfusion (OR 26.50; 95%-CI 9.33-83.61) and good collaterals (OR 9.69; 95%-CI 2.28-59.27) were independent predictors of favorable outcome along with female sex (OR 0.35; 95%-CI 0.14-0.85), younger age (OR 0.88; 95%-CI 0.83-0.92) and higher NCCT ASPECTS (OR 2.54; 95%-CI 1.01-6.63). Outcome was best in patients with good collaterals and successful reperfusion, but there was no statistical interaction between collaterals and reperfusion. CONCLUSIONS: CTA-collateral status was the strongest pretherapeutic predictor of favorable outcome in ischemic stroke patients treated with EVT. CTA-collaterals are thus well suited for patient selection in EVT. However, the independent effect of reperfusion on outcome tended to be stronger than that of CTA-collaterals.

Ipsilateral Sinus Hypoplasia and Poor Leptomeningeal Collaterals as Midline Shift Predictors.

BACKGROUND: We explore the role of dural sinus morphology, leptomeningeal collaterals, and clot localization in the development of malignant brain edema in acute ischemic stroke in anterior circulation. METHODS: This is a single-center retrospective study of consecutive stroke patients with acute occlusion (middle cerebral artery M1 ± intracranial internal carotid artery) treated with intravenous thrombolysis (from November 2009 to November 2014). Admission computed tomography angiography data were evaluated for hypoplasia of dural sinuses, leptomeningeal collaterals, and clot location. Primary outcome was midline shift (<5 mm versus ≥5 mm) on follow-up computed tomography. Secondary outcomes were infarct volume and modified Rankin Scale score of 2 or lower at 90 days. Multivariate logistic regression was used. RESULTS: Of 86 patients (49 females), 36 (42%) had poor collaterals, 26 (30%) had ipsilesional sinus hypoplasia, and 38 (44%) had proximal clots. A midline shift of 5 mm or higher was diagnosed in 14 patients (16%). Infarct volume was larger in the group with midline shift (median: 318 mL [interquartile range {IQR} = 260-350]) than in the group without midline shift (median: 44 mL [IQR = 28-60]) (P = .007). In multivariate analysis, poor leptomeningeal collaterals (odds ratio [OR] = .11, 95% confidence interval [CI] = .03-.44, P = .002 for good collaterals) and ipsilesional sinus hypoplasia (OR = 6.43, 95% CI = 1.5-46.1, P = .008) were independently associated with a midline shift of 5 mm or higher. CONCLUSION: Patients with poor leptomeningeal collaterals and ipsilesional hypoplasia of dural sinuses are more likely to develop midline shift.

Cerebral collaterals and collateral therapeutics for acute ischemic stroke.

Cerebral collaterals are vascular redundancies in the cerebral circulation that can partially maintain blood flow to ischemic tissue when primary conduits are blocked. After occlusion of a cerebral artery, anastomoses connecting the distal segments of the MCA with distal branches of the ACA and PCA (known as leptomeningeal or pial collaterals) allow for partially maintained blood flow in the ischemic penumbra and delay or prevent cell death. However, collateral circulation varies dramatically between individuals, and collateral extent is significant predictor of stroke severity and recanalization rate. Collateral therapeutics attempt to harness these vascular redundancies by enhancing blood flow through pial collaterals to reduce ischemia and brain damage after cerebral arterial occlusion. While therapies to enhance collateral flow remain relatively nascent neuroprotective strategies, experimental therapies including inhaled NO, transient suprarenal aortic occlusion, and electrical stimulation of the parasympathetic sphenopalatine ganglion show promise as collateral therapeutics with the potential to improve treatment of acute ischemic stroke.

Occurence and variability in acute formation of leptomeningeal collaterals in proximal middle cerebral artery occlusion.

BACKGROUND: We performed this study to semi-quantitatively characterize the formation of leptomeningeal collaterals in acute middle cerebral artery (MCA) occlusion caused by intravascular balloon inflation. METHODS: The anatomic extent of leptomeningeal collateral blood flow from the anterior cerebral artery territory to the MCA territory during occlusion of the M1 segment was graded based on angiographically visible retrograde reconstitution of the MCA segments on the delayed venous phase prior to and during inflation of the balloon. RESULTS: During MCA occlusion, the leptomeningeal collaterals markedly improved in 5 of 7 patients and were graded as 1 (retrograde filling of distal M1 segment) in 3 patients, 2 (retrograde filling of proximal M2 segment) in 1 patient, 4 (retrograde filling of M3 segment) in 1 patient and 5 (none or minimal) in 2 patients. CONCLUSION: Leptomeningeal collaterals from the anterior cerebral artery can form rapidly during MCA occlusion with considerable individual variability.

Leptomeningeal collaterals in acute ischemic stroke.

INTRODUCTION: The leptomeningeal collaterals are a subsidiary network of vascular channels that act as anastomotic channels in conditions where cerebral blood flow is pathologically altered. These secondary collateral pathways may be utilized when collateral flow through the circle of Willis is inadequate. SUMMARY OF REVIEW: The review highlights the importance of leptomeningeal (pial) anastomoses in the brain especially in conditions of hemodynamic impairment such as ischemic stroke. The historical perspective regarding the role of these vessels is discussed. New advancements in the diagnostic and treatment modalities for the evaluation and optimization of these vessels are identified. CONCLUSION: Evaluation and optimization of the leptomeningeal collaterals in ischemic stroke represents an important venue in prevention and treatment of cerebral ischemia.