Collaterals and stroke reperfusion: Too few leads to too much.

Adequate reperfusion after ischemic stroke is a major determinant of functional outcome yet remains unpredictable and insufficient for most survivors. In this issue of Neuron, Binder et al.1 identify leptomeningeal collaterals (LMCs) in mice and human patients as a key factor in regulating reperfusion and hemorrhagic transformation following stroke.

[Correlation between insulin resistance and coronary collateral circulation in patients with chronic total coronary occlusion].

OBJECTIVE: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism. METHODS: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis. RESULTS: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways. CONCLUSION: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

The Los Angeles motor scale (LAMS) is independently associated with CT perfusion collateral status markers.

BACKGROUND AND AIM: The Los Angeles Motor Scale (LAMS) is an objective tool that has been used to rapidly assess and predict the presence of large vessel occlusion (LVO) in the pre-hospital setting successfully in several studies. However, studies assessing the relationship between LAMS score and CT perfusion collateral status (CS) markers such as cerebral blood volume (CBV) index, and hypoperfusion intensity ratio (HIR) are sparse. Our study therefore aims to assess the association of admission LAMS score with established CTP CS markers CBV Index and HIR in AIS-LVO cases. MATERIALS AND METHODS: In this prospectively collected, retrospectively reviewed analysis, inclusion criteria were as follows: a) CT angiography (CTA) confirmed anterior circulation LVO from 9/1/2017 to 10/01/2023, and b) diagnostic CT perfusion (CTP). Logistic regression analysis was performed to assess the relationship between admission LAMS with CTP CS markers HIR and CBV Index. p ≤ 0.05 was considered significant. RESULTS: In total, 285 consecutive patients (median age = 69 years; 56 % female) met our inclusion criteria. Multivariable logistic regression analysis adjusting for sex, age, ASPECTS, tPA, premorbid mRS, admission NIH stroke scale, prior history of TIA, stroke, atrial fibrillation, diabetes mellitus, hyperlipidemia, coronary artery disease and hypertension, admission LAMS was found to be independently associated with CBV Index (adjusted OR:0.82, p < 0.01), and HIR (adjusted OR:0.59, p < 0.05). CONCLUSION: LAMS is independently associated with CTP CS markers, CBV index and HIR. This finding suggests that LAMS may also provide an indirect estimate of CS.

Retrospective Evaluation of the Effect of Lumbar Sympathetic Blockade on Pain Scores, Fontaine Classification, and Collateral Perfusion Status in Patients with Lower Extremity Peripheral Arterial Disease.

Background and Objectives: The aim of this retrospective study was to evaluate the effect of lumbar sympathetic block (LSB) on pain scores, Fontaine Classification, and collateral perfusion status in patients with lower extremity peripheral artery disease (PAD), in whom revascularization is impossible. Material and Methods: Medical records of 21 patients with PAD who underwent LSB with a combination of local anesthetics, steroids, and patient follow-up forms containing six-month follow-ups between January 2020 and March 2021 were retrospectively reviewed. Numeric Rating Scale (NRS), Pain Detect Questionnaire (PDQ) scores, Fontaine Classification Stages, and collateral perfusion status (collateral diameter and/or development of neovascularization) evaluated by arterial color Doppler Ultrasound (US) from the medical records and follow-up forms of the patients were reviewed. Results: NRS and PDQ scores were significantly lower, and regression of the Fontaine Classification Stages was significantly better after the procedure at the first, third, and sixth month than at the baseline values (p < 0.001). Only four patients (19%) had collaterals before the procedure. An increase in the collateral diameter after LSB was noted in three out of four patients. Before the procedure, 17 patients had no prominent collateral. However, in thirteen of these patients, after LSB, neovascularization was detected during the six-month follow-up period (three patients in the first month, seven patients in the third month, and thirteen patients in the sixth month). The number of patients evolving neovascularization after LSB was found to be statistically significant at the third and sixth months compared to the initial examination (p < 0.001). Conclusions: LSB with the use of local anesthetic and steroids in patients with lower extremity PAD not only led to lower NRS and PDQ scores, but also resulted in regressed Fontaine Classification Stages and better collateral perfusion status.

Prognostic Nutritional Index is Associated with the Degree of Coronary Collateral Circulation in Stable Angina Patients with Chronic Total Occlusion. / O Índice Nutricional Prognóstico está Associado ao Grau de Circulação Colateral Coronariana em Pacientes com Angina Estável e Oclusão Total Crônica.

BACKGROUND: Coronary collateral circulation (CCC) can effectively improve myocardial blood supply to the area of CTO (chronic total coronary occlusion) and can, thus, improve the prognosis of patients with stable coronary syndrome (SCS). The degree of inflammation and some inflammation markers were associated with the development of collaterals. OBJECTIVE: To investigate whether prognostic nutritional index (PNI) has an association with the development of CCC in patients with SCS. METHODS: A total of 400 SCS patients with the presence of CTO in at least one major epicardial coronary artery were included in this study. The patients were divided into two groups according to the Rentrop score. Scores of 0 to 1 were considered poor developed CCC, and scores of 2 to 3 were accepted as good developed CCC. Statistical significance was set as a p-value < 0.05 for all analyses. RESULTS: The mean age of the study cohort was 63±10 years; 273 (68.3%) were males. The poor-developed CCC group had a significantly lower PNI level compared with the good-developed CCC group (38.29±5.58 vs 41.23±3.85, p< 0.001). In the multivariate analysis, the PNI (odds ratio 0.870; 95% confidence interval 0.822-0.922; p< 0.001) was an independent predictor of poorly developed CCC. CONCLUSION: The PNI can be used as one of the independent predictors of CCC formation. It was positively associated with the development of coronary collaterals in SCS patients with CTO.

FUNDAMENTO: A circulação colateral coronária (CCC) pode efetivamente melhorar o suprimento sanguíneo miocárdico para a área de OCT (oclusão coronariana total crônica) e pode, assim, melhorar o prognóstico de pacientes com síndrome coronariana estável (SCE). O grau de inflamação e alguns marcadores de inflamação foram associados ao desenvolvimento de colaterais. OBJETIVO: Investigar se o índice nutricional prognóstico (INP) tem associação com o desenvolvimento de CCC em pacientes com SCE. MÉTODOS: Um total de 400 pacientes com SCE com presença de OTC em pelo menos uma importante artéria coronária epicárdica foi incluído neste estudo. Os pacientes foram divididos em dois grupos de acordo com o escore Rentrop. Escores de 0 a 1 foram considerados CCC pouco desenvolvidas e escores de 2 a 3 foram aceitos como CCC bem desenvolvidas. A significância estatística foi definida como um valor p < 0,05 para todas as análises. RESULTADOS: A média de idade da coorte do estudo foi de 63±10 anos; 273 (68,3%) eram do sexo masculino. O grupo CCC pouco desenvolvido apresentou um nível de INP significativamente mais baixo em comparação com o grupo CCC bem desenvolvido (38,29±5,58 vs 41,23±3,85, p<0,001). Na análise multivariada, o INP (odds ratio 0,870; intervalo de confiança de 95% 0,822-0,922; p<0,001) foi um preditor independente de CCC pouco desenvolvida. CONCLUSÃO: O INP pode ser utilizado como um dos preditores independentes da formação do CCC. Foi positivamente associado ao desenvolvimento de colaterais coronárias em pacientes com SCE com OTC.

Transcoronary Gradients of Mechanosensitive MicroRNAs as Predictors of Collateral Development in Chronic Total Occlusion.

Background and Objectives: In this present study, we investigated the impact of mechanosensitive microRNAs (mechano-miRs) on the collateral development in 126 chronic total occlusion (CTO) patients, selected from 810 undergoing angiography. Materials and Methods: We quantified the collateral blood supply using the collateral flow index (CFI) and assessed the transcoronary mechano-miR gradients. Results: The patients with favorable collaterals had higher CFI values (0.45 ± 0.02) than those with poor collaterals (0.38 ± 0.03, p < 0.001). Significant differences in transcoronary gradients were found for miR-10a, miR-19a, miR-21, miR-23b, miR-26a, miR-92a, miR-126, miR-130a, miR-663, and let7d (p < 0.05). miR-26a and miR-21 showed strong positive correlations with the CFI (r = 0.715 and r = 0.663, respectively), while let7d and miR-663 were negatively correlated (r = -0.684 and r = -0.604, respectively). The correlations between cytokine gradients and mechano-miR gradients were also significant, including Transforming Growth Factor Beta with miR-126 (r = 0.673, p < 0.001) and Vascular Endothelial Growth Factor with miR-10a (r = 0.602, p = 0.002). A regression analysis highlighted the hemoglobin level, smoking, beta-blocker use, miR-26a, and miR-663 as significant CFI determinants, indicating their roles in modulating the collateral vessel development. Conclusions: These findings suggest mechanosensitive microRNAs as predictive biomarkers for collateral circulation, offering new therapeutic perspectives for CTO patients.

MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study.

BACKGROUND: Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). METHODS: We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. FINDINGS: Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40-94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4-569.6] vs 441 [IQR 223.4-731.5] ng/ml, p < 0.0001) but not MMP-2 concentrations were increased within collateral blood vessels. The median MMP-9 expression level of invading neutrophils was elevated (fluorescence intensity, arbitrary unit: 2276 [IQR 1007-5086] vs 3078 [IQR 1108-7963], p = 0.0018). Gelatine zymography experiments indicated the locally confined proteolytic activity of MMP-9 but not of MMP-2. Pretherapeutic MMP-9 release into stroke-affected brain regions predicted the degree of intracerebral haemorrhages and clinical stroke severity after recanalisation, and independently increased the odds of space-occupying parenchymal haematomas (HBC1c-3a) by 1.54 times, and the odds of severe disability or death (mRS ≥5 at hospital discharge) by 2.33 times per 1000 ng/ml increase. Excessive concentrations of MMP-9 indicated impending parenchymal haematomas and severe disability or death with high specificity. INTERPRETATION: Measurement of MMP-9 within collateral blood vessels is feasible and identifies patients with stroke at risk of major intracerebral haemorrhages and poor outcome before therapeutic recanalisation by EVT, thereby providing evidence of the concept validity of ultra-early local stroke biomarkers. FUNDING: This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Würzburg.

Circulating Progenitor Cells and Coronary Collaterals in Chronic Total Occlusion.

BACKGROUND: The role of circulating progenitor cells (CPC) in collateral formation that occurs in the presence of chronic total occlusions (CTO) of a coronary artery is not well established. In stable patients with a CTO, we investigated whether CPC levels are associated with (a) collateral development and (b) ischemic burden, as measured by circulating high sensitivity troponin-I (hsTn-I) levels. METHODS: CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34 and both CD34 and CD133 epitopes. The association between CPC counts and both Rentrop collateral grade (0, 1, 2, or 3) and hsTn-I levels were evaluated using multivariate regression analysis, after adjusting for demographic and clinical characteristics. RESULTS: In 89 patients (age 65.5, 72% male, 27% Black), a higher CPC count was positively associated with a higher Rentrop collateral grade; [CD34+ adjusted odds ratio (OR) 1.49 95% confidence interval (CI) (0.95, 2.34) P = 0.082] and [CD34+/CD133+ OR 1.57 95% CI (1.05, 2.36) P = 0.028]. Every doubling of CPC counts was also associated with lower hsTn-I levels [CD34+ ß -0.35 95% CI (-0.49, -0.15) P = 0.002] and [CD34+/CD133+ ß -0.27 95% CI (-0.43, -0.08) P = 0.009] after adjustment. CONCLUSION: Individuals with higher CPC counts have greater collateral development and lower ischemic burden in the presence of a CTO.

Association of Carotid Artery Disease with Collateralization and Infarct Growth in Patients with Acute Middle Cerebral Artery Occlusion.

BACKGROUND AND PURPOSE: Collaterals are important in large vessel occlusions (LVO), but the role of carotid artery disease (CAD) in this context remains unclear. This study aimed to investigate the impact of CAD on intracranial collateralization and infarct growth after thrombectomy in LVO. MATERIALS AND METHODS: All patients who underwent thrombectomy due to M1 segment occlusion from 01/2015 to 12/2021 were retrospectively included. Internal carotid artery stenosis according to NASCET was assessed on the affected and nonaffected sides. Collaterals were assessed according to the Tan score. Infarct growth was quantified by comparing ASPECTS on follow-up imaging with baseline ASPECTS. RESULTS: In total, 709 patients were included, 118 (16.6%) of whom presented with CAD (defined as severe stenosis ≥70% or occlusion ipsilaterally), with 42 cases (5.9%) being contralateral. Good collateralization (Tan 3) was present in 56.5% of the patients with ipsilateral CAD and 69.1% of the patients with contralateral CAD. The ipsilateral stenosis grade was an independent predictor of good collateral supply (adjusted OR: 1.01; NASCET point, 95% CI: 1.00-1.01; P = .009), whereas the contralateral stenosis grade was not (P = .34). Patients with ipsilateral stenosis of ≥70% showed less infarct growth (median ASPECTS decay: 1; IQR: 0-2) compared with patients with 0%-69% stenosis (median: 2; IQR: 1-3) (P = .005). However, baseline ASPECTS was significantly lower in patients with stenosis of 70%-100% (P < .001). The results of a multivariate analysis revealed that increasing ipsilateral stenosis grade (adjusted OR: 1.0; 95% CI: 0.99-1.00; P = .004) and good collateralization (adjusted OR: 0.5; 95% CI: 0.4-0.62; P < .001) were associated with less infarct growth. CONCLUSIONS: CAD of the ipsilateral ICA is an independent predictor of good collateral supply. Patients with CAD tend to have larger baseline infarct size but less infarct growth.

Is the collateral circulation pattern in the hard palate affected by cleft deformity?

OBJECTIVES: To evaluate the influence of collateral vascularization on surgical cleft palate closure and deformities. MATERIALS AND METHODS: Corrosion casting was performed using red-colored acrylic resin in twelve fresh adult cadavers with a normal hard palate. Additionally, white-colored barium sulfate was injected into a fetus with a unilateral complete cleft palate, and layer-by-layer tissue dissection was performed. Both substances were injected into the external carotid arteries. Corrosion casting involved dissolving the soft and hard tissues of the orofacial area utilizing an enzymatic solution. RESULTS: In normal palates, bilateral intraosseous infraorbital arteries formed a network in the premaxilla with the intraosseous nasopalatine- and greater palatine arteries (GPAs). The perforating GPAs anastomosed with the sphenopalatine artery sub-branches. Bilateral extraosseous GPA anastomoses penetrated the median palatine suture. Complex vascularization in the retrotuberal area was detected. In the cleft zone, anastomoses were omitted, whereas in the non-cleft zone, enlarged GPAs were distributed along the cleft edges and followed the anatomical course anteriorly to initiate the network with facial artery sub-branches. CONCLUSIONS: The anatomical subunits of the palate exhibited distinct anastomosis patterns. Despite omitted anastomoses with collateral circulation in the cleft zone, arteries maintained their anatomical pattern as seen in the normal specimen in the non-cleft zone. CLINICAL RELEVANCE: Based on the findings in normal- and cleft palates, surgeons may expect developed anastomosis patterns in the non-cleft zone. Due to the lack of microcirculation in the cleft zone, the existent anastomoses should be maintained as much as possible by the surgical technique. This applies anteriorly in the incisive canal territory, alveolar ridges, and posteriorly in the retrotuberal area.

Retrograde chronic total occlusion percutaneous coronary intervention via ipsilateral collaterals.

BACKGROUND: There is limited data on retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) via ipsilateral epicardial collaterals (IEC). AIMS: To compare the clinical and angiographic characteristics, and outcomes of retrograde CTO PCI via IEC versus other collaterals in a large multicenter registry. METHODS: Observational cohort study from the Prospective Global registry for the study of Chronic Total Occlusion Intervention (PROGRESS-CTO). RESULTS: Of 4466 retrograde cases performed between 2012 and 2023, crossing through IEC was attempted in 191 (4.3%) cases with 50% wiring success. The most common target vessel in the IEC group was the left circumflex (50%), in comparison to other retrograde cases, where the right coronary artery was most common (70%). The Japanese CTO score was similar between the two groups (3.13 ± 1.23 vs. 3.06 ± 1.06, p = 0.456); however, the IEC group had a higher Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score (1.95 ± 1.02 vs. 1.27 ± 0.92, p < 0.0001). The most used IEC guidewire was the SUOH 03 (39%), and the most frequently used microcatheter was the Caravel (43%). Dual injection was less common in IEC cases (66% vs. 89%, p < 0.0001). Technical (76% vs. 79%, p = 0.317) and procedural success rates (74% vs. 79%, p = 0.281) were not different between the two groups. However, IEC cases had a higher procedural complications rate (25.8% vs. 16.4%, p = 0.0008), including perforations (17.3% vs. 9.0%, p = 0.0001), pericardiocentesis (3.1% vs. 1.2%, p = 0.018), and dissection/thrombus of the donor vessel (3.7% vs. 1.2%, p = 0.002). CONCLUSION: The use of IEC for retrograde CTO PCI was associated with similar technical and procedural success rates when compared with other retrograde cases, but higher incidence of periprocedural complications.

Collateral Round Ligament Arterial Supply of Placenta Accreta Spectrum and Considerations for Prophylactic Balloon Occlusion Catheter Placement.

Internal iliac artery (IIA) balloon occlusion catheters have been commonly inserted to decrease the risk of postpartum hemorrhage in placenta accreta spectrum disorders; however, there has been mixed success in clinical studies. Placement of an infrarenal aortic balloon has shown more consistent effectiveness in recent studies. A possible reason for this is collateral arterial supply to the placenta from external iliac artery branches. Retrospective chart review was conducted of angiography images during prophylactic IIA balloon occlusion catheter insertion over a 7-year period. Sixty-two individual cases were identified. Digital subtraction angiography (DSA) was performed in 32 (52%) cases, and 20 (62%) showed collateral blood supply from branches of the external iliac arteries, namely the round ligament artery. In conclusion, a high proportion of placenta accreta spectrum cases have arterial blood supply from branches of the external iliac artery, which may explain the discrepancy in effectiveness seen between IIA and infrarenal aortic sites of balloon occlusion catheter placement.

[A case of suspected vertebral artery stump syndrome assessed by CT angiography].

A 55-year-old man developed ischemic stroke in the bilateral cerebellar hemispheres and bilateral occipital lobes. He was admitted to our hospital 17 months later with recurrent ischemic stroke in the posterior circulation. The left vertebral artery (VA) was occluded on brain magnetic resonance angiography but was visualized with a delay on continuous three-phase CT angiography (CTA). Conventional angiography confirmed a to-and-fro blood flow pattern at the distal end of the left VA, therefore the patient was diagnosed with VA stump syndrome (VASS). VASS is a recurrent posterior circulation ischemic stroke caused by thrombi in an occluded unilateral VA. VASS should be suspected in patients with unilateral VA occlusion and repeated posterior-circulation ischemic stroke. The diagnostic criteria for VASS include confirmation of VA occlusion and the presence of an antegrade flow component at the distal end. In this case, the presence of collateral circulation in the VA was suspected based on CTA findings, leading to the diagnosis of VASS. It was thus suggested that devising the imaging method of CTA may help diagnose VASS.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A thyroidea ima artery variation providing collateral circulation to the mediastinum.

The thyroidea ima artery (TIA) is a highly variable arterial deviation of the blood supply to the thyroid gland with critical implications for surgical neck procedures such as tracheostomy. Though relatively common in the population at large (~ 4%), most TIA variations are related to the origin of the artery and whether it emerges from the common sites of the brachiocephalic trunk, aortic arch, and right common carotid artery, or another more unique vessel-as opposed to its dispersion pattern. TIA variants generally supply the thyroid gland, occasionally co-occurring with absent thyroid arteries. Here, we report on a unique case of a four-pronged variation of the TIA discovered during an anatomy laboratory dissection of first-year medical students. This variant originated from the brachiocephalic trunk and had three branches terminating in the thyroid gland and a fourth branch traveling into the thorax to provide accessory circulation in the mediastinum. Specifically, small arterial branches from the inferior TIA branch supplied the anterior pericardium and surrounding adipose tissue, in addition to normal pericardiacophrenic circulation. We discuss the potential embryological and clinical relevance of this unique variation and voice further support for imaging as a requirement before surgical neck procedures to prevent catastrophic bleeding in the event of a TIA variant.

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.