Vertebrobasilar artery elongation in migraine-a retrospective cross-sectional study.

BACKGROUND: Numerous but inconclusive findings have sparked an ongoing debate about whether the arteries of migraine patients undergo vascular alterations. The outlet angle of the superior cerebellar artery (SUCA) and the lateral displacement of basilar arteries are good surrogate parameters for determining elongation of the vertebrobasilar arteries. METHODS: We retrospectively determined the SUCA outlet angle and the lateral displacement of the basilar artery in 63 patients with migraine (30.6 ± 8.9 years, 84% women, 16% chronic migraine, 60% migraine with aura) and compared these with 126 age- and sex-matched control subjects. RESULTS: In patients with migraine, the SUCA outlet angle was lower (159 ± 26° vs. 169 ± 29°, p = 0.020) and the lateral displacement of the basilar artery was greater (3.7 ± 2.7 mm vs. 2.8 ± 2.4 mm, p = 0.020) than in the control subjects. Age, gender, migraine characteristics and presence of any cardiovascular risk factors did not affect the SUCA outlet angle or lateral displacement of the basilar artery. CONCLUSION: Migraine patients exhibited a lower SUCA outlet angle and greater lateral displacement of the basilar arteries. Both may be attributable to the elongation of the vertebrobasilar arteries, which is an indication of arterial wall pathology in migraine.

One-Year Outcome After Endovascular Treatment for Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: The BASILAR registry, a nationwide prospective nonrandomized study conducted in China, enrolled consecutive patients with acute basilar artery occlusion receiving endovascular treatment or conventional-treatment from January 2014 to May 2019. This article aimed to report the results of clinical follow-up at one year among these patients. METHODS: The primary outcome was the modified Rankin Scale at one year, assessed as a common odds ratio using ordinal logistic regression analysis adjusted for prespecified prognostic factors. Secondary outcomes included the modified Rankin Scale-based outcome group at one year (0-1, 0-2, or 0-3) and all-cause death. RESULTS: Of the 829 patients enrolled in the original BASILAR registry, one-year data were available for 785 patients (94.7%). The distribution of outcomes on the modified Rankin Scale favored endovascular treatment over conventional-treatment (adjusted common odds ratio, 4.50 [95% CI, 2.81-7.29]; P<0.001). The cumulative one-year mortality rate was 54.6% in the endovascular treatment group versus 83.5% in the conventional-treatment group (adjusted odds ratio, 4.36 [95% CI, 2.69-7.29]; P<0.001). CONCLUSIONS: The beneficial effect of endovascular treatment on functional outcome at one year in patients with acute basilar artery occlusion is similar to that reported at 90 days in the original study. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Interrelations of Cerebral Hemodynamics with Parameters of Cardiac Function and Brain Tissue in Patients with Ischemic Stroke.

We analyzed interrelations between the cerebral blood flow, cardiac output, and condition of the brain substance in 530 patients with ischemic stroke. Dependencies between the linear blood flow velocities in all arteries supplying the brain, as well as between the total volume blood flow through the internal carotid arteries and left ventricular stroke volume were revealed. The severity of atrophy was maximum in the parietal lobes (median 1.5 (1.0; 2.0)) and minimum in the occipital lobes (median 0.5 (0; 1.0)). Temporal lobes cortical atrophy significantly correlated with changes in the limbic system and in the periventricular and deep white matter; a significant weak inverse correlation of this parameter with blood flow in the middle cerebral artery was also found. Changes in the periventricular white matter (but not in deep white matter) demonstrated a significant inverse correlation with blood flow in the middle and anterior cerebral arteries.

Computed Tomography Perfusion Deficit Volumes Predict Functional Outcome in Patients With Basilar Artery Occlusion.

Background and Purpose: Basilar artery occlusion is associated with high morbidity and mortality. Optimal imaging and treatment strategy are still controversial and prognosis estimation challenging. We, therefore, aimed to determine the predictive value of computed tomography perfusion (CTP) parameters for functional outcome in patients with basilar artery occlusion in the context of endovascular treatment. Methods: Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score on noncontrast computed tomography, computed tomography angiography (CTA) source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps. Good functional outcome was defined as modified Rankin Scale score ≤3 at 90 days. Statistical analysis included binary logistic regressions and receiver operating characteristics analyses. Results: Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, National Institutes of Health Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome (P<0.05). In multivariate analyses, Basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score (odds ratio range, 1.31­2.10 [95% CI, 1.00­7.24]), and perfusion deficit volumes on all CTP maps (odds ratio range, 0.77­0.98 [95% CI, 0.63­1.00]) remained as independent outcome predictors. Cerebral blood flow deficit volume yielded the best performance for the classification of good clinical outcome with an area under the curve of 0.92 (95% CI, 0.84­0.99). Age and admission National Institutes of Health Stroke Scale had lower discriminatory power (area under the curve, <0.7). Conclusions: CTP imaging parameters contain prognostic information for functional outcome in patients with stroke due to basilar artery occlusion and may identify patients with higher risk of disability at an early stage of hospitalization.

Evaluation of hemodynamic characteristics in posterior circulation infarction patients with vertebral artery dominance by color doppler flow imaging and transcranial doppler sonography.

PURPOSE: The aim of this study was to investigate the hemodynamic characteristics of posterior circulation infarction (PCI) patients with the vertebral artery dominance (VAD) using Color Doppler flow imaging (CDFI) and Transcranial Doppler sonography (TCD) and to explore the pathogenesis of PCI caused by VAD. MATERIALS AND METHODS: A total of 186 consecutive PCI patients were enrolled. All the patients underwent magnetic resonance (MR) examination and the clinical data were collected. According to the brain magnetic resonance angiography (MRA), the patients were divided into VAD and non-VAD groups. CDFI and TCD were performed to identify the hemodynamic parameters of the vertebral artery (VA) and basilar artery (BA). RESULTS: The male population was significantly more frequent in the VAD group (71.3%) as compared to the non-VAD group (53.1%). The significant difference in hemodynamic parameters was observed between VAD and non-VAD groups. Resistance index (RI) of extracranial and intracranial VA was different as well. There were also differences in the VA side-to-side diameter difference-value, peak velocity (Vp), mean velocity (Vm) and pulsatility index (PI) with varying degrees of BA curvature. CONCLUSIONS: VA and BA hemodynamic changes caused by VAD may be an important risk factor in the process of occurrence of PCI. The combination of CDFI and TCD can help to detect the hemodynamic changes in the intracranial and extracranial segments of VA and BA. This can have important clinical value in understanding the pathogenesis of PCI.

Quantification of Cerebral Perfusion using Laser Speckle Imaging and Infarct Volume using MRI in a Pre-clinical Model of Posterior Circulation Stroke.

BACKGROUND: Basilar artery occlusion (BAO) is a subset of posterior circulation stroke that carries a mortality as high as 90%.  The current clinical standard to diagnose ischemic stroke include computerized tomography (CT), CT angiography and perfusion and magnetic resonance imaging (MRI). Large animal pre-clinical models to accurately reflect the clinical disease as well as methods to assess stroke burden and evaluate treatments are lacking. METHODS: We describe a canine model of large vessel occlusion (LVO) stroke in the posterior circulation, and developed a laser speckle imaging (LSI) protocol to monitor perfusion changes in real time.  We then utilized high b-value DWI (b=1800s/mm2) MRI to increase detection sensitivity. We also evaluated the ability of magnetic resonance angiography (MRA) to assess arterial occlusion and correlate with DSA. Finally, we verified infarct size from apparent diffusion coefficient (ADC) mapping with histology.  Results:  Administration of thromboembolism occluded the basilar artery as tracked by DSA (n=7).   LSI correlated with DSA, demonstrating a reduction in perfusion after stroke onset that persisted throughout the experiment, allowing us to monitor perfusion in real time.  DWI with an optimized b-value for dogs illustrated the stroke volume and allowed us to derive ADC and magnetic resonance angiography (MRA) images. The MRA performed at the end of the experiment correlated with DSA performed after occlusion. Finally, stroke burden on MRI correlated with histology. CONCLUSIONS: Our studies demonstrate real time perfusion imaging using LSI of a canine thromboembolic LVO model of posterior circulation stroke, which utilizes multimodal imaging important in the diagnosis and treatment of ischemic stroke.

Exosomal microRNA-23b-3p from bone marrow mesenchymal stem cells maintains T helper/Treg balance by downregulating the PI3k/Akt/NF-κB signaling pathway in intracranial aneurysm.

Bone marrow mesenchymal stem cells (BMSCs) are involved in cancer initiation and metastasis, and sometimes mediate cell communication by releasing exosomes and delivering microRNAs (miRNAs). The study aims to investigate the effects of exosomal hsa-miR-23b-3p derived from human BMSCs on intracranial aneurysm (IA). Firstly, human BMSCs-derived exosomes were extracted by ultra-high speed centrifugation. After clinical specimen collection, imbalance of T helper (Th) 17/Treg was found in patients with IA. Then, basilar artery aneurysm models were established and BMSCs-derived exosomes were isolated and identified. The results showed that BMSCs-derived exosomes improved pathological remodeling of IA wall, upregulated the contractile phenotype and inhibited the secretory phenotype of smooth muscle cells and reduced the number of Th17 cells to maintain the balance of Th17/Treg. In addition, human BMSCs-derived exosomes inhibited the activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway and maintained Th17/Treg balance, which in turn interfered with aneurysm formation. Finally, the targeting relationship between hsa-miR-23b-3p and KLF5 was confirmed. We further noted that BMSCs-derived exosomal hsa-miR-23b-3p inhibited IA formation by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway. All in all, our study concluded that BMSCs-derived exosomal hsa-miR-23b-3p could maintain Th17/Treg balance by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway, thus inhibit IA formation.

Changes in the cerebrospinal fluid lipid profile following subarachnoid hemorrhage in a closed cranium model: Correlations to cerebral vasospasm, neuronal cell death and Interleukin-6 synthesis. A pilot study.

BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.

Delayed extensive brain edema caused by the growth of a giant basilar apex aneurysm treated with basilar artery obliteration: a case report.

BACKGROUND: Partially thrombosed giant aneurysms at the basilar apex (BA) artery are challenging lesions with a poor prognosis if left untreated. Here we describe a rare case of extensive brain edema after growth of a surgically treated and thrombosed giant basilar apex aneurysm. CASE PRESENTATION: We performed a proximal surgical basilar artery occlusion on a 64-year-old female with a partially thrombosed giant BA aneurysm. MRI showed no ischemic lesions but showed marked edema adjacent to the aneurysm. She had a good recovery, but 3 months after surgical occlusion, her gait deteriorated together with urinary incontinence and worsening right hemiparesis. MRI showed that the aneurysm had grown and developed intramural hemorrhage, which caused extensive brain edema and obstructive hydrocephalus. She was treated by a ventriculoperitoneal shunt placement. Follow-up MRI showed progressive brain edema resolution, complete thrombosis of the lumen and shrinkage of the aneurysm. At 5 years follow-up the patient had an excellent functional outcome. CONCLUSIONS: Delayed growth of a surgically treated and thrombosed giant aneurysm from wall dissection demonstrates that discontinuity with the initial parent artery does not always prevent progressive enlargement. The development of transmural vascular connections between the intraluminal thrombus and adventitial neovascularization by the vasa vasorum on the apex of the BA seems to be a key event in delayed aneurysm growth. Extensive brain edema might translate an inflammatory edematous reaction to an abrupt enlargement of the aneurysm.

Increased tortuosity of basilar artery might be associated with higher risk of aneurysm development.

OBJECTIVES: We analysed tortuosity of basilar artery (BA) to determine its relationship with the presence of aneurysm. METHODS: We retrospectively analysed 71 patients with BA aneurysms along with 71 age- and risk factors-matched control patients without BA aneurysm. From patients' medical records, we obtained their history including previous and current diseases and medications. For each patient, we calculated relative length (RL), sum of angle metrics (SOAM), triangular index (TI), product of angle distance (PAD) and inflexion count metrics (ICM). We used t-test and Mann-Whitney U test for continuous variables and χ2 test for dichotomised variables. To find independent predictors of BA aneurysm, we employed logistic regression analysis. RESULTS: We found significant positive correlation between age and SOAM (R = 0.195, p = 0.02) and PAD (R = 0.199, p = 0.018). Our study also showed that patients with BA aneurysm had significantly higher SOAM (0.21 ± 0.16 vs. 0.11 ± 0.08; p < 0.01), PAD (0.30 ± 0.19 vs. 0.18 ± 0.11; p < 0.01), TI (0.23 ± 0.23 vs. 0.10 ± 0.16; p < 0.01) and ICM (0.20 ± 0.16 vs. 0.15 ± 0.11; p = 0.045). In multivariate logistic regression analysis, after adjustment for all possible confounders, SOAM (OR = 1.086; 95% CI 1.046-1.136; p < 0.01) and TI (OR = 1.004; 95%C: 1.002-1.006; p < 0.01) remained independently associated with higher risk of BA aneurysm. CONCLUSIONS: Increased tortuosity of BA is associated with higher risk of its aneurysm development. KEY POINTS: • Basilar artery sum of angle metrics and product of angle distance are correlated with age. • Basilar artery tortuosity is independently associated with higher risk of its aneurysm development. • Basilar artery tortuosity is positively correlated with its diameter and bifurcation angle.

Mechanical Thrombectomy for Tandem Vertebrobasilar Stroke: Characteristics and Treatment Outcome.

Background and Purpose- Tandem vertebrobasilar strokes are not well-known causes of posterior circulation stroke. The purpose of this study was to investigate the characteristics and outcome of mechanical thrombectomy in patients with tandem vertebrobasilar stroke. Methods- Acute basilar artery occlusion patients with tandem vertebral artery (VA) stenosis/occlusion who underwent mechanical thrombectomy were retrospectively analyzed. Concomitant tandem VA steno-occlusion was defined as severe stenosis/occlusion of the extracranial VA with impaired flow. Clinical/angiographic characteristics, recanalization rate, procedure time, and clinical outcome were evaluated with comparisons according to the treatment strategy. Results- Tandem vertebrobasilar occlusion was identified in 24.6% (55 of 224) of the acute basilar artery occlusion patients. Overall successful recanalization and good clinical outcome was achieved in 87.2% (48 of 55) and 30.9% (17 of 55) of the patients. There were no significant differences in procedure time, recanalization rate, and clinical outcome in comparisons of the VA access route selection or angioplasty of the tandem VA lesion. Two patients developed short-term recurrent basilar artery occlusion when angioplasty of the tandem VA lesion was not performed. Good clinical outcome was more likely with lower baseline National Institutes of Health Stroke Scale score (odds ratio, 0.87 [95% CI, 0.787-0.961]; P=0.006) and short onset-to-recanalization time (odds ratio, 0.993 [95% CI, 0.987-0.999]; P=0.03). Conclusions- Tandem vertebrobasilar occlusion may be a frequent pathological mechanism of posterior circulation stroke. Good outcome may be achieved by strategic choice of the access route and selective angioplasty of the tandem VA lesion.

Correlation between Arteriole Membrane Potential and Cerebral Vasospasm after Subarachnoid Hemorrhage in Rats.

OBJECTIVES: Microvessel constriction plays an important role in delayed cerebral ischemia after aneurismal subarachnoid hemorrhage (SAH). This constriction has been demonstrated in both animal model and clinical operation. The present study examined the time-related membrane potential (Em) alteration of arterioles isolated from SAH model rats and the correlation between the potential alteration of arterioles and the diameter of basilar artery. MATERIALS AND METHODS: Sprague-Dawley rats (n = 90), weighing 300 g to 350 g, were divided into t control, sham, and SAH groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats. The Em of arterioles and basilar artery diameter was measured using whole-cell clamp recordings and pressure myograph, respectively, 1, 3, 5, 7, and 14 days after SAH. The correlation was evaluated using Pearson correlation coefficients. RESULTS: The Em of arterioles in the SAH group depolarized on days 3, 5, and 7, and peaked on day 7. The diameters significantly decreased on days 1, 3, 5, 7, and 14, and the smallest diameter was observed on day 7. A significant correlation between potential alteration of arterioles and diameter of basilar artery was found. CONCLUSIONS: Similar to the artery, arteriole constriction is also involved in the pathophysiological events of delayed cerebral ischemia.

Influence of Vertebrobasilar Stenotic Lesion Rigidity on the Outcome of Angioplasty and Stenting.

Stenotic lesion rigidity (SLR) has an unclear influence on the outcome of percutaneous transluminal angioplasty and stenting (PTAS) for intracranial arterial stenosis. This study evaluated the outcome of PTAS and the relationship of vertebrobasilar SLR to features on vessel wall MRI (VW-MRI) for identifying pathologies of vertebrobasilar stenosis (VBS) and evaluating PTAS outcome. We retrospectively evaluated the results of PTAS in 31 patients with severe VBS. Stenotic lesions were classified as soft (based on predilatation pressure [PP] ≦ 4 atm) in 15 patients or hard (PP >4 atm) in 16 patients. We examined the relationship of SLR to clinical and MR findings. Patients with hard vs soft lesions had atherosclerosis (8/16 [50.0%] vs 2/15 [13.3%]), dissection (0/16 [0.0%] vs 12/15 [80.0%]), and dissection in atherosclerosis (8/16 [50.0%] vs 1/15 [6.7%], P < 0.0001); high intensity signal on the T1WI of VW-MRI (5/16 [31.3%] vs 14/15 [93.3%]) and iso- to low intensity signal (11/16 [68.7%] vs 1/15 [6.7], P = 0.001), and significant in-stent restenosis (>50%) in 5/15 (33.3%) vs 0/15 (0.0%) (P = 0.0421) in the 30 patients who successfully completed PTAS. Vertebrobasilar SLR correlated well with lesion etiology, findings on VW-MRI, and PTAS outcome. Patients with hard stenotic lesions need close follow-up after PTAS.

Anatomical Variations of Vertebrobasilar Artery are Closely Related to the Occurrence of Vertebral Artery Dissection-An MR Angiography Study.

GOAL: Intracranial arterial dissection is a major cause of ischemic stroke and subarachnoid hemorrhage in relatively young patients. We assessed the hypothesis that the tortuosity of the vertebrobasilar artery is associated with the occurrence of vertebral artery (VA) dissection, using MR angiography (MRA). MATERIALS AND METHODS: This study enrolled 43 patients with VA dissection, and 63 age- and sex-matched healthy subjects were used as the controls. MRA was employed to evaluate the presence of dominant VA and the lateral shift of vertebrobasilar junction in both groups. The VA diameters were considered different when the difference was greater than .3 mm. These anatomical variations were divided into 3 types: Type 1 (vertebrobasilar junction within 2 mm from the midline), Type 2 (>2 mm-lateral shift of vertebrobasilar junction to the ipsilateral side of the dominant VA), and Type 3 (>2 mm-lateral shift of vertebrobasilar junction to the contralateral side of the dominant VA). FINDINGS: The presence of dominant VA and the lateral shift of vertebrobasilar junction were more prevalent in patients with VA dissection than in the controls (OR: 3.46, P = .013, and OR: 4.51, P = .001, respectively). The lateral shift of vertebrobasilar junction was classified into Type 1 (n = 6), Type 2 (n = 13), and Type 3 (n = 17) among patients with VA dissection, while into Type 1 (n = 20), Type 2 (n = 8), and Type 3 (n = 7) among the controls. Type 3 predominance was observed in patients with VA dissection (P = .02). CONCLUSIONS: Anatomical variations of the vertebrobasilar artery may play an important role in the occurrence of VA dissection.

Large Vessel Occlusion in Acute Ischemic Stroke Patients: A Dual-Center Estimate Based on a Broad Definition of Occlusion Site.

BACKGROUND: Accurate assessment of the frequency of large vessel occlusion (LVO) is important to determine needs for neurointerventionists and thrombectomy-capable stroke facilities. Current estimates vary from 13% to 52%, depending on acute ischemic stroke (AIS) definition and methods for AIS and LVO determination. We sought to estimate LVO prevalence among confirmed and suspected AIS patients at 2 comprehensive US stroke centers using a broad occlusion site definition: internal carotid artery (ICA), first and second segments of the middle cerebral artery (MCA M1,M2), the anterior cerebral artery, vertebral artery, basilar artery, or the proximal posterior cerebral artery. METHODS: We analyzed prospectively maintained stroke databases of patients presenting to the centers between January and December 2017. ICD-10 coding was used to determine the number of patients discharged with an AIS diagnosis. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) was reviewed to determine LVO presence and site. Percentages of patients with LVO among the confirmed AIS population were reported. RESULTS: Among 2245 patients with an AIS discharge diagnosis, 418 (18.6%:95% confidence interval [CI] 17.3%-20.0%) had LVO documented on CTA or MRA. Most common occlusion site was M1 (n=139 [33.3%]), followed by M2 (n=114 [27.3%]), ICA (n=69[16.5%]), and tandem ICA-MCA lesions (n=44 [10.5%]). Presentation National Institutes of Health Stroke Scale scores were significantly different for different occlusion sites (P=.02). CONCLUSIONS: The LVO prevalence in our large series of consecutive AIS patients was 18.6% (95% CI 17.3%-20.0%). Despite the use of a broad definition, this estimate is less than that reported in most previous studies.

Migraine Genetic Variants Influence Cerebral Blood Flow.

OBJECTIVE: To investigate the association of migraine genetic variants with cerebral blood flow (CBF). BACKGROUND: Migraine is a common disorder with many genetic and non-genetic factors affecting its occurrence. The exact pathophysiological mechanisms underlying the disease remain unclear, but are known to involve hemodynamic and vascular disruptions. Recent genome-wide association studies have identified 44 genetic variants in 38 genetic loci that affect the risk of migraine, which provide the opportunity to further disentangle these mechanisms. METHODS: We included 4665 participants of the population-based Rotterdam Study (mean age 65.0 ± 10.9 years, 55.6% women). Cross-sectional area (mm2 ), flow velocity (mm/s), and blood flow (mL/min) were measured in both carotids and the basilar artery using 2-dimensional phase-contrast magnetic resonance imaging. We analyzed 43 previously identified migraine variants separately and calculated a genetic risk score (GRS). To assess the association with CBF, we used linear regression models adjusted for age, sex, and total brain volume. Hierarchical clustering was performed based on the associations with CBF measures and tissue enrichment. RESULTS: The rs67338227 risk allele was associated with higher flow velocity and smaller cross-sectional area in the carotids (Pminimum  = 3.7 × 10-8 ). Other variants were related to CBF with opposite directions of effect, but not significantly after multiple testing adjustments (P < 1.4 × 10-4 ). The migraine GRS was not associated with CBF after multiple testing corrections. Migraine risk variants were found to be enriched for flow in the basilar artery (λ = 2.39). CONCLUSIONS: These findings show that genetic migraine risk is complexly associated with alterations in cerebral hemodynamics.

Differential blockade by huperzine A and donepezil of sympathetic nicotinic acetylcholine receptor-mediated nitrergic neurogenic dilations in porcine basilar arteries.

Nicotinic acetylcholine receptor activation on the perivascular sympathetic nerves via axo-axonal interaction mechanism causes norepinephrine release, which triggers the neurogenic nitrergic relaxation in basilar arteries to meet the need of a brain. Donepezil and huperzine A, which are the cholinesterase inhibitors used for Alzheimer's disease therapy, exert controversial effects on nicotinic acetylcholine receptors. Therefore, we investigated how donepezil and huperzine A via the axo-axonal interaction regulate the neurogenic vasodilation of isolated porcine basilar arteries and define their action on different subtypes of the nicotinic acetylcholine receptor by using blood vessel myography, calcium imaging, and electrophysiological techniques. Both nicotine (100 µM) and transmural nerve stimulation (TNS, 8 Hz) induce NO-mediated dilation in the arteries. Nicotine-induced vasodilations were concentration-dependently inhibited by huperzine A and donepezil, with the former being 30 fold less potent than the latter. Both cholinesterase inhibitors weakly and equally decreased TNS-elicited nitrergic vasodilations. Neither huperzine A nor donepezil affected isoproterenol (a ß adrenoceptor-agonist)- or sodium nitroprusside (a NO donor)-induced vasodilation. Further, huperzine A was less potent than donepezil in inhibiting nicotine-elicited calcium influxes in rodent superior cervical ganglionic neurons and inward currents in α7- and α3ß2-nicotinic acetylcholine receptor-expressing Xenopus oocytes. In conclusion, huperzine A may exert less harmful effect over donepezil on maintaining brainstem circulation and on the nicotinic acetylcholine receptor-associated cognition deficits during treatment for Alzheimer's disease.

Endovascular treatment for acute basilar artery occlusion: a single center retrospective observational study.

BACKGROUND: Endovascular treatment (EVT) is now considered the gold standard for select patient populations with anterior circulation stroke; however, data on the treatment of posterior circulation stroke are less clear. This study aims to determine the characteristics and treatment outcomes of patients with acute basilar artery occlusion (BAO) and to evaluate the effectiveness and safety of EVT for patients with acute BAO in a high-volume stroke center. METHODS: This study included 187 consecutive patients with acute BAO who underwent EVT from January 2012 to July 2018 in the Beijing Tiantan Hospital. The baseline characteristics, procedure parameters, and functional outcome were assessed. RESULTS: Among the 187 patients, 138 (73.8%) underwent mechanical thrombectomy with a stent retriever, 33 (17.6%) underwent direct intracranial angioplasty (balloon dilation and/or stent implantation) for underlying severe intracranial atherosclerotic disease, and 91 (48.7%) underwent combined mechanical thrombectomy and angioplasty. Successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b-3] was achieved in 158 patients (84.5%). Overall, the rates of functional independence [modified Rankin Scale (mRS) 0-2] and favorable outcome (mRS 0-3) at 90 days were 36.4 and 49.2%, respectively, and 90-day all-cause mortality was 20.3%. CONCLUSION: EVT was effective and safe for treating patients with acute BAO.

Exploration of Physiological and Pathophysiological Implications of miRNA-143 and miRNA-145 in Cerebral Arteries.

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with a high short-term mortality rate which leads to cognitive impairments that reduce the quality of life of the majority of patients. The miRNA-143/145 cluster is highly expressed in vascular smooth muscle cells (VSMC) and has been shown to be necessary for differentiation and function, as well as an important determinant for phenotypic modulation/switching of VSMCs in response to vascular injury. We aimed to determine whether miRNA-143 and miRNA-145 are important regulators of phenotypical changes of VSMCs in relation to SAH, as well as establishing their physiological role in the cerebral vasculature. We applied quantitative PCR to study ischemia-induced alterations in the expression of miRNA-143 and miRNA-145, for rat cerebral vasculature, in an ex vivo organ culture model and an in vivo SAH model. To determine the physiological importance, we did myograph studies on basilar and femoral arteries from miRNA-143/145 knockout mice. miRNA-143 and miRNA-145 are not upregulated in the vasculature following our SAH model, despite the upregulation of miR-145 in the organ culture model. Regarding physiological function, miRNA-143 and miRNA-145 are very important for general contractility in cerebral vessels in response to depolarization, angiotensin II, and endothelin-1. Applying an anti-miRNA targeting approach in SAH does not seem to be a feasible approach because miRNA-143 and miRNA-145 are not upregulated following SAH. The knockout mouse data suggest that targeting miRNA-143 and miRNA-145 would lead to a general reduced contractility of the cerebral vasculature and unwanted dedifferentiation of VSMCs.