Middle Cerebral Artery Diameter Research Articles

Validation of a Simplified Model for Subarachnoid Hemorrhage in Mice.

Subarachnoid hemorrhage (SAH) represents a severe injury to the brain and is associated with a high mortality (40%). Several experimental SAH models are described in the literature requiring specialized equipment and a high degree of surgical expertise. Our goal was to validate a simplified, cost-effective model to permit future studies of SAH. SAH was induced by injection of homologous blood into the cisterna magna. Perfusion-fixation then perfusion of gelatinous India ink was performed. Brains and brainstems were collected and imaged for analysis of cerebral vasospasm. Triphenyl tetrazolium chloride (TTC) staining was used to analyze brain tissue cell death 24 hours following stroke. A composite neuroscore was utilized to assess SAH-related neurologic deficits. Anterior cerebral artery and basilary artery diameters were significantly reduced at 24 hours post SAH induction. Middle cerebral artery diameter was also reduced; however, the results were not significant. TTC staining showed no infarcted tissue. Neuroscores were significantly lower in the SAH mice, indicating the presence of functional deficits. This simplified model of SAH elicits pathological changes consistent with those described for more complex models in the literature. Therefore, it can be used in future preclinical studies examining the pathophysiology of SAH and novel treatment options.

Alcohol and pregnenolone interaction on cerebral arteries through targeting of vascular smooth muscle - and voltage-gated K+ channels of big conductance.

Despite the significant number of people who may be taking pregnenolone supplements while drinking alcohol (ethanol), the widely documented cerebrovascular actions of pregnenolone and ethanol, and the critical dependence of cerebrovascular function on cerebral artery diameter, there are no studies addressing the effect of pregnenolone + ethanol in combination on cerebral artery diameter. We investigated this by evaluating the effect of this combination on middle cerebral artery diameter in male and female C57BL/6J mice, both in vivo and in vitro. The use of de-endothelialized, in vitro pressurized middle cerebral artery segments allowed us to conduct a concentration-response study of constriction induced by pregnenolone ± ethanol, in which drug action could be evaluated independently of circulating and endothelial factors. In both male and female animals, pregnenolone at lower concentrations (≤1 μM) was found to synergize with 50 mM ethanol to cause vasoconstriction. In both sexes, this synergism was lost as one or both vasoconstrictors approached their maximally effective concentrations (75 mM and 10 μM for ethanol and pregnenolone, respectively), whether this was evaluated in vitro or in vivo using a cranial window. Vasoconstriction by pregnenolone + ethanol was abolished by 1 μM paxilline, indicating BK channel involvement. Moreover, cell-free recordings of BK channel activity in cerebral artery myocyte membranes showed that 10 μM pregnenolone and pregnenolone +50 mM ethanol reduced channel activity to an identical extent, suggesting that these drugs inhibit cerebrovascular BK channels via a common mechanism or mechanisms. Indeed, pregnenolone was found to disrupt allosteric coupling to -driven gating, as previously reported for ethanol.

Differential Functional Contribution of BK Channel Subunits to Aldosterone-Induced Channel Activation in Vascular Smooth Muscle and Eventual Cerebral Artery Dilation.

Calcium/voltage-activated potassium channels (BK) control smooth muscle (SM) tone and cerebral artery diameter. They include channel-forming α and regulatory β1 subunits, the latter being highly expressed in SM. Both subunits participate in steroid-induced modification of BK activity: β1 provides recognition for estradiol and cholanes, resulting in BK potentiation, whereas α suffices for BK inhibition by cholesterol or pregnenolone. Aldosterone can modify cerebral artery function independently of its effects outside the brain, yet BK involvement in aldosterone's cerebrovascular action and identification of channel subunits, possibly involved in steroid action, remains uninvestigated. Using microscale thermophoresis, we demonstrated that each subunit type presents two recognition sites for aldosterone: at 0.3 and ≥10 µM for α and at 0.3-1 µM and ≥100 µM for β1. Next, we probed aldosterone on SM BK activity and diameter of middle cerebral artery (MCA) isolated from β1-/- vs. wt mice. Data showed that β1 leftward-shifted aldosterone-induced BK activation, rendering EC50~3 μM and ECMAX ≥ 10 μM, at which BK activity increased by 20%. At similar concentrations, aldosterone mildly yet significantly dilated MCA independently of circulating and endothelial factors. Lastly, aldosterone-induced MCA dilation was lost in β1-/- mice. Therefore, β1 enables BK activation and MCA dilation by low µM aldosterone.

Protective effects of histone deacetylase 6 specific inhibitor tubastatin A on subarachnoid hemorrhage in rats and the underlying mechanisms.

Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms. Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubAL group (giving 25 mg/kg TubA), and a SAH+TubAH group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery. The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubAH group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubAL group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) . HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.

Determination of the Unilaterally Damaged Region May Depend on the Asymmetry of Carotid Blood Flow Velocity in Hemiparkinsonian Monkey: A Pilot Study.

The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson's disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.

Anatomical effects on the relationship between brain arterial diameter and length: The Northern Manhattan Study.

In patients with dolichoectasia, it is uncertain how dilatation and/or elongation relate to each other. We aimed to examine the correlation between arterial diameter and length within arteries and across the circle of Willis (COW). We included stroke-free participants in the Northern Manhattan Study who underwent magnetic resonance angiography. Intracranial artery diameters and lengths were obtained with semiautomated commercial software and were adjusted for head size. We first investigated the correlation between diameters and length using Pearson's correlation coefficient. We then built generalized linear models adjusted for demographics and risk factors. Among 1210 participants included in the analysis (mean age 71 ± 9 years, 59% women, 65% Hispanic), a larger basilar artery (BA) diameter correlated with greater BA length (r = .3), and left and right middle cerebral artery (MCA) diameters correlated with one another (r = .4). Across the COW, BA diameter correlated with MCA diameters (r=.3 for both). In adjusted analyses, MCA diameters were associated with larger posterior circulation diameters (β=0.07), MCA and BA lengths (β=0.003 and β=0.002, respectively), presence of fetal posterior cerebral artery (PCA), (β=0.11), and a complete COW (β=-0.02). Similarly, BA length was associated with a fetal PCA (β=1.1), and BA diameter was associated with anterior circulation diameters (β = 0.15) and presence of fetal PCA (β = -0.4). COW configuration should be considered when using arterial diameter cutoffs to define dolichoectasia. Further studies are needed to discern whether arterial diameter or length best identify individuals at risk of vascular events attributable to dolichoectasia.

Arachnoid membrane as a source of sphingosine-1-phosphate that regulates mouse middle cerebral artery tone

Growing evidence indicates that perivascular tissue is critical to modulate vessel function. We hypothesized that the arachnoid membrane surrounding middle cerebral artery (MCA) regulates its function via sphingosine-1-phosphate (S1P)-induced vasoconstriction. The MCA from 3- to 9-month-old male and female wild-type (Oncine France 1 and C57BL/6) mice and sphingosine kinase 2 knockout (SphK2-/-) mice in the C57BL/6 background was mounted in pressure myographs with and without arachnoid membrane. Raman microspectroscopy and imaging were used for in situ detection of S1P. The presence of arachnoid tissue was associated with reduced external and lumen MCA diameters, and with an increase in basal tone regardless of sex and strain background. Strong S1P-positive signals were detected in the arachnoid surrounding the MCA wall in both mice models, as well as in a human post-mortem specimen. Selective S1P receptor 3 antagonist TY 52156 markedly reduced both MCA vasoconstriction induced by exogenous S1P and arachnoid-dependent basal tone increase. Compared to 3-month-old mice, the arachnoid-mediated contractile influence persisted in 9-month-old mice despite a decline in arachnoid S1P deposits. Genetic deletion of SphK2 decreased arachnoid S1P content and vasoconstriction. This is the first experimental evidence that arachnoid membrane regulates the MCA tone mediated by S1P.

Abstract 35: Gamma Adducin Dysfunction Leads To Cerebrovascular Distention, Blood Brain Barrier Leakage, And Cognitive Deficits In The Fawn-hooded Hypertensive Rats

We have previously identified an inactivating mutation of ADD3 in FHH rats which is associated with impaired myogenic reactivity of renal arterioles and podocyte function, and contributes to the development of CKD. We have found that SNPs in human ADD1 or ADD3 in the same region as Add3 in FHH rats are linked to reductions in brain volumes and impaired performance on cognitive tests in 4,286 elderly patients (67-90 years old) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), but the mechanisms of these pathologies are unclear. The present study examined cerebral hemodynamics and cognitive function in FHH versus FHH.1BN and FHH. Add3 rats that express the WT Add3 gene. The myogenic responses of the middle cerebral artery (MCA) and parenchymal arterioles (PA) were impaired in FHH rats. MCA diameter decreased by 15-20% in FHH.1BN (n = 27) and FHH. Add3 (n = 10) transgenic rats, but increased by 9 ± 3% in FHH rats (n = 15) when perfusion pressure was increased from 40 to 160 mmHg. PA diameter increased by 3.16 ± 2.79% in FHH (n = 5) rats versus a 19 ± 3% and 13 ± 2% decrease FHH. Add3 (n = 4) and FHH.1BN (n = 6), respectively, when pressure was increased from 10 to 40 mmHg. Autoregulation of surface and deep cortical blood flow was impaired in FHH rats and rose by 48 ± 3% (n = 22) and 41 ± 3% (n = 12), respectively, versus 32 ± 3% (n = 7) and 16 ± 5% (n = 6) in FHH. Add3 rats when MAP was increased from 100 to 160 mmHg. By using a fluorescent microscope to examine 60 μm brain sections, it was revealed that the outer diameters of PAs were distended in FHH in comparison to FHH.1BN and FHH. Add3 transgenic rats when systemic pressure was increased to 160 mmHg. Blood brain barrier leakage was also greater in FHH rats than in FHH.1BN and FHH. Add3 rats after acute elevations in pressure. FHH (n=16) rats took 40- 50% longer to navigate an eight-arm water maze than FHH. Add3 (n=11) and FHH.1BN (n=7) rats. These results indicate that variants that alter Add3 function promote cognitive dysfunction in FHH rats by altering cerebral hemodynamics and may play a similar role in cognitive deficits in elderly patients in the ARIC-NCS study. This study suggests that blood pressure should be strictly controlled in hypertensive patients identified with ADD3 variants to prevent dementia.

Characterization of Lenticulostriate Arteries and Its Associations With Vascular Risk Factors in Community-Dwelling Elderly.

Lenticulostriate arteries (LSAs) supply blood to important subcortical areas and are, therefore, essential for maintaining the optimal functioning of the brain’s most metabolically active nuclei. Past studies have demonstrated the potential for quantifying the morphology of LSAs as biomarkers of vascular fragility or underlying arteriopathies. Thus, the current study aims to evaluate the morphological features of LSAs, their potential value in cerebrovascular risk stratification, and their concordance with other vascular risk factors in community-dwelling elderly people. A total of 125 community-dwelling elderly subjects who underwent a brain MRI scan were selected from our prospectively collected imaging database. The morphological measures of LSAs were calculated on the vascular skeletons obtained by manual tracing, and the number of LSAs was counted. Additionally, imaging biomarkers of small vessel disease were evaluated, and the diameters of major cerebral arteries were measured. The effects of vascular risk factors on LSA morphometry, as well as the relationship between LSA measures and other imaging biomarkers, were investigated. We found that smokers had shorter (p = 0.04) and straighter LSAs (p < 0.01) compared to nonsmokers, and the presence of hypertension is associated with less tortuous LSAs (p = 0.03) in community-dwelling elderly. Moreover, the middle cerebral artery diameter was positively correlated with LSA count (r = 0.278, p = 0.025) and vessel tortuosity (r = 0.257, p = 0.04). The posterior cerebral artery diameter was positively correlated with vessel tortuosity and vessel length. Considering the scarcity of noninvasive methods for measuring small artery abnormalities in the brain, the LSA morphological measures may provide valuable information to better understand cerebral small vessel degeneration during aging.

BK channel-forming slo1 proteins mediate the brain artery constriction evoked by the neurosteroid pregnenolone

Pregnenolone is a neurosteroid that modulates glial growth and differentiation, neuronal firing, and several brain functions, these effects being attributed to pregnenolone actions on the neurons and glial cells themselves. Despite the vital role of the cerebral circulation for brain function and the fact that pregnenolone is a vasoactive agent, pregnenolone action on brain arteries remain unknown. Here, we obtained in vivo concentration response curves to pregnenolone on middle cerebral artery (MCA) diameter in anesthetized male and female C57BL/6J mice. In both male and female animals, pregnenolone (1 nM-100 μM) constricted MCA in a concentration-dependent manner, its maximal effect reaching ~22–35% decrease in diameter. Pregnenolone action was replicated in intact and de-endothelialized, in vitro pressurized MCA segments with pregnenolone evoking similar constriction in intact and de-endothelialized MCA. Neurosteroid action was abolished by 1 μM paxilline, a selective blocker of Ca2+ - and voltage-gated K+ channels of large conductance (BK). Cell-attached, patch-clamp recordings on freshly isolated smooth muscle cells from mouse MCAs demonstrated that pregnenolone at concentrations that constricted MCAs in vitro and in vivo (10 μM), reduced BK activity (NPo), with an average decrease in NPo reaching 24.2%. The concentration-dependence of pregnenolone constriction of brain arteries and inhibition of BK activity in intact cells were paralleled by data obtained in cell-free, inside-out patches, with maximal inhibition reached at 10 μM pregnenolone. MCA smooth muscle BKs include channel-forming α (slo1 proteins) and regulatory β1 subunits, encoded by KCNMA1 and KCNMB1, respectively. However, pregnenolone-driven decrease in NPo was still evident in MCA myocytes from KCNMB1−/− mice. Following reconstitution of slo1 channels into artificial, binary phospholipid bilayers, 10 μM pregnenolone evoked slo1 NPo inhibition which was similar to that seen in native membranes. Lastly, pregnenolone failed to constrict MCA from KCNMA1−/− mice. In conclusion, pregnenolone constricts MCA independently of neuronal, glial, endothelial and circulating factors, as well as of cell integrity, organelles, complex membrane cytoarchitecture, and the continuous presence of cytosolic signals. Rather, this action involves direct inhibition of SM BK channels, which does not require β1 subunits but is mediated through direct sensing of the neurosteroid by the channel-forming α subunit.

P0033 / #1954: THE EFFECT OF HYPERTONIC SALINE ON INCREASED INTRACRANIAL PRESSURE IN TRAUMATIC BRAIN INJURY: PROSPECTIVE STUDY WITH NON-INVASIVE METHOD

Aims & Objectives: Transcranial Doppler (TCD) ultrasound examination is a noninvasive method for determination of intracranial pressure. The main goal of this study was to show the effectiveness of hypertonic salin infusions in reducing intracranial pressure (ICP) by using TCD ultrasound. Methods: We included all patients with mild to severe traumatic brain injury (TBI) in our intensive care unit. TCD ultrasound examinations were performed by intensivists before and after hypertonic salin infusions. We used the pulsatility index (PI) of both middle cerebral artery and optic nerve sheet diameter (ONSD) and applied the ICP equations. Results: Seventeen patients with mild to severe TBI and 12 patients in control group were included. All measurements on the TBI patients performed after a first hypertonic salin as a salvage therapy in the emergency room. The median GCSs of the patients at admission and discharge were 10 and 15 respectively. There was a significant decrease in PI after the 3rd measurement in post-hoc multiple comparisons (p=0.004). On the other hand, it was found that the decrease in ONSD became evident after the 5th measurement (p<0.0001). Eight of 17 had axonal injury findings in MRI. Two of the patients had decompressive craniectomy and none of them had died. Conclusions: The repeated hypertonic salin infusions reduce the ICP in traumatic brain injury in children and related improved GCSs. Calculation of ICP using PI and ONSD measured via TCD is a safe and fast method to determine the ICP noninvasively.

The effects of sevoflurane anesthesia on hemodynamics and cerebral artery diameters in endovascular treatment of intracranial aneurysm: A pilot study.

Cerebral autoregulation is a steady-state of cerebral blood flow despite major changes in arterial blood pressure. Inhalation anesthetics are cerebral vasodilators. In <1 MAC values, the net effect is a moderate decrease in cerebral blood flow and maintenance of responsiveness to carbon dioxide. This study aims to investigate the effects of steady-state sevoflurane anesthesia on hemodynamic and cerebral artery diameter measurements in patients undergoing flow diverter device placement under general anesthesia. Forty-six patients aged 18-70 years who underwent flow diverter devices under general anesthesia were included in this study. Routine monitoring was performed on the patients. Mean arterial pressure (MAP) values were recorded. Internal carotid artery, middle cerebral artery and anterior cerebral artery diameter measurements were made from digital subtraction angiography (DSA) images of patients with anterior aneurysms. Baseline artery, right posterior cerebral artery and left posterior cerebral artery diameter measurements were made from DSA images of patients with posterior aneurysms. These measurements were recorded as preoperative measurements. The same measurements were made from the DSA images performed before the Flow diverter device placement procedure performed under steady-state sevoflurane anesthesia for the same patients. These measurements were recorded as peroperative measurements. The average age of the patients was 56.6±15.1. The MAP of the patients before induction was 76.28±5.13 mmHg, MAP after induction was 64.36±3.23 mmHg, and MAP during sevoflurane anesthesia was 68.26±4.30 mmHg, there was a statistically significant difference. There was a statistically significant difference between the preoperative and perioperative values of anterior cerebral artery diameters. There was a strong relationship between the MAP change percentage and the ICA diameter change percentage (p<0.001, p=-0.785) and a moderate relationship between the MCA diameter change percentage (p=0.033, p=-0.338). In patients undergoing flow diverter devices, <1 MAC sevoflurane has a hemodynamic effect and creates significant vasodilation in the cerebral artery diameters.

Imaging transcranial Doppler ultrasound to measure middle cerebral artery blood flow: the importance of measuring vessel diameter.

Cerebral blood flow (CBF) is commonly inferred from blood velocity measurements in the middle cerebral artery (MCA), using nonimaging, transcranial Doppler ultrasound (TCD). However, both blood velocity and vessel diameter are critical components required to accurately determine blood flow, and there is mounting evidence that the MCA is vasoactive. Therefore, the aim of this study was to employ imaging TCD (ITCD), utilizing color flow images and pulse wave velocity, as a novel approach to measure both MCA diameter and blood velocity to accurately quantify changes in MCA blood flow. ITCD was performed at rest in 13 healthy participants (7 men/6 women; 28 ± 5 yr) with pharmaceutically induced vasodilation [nitroglycerin (NTG), 0.8 mg] and without (CON). Measurements were taken for 2 min before and for 5 min following NTG or sham delivery (CON). There was more than a fivefold, significant, fall in MCA blood velocity in response to NTG (∆-4.95 ± 4.6 cm/s) compared to negligible fluctuation in CON (∆-0.88 ± 4.7 cm/s) (P < 0.001). MCA diameter increased significantly in response to NTG (∆0.09 ± 0.04 cm) compared with the basal variation in CON (∆0.00 ± 0.04 cm) (P = 0.018). Interestingly, the product of the NTG-induced fall in MCA blood velocity and increase in diameter was a significant increase in MCA blood flow following NTG (∆144 ± 159 ml/min) compared with CON (∆-5 ± 130 ml/min) (P = 0.005). These juxtaposed findings highlight the importance of measuring both MCA blood velocity and diameter when assessing CBF and document ITCD as a novel approach to achieve this goal.

Factors associated with temporal window failure in transcranial Doppler sonography.

Temporal window failure (TWF) is found in 8-20% of subjects. There are still insufficient studies about the factors affecting TWF. We aimed to elucidate the underlying causes of TWF. We analyzed 376 patients who underwent both transcranial Doppler sonography and cerebral angiographic imaging. They were divided into two groups: with and without TWF. Demographics, cardiovascular factors, degree of stenosis from the proximal intracranial artery to the middle cerebral artery (MCA), MCA diameter, and skull features were examined. The subjects were 314 TWF-negative patients and 62 TWF-positive patients. The TWF-negative group was younger than that of the TWF-positive group (67.0 ± 12.1 vs. 75.2 ± 9.4, p < 0.001). The proportion of men in the TWF-negative group was higher than in the TWF-positive group (71% vs. 29%; p < 0.001). The TWF-negative group had a higher smoking rate than the TWF-positive group (34.4% vs. 12.9%; p = 0.001). In multivariate logistic regression analysis, age (odds ratio (OR), 1.05; p = 0.019), sex (OR, 4.64; p = 0.002), temporal bone thickness (OR, 6.03; p < 0.001), temporal bone density (OR, 0.996; p = 0.002), and soft tissue thickness (OR, 1.31; p = 0.004) significantly affected TWF. In addition to age, sex, temporal bone thickness, and temporal bone density which were previously reported as variables associated with TWF, we confirmed that soft tissue thickness of the temporal area is a new associated factor of TWF. Measuring soft tissue thickness of the temporal area for patients with suspected TWF could be useful in identifying measurement error due to technical problems.

Abstract TP203: Factors Associated With Temporal Window Failure in Transcranial Doppler Sonography

Background and purpose: Temporal window failure (TWF) is found in 8-20% of subjects. Although it has been reported that, it is more common for the elderly and females, there are not enough studies on this topic. This study aimed to identify new factors affecting TWF. Methods: This study analyzed 376 patients who underwent both transcranial Doppler sonography (TCD) and cerebral angiographic imaging among patients visited the neurology department of Chonbuk National University Hospital from January to December 2018. They were divided into two groups depending on the presence of TWF. Afterward, demographics and cardiovascular factors, degree of stenosis from proximal intracranial artery (ICA) to the middle cerebral artery (MCA), and MCA diameter and skull features were examined. Results: The mean age of the patients was 68.4±12.1 years old and 241 of them (64.1%) were male. The study subjects were composed of 314 TWF negative patients (83.5%) and 62 TWF positive patients (16.5%). The stenosis from the proximal ICA to the 2/3 segment of the MCA proximal was not different between the two groups. Factors affecting TWF were analyzed using multivariate logistic regression analysis and the results showed that age (odds ratio [OR], 1.05; p =0.019), female (OR, 4.64; p =0.002), temporal bone thickness (OR, 6.03; p &lt;0.001), temporal bone density (OR, 0.996; p =0.002), and soft tissue thickness (OR, 1.31; p =0.004) significantly affected TWF. Conclusions: We confirmed that the soft tissue thickness of the temporal area was a new associated factor of TWF in addition to the previously reported age, sex, temporal bone thickness, and temporal bone density. The results implied that measuring the soft tissue thickness of the temporal area for patients with suspected TWF would be useful to clinically identify the measurement error due to a technical problem.

No significant change of extracranial conduit vessel diameter during cerebral vasomotor reactivity test with moderately‐altered end‐tidal CO2

Cerebral vasomotor reactivity (CVMR) is often assessed using transcranial Doppler (TCD) to measure the cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA). Recently the validity of this technique has been questioned because of the assumption that MCA diameter does not change. The goal of this work was to test if the extracranial cerebral arteries, i.e. internal carotid and vertebral arteries (ICA and VA), have a significant diameter change during moderate alteration of end‐tidal carbon dioxide (ETCO2). Fifteen healthy subjects (6 males; age: 32±10 yrs) were enrolled. The CBFV at the MCA was continuously recorded with TCD during an 8‐min CVMR test, i.e. 2‐min resting ventilation, 2‐min inspiration of 5% CO2, 21% O2, balance nitrogen, 2‐min recovery, and 2‐min mild hyperventilation. 8 min protocol was repeated on the same subjects, to allow measurement of ICA diameter during one run and VA during the other using high‐frequency ultrasound. CVMR is expressed as the percent change in MCA's CBFV per mmHg change in ETCO2, as quantified by the slope of this relationship. The time‐averaged diameter during each static stage was measured offline with echo‐tracking software. All results presented as Mean ± SD. The experimental protocol resulted in a moderated change of ETCO2 (mmHg) during 5% CO2 inspiration (+6.9±2.0) and mild hyperventilation (−14.8±5.8) relative to the baseline values (34.6±2.7). Both hypercapnic and hypocapnic stages showed no significant changes (relative to the baseline) in blood pressure, heart rate, diameters of ICA (5.23±0.83 and 5.21±0.71, vs. baseline 5.22 ±0.83 mm; P = 0.88 and 0.86) and VA (3.91±0.69 and 3.91±0.72, vs. baseline 3.87±0.65 mm; P = 0.40 and 0.55), except for a slight increase (+7±8 bpm, P &lt; 0.001) of HR during hypocapnia. The individual variation of the diameter response showed no correlation with the concurrent blood pressure, heart rate, and CBFV responses. Based on these results, we concluded that the TCD appears to still be a reliable method to assess the CBF response during CVMR test with a moderate change of ETCO2, as no significant change of the conduit vessel diameter is likely to occur. However, future work is necessary to confirm that flow changes in the extracranial arteries are reflective of relative changes in TCD values.Support or Funding InformationSupported by the Funding from Rutgers University and U.S. Department of Defense.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Propofol/Remifentanil Anesthesia Might Not Alter the Middle Cerebral Artery Diameter by Digital Subtraction Angiography.

Transcranial Doppler (TCD) of the middle cerebral artery (MCA) enables the measurement of the mean blood velocity (MCAVm) and the estimation of the cerebral blood flow (CBF), provided that no significant changes occur in the MCA diameter (MCADiam). Previous studies described a decrease in the MCAVm associated with the induction of total intravenous anesthesia (TIVA) by propofol and remifentanil. This decrease in blood velocity might be interpreted as a decrease in the CBF only where the MCADiam is not modified across TCD examinations. In this observational study, we measured the MCADiam of 24 subjects (almost exclusively females) on digital subtraction angiography under awake and TIVA conditions. Across the two phases, we observed a decrease in the mean arterial blood pressure (from 84 ± 9 to 71 ± 6mmHg; p < 0.001) and heart rate (76 ± 10 vs. 65 ± 8 beats/min; p < 0.001), and a concomitant decrease in the MCAVm (61 vs. 42cm/s; p < 0.001). In contrast, the MCADiam did not vary in association with TIVA (2.3 ± 0.2 vs. 2.3 ± 0.2mm; p = 0.52). Those results suggested that in this population, no significant changes in the MCADiam are associated with TIVA.

Superficial temporal artery-to-middle cerebral artery bypass in combination with indirect revascularization in moyamoya patients ≤ 3 years of age.

OBJECTIVE Revascularization is indicated in the management of moyamoya disease (MMD), with options that include direct and indirect techniques. Indirect bypass is popular in young children because the diminutive caliber of donors and recipients makes direct bypass difficult. The authors reviewed a series of patients treated with direct superficial temporal artery (STA)–to–middle cerebral artery (MCA) bypass in combination with encephalomyosynangiosis (EMS) in children 3 years or younger to demonstrate feasibility and safety. METHODS A retrospective review of all surgeries for MMD over a 19-year period identified 11 procedures in 6 patients. Surgical results, angiographic outcomes, and clinical outcomes were analyzed. RESULTS Patients had a mean age of 22.4 months. The symptomatic hemisphere was revascularized first, and the contralateral hemisphere was revascularized on average 2.8 months later in 5 patients. All direct bypasses were patent postoperatively and remained patent at late follow-up (mean 4.1 years), with both STA and MCA diameters increasing significantly (n = 5, p < 0.03). At last follow-up (mean follow-up duration, 5.0 years), favorable outcomes (modified Rankin Scale scores 0–2) were observed in 5 of the 6 patients (83%), with 1 dependent patient remaining unchanged postoperatively. CONCLUSIONS Direct STA-MCA bypass in combination with EMS for MMD is feasible and safe in patients 3 years or younger, based on favorable clinical and radiological outcomes in this patient cohort. Direct bypass should be considered when immediate revascularization is needed, without the biological delay associated with indirect bypass. ABBREVIATIONS EDAS = encephaloduroarteriosynangiosis; EMS = encephalomyosynangiosis; MCA = middle cerebral artery; MMD = moyamoya disease; mRS = modified Rankin Scale; STA = superficial temporal artery; TIA = transient ischemic attack.

Reversible Brain Edema Associated with Flow Diverter Stent Procedures: A Retrospective Single- Center Study to Evaluate Frequency, Clinical Evolution, and Possible Mechanism

Hemorrhage and ischemia after flow diverter stent (FDS) procedures for intracranial aneurysms are the most common complications and have been extensively described. Temporary brain edema (TBE) is an unknown complication that could be associated with particular FDS procedures. To estimate the frequency, clinical presentation, imaging findings, and possible mechanisms associating TBE with FDS. Unruptured aneurysms treated with FDS implantation performed in our service from June 2015 to March 2018 were reviewed. Medical antecedents, endovascular procedure, clinical assessments before and after treatment, aneurysm characteristics, and image records were collected. Artery diameters of patients in whom TEB developed were also calculated to investigate any correlation between TBE and anatomic descriptors. A total of 179 FDS procedures in 176 patients were reviewed. Six patients (3.4%) presented with symptomatic TBE, and all TBE patients had undergone FDS implantation from the middle cerebral artery (MCA) to the internal carotid artery (ICA). A Pearson product-moment correlation coefficient (PPCC) found smaller MCA diameters and MCA/ICA ratios in these 6 patients (respectively PPCC=-0.619, P < 0.04; PPCC=-0.647, P < 0.03). Hemorrhagic and ischemic complications were less frequent than TBE (2.3% and 1.1% vs. 3.4%). TBE was more frequent than ischemic or hemorrhagic complications after FDS in this study. TBE seemed to be associated with a particular FDS positioning in small arteries, inducing flow changes and disruption of the blood-brain barrier.

Arterial diameter and the gender disparity in stroke thrombectomy outcomes

BackgroundCompared with males, females consistently fare worse following mechanical thrombectomy for large vessel ischemic strokes. Understanding why this gender disparity occurs may guide improvements in future treatment strategies. In this...