Angiographic classification of chronic subdural hematoma.

Background and purpose:

Chronic subdural hematoma (cSDH) is a challenging pathology with high recurrence rate after surgical treatment and may seriously affect the patient’s quality of life. Membrane formation with angiogenesis plays an important role in the evolution of the disease, providing a promising target for endovascular therapy. Our goal is to categorize angiographic patterns of chronic subdural hematoma for standardized reporting purposes.

In our retrospective analysis of prospective data collection, we analyzed angiographic properties of all high recurrence risk patients with cSDH, who were treated by embolization in our hospital between February 2019 and June 2020. Altogether 17 patients were included in the analysis. 

Based on superselective angiography of the middle meningeal artery (MMA) in the two standard, AP and lateral views, three distinct categories of dural supply were defined: normal vascular pattern (Grade I), cottonwool appearance without enlargement of the MMA branches (Grad II) and strong cottonwool like staining with dilatative remodelling of the MMA branches (Grade III).

The proposed grading system of the angiographic appearance of cSDH, representing the pathophysiological evolution of the disease should be correlated to therapeutic success rates and could be applied in future clinical studies.

Impact of age on mechanical thrombectomy and clinical outcome in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is less effective in patients aged 80 years or older. Our goal was to better understand the impact of age in general on recanalization rates and clinical outcome. METHODS: We performed a retrospective analysis of our prospective database of adult patients with acute ischemic stroke due to large vessel occlusions, who had undergone mechanical thrombectomy between 2019 and mid-2021. The cohort was categorized into five age groups: 18 - 49, 50 - 59, 60 - 69, 70 - 79 and ≥ 80 years. Our primary outcome measure was clinical outcome at three months after mechanical thrombectomy, measured by the mRS score. Secondary outcomes were procedure times and rates of successful recanalization, defined by mTICI ≥ 2b. RESULTS: Data of 264 patients were analyzed. There were no significant differences in procedure times (p = 0.46) or in rates of successful recanalization (p = 0.49) between age groups. There was a significant association of age and mRS score at three months (p < 0.0001): From youngest to oldest group, odds of functional independence (mRS ≤ 2) decreased (80.0% vs. 21.3%) and odds of death (mRS 6) increased (13.3% vs. 57.3%). Increasing age was significantly associated with lower rates of functional independence (OR 0.93; [95% CI 0.90 - 0.95]), higher rates of care dependency (OR 1.04; [95% CI 1.01 - 1.07]) and higher mortality rates (OR 1.06; [95% CI 1.04 - 1.09]). CONCLUSION: Higher age had no significant impact on recanalization times or recanalization rates but was strongly associated with worse clinical outcome after mechanical thrombectomy.

Stent reconstruction in intracranial atherosclerotic disease related acute ischemic stroke results in high revascularization rates.

OBJECTIVES: Intracranial atherosclerotic disease (ICAD) is a major cause of large vessel occlusion (LVO) in acute ischemic stroke (AIS). Our study aimed to analyze the effect of percutaneous transluminal angioplasty and stenting (PTAS) in patients with ICAD undergoing rescue treatment in terms of functional outcome and mortality rate at 90 days and compare the results to LVO with thromboembolic origins. MATERIALS AND METHODS: A retrospective review of a mechanical thrombectomy (MT) single center database from 01/2019 to 09/2021 was carried out using chart review and angiogram analysis. From 469 acute stroke patients, 361 patients were enroled in the study, of whom twenty-four (6.6%) were diagnosed with underlying ICAD and treated with angioplasty and stent reconstruction (PTAS) with a standardized medication protocol. Successful reperfusion, peri-procedural complications, and functional independence at 90 days were collected as outcomes. RESULTS: There was no difference in age or admission National Institutes of Health Stroke Scale (NIHSS). Onset to groin puncture (median 460 vs 277 min, P = 0.019) was significantly longer in the ICAD group. The procedure time (median 73 vs 60 min, P = 0.137) did not differ. Successful reperfusion was achieved in 95.8% of ICAD and 91.1% of the remaining patients (P = 0.445). Functional independence (mRS ≤ 2) at 90 days was achieved in 45.8% (11/24) and 42.7% (144/337, (P = 0.767)). The mortality rates (mRS 6) at 90 days were similar (29.2% vs 29.4% (P = 0.983)). CONCLUSION: Despite significantly longer treatment delays, the outcome and revascularization rates of ICAD patients were similar to the thromboembolic cohort. Our proposed protocol of PTAS and medication protocol in ICAD was effective with a similar safety profile as MT in general.

Myelin quantification with MRI: A systematic review of accuracy and reproducibility.

OBJECTIVES: Currently, multiple sclerosis is treated with anti-inflammatory therapies, but these treatments lack efficacy in progressive disease. New treatment strategies aim to repair myelin damage and efficacy evaluation of such new therapies would benefit from validated myelin imaging techniques. Several MRI methods for quantification of myelin density are available now. This systematic review aims to analyse the performance of these MRI methods. METHODS: Studies comparing myelin quantification by MRI with histology, the current gold standard, or assessing reproducibility were retrieved from PubMed/MEDLINE and Embase (until December 2019). Included studies assessed both myelin histology and MRI quantitatively. Correlation or variance measurements were extracted from the studies. Non-parametric tests were used to analyse differences in study methodologies. RESULTS: The search yielded 1348 unique articles. Twenty-two animal studies and 13 human studies correlated myelin MRI with histology. Eighteen clinical studies analysed the reproducibility. Overall bias risk was low or unclear. All MRI methods performed comparably, with a mean correlation between MRI and histology of R2=0.54 (SD=0.30) for animal studies, and R2=0.54 (SD=0.18) for human studies. Reproducibility for the MRI methods was good (ICC=0.75-0.93, R2=0.90-0.98, COV=1.3-27%), except for MTR (ICC=0.05-0.51). CONCLUSIONS: Overall, MRI-based myelin imaging methods show a fairly good correlation with histology and a good reproducibility. However, the amount of validation data is too limited and the variability in performance between studies is too large to select the optimal MRI method for myelin quantification yet.

Respiratory motion artifacts during arterial phase imaging with gadoxetic acid: Can the injection protocol minimize this drawback?

PURPOSE: To determine which of three gadoxetic acid injection techniques best reduced the contrast-related arterial-phase motion artifacts. MATERIALS AND METHODS: This Institutional Review Board (IRB)-approved, retrospective study included a cohort of 78 consecutive patients who each had serial gadoxetic acid-enhanced 3.0T magnetic resonance imaging (MRI) of the liver (0.025 mmol/kg body weight) performed with at least two of three injection techniques: M1 test bolus, undiluted, power-injected 1 mL/s; M2 test bolus, diluted 50% with saline, power-injected 1 mL/s; M3 fixed delay, undiluted, manually injected. Blinded to the injection method, three readers independently rated the randomized images for arterial-phase motion artifacts, arterial-phase timing, and arterial-phase lesion visibility using a four-point Likert scale. RESULTS: Regarding respiratory artifacts, gadoxetic acid arterial-phase images were judged better with M3 (2.7 ± 0.7) and were significantly less than those with M1 (2.1 ± 1.1) (P = 0.0001). Arterial-phase M2 (2.50 ± 0.89) images were rated significantly better than arterial-phase M1 images (P = 0.012), but the difference between arterial-phase images with M3 and M2 scores was not statistically significant (P = 0.49). Arterial-phase timing was significantly better for M1 compared to M3, and for M2 compared to M3 (P < 0.0001 for both). The area under the curve was 0.59-0.68. However, there was no significant difference between M1 and M2 (P = 0.35). With regard to arterial-phase lesion visibility, there was no significant difference in the ratings between any of the three injection techniques (P = 0.29-0.72). Interreader agreement was moderate to substantial (κ = 0.41-0.62). CONCLUSION: A diluted, power-injected protocol (M2) seems to provide good timing and minimize artifacts compared with two other injection methods. No significant difference was found in lesion visibility between these three methods. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1107-1114.

A two-state model for the diffusion of the A2A adenosine receptor in hippocampal neurons: agonist-induced switch to slow mobility is modified by synapse-associated protein 102 (SAP102).

The A2A receptor is a class A/rhodopsin-like G protein-coupled receptor. Coupling to its cognate protein, Gs, occurs via restricted collision coupling and is contingent on the presence of cholesterol. Agonist activation slows diffusion of the A2A adenosine receptor in the lipid bilayer. We explored the contribution of the hydrophobic core and of the extended C terminus by examining diffusion of quantum dot-labeled receptor variants in dissociated hippocampal neurons. Single particle tracking of the A2A receptor(1-311), which lacks the last 101 residues, revealed that agonist-induced confinement was abolished and that the agonist-induced decrease in diffusivity was reduced substantially. A fragment comprising the SH3 domain and the guanylate kinase domain of synapse-associated protein 102 (SAP102) was identified as a candidate interactor that bound to the A2A receptor C terminus. Complex formation between the A2A receptor and SAP102 was verified by coimmunoprecipitation and by tracking its impact on receptor diffusion. An analysis of all trajectories by a hidden Markov model was consistent with two diffusion states where agonist activation reduced the transition between the two states and, thus, promoted the accumulation of the A2A receptor in the compartment with slow mobility. Overexpression of SAP102 precluded the access of the A2A receptor to a compartment with restricted mobility. In contrast, a mutated A2A receptor (with (383)DVELL(387) replaced by RVRAA) was insensitive to the action of SAP102. These observations show that the hydrophobic core per se does not fully account for the agonist-promoted change in mobility of the A2A receptor. The extended carboxyl terminus allows for regulatory input by scaffolding molecules such as SAP102.

Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor.

The adenosine A2A receptor is a prototypical rhodopsin-like G protein-coupled receptor but has several unique structural features, in particular a long C terminus (of >120 residues) devoid of a palmitoylation site. It is known to interact with several accessory proteins other than those canonically involved in signaling. However, it is evident that many more proteins must interact with the A2A receptor, if the trafficking trajectory of the receptor is taken into account from its site of synthesis in the endoplasmic reticulum (ER) to its disposal by the lysosome. Affinity-tagged versions of the A2A receptor were expressed in HEK293 cells to identify interacting partners residing in the ER by a proteomics approach based on tandem affinity purification. The receptor-protein complexes were purified in quantities sufficient for analysis by mass spectrometry. We identified molecular chaperones (heat-shock proteins HSP90α and HSP70-1A) that interact with and retain partially folded A2A receptor prior to ER exit. Complex formation between the A2A receptor and HSP90α (but not HSP90ß) and HSP70-1A was confirmed by co-affinity precipitation. HSP90 inhibitors also enhanced surface expression of the receptor in PC12 cells, which endogenously express the A2A receptor. Finally, proteins of the HSP relay machinery (e.g. HOP/HSC70-HSP90 organizing protein and P23/HSP90 co-chaperone) were recovered in complexes with the A2A receptor. These observations are consistent with the proposed chaperone/coat protein complex II exchange model. This posits that cytosolic HSP proteins are sequentially recruited to folding intermediates of the A2A receptor. Release of HSP90 is required prior to recruitment of coat protein complex II components. This prevents premature ER export of partially folded receptors.

Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine.

Ibogaine is a psychoactive indole alkaloid. Its use as an antiaddictive agent has been accompanied by QT prolongation and cardiac arrhythmias, which are most likely caused by human ether a go-go-related gene (hERG) potassium channel inhibition. Therefore, we studied in detail the interaction of ibogaine with hERG channels heterologously expressed in mammalian kidney tsA-201 cells. Currents through hERG channels were blocked regardless of whether ibogaine was applied via the extracellular or intracellular solution. The extent of inhibition was determined by the relative pH values. Block occurred during activation of the channels and was not observed for resting channels. With increasing depolarizations, ibogaine block grew and developed faster. Steady-state activation and inactivation of the channel were shifted to more negative potentials. Deactivation was slowed, whereas inactivation was accelerated. Mutations in the binding site reported for other hERG channel blockers (Y652A and F656A) reduced the potency of ibogaine, whereas an inactivation-deficient double mutant (G628C/S631C) was as sensitive as wild-type channels. Molecular drug docking indicated binding within the inner cavity of the channel independently of the protonation of ibogaine. Experimental current traces were fit to a kinetic model of hERG channel gating, revealing preferential binding of ibogaine to the open and inactivated state. Taken together, these findings show that ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time.

Ongoing Geometric Remodeling of the Parent Artery After Flow-Diverter Stent Reconstruction in Cerebral Aneurysms: The Device Design Matters.

OBJECTIVE: Configuration changes of the parent artery (PA) after flow-diverter (FD) stent reconstruction, caused by the bending force of the device, may have an additional role in aneurysm occlusion as a result of the secondary alteration of intra-aneurysmal hemodynamics related to the geometry alteration of the vessel. To determine the degree of PA deformation and aneurysm occlusion rates after deployment of 2 different types of FD. METHODS: Patients treated with 2 different designs of cobalt-chromium braid (48 and 64 wire braid) structure FD were subject to analysis. Vascular angle changes at the level of the reconstructed segment immediately after FD deployment and at 1 year follow-up were measured and the potential relationship with aneurysmal occlusion rate was analyzed. RESULTS: Forty-two patients harboring 48 aneurysms were included in the present study. The aneurysms were divided into side wall (85.4%) and bifurcation types (14.6%). Twenty-six aneurysms were treated using the Pipeline FD (48 wire braid; 54.2%) and 22 using the Evolve FD (64 wire braid; 45.8%). Of the 48 aneurysms, 42 (87.5%) met the primary end point of complete occlusion at 12 months. The median postdeployment angle change was 7.04°± 4.59° for the Pipeline and 5.05°± 2.49° for the Evolve, whereas the median 12 months follow-up angle change was 15.49°± 10.99° and 10.01°± 8.83°, respectively. PA angle changes were significantly higher in the bifurcation group compared with the side wall group both during procedure and at 12 months follow-up. Angle change had a statistically nonsignificant association with complete aneurysm occlusion. CONCLUSIONS: PA deformation starts immediately after deployment and remodeling continues for 1 year after. Aneurysms located in the vessel bifurcation were more prone to PA straightening after FD deployment than were side wall aneurysms. Furthermore, Pipeline seemed to be more prone to inducing vascular deformation, compared with Evolve.

Dynamic Perviousness Predicts Revascularization Success in Acute Ischemic Stroke.

BACKGROUND: The predictive value of thrombus perviousness in acute ischemic stroke (AIS), as measured by computed tomography (CT), has been intensively studied with conflicting results. In this study, we investigate the predictive potential of the novel concept of dynamic perviousness using three-dimensional (3D) volumetric evaluation of occlusive thrombi. METHODS: The full thrombus volume in 65 patients with a hyperdense artery sign on non-contrast CT (NCCT), who underwent mechanical thrombectomy (MT), was segmented. Perviousness maps were computed voxel-wise for the entire thrombus volume as thrombus attenuation increase (TAI) between NCCT and CT angiography (CTA) as well as between CTA and late venous phase CT (CTV). Perviousness was analyzed for its association with NIHSS at admission, Thrombolysis In Cerebral Infarction (TICI) score, and number of MT passes. RESULTS: The mean late-uptake TAI of thrombi with NIHSS scores greater than 21 at admission was approximately 100% higher than for lower scored NIHSS (p between 0.05 and 0.005). Concerning revascularization results, thrombi requiring less than four MT passes had ca. 80% higher group mean late-uptake TAI than clots requiring four or more passes (p = 0.03), and thrombi with TICI score III had ca. 95% higher group mean late-uptake TAI than thrombi with TICI II (p = 0.03). Standard perviousness showed no significant correlation with MT results. CONCLUSION: Standard thrombus perviousness of 3D clot volume is not associated with revascularization results in AIS. In contrast, dynamic perviousness assessed with a voxel-wise characterization of 3D thrombi volume may be a better predictor of MT outcomes than standard perviousness.

Dynamic Perviousness: A Novel Imaging Marker for Predicting Mechanical Thrombectomy Outcomes in Acute Ischemic Stroke.

BACKGROUND: The predictive value of thrombus standard perviousness (SP) in acute ischemic stroke (AIS) for the technical success rates of mechanical thrombectomy (MT) or functional outcomes is not yet conclusive. We investigated the relationship between dynamic perviousness (DP) and revascularization results using time-dependent enhancement curve types determined with computed tomography (CT). METHODS: A retrospective analysis of 137 AIS patients was performed. DP was calculated as the thrombus attenuation increase (TAI) using three time points and categorized into four groups: (1) no enhancement (CNE); (2) late enhancement (CLE); (3) early enhancement with washout (CW); (4) early enhancement without washout (CNW). Associations with the technical success rate and functional outcomes were assessed. RESULTS: Late enhancement (CLE) had approximately two times higher odds for successful MT as compared to clots with other enhancement dynamics. The odds ratios (logistic regression model with CNW as the reference) for the TICI III scores were 4.04 (p = 0.067), 1.82 (p = 0.3), and 1.69 (p = 0.4) for CLE, CW, and CNE, respectively. The NIHSS scores at discharge and mRS scores at three months showed regression coefficients (linear regression model with CNW as reference) of -3.05 (p = 0.10), -1.17 (p = 0.51), and -1.24 (p = 0.47); and -1.30 (p = 0.097), -0.85 (p = 0.25), and -0.15 (p = 0.83) for CLE, CW, and CNE, respectively. CONCLUSIONS: Thrombi with late enhancement patterns showed a higher revascularization rate and better outcomes as compared to clots with early uptake or no washout.

Endovascular embolization as a stand-alone treatment of head and neck paragangliomas with long-term tumor control.

BACKGROUND AND PURPOSE: The impact of therapeutic embolization as a stand-alone treatment of head and neck paragangliomas considered surgically high-risk remains insufficiently understood. The aim of this study was to investigate the procedural risks and long-term volumetric development in head and neck paragangliomas with high surgical risk following therapeutic endovascular embolization as stand-alone treatment. MATERIALS AND METHODS: A retrospective database review of patients who underwent endovascular embolization as primary treatment for head and neck paragangliomas lacking appropriate curative treatment options at our institution (from January 2000 to February 2023) was conducted. Tumor volumetric analyses were performed before embolization and during follow-up. To assess the changes in tumor volume over time, the measurements were performed after embolization, first at 6 months and then on a yearly basis up to 6 years (mean follow-up time was: 33.7 ± 24.4 months). Subgroup analyses were conducted for vagal and jugular/jugulotympanic paragangliomas. RESULTS: A total of 32 head and neck paragangliomas in 28 patients (mean age, 56.1 years ± 16.5 [standard deviation]; 18 female) with therapeutic embolization as stand-alone treatment were evaluated, of which 11 were vagal paragangliomas, 15 jugular/jugulotympanic paragangliomas and 6 carotid body tumors. After a mean follow-up duration of 33.7 ± 24.4 months tumor control was achieved in 75%, with significant median tumor volume reduction at 6 months (p = .02, n = 21). Vagal paragangliomas responded the most to embolization with a significantly decreased median volume from 22.32 cm3; to 19.09 cm3 (p = .008, n = 8). Transient complications occurred in 3.4%. CONCLUSIONS: Therapeutic embolization as a stand-alone treatment offers a low-risk control of tumor growth in surgically high-risk lesions, with a significant reduction in tumor volume after treatment. Among the different subtypes, vagal paragangliomas exhibited the strongest and longest regression of the tumor volume.ABBREVIATIONS: HNPGL = head and neck paragangliomas; IQR = interquartile range; JTP = jugular/jugulotympanic paragangliomas; PVA = polyvinyl alcohol; VP = vagal paragangliomas.

Dynamic Perviousness Has Predictive Value for Clot Fibrin Content in Acute Ischemic Stroke.

Dynamic perviousness is a novel imaging biomarker, with clot density measurements at multiple timepoints to allow longer contrast to thrombus interaction. We investigated the correlations between dynamic perviousness and clot composition in the setting of acute ischemic stroke. Thirty-nine patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) were analyzed. Patients received a three-phase CT imaging pre-thrombectomy and histopathological analysis of retrieved clots. Clot densities for every phase and change in densities between phases were calculated, leading to four patterns of dynamic perviousness: no contrast uptake, early contrast uptake with and without washout and late uptake. Clots were categorized into three groups based on dominant histologic composition: red blood cell (RBC)-rich, fibrin/platelet-rich and mixed. Clot composition was correlated with dynamic perviousness using the Kruskal-Wallis test and Pearson's correlation analysis. The dynamic perviousness categories showed a significant difference between fibrin-rich clots when compared to RBC-rich plus mixed groups. The uptake without washout category had significantly fewer fibrin clots compared to the uptake with washout (p = 0.036), and nearly significantly fewer fibrin clots when compared to the no uptake category (p = 0.057). Contrast uptake with different patterns of contrast washout showed significant differences of the likelihood for fibrin-rich clots.

The volume of steal phenomenon is associated with neurological deterioration in patients with large-vessel occlusion minor stroke not eligible for thrombectomy.

INTRODUCTION: A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort. PATIENTS AND METHODS: From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration. RESULTS: Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930). DISCUSSION: Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging. CONCLUSION: The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT.

Visualization of intracranial aneurysms treated with Woven EndoBridge (WEB) devices using Ultrashort Echo Time Magnetic Resonance Imaging (UTE-MRI).

BACKGROUND AND PURPOSE: Assessing treatment success of intracranial aneurysms treated with Woven EndoBridge (WEB) devices using MRI is important in follow-up imaging. Depicting both the device configuration as well as reperfusion is challenging due to susceptibility artefacts. We evaluated the usefulness of contrast-enhanced 3D-Ultrashort Echo-Time (UTE) sequence in this setting. MATERIALS AND METHODS: In this prospective study, 12 patients (9 female) with 15 treated aneurysms were included. These 12 patients underwent 18 MRI examinations. Follow-up UTE-MRI controls were performed on the same 3-Tesla scanner. We compared the visualization of device configuration, artifact-related virtual stenosis of the parent vessel and WEB occlusion scale in 3D isotropic UTE-MRI post-contrast with standard time-of-flight (TOF) MR-angiography with (CE) and without intravenous contrast as well as DSA. Two interventional neuroradiologists rated the images separately and in consensus. RESULTS: Visualization of the WEB device position and configuration was rated superior or highly superior using the UTE sequence in 17/18 MRIs compared to TOF-MRA. Artifact-related virtual stenosis of the parent vessel was significantly lower in UTE-MRI compared to TOF and CE-TOF. Reperfusion was visible in 8/18 controls in DSA. TOF was able to grade reperfusion correctly in 16 cases, CE-TOF in 16 cases and UTE in 17 cases. CONCLUSIONS: Contrast-enhanced UTE is a novel MRI sequence that shows benefit compared to standard sequences in non-invasive and radiation-free follow-up imaging of intracranial aneurysms treated using the WEB-device. ABBREVIATIONS: ACoA = anterior communicating artery, BA = basilar artery, CEA = contrast enhanced angiography, ICA = internal carotid artery, MCA = middle cerebral artery, PCom = posterior communicating artery TOF-CE = contrast enhanced time-of-flight angiography, UTE = ultra-short echo time, WEB = woven endobridge.

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.

Reengineering the collision coupling and diffusion mode of the A2A-adenosine receptor: palmitoylation in helix 8 relieves confinement.

The A(2A)-adenosine receptor undergoes restricted collision coupling with its cognate G protein G(s) and lacks a palmitoylation site at the end of helix 8 in its intracellular C terminus. We explored the hypothesis that there was a causal link between the absence of a palmitoyl moiety and restricted collision coupling by introducing a palmitoylation site. The resulting mutant A(2A)-R309C receptor underwent palmitoylation as verified by both mass spectrometry and metabolic labeling. In contrast to the wild type A(2A) receptor, the concentration-response curve for agonist-induced cAMP accumulation was shifted to the left with increasing expression levels of A(2A)-R309C receptor, an observation consistent with collision coupling. Single particle tracking of quantum dot-labeled receptors confirmed that wild type and mutant A(2A) receptor differed in diffusivity and diffusion mode; agonist activation resulted in a decline in mean square displacement of both receptors, but the drop was substantially more pronounced for the wild type receptor. In addition, in the agonist-bound state, the wild type receptor was frequently subject to confinement events (estimated radius 110 nm). These were rarely seen with the palmitoylated A(2A)-R309C receptor, the preferred diffusion mode of which was a random walk in both the basal and the agonist-activated state. Taken together, the observations link restricted collision coupling to diffusion limits imposed by the absence of a palmitoyl moiety in the C terminus of the A(2A) receptor. The experiments allowed for visualizing local confinement of an agonist-activated G protein-coupled receptor in an area consistent with the dimensions of a lipid raft.

Single antiplatelet regimen in flow diverter treatment of cerebral aneurysms: The drug matters. A systematic review and meta-analysis.

BACKGROUND: Hemorrhagic and thromboembolic complications (TECs) are the main concerns in the endovascular treatment of intracranial aneurysms using flow diverter devices (FDs). The clinical demand for single antiplatelet therapy (SAPT) is increasing especially with the development of devices with lower thrombogenicity profile. However, the safety of SAPT is not well established. OBJECTIVE: To analyze the safety and efficacy of SAPT in terms of ischemic and hemorrhagic complications in patients undergoing FDs treatment for cerebral aneurysms. METHODS: A systematic literature search and meta-analysis were conducted in PubMed, Ovid MEDLINE, Ovid Embase, and Web of Science from January 2010 until October 2022. Twelve articles which reported SAPT and data on hemorrhagic, TECs, and mortality following FDs treatment were included. RESULTS: Overall, the 12 studies involved 237 patients with 295 aneurysms. Five investigated the safety and efficacy of SAPT in 202 unruptured aneurysms. Six studies focused on 57 ruptured aneurysms. One study included both ruptured and unruptured aneurysms. Among the 237 patients, prasugrel was most often used as SAPT in 168 cases (70.9%), followed by aspirin in 42 (17.7%) patients, and by ticagrelor in 27 (11.4%). Overall, the hemorrhagic complication rate was 0.1% (95% CI 0% to 1.8%). The TEC rate was 7.6% (95% CI 1.7% to 16.1%). In the subgroup analysis, the TEC rates of prasugrel monotherapy of 2.4% (95% CI 0% to 9.3%) and ticagrelor monotherapy of 4.2% (95% CI 0.1% to 21.1%) were lower than of aspirin monotherapy 20.2% (95% CI 5.9% to 38.6%). The overall mortality rate was 1.3% (95% CI 0% to 6.1%). CONCLUSION: According to the available data, SAPT regimen in patients undergoing FDs treatment for cerebral aneurysms has an acceptable safety profile, especially with the use of ADP-receptor antagonists.

Dual-Energy Computed Tomography in Stroke Imaging : Value of a New Image Acquisition Technique for Ischemia Detection after Mechanical Thrombectomy.

OBJECTIVE: To assess if a new dual-energy computed tomography (DECT) technique enables an improved visualization of ischemic brain tissue after mechanical thrombectomy in acute stroke patients. MATERIAL AND METHODS: The DECT head scans with a new sequential technique (TwinSpiral DECT) were performed in 41 patients with ischemic stroke after endovascular thrombectomy and were retrospectively included. Standard mixed and virtual non-contrast (VNC) images were reconstructed. Infarct visibility and image noise were assessed qualitatively by two readers using a 4-point Likert scale. Quantitative Hounsfield units (HU) were used to assess density differences of ischemic brain tissue versus healthy tissue on the non-affected contralateral hemisphere. RESULTS: Infarct visibility was significantly better in VNC compared to mixed images for both readers R1 (VNC: median 1 (range 1-3), mixed: median 2 (range 1-4), p < 0.05) and R2 (VNC: median 2 (range 1-3), mixed: 2 (range 1-4), p < 0.05). Qualitative image noise was significantly higher in VNC compared to mixed images for both readers R1 (VNC: median 3, mixed: 2) and R2 (VNC: median 2, mixed: 1, p < 0.05, each). Mean HU were significantly different between the infarcted tissue and the reference healthy brain tissue on the contralateral hemisphere in VNC (infarct 24 ± 3) and mixed images (infarct 33 ± 5, p < 0.05, each). The mean HU difference between ischemia and reference in VNC images (mean 8 ± 3) was significantly higher (p < 0.05) compared to the mean HU difference in mixed images (mean 5 ± 4). CONCLUSION: TwinSpiral DECT allows an improved qualitative and quantitative visualization of ischemic brain tissue in ischemic stroke patients after endovascular treatment.