Hemorrhagic Moyamoya Angiopathy in European Patients.

BACKGROUND: Moyamoya angiopathy (MMA) is an important cause of juvenile stroke but an overall rare disease among European populations compared with East Asian cohorts. Consecutively, hemorrhagic MMA is described well in East Asian cohorts, but knowledge in non-Asian patients is limited. Literature suggests that disease presentation may vary between those cohorts, also including hemorrhage frequencies. Hence, this article aims to analyze hemorrhagic MMA in European patients. METHODS: We screened for patients of European origin with MMA from a single-center consecutive database of a German hospital specialized on MMA. Those who had a record of intracranial hemorrhage were analyzed individually regarding the type of hemorrhage and use of antiplatelet therapy before and after bleeding onset. To identify associated factors of intracranial hemorrhage, an age- and sex-matched control group was identified from the pool of patients without a history of hemorrhage. Both groups had a comparable follow-up time and were compared in terms of disease presentation, therapeutic interventions, and imaging characteristics, using both univariate tests and multivariate logistic regression analysis. RESULTS: From a pool of 332 patients with MMA we identified 288 of European ancestry. From those, 36 had a record of intracranial hemorrhage (12.5%). Thirty-three patients presenting with 37 events were included for further analysis and case-control-comparison. Most events were intracerebral hemorrhage (n=20; 54%) and subarachnoid hemorrhage (n=11; 30%). 78% developed hemorrhage although no antiplatelet therapy was in use (n=29). Seven patients developed intracranial hemorrhage ipsilateral to prior bypass surgery (21%), while 29 of the control patients had a bypass surgery (88%; P=0.0001). There was no significant difference in terms of unilateral or bilateral disease type, history of hypertension, as well as imaging characteristics (high Suzuki stage and the presence of collateral pathways in conventional angiography, as well as ischemic defects and the presence of microbleeds on cerebral magnetic resonance imaging; P>0.05 in multivariate analysis, respectively). CONCLUSIONS: Bypass surgery was negatively associated with the development of intracranial hemorrhage in MMA in European patients. There was no difference in terms of a history of hypertension between groups, indicating that blood pressure is not the major contributor for rupture of fragile collateral vessels. The investigated imaging characteristics were not associated to hemorrhage onset and, therefore, are not suitable as a tool of screening for patients at risk.

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND: There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS: Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS: In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS: Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies.

Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed?

BACKGROUND: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT-as compared to no-IVT-may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. METHODS: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score <6) isolated internal carotid artery occlusion patients treated within 4.5 hours of symptoms onset with either IVT or antithrombotic therapy between 2006 and 2020 (inclusion date varied among centers). Primary outcome was END within 24 hours (≥4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END7d) and 3-month modified Rankin Scale score 0 to 1. RESULTS: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07-3.92]; P=0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P=0.09). However, END7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END7d: adjusted hazard ratio, 1.29 [95% CI, 0.75-2.23]; P=0.37; modified Rankin Scale score of 0-1: adjusted odds ratio, 1.1 [95% CI, 0.6-2.2]; P=0.71). END7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9-10.1) versus 20.4 hours (interquartile range, 7.8-34.4), respectively, P<0.01. CONCLUSIONS: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END-particularly END due to artery-to-artery embolism-occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants.

BACKGROUND: Proteinuria is a well-known risk factor for progressive kidney impairment. Recently, C-terminal cubilin (CUBN) variants have been associated with isolated proteinuria without progression of kidney disease. METHODS: Genetic testing of 347 families with proteinuria of suspected monogenic cause was performed by next-generation sequencing of a custom-designed kidney disease gene panel. Families with CUBN biallelic proteinuria-causing variants were studied at the clinical, genetic, laboratory and pathologic levels. RESULTS: Twelve families (15 patients) bearing homozygous or compound heterozygous proteinuria-causing variants in the C-terminal CUBN gene were identified, representing 3.5% of the total cohort. We identified 14 different sequence variants, five of which were novel. The median age at diagnosis of proteinuria was 4 years (range 9 months to 44 years), and in most cases proteinuria was detected incidentally. Thirteen patients had moderate to severe proteinuria at diagnosis without nephrotic syndrome. These patients showed lack of response to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, normal kidney biopsy and preservation of normal kidney function over time. The two remaining patients presented a more severe phenotype, likely caused by associated comorbidities. CONCLUSIONS: Identification of C-terminal pathogenic CUBN variants is diagnostic of an entity characterized by glomerular proteinuria, normal kidney histology and lack of response to ACEi/ARB treatment. This study adds evidence and increases awareness about albuminuria caused by C-terminal variants in the CUBN gene, which is a benign condition usually diagnosed in childhood with preserved renal function until adulthood.

Beyond the Epileptic Focus: Functional Epileptic Networks in Focal Epilepsy.

Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG-fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG-fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.

[Atherosclerosis of the intracranial arteries and of the extracranial carotid artery.] / Atherosklerose der intrakraniellen Arterien und der extrakraniellen Karotis.

Atherosclerosis of the intracranial arteries and of the extracranial carotid artery. Abstract. Intracranial atherosclerotic stenoses are the most common cause of ischemic stroke worldwide. Nowadays, three therapeutic approaches are available for consideration for patients with intracranial atherosclerotic stenoses: A conservative therapy (best medical treatment, management of vascular risk factors and healthy lifestyle), endovascular and surgical therapy. Conservative approach has been recommended for patients with asymptomatic intracranial atherosclerotic stenoses, as well as for those with symptomatic stenoses. Endovascular therapy should be considered as a treatment option for carefully selected patients with recurrent ischemic strokes attributed to the stenotic artery while receiving best medical therapy. Surgical revascularisation is rarely favored in patients with intracranial stenoses. In patients with extracranial atherosclerotic stenoses, carotid endarterectomy (CEA) has been associated with a lower risk of death and recurrent stroke when compared to carotid angioplasty and stenting (CAS). Especially in elderly patients over 70 years of age CEA is preferred over CAS due to the twofold increased 30-day risk of recurrent stroke or death in patients treated with CAS. Results from contemporary studies using modern techniques and devices are expected. It remains unclear whether patients with asymptomatic extracranial atherosclerotic stenoses receiving best medical treatment would benefit of invasive procedures such as CEA or CAS.

Extensive immune reconstitution inflammatory syndrome in Fingolimod-associated PML: a case report with 7 Tesla MRI data.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare complication of patients treated with fingolimod. CASE PRESENTATION: Routine MRI eventually led to diagnosis of asymptomatic early PML that remained stable after discontinuation of fingolimod. As blood lymphocyte counts normalized, signs of immune reconstitution inflammatory syndrome (IRIS) and renewed MS activity developed. Both, advanced laboratory and ultrahigh field MRI findings elucidated differences between PML and MS. CONCLUSIONS: In our case, early discontinuation of fingolimod yielded a good outcome, lymphocyte counts reflected immune system activity, and paraclinical findings helped to differentiate between PML-IRIS and MS.

Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency.

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18 controls (aged 3-16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.

Decreased glutathione and low catalase activity contribute to oxidative stress in children with α-1 antitrypsin deficiency.

BACKGROUND: Recent investigations in animal models have revealed oxidative stress and oxidative damage in the pathogenesis of alpha-1 antitrypsin deficiency (AATD). However, no data are available on the oxidative stress status and antioxidant enzyme activity in these patients. This study was aimed to analyse the oxidative stress profile and enzymatic antioxidant defence mechanisms in children with AATD. METHODS: Oxidative stress parameters and the activity of the main antioxidant enzymes were prospectively measured in serum of fifty-one children diagnosed with AATD and thirty-eight control individuals. RESULTS: Oxidative stress was increased in the serum of children with intermediate- (MZ; SZ) and high-risk (ZZ) phenotypes for developing AATD-related emphysema and/or liver disease. When compared with the control group, intermediate- and high-risk groups showed significantly lower total glutathione and reduced glutathione levels, decreased catalase activity and increased glutathione peroxidase activity leading to an accumulation of hydrogen peroxide that would explain the significantly increased levels of oxidative stress biomarkers observed in these patients. No differences were observed between the control (MM) and the low-risk (MS; SS) groups. A gradation in oxidative stress parameters was observed when patients were compared among themselves, in that the expression of the Z allele produces a higher oxidative stress status in homozygous (ZZ) than in heterozygous (MZ; SZ) patients. CONCLUSIONS: Increased oxidative stress, together with reduced antioxidant defence are involved in the pathophysiology of AATD at early stages, opening up a new rationale for the use of antioxidant therapies in the treatment of the disease.

MCMC Methods for Parameter Estimation in ODE Systems for CAR-T Cell Cancer Therapy.

Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in treating resistant hematologic cancers. It is based on genetically modifying T cells transferred from the patient or a donor. Although its implementation has increased over the last few years, CAR-T has many challenges to be addressed, for instance, the associated severe toxicities, such as cytokine release syndrome. To model CAR-T cell dynamics, focusing on their proliferation and cytotoxic activity, we developed a mathematical framework using ordinary differential equations (ODEs) with Bayesian parameter estimation. Bayesian statistics were used to estimate model parameters through Monte Carlo integration, Bayesian inference, and Markov chain Monte Carlo (MCMC) methods. This paper explores MCMC methods, including the Metropolis-Hastings algorithm and DEMetropolis and DEMetropolisZ algorithms, which integrate differential evolution to enhance convergence rates. The theoretical findings and algorithms were validated using Python and Jupyter Notebooks. A real medical dataset of CAR-T cell therapy was analyzed, employing optimization algorithms to fit the mathematical model to the data, with the PyMC library facilitating Bayesian analysis. The results demonstrated that our model accurately captured the key dynamics of CAR-T cell therapy. This conclusion underscores the potential of parameter estimation to improve the understanding and effectiveness of CAR-T cell therapy in clinical settings.

DOT sign indicates persistent hypoperfusion and poor outcome in patients with incomplete reperfusion following thrombectomy.

BACKGROUND: Distal occlusions associated with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction,

Incidence, Risk Factors, and Clinical Implications of Subarachnoid Hyperdensities on Flat-Panel Detector CT following Mechanical Thrombectomy in Patients with Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Flat-panel detector CT immediately after mechanical thrombectomy can detect complications, including early hemorrhagic transformation and subarachnoid hyperdensities. The clinical significance of subarachnoid hyperdensities in patients undergoing mechanical thrombectomy remains unclear. MATERIALS AND METHODS: We studied 223 patients who underwent mechanical thrombectomy for anterior circulation stroke who had flat-panel detector CT performed immediately after the procedure and had follow-up imaging within 24 hours. Subarachnoid hyperdensity severity was categorized into 5 grades (subarachnoid hyperdensities, 0: absent to subarachnoid hyperdensities, IV: extensive). Baseline and procedural characteristics as well as outcome measures were analyzed using group comparisons and multivariable logistic regression analyses. RESULTS: Overall, 100/223 (45%) patients showed subarachnoid hyperdensities on immediate postinterventional flat-panel detector CT. The factors associated with an increased subarachnoid hyperdensity risk were the following: medium-vessel occlusion or distal-vessel occlusion compared with a large-vessel occlusion, a more distal device position, a higher number of device passes, a larger volume of contrast applied, worse final reperfusion expanded TICI, and after receiving IV thrombolysis. The occurrence of subarachnoid hyperdensity grades II-IV was independently associated with worse functional outcomes (adjusted OR for mRS, 3-6: 2.2; 95% CI 1.1-4.3), whereas patients with subarachnoid hyperdensity grade I had outcomes similar to those in patients without subarachnoid hyperdensities. CONCLUSIONS: Our study identified risk factors for subarachnoid hyperdensities, most of which reflect increasingly challenging procedures or more peripheral recanalization attempts. The presence of subarachnoid hyperdensity grades II-IV was associated with poorer outcomes, suggesting the need for personalized strategies to reduce its incidence and severity or potentially improve recovery after subarachnoid hyperdensities.

Basilar Artery Perforator Aneurysms - The Phantom Menace of the Intracranial Universe.

Cerebral perforators are end-arteries that vascularize specific deep territories in the cerebral hemispheres and brainstem. Due to improved imaging quality, these aneurysms are increasingly diagnosed in clinical routine. High resolution 3D angiographic images are mandatory and in some occasions fusion images might be helpful to detect these aneurysms. Basilar artery perforator aneurysms (or BAPAs) are one of the most common subtypes of perforator aneurysms and might cause subarachnoid hemorrhage along the brainstem (perimesencephalic hemorrhage). Due to the limited evidence, the management of BAPAs may pose a challenge in clinical routine. While some aneurysms can be managed conservatively, a few might require treatment to prevent rebleeding. We present the cases of two patients with BAPAs managed at our center in order to increase the awareness on these potentially underdiagnosed aneurysms.

Flat-panel Detector Perfusion Imaging and Conventional Multidetector Perfusion Imaging in Patients with Acute Ischemic Stroke : A Comparative Study.

PURPOSE: Flat-panel detector computed tomography (FDCT) is increasingly used in (neuro)interventional angiography suites. This study aimed to compare FDCT perfusion (FDCTP) with conventional multidetector computed tomography perfusion (MDCTP) in patients with acute ischemic stroke. METHODS: In this study, 19 patients with large vessel occlusion in the anterior circulation who had undergone mechanical thrombectomy, baseline MDCTP and pre-interventional FDCTP were included. Hypoperfused tissue volumes were manually segmented on time to maximum (Tmax) and time to peak (TTP) maps based on the maximum visible extent. Absolute and relative thresholds were applied to the maximum visible extent on Tmax and relative cerebral blood flow (rCBF) maps to delineate penumbra volumes and volumes with a high likelihood of irreversible infarcted tissue ("core"). Standard comparative metrics were used to evaluate the performance of FDCTP. RESULTS: Strong correlations and robust agreement were found between manually segmented volumes on MDCTP and FDCTP Tmax maps (r = 0.85, 95% CI 0.65-0.94, p < 0.001; ICC = 0.85, 95% CI 0.69-0.94) and TTP maps (r = 0.91, 95% CI 0.78-0.97, p < 0.001; ICC = 0.90, 95% CI 0.78-0.96); however, direct quantitative comparisons using thresholding showed lower correlations and weaker agreement (MDCTP versus FDCTP Tmax 6 s: r = 0.35, 95% CI -0.13-0.69, p = 0.15; ICC = 0.32, 95% CI 0.07-0.75). Normalization techniques improved results for Tmax maps (r = 0.78, 95% CI 0.50-0.91, p < 0.001; ICC = 0.77, 95% CI 0.55-0.91). Bland-Altman analyses indicated a slight systematic underestimation of FDCTP Tmax maximum visible extent volumes and slight overestimation of FDCTP TTP maximum visible extent volumes compared to MDCTP. CONCLUSION: FDCTP and MDCTP provide qualitatively comparable volumetric results on Tmax and TTP maps; however, direct quantitative measurements of infarct core and hypoperfused tissue volumes showed lower correlations and agreement.

Connecting the DOTs: a novel imaging sign on flat-panel detector CT indicating distal vessel occlusions after thrombectomy.

BACKGROUND: Immediate non-contrast post-interventional flat-panel detector CT (FPDCT) has been suggested as an imaging tool to assess complications after endovascular therapy (EVT). We systematically investigated a new imaging finding of focal hyperdensities correlating with remaining distal vessel occlusion after EVT. METHODS: A single-center retrospective analysis was conducted for all acute ischemic stroke patients admitted between July 2020 and December 2022 who underwent EVT and immediate post-interventional FPDCT. A blinded core lab performed reperfusion grading on post-interventional digital subtraction angiography (DSA) images and evaluated focal hyperdensities on FPDCT (here called the distal occlusion tracker (DOT) sign). DOT sign was defined as a tubular or punctiform, vessel confined, hyperdense signal within the initial occlusion target territory. We assessed sensitivity and specificity of the DOT sign when compared with DSA findings. RESULTS: The median age of the cohort (n=215) was 74 years (IQR 63-82) and 58.6% were male. The DOT sign was positive in half of the cohort (51%, 110/215). The DOT sign had high specificity (85%, 95% CI 72% to 93%), but only moderate sensitivity (63%, 95% CI 55% to 70%) for detection of residual vessel occlusions. In comparison to the core lab, operators overestimated complete reperfusion in a quarter of the entire cohort (25%, 53/215). In more than half of these cases (53%, 28/53) there was a positive DOT sign, which could have mitigated this overestimation. CONCLUSION: The DOT sign appears to be a frequent finding on immediate post-interventional FPDCT. It correlates strongly with incomplete reperfusion and indicates residual distal vessel occlusions. In the future, it may be used to complement grading of reperfusion success and may help mitigating overestimation of reperfusion in the acute setting.

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE: Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS: We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS: In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION: Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable.

Value of Immediate Flat Panel Perfusion Imaging after Endovascular Therapy (AFTERMATH): A Proof of Concept Study.

BACKGROUND AND PURPOSE: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. MATERIALS AND METHODS: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). RESULTS: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). CONCLUSIONS: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.

Baseline characteristics and outcome of stroke patients after endovascular therapy according to previous symptomatic vascular disease and sex.

Aim: The aim of this study was to investigate baseline characteristics and outcome of patients after endovascular therapy (EVT) for acute large vessel occlusion (LVO) in relation to their history of symptomatic vascular disease and sex. Methods: Consecutive EVT-eligible patients with LVO in the anterior circulation admitted to our stroke center between 04/2015 and 04/2020 were included in this observational cohort study. All patients were treated according to a standardized acute ischaemic stroke (AIS) protocol. Baseline characteristics and successful reperfusion, recurrent/progressive in-hospital ischaemic stroke, symptomatic in-hospital intracranial hemorrhage, death at discharge and at 3 months, and functional outcome at 3 months were analyzed according to previous symptomatic vascular disease and sex. Results: 995 patients with LVO in the anterior circulation (49.4% women, median age 76 years, median admission NIHSS score 14) were included. Patients with multiple vs. no previous vascular events showed higher mortality at discharge (20% vs. 9.3%, age/sex - adjustedOR = 1.43, p = 0.030) and less independency at 3 months (28.8% vs. 48.8%, age/sex - adjustedOR = 0.72, p = 0.020). All patients and men alone with one or multiple vs. patients and men with no previous vascular events showed more recurrent/progressive in-hospital ischaemic strokes (19.9% vs. 6.4% in all patients, age/sex - adjustedOR = 1.76, p = 0.028) (16.7% vs. 5.8% in men, age-adjustedOR = 2.20, p = 0.035). Men vs. women showed more in-hospital symptomatic intracranial hemorrhage among patients with one or multiple vs. no previous vascular events (23.7% vs. 6.6% in men and 15.4% vs. 5.5% in women, OR = 2.32, p = 0.035/age - adjustedOR = 2.36, p = 0.035). Conclusions: Previous vascular events increased the risk of in-hospital complications and poorer outcome in the analyzed patients with EVT-eligible LVO-AIS. Our findings may support risk assessment in these stroke patients and could contribute to the design of future studies.

Unleashing the potential of 5-Aminolevulinic acid: Unveiling a promising target for cancer diagnosis and treatment beyond photodynamic therapy.

The therapeutic properties of 5-aminolevulinic acid (5-ALA) have been extensively studied for cancer detection and treatment using photodynamic therapy (PDT). When administered externally, 5-ALA is converted to protoporphyrin IX (PpIX) in cancer cells, which generates reactive oxygen species (ROS) upon exposure to light. This process enables targeted cell death induction and cancer detection. Given the highly conserved nature of heme biosynthesis over billions of years, we hypothesized that natural mechanisms might exist to prevent excessive accumulation of PpIX or heme resulting from 5-ALA overload. Therefore, we anticipated alterations in protein expression profiles upon exogenous administration of 5-ALA. To understand cellular responses to 5-ALA, we investigated protein expression changes and identified OR1B1 as a promising target in bladder, prostate, lung, and cervical cancer cells. OR1B1 expression was observed only with 5-ALA and ferrous chloride, highlighting the central role of heme in this discovery. Immunofluorescence and electron microscopy confirmed OR1B1's sub-cellular localization. These findings suggest that 5-ALA transformation in cancer cells and OR1B1 expression have potential for enhancing cancer detection and developing alternative treatments, including immunotherapy. This approach overcomes the limitations of PDT and opens new avenues for effective and targeted cancer interventions.

Evaluation of Sine Spin flat detector CT imaging compared with multidetector CT.

BACKGROUND: Flat detector computed tomography (FDCT) is widely used for periprocedural imaging in the angiography suite. Sine Spin FDCT (SFDCT) is the latest generation of cone beam CT using a double oblique trajectory for image acquisition to reduce artefacts and improve soft tissue brain imaging. This study compared the effective dose, image quality and diagnostic performance of the latest generation of SFDCT with multidetector CT (MDCT). METHODS: An anthropomorphic phantom equipped with MOSFET detectors was used to measure the effective dose of the new 7sDCT Sine Spin protocol on a latest generation biplane angiographic C-arm system. Diagnostic performance was evaluated on periprocedurally acquired SFDCT for depiction of anatomical details, detection of hemorrhage, and ischemia and was compared with preprocedurally acquired MDCT. Inter- and intra-rater correlation as well as sensitivity and specificity were calculated. RESULTS: Both modalities showed equal diagnostic performance in the supratentorial ventricular system. SFDCT provided inferior image quality in grey-white matter differentiation and infratentorial structures. Intraventricular, subarachnoid and parenchymal hemorrhages were diagnosed with a sensitivity of 83.3%, 84.2% and 75% and a specificity of 97.3%, 80.0% and 100%, respectively; early ischemic lesions with a sensitivity of 73.3% and specificity 94.7%. The effective dose measured for the 7sDCT Sine Spin protocol was 2 mSv. CONCLUSIONS: Our findings confirm the high diagnostic sensitivity and specificity of SFDCT in detecting intracranial hemorrhage and early ischemic lesions. The delineation of grey-white matter differentiation and infratentorial structures remains a limiting factor. In comparison to previous studies, the new 7sDCT Sine Spin protocol showed a lower effective dose.