Spatial colocalization of imaging markers in iatrogenic cerebral amyloid angiopathy with the site of surgery: A metaanalysis.

INTRODUCTION: Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA. Imaging features are overlapping with spontaneous CAA. However, in iCAA imaging features have not been systematically described so far. The aim of this metaanalysis was to evaluate if any of the described imaging features showed colocalization with the initial site of surgery. MATERIAL AND METHODS: A systematic review of the medical literature was performed. Patients with probable iCAA were included if the route of potential entry of amyloid into the CNS was unambiguous. RESULTS: 24 patients from 19 reports could be included. 84 ICHs were reported. 11 of the first ever ICH (69%, p = 0.0498, Fisher's exact test) occurred ipsilateral to the site of the initial surgery, whereas 59% of all ICH (n = 63, p = 0.126, Fisher's exact test) occurred ipsilateral to the site of the initial surgery. No cerebellar hemorrhages (0%) were reported. In 5 of 8 patients, ipsilateral hemorrhagic and non-hemorrhagic manifestations were present before symptom onset and/or occurrence of ICH. DISCUSSION: This metananalysis of the imaging markers of iCAA revealed a spatial colocalization of first ICH with the site of the surgery. Imaging studies with patients at risk for iCAA after exposure to lyophilized dura should be conducted.

Aß38 and Aß43 do not differentiate between Alzheimer's disease and cerebral amyloid angiopathy.

Differential diagnosis between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) using cerebrospinal fluid (CSF) biomarkers is challenging. A recent study suggested that the addition of Aß38 and Aß43 to a standard AD biomarker panel (Aß40, Aß42, t-tau, p-tau) to improve the differential diagnosis. We tested this hypothesis in an independent German cohort of CAA and AD patients and controls using the same analytical techniques. We found excellent discrimination between AD and controls and between CAA and controls, but not between AD and CAA. Adding Aß38 and Aß43 to the panel did not improve the discrimination between AD and CAA.

Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. / Auswertung der DeGIR-Registerdaten zur endovaskulären Therapie von zerebralen Vasospasmen in Deutschland 2018­2021: Ein Überblick über die aktuelle Versorgungssituation.

BACKGROUND: Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany. METHODS: Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality. RESULTS: 3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001). CONCLUSION: EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation. KEY POINTS: · In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better.. CITATION FORMAT: · Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.

Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy.

Background: Cerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation. Methods: Retrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed. Results: Between 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA. Conclusion: Approximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB.

Non-contrast computed tomography features predict intraventricular hemorrhage growth.

OBJECTIVES: Non-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth. METHODS: Patients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models. RESULTS: A total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16-2.44]; p = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48-2.64]; p = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91-3.53]; p = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion. CONCLUSIONS: NCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies. CLINICAL RELEVANCE STATEMENT: Non-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies. KEY POINTS: • NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences. • The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion. • Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19 : Results of a retrospective multicenter neuroimaging-based study from three central European countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. MATERIALS AND METHODS: Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. RESULTS: 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. DISCUSSION: AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.

Characterizing mixed location hemorrhages/microbleeds with CSF markers.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. PATIENTS AND METHODS: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. RESULTS: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. CONCLUSION: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Can novel CT-and MR-based neuroimaging biomarkers further improve the etiological diagnosis of lobar intra-cerebral hemorrhage?

Lobar hematomas represent around half of all supratentorial hemorrhages and have high mortality and morbidity. Their management depends on the underlying cause. Apart from local causes such as vascular malformation, which are rare and can usually be easily excluded thanks to imaging, the vast majority of lobar hematomas equally frequently result from either hypertensive arteriolopathy (HA) or cerebral amyloid angiopathy (CAA). Distinguishing between CAA and HA is important for prognostication (risk of recurrence nearly sevenfold higher in the former), for decision-making regarding, e.g., antithrombotic therapies (for other indications) and for clinical trials of new therapies. Currently, a non-invasive diagnosis of probable CAA can be made using the MR-based modified Boston criteria, which have excellent specificity but moderate sensitivity against histopathological reference, leading to the clinically largely irrelevant diagnosis of "possible CAA". Furthermore, the Boston criteria cannot be applied when both lobar and deep MRI hemorrhagic markers are present, a not uncommon situation. Here we propose to test whether new CT and MR-based imaging biomarkers, namely finger-like projections of the hematoma and adjacent subarachnoid hemorrhage on acute-stage CT or MRI, and remote punctate diffusion-weighted imaging ischemic lesions on acute or subacute-stage MRI, have the potential to improve the performance of the Boston criteria. Furthermore, we also propose to test whether clinical-radiological biomarkers may also allow a positive diagnosis of HA to be made in lobar hematomas, which, if feasible, would not only further reduce the prevalence of "possible CAA" but also permit a diagnosis of HA and/or CAA to be made in the presence of mixed deep and lobar MRI hemorrhagic markers.

Brain Tissue Conductivity in Focal Cerebral Ischemia.

BACKGROUND: Cerebral ischemia leads to oxygen depletion with rapid breakdown of transmembrane transporters and subsequent impaired electrolyte haemostasis. Electric properties tomography (EPT) is a new contrast in MRI which delivers information on tissue electrical conductivity. In the clinical realm it has been mostly used for tumour mapping. Ischemic cerebral stroke is another promising but neglected application. It might deliver additional information on tissue viability and possible response to therapy. AIM: The aim of this study was to demonstrate tissue conductivity in a rodent model of stroke. Further, we aimed to compare electric conductivity in ischemic and non-ischemic cerebral tissue. MATERIALS AND METHODS: Two male Wistar rats were used in this study and were subjected to permanent MCAO. The animals were scanned in a 3 Tesla system (Philips Achieva/Best, the Netherlands) using a dedicated solenoid animal coil (Philips/Hamburg, Germany). In addition to diffusion weighted imaging (DWI), EPT was performed using a steady-state free-precession (SSFP) sequence (repetition time/echo time = 4.5/2.3 ms, measured voxel size = 0.6 × 0.6 × 1.2 mm3, flip angle = 38°, number of excitations = 4). From the transceive phase ϕ of these SSFP scans, conductivity σ was estimated by the equation σ = Δϕ/(2µ0ω) with Δ the Laplacian operator, µ0 the magnetic permeability, and ω the Larmor frequency. Subsequently, a median filter was applied, which was locally restricted to voxels with comparable signal magnitude. RESULTS: The animals exhibited an infarct as demonstrated on DWI. Conductivity within the infarcted region was 60-70 % of the conductivity of not affected contralateral tissue (0.39 ± 0.07 S/m and 0.31 ± 0.14 S/m vs. 0.64 ± 0.15 S/m and 0.66 ± 0.16 S/m, respectively). DISCUSSION: Infarcted tissue exhibited decreased conductivity. Further in-vivo experiments with examination of the influence of reperfusion status and temporal evolution of the infarcted areas should be conducted. Depiction of the ischemic penumbra and possibly subclassification of the DWI lesion still seems to be a fruitful target for further studies.

Thrombus Density in Acute Basilar Artery Occlusion Depends on Slice Thickness and the Method of Manual Thrombus Delineation.

Introduction: High thrombus attenuation on CT has been suggested as a predictor of successful recanalization. It is as well speculated that thrombi of different density may be susceptible to different methods of mechanical thrombectomy. In this study we sought to determine the effect of different methods of manual thrombus delineation and reconstructed slice thickness on thrombus density. Material and Methods: Fifty-six patients with acute occlusion of the basilar artery treated with endovascular therapy were retrospectively included. Clinical, demographic, radiological and outcome parameters were collected. Two raters measured absolute and relative thrombus density employing three different methods (one region of interest, three regions of interest, whole thrombus delineation) and using three different reconstructed slice thicknesses (0.625, 2.5 and 5 mm) of the original admission CT. Results: Thirty-nine patients were successfully recanalized (thrombolysis in cerebral infarction score ≥ 2b). Good clinical outcome (modified Rankin scale ≤ 2) occurred significantly more often in the recanalized group (36 vs. 6%, p = 0.023, Fisher's exact test), in the non-recanalized group symptomatic intracranial hemorrhage occurred more often (9 vs. 29%, p = 0.001, Fisher's exact test). Absolute and relative thrombus density were largely different between methods and slice thicknesses. Multiple regression showed a decrease of thrombus density with increasing slice thickness (ß = −3.98, p < 0.001) and logistic regression showed a statistically significant but very small relation between density and recanalization (ß = 0.006, odds ratio (95% confidence interval) = 1.006 (1.003−1.01), p < 0.001). Conclusions: The methods for manual thrombus delineation and reconstructed slice thickness had a significant influence on absolute and relative thrombus density. Density alone may be of limited value as a predictive marker for recanalization success in acute occlusion of the basilar artery. Standards for density measurements must be defined when comparing different studies and when evaluating different methods of mechanical thrombectomy.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis.

BACKGROUND: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. METHODS: Beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. RESULTS: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. CONCLUSION: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study.

BACKGROUND AND PURPOSE: The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. METHODS: In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. RESULTS: The model. RESULTS: yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. CONCLUSIONS: EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Cerebrovascular Collateral Integrity in Pediatric Large Vessel Occlusion: Analysis of the Save ChildS Study.

BACKGROUND AND OBJECTIVES: Robust cerebrovascular collaterals in adult stroke patients have been associated with longer treatment windows, better recanalization rates, and improved outcomes. No studies have investigated the role of collaterals in pediatric stroke. The primary aim was to determine whether favorable collaterals correlated with better radiographic and clinical outcomes in children with ischemic stroke who underwent thrombectomy. METHODS: This study analyzed a subset of children enrolled in SaveChildS, a retrospective, multi-center, observational cohort study of 73 pediatric stroke patients who underwent thrombectomy between 2000-2018 at 27 US and European centers. Included patients had baseline angiographic imaging and follow-up modified Rankin Scale scores available for review. Posterior circulation occlusions were excluded. Cerebrovascular collaterals were graded on acute neuroimaging by 2 blinded neuroradiologists according to the Tan collateral score, where favorable collaterals are defined as >50% filling and unfavorable collaterals as <50% filling distal to the occluded vessel. Collateral status was correlated with clinical and neuroimaging characteristics and outcomes. Between-group comparisons were performed using the Wilcoxon rank-sum test for continuous variables or Fisher's exact test for binary variables. RESULTS: Thirty-three children (mean age 10.9 [SD±4.9]) years were included; 14 (42.4%) had favorable collaterals. Median final stroke volume as a percent of total brain volume (TBV) was significantly lower in patients with favorable collaterals (1.35% [IQR 1.14-3.76] versus 7.86% [1.54-11.07], p=0.049). Collateral status did not correlate with clinical outcome, infarct growth or final ASPECTS in our cohort. Patients with favorable collaterals had higher baseline ASPECTS (7 [IQR 6-8] versus 5.5 [4-6], p=0.006), smaller baseline ischemic volume (1.57% TBV [IQR 1.09-2.29] versus 3.42% TBV [IQR 1.26-5.33], p=0.035) and slower early infarct growth rate (2.4 mL/hr [IQR 1.5-5.1] versus 10.4 mL/hr [IQR 3.0-30.7], p=0.028). DISCUSSION: Favorable collaterals were associated with smaller final stroke burden and slower early infarct growth rate, but not with better clinical outcome in our study. Prospective studies are needed to determine the impact of collaterals in childhood stroke. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in children with ischemic stroke undergoing thrombectomy, favorable collaterals were associated with improved radiographic outcomes but not with better clinical outcomes.