Can Perfusion-Based Brain Tissue Oxygenation MRI Support the Understanding of Cerebral Abscesses In Vivo?

PURPOSE: The clinical condition of a brain abscess is a potentially life-threatening disease. The combination of MRI-based imaging, surgical therapy and microbiological analysis is critical for the treatment and convalescence of the individual patient. The aim of this study was to evaluate brain tissue oxygenation measured with dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) in patients with brain abscess and its potential benefit for a better understanding of the environment in and around brain abscesses. METHODS: Using a local database, 34 patients (with 45 abscesses) with brain abscesses treated between January 2013 and March 2021 were retrospectively included in this study. DSC-PWI imaging and microbiological work-up were key inclusion criteria. These data were analysed regarding a correlation between DSC-PWI and microbiological result by quantifying brain tissue oxygenation in the abscess itself, the abscess capsula and the surrounding oedema and by using six different parameters (CBF, CBV, CMRO2, COV, CTH and OEF). RESULTS: Relative cerebral blood flow (0.335 [0.18-0.613] vs. 0.81 [0.49-1.08], p = 0.015), relative cerebral blood volume (0.44 [0.203-0.72] vs. 0.87 [0.67-1.2], p = 0.018) and regional cerebral metabolic rate for oxygen (0.37 [0.208-0.695] vs. 0.82 [0.55-1.19], p = 0.022) were significantly lower in the oedema around abscesses without microbiological evidence of a specific bacteria in comparison with microbiological positive lesions. CONCLUSIONS: The results of this study indicate a relationship between brain tissue oxygenation status in DSC-PWI and microbiological/inflammatory status. These results may help to better understand the in vivo environment of brain abscesses and support future therapeutic decisions.

Accuracy of Dose-Saving Artificial-Intelligence-Based 3D Angiography (3DA) for Grading of Intracranial Artery Stenoses: Preliminary Findings.

BACKGROUND AND PURPOSE: Based on artificial intelligence (AI), 3D angiography (3DA) is a novel postprocessing algorithm for "DSA-like" 3D imaging of cerebral vasculature. Because 3DA requires neither mask runs nor digital subtraction as the current standard 3D-DSA does, it has the potential to cut the patient dose by 50%. The object was to evaluate 3DA's diagnostic value for visualization of intracranial artery stenoses (IAS) compared to 3D-DSA. MATERIALS AND METHODS: 3D-DSA datasets of IAS (nIAS = 10) were postprocessed using conventional and prototype software (Siemens Healthineers AG, Erlangen, Germany). Matching reconstructions were assessed by two experienced neuroradiologists in consensus reading, considering image quality (IQ), vessel diameters (VD1/2), vessel-geometry index (VGI = VD1/VD2), and specific qualitative/quantitative parameters of IAS (e.g., location, visual IAS grading [low-/medium-/high-grade] and intra-/poststenotic diameters [dintra-/poststenotic in mm]). Using the NASCET criteria, the percentual degree of luminal restriction was calculated. RESULTS: In total, 20 angiographic 3D volumes (n3DA = 10; n3D-DSA = 10) were successfully reconstructed with equivalent IQ. Assessment of the vessel geometry in 3DA datasets did not differ significantly from 3D-DSA (VD1: r = 0.994, p = 0.0001; VD2:r = 0.994, p = 0.0001; VGI: r = 0.899, p = 0.0001). Qualitative analysis of IAS location (3DA/3D-DSA:nICA/C4 = 1, nICA/C7 = 1, nMCA/M1 = 4, nVA/V4 = 2, nBA = 2) and the visual IAS grading (3DA/3D-DSA:nlow-grade = 3, nmedium-grade = 5, nhigh-grade = 2) revealed identical results for 3DA and 3D-DSA, respectively. Quantitative IAS assessment showed a strong correlation regarding intra-/poststenotic diameters (rdintrastenotic = 0.995, pdintrastenotic = 0.0001; rdpoststenotic = 0.995, pdpoststenotic = 0.0001) and the percentual degree of luminal restriction (rNASCET 3DA = 0.981; pNASCET 3DA = 0.0001). CONCLUSIONS: The AI-based 3DA is a resilient algorithm for the visualization of IAS and shows comparable results to 3D-DSA. Hence, 3DA is a promising new method that allows a considerable patient-dose reduction, and its clinical implementation would be highly desirable.

Extended Multimodal Flat Detector CT Imaging in Acute Ischemic Stroke: A Pilot Study.

By using Flat detector computed tomography (FD-CT), a one-stop-shop approach in the diagnostic workup of acute ischemic stroke (AIS) might be achieved. Although information on upstream vessels is warranted, dedicated FD-CT protocols which include the imaging of the cervical vasculature are still lacking. We aimed to prospectively evaluate the implementation of a new multimodal FD-CT protocol including cervical vessel imaging in AIS patients. In total, 16 patients were included in this study. Eight patients with AIS due to large vessel occlusion (LVO) prospectively received a fully multimodal FD-CT imaging, including non-enhanced flat detector computed tomography (NE-FDCT), dynamic perfusion flat detector computed tomography (FD-CTP) and flat detector computed tomography angiography (FD-CTA) including cervical imaging. For comparison of time metrics and image quality, eight AIS patients, which received multimodal CT imaging, were included retrospectively. Although image quality of NE-FDCT and FD-CTA was rated slightly lower than NE-CT and CTA, all FD-CT datasets were of diagnostic quality. Intracerebral hemorrhage exclusion and LVO detection was reliably possible. Median door-to-image time was comparable for the FD-CT group and the control group (CT:30 min, IQR27-58; FD-CT:44.5 min, IQR31-55, p = 0.491). Door-to-groin-puncture time (CT:79.5 min, IQR65-90; FD-CT:59.5 min, IQR51-67; p = 0.016) and image-to-groin-puncture time (CT:44 min, IQR30-50; FD-CT:14 min, IQR12-18; p < 0.001) were significantly shorter, when patients were directly transferred to the angiosuite, where FD-CT took place. Our study indicates that using a new fully multimodal FD-CT approach including imaging of cervical vessels for first-line imaging in AIS patients is feasible and comparable to multimodal CT imaging with substantial potential to streamline the stroke workflow.

Can flat-detector CT after successful endovascular treatment predict long-term outcome in patients with large vessel occlusion? An Alberta Stroke Programme Early CT Score-based study.

PURPOSE: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. METHODS: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). RESULTS: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10-9) vs. median ASPECTS 9 (10-7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI - 0.102-0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003-0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). CONCLUSION: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome.

Prognostic Accuracy of CTP Summary Maps in Patients with Large Vessel Occlusive Stroke and Poor Revascularization after Mechanical Thrombectomy-Comparison of Three Automated Perfusion Software Applications.

Background: Innovative automated perfusion software solutions offer support in the management of acute stroke by providing information about the infarct core and penumbra. While the performance of different software solutions has mainly been investigated in patients with successful recanalization, the prognostic accuracy of the hypoperfusion maps in cases of futile recanalization has hardly been validated. Methods: In 39 patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation and poor revascularization (thrombolysis in cerebral infarction (TICI) 0-2a) after mechanical thrombectomy (MT), hypoperfusion analysis was performed using three different automated perfusion software solutions (A: RAPID, B: Brainomix e-CTP, C: Syngo.via). The hypoperfusion volumes (HV) as Tmax > 6 s were compared with the final infarct volumes (FIV) on follow-up CT 36−48 h after futile recanalization. Bland−Altman analysis was applied to display the levels of agreement and to evaluate systematic differences. Based on the median hypoperfusion intensity ratio (HIR, volumetric ratio of tissue with a Tmax > 10 s and Tmax > 6 s) patients were dichotomized into high- and low-HIR groups. Subgroup analysis with favorable (<0.6) and unfavorable (≥0.6) HIR was performed with respect to the FIV. HIR was correlated to clinical baseline and outcome parameters using Pearson's correlation. Results: Overall, there was good correlation without significant differences between the HVs and the FIVs with package A (r = 0.78, p < 0.001) being slightly superior to B and C. However, levels of agreement were very wide for all software applications in Bland-Altman analysis. In cases of large infarcts exceeding 150 mL the performance of the automated software solutions generally decreased. Subgroup analysis revealed the FIV to be generally underestimated in patients with HIR ≥ 0.6 (p < 0.05). In the subgroup with favorable HIR, however, there was a trend towards an overestimation of the FIV. Nevertheless, packages A and B showed good correlation between the HVs and FIVs without significant differences (p > 0.2), while only package C significantly overestimated the FIV (−54.6 ± 56.0 mL, p = 0.001). The rate of modified Rankin Scale (mRS) 0−3 after 3 months was significantly higher in favorable vs. unfavorable HIR (42.1% vs. 13.3%, p = 0.02). Lower HIR was associated with higher Alberta Stroke Program Early CT Score (ASPECTS) at presentation and on follow-up imaging, lower risk of malignant edema, and better outcome (p < 0.05). Conclusion: Overall, the performance of the automated perfusion software solutions to predict the FIV after futile recanalization is good, with decreasing accuracy in large infarcts exceeding 150 mL. However, depending on the HIR, FIV can be significantly over- and underestimated, with Syngo showing the widest range. Our results indicate that the HIR can serve as valuable parameter for outcome predictions and facilitate the decision whether or not to perform MT in delicate cases.

Correlation between clinical severity and extent of autonomic cardiovascular impairment in the acute phase of subarachnoid hemorrhage.

BACKGROUND AND AIM: To assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH). METHODS: In this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R-R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers. RESULTS: RRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9-402.4) ms2 vs 442.3 (246.8-921.2) ms2, p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2-3.7) ms2 vs 3.7 (3.1-5.3) ms2, p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7-710.4) ms2 vs 72.1 (10.1-175.9) ms2, p = 0.001, rho = - 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3-5.4) ms2 vs 1.6 (1.0-2.8) ms2, p < 0.001, rho = - 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation). CONCLUSION: Within the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome.

Change your Angle of View : Sinusoidal C-Arm Movement in Cranial Flat-panel CT to Improve Image Quality.

BACKGROUND: Artifacts from surrounding bony structures, especially from the petrous bones, regularly impair soft tissue computed tomography (CT) imaging of the middle and posterior fossa. This affects flat-panel CT in particular. Sinusoidal movement of the C­arm during acquisition (i.e. craniocaudal tilting along with semicircular rotation) is supposed to reduce artifacts, thus enhancing soft tissue imaging quality. METHODS: In the work-up of ischemic stroke or subarachnoid hemorrhage 40 patients underwent multi-slice CT (MS-CT) and either plain circular (cFP-CT; n = 20) or sinusoidal (sFP-CT; n = 20) flat-panel CT within a short interval. Two independent readers analyzed MS-CT and FP-CT datasets for recognizability of eight different brain structures and three typical types of artifacts according to a predetermined score. RESULTS: Interrater reliability was moderate for cFP-CT (κ = 0.575) and good to very good for ratings of MS-CT and sFP-CT (κ = 0.651 to κ = 1). MS-CT was rated to be significantly better than cFP-CT and sFP-CT (p < 0.0001) in the overall score. Yet, sFP-CT was rated to be significantly superior to cFP-CT (overall p < 0.0001) regarding most anatomical regions and petrous bone artifacts. CONCLUSION: Compared to a standard circular protocol, sinusoidal C­arm movement in cranial FP-CT can significantly reduce artifacts in the posterior fossa and, moreover, can improve visualization of most supratentorial and infratentorial anatomical structures.

A novel use of time separation technique to improve flat detector CT perfusion imaging in stroke patients.

BACKGROUND: CT perfusion imaging (CTP) is used in the diagnostic workup of acute ischemic stroke (AIS). CTP may be performed within the angio suite using flat detector CT (FDCT) to help reduce patient management time. PURPOSE: In order to significantly improve FDCT perfusion (FDCTP) imaging, data-processing algorithms need to be able to compensate for the higher levels of noise, slow rotation speed, and a lower frame rate of current FDCT devices. METHODS: We performed a realistic simulation of FDCTP acquisition based on CTP data from seven subjects. We used the time separation technique (TST) as a model-based approach for FDCTP data processing. We propose a novel dimension reduction in which we approximate the time attenuation curves by a linear combination of trigonometric functions. Our goal was to show that the TST can be used even without prior assumptions on the shape of the attenuation profiles. RESULTS: We first demonstrated that a trigonometric basis is suitable for dimension reduction of perfusion data. Using simulated FDCTP data, we have shown that a trigonometric basis in the TST provided better results than the classical straightforward processing even with additional noise. Average correlation coefficients of perfusion maps were improved for cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT) maps. In a moderate noise scenario, the average Pearson's coefficient for the CBF map was improved using the TST from 0.76 to 0.81. For the MTT map, it was improved from 0.37 to 0.45. Furthermore, we achieved a total processing time from the reconstruction of FDCTP data to the generation of perfusion maps of under 5 min. CONCLUSIONS: In our study cohort, perfusion maps created from FDCTP data using the TST with a trigonometric basis showed equivalent perfusion deficits to classic CT perfusion maps. It follows, that this novel FDCTP technique has potential to provide fast and accurate FDCTP imaging for AIS patients.

Simplified Edinburgh CT Criteria for Identification of Lobar Intracerebral Hemorrhage Associated With Cerebral Amyloid Angiopathy.

BACKGROUND AND OBJECTIVES: In patients with lobar intracerebral hemorrhage (ICH), etiologic characterization represents a tradeoff between feasibility, resource allocation, and diagnostic certainty. This study investigated the accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy (CAA). METHODS: This external validation analyzed 210 consecutive patients with lobar ICH and available CT and MRI studies from a prospective single-center observational cohort study (2006-2015, Longitudinal Cohort Study on ICH Care [UKER-ICH,] NCT03183167). We investigated the interrater variability and diagnostic accuracy of the simplified Edinburgh CT-based criteria for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the utility of the simplified Edinburgh criteria by decision curve analysis, comparing the theoretical clinical net benefit (weighted benefit-harm at varying threshold probabilities) of the high-risk category (finger-like projections and subarachnoid hemorrhage) for ruling in and the low-risk category (neither finger-like projections nor subarachnoid hemorrhage) for ruling out with the assumptions of no or all patients having CAA (default strategies). RESULTS: Of 210 patients, 70 (33.3%) had high risk, 67 (31.9%) had medium risk, and 73 (34.8%) had low risk for CAA-associated ICH according to simplified Edinburgh CT criteria, showing moderate interrater variability. Discrimination was good (area under the receiver operating characteristics curve 0.74, 95% CI 0.67-0.81) without evidence of poor calibration (Hosmer-Lemeshow, p = 0.54) for validation of MRI-based diagnosis of probable CAA (n = 94 of 210, 44.8%). The rule-in criteria (high risk), had 87.1% (79.3%-92.3%) specificity, and the rule-out criteria (low risk), had 80.9% (71.1%-88.0%) sensitivity. Decision curve analysis suggested a theoretical clinical net benefit for ruling in but not for ruling out probable CAA compared to default strategies. DISCUSSION: Applying the simplified Edinburgh CT criteria during diagnostic workup seems clinically useful and may accurately identify CAA in patients with lobar ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03183167. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with lobar hemorrhages, the simplified Edinburgh criteria accurately identify those at high risk of CAA.

Pulsed Arterial Spin Labeling and Segmented Brain Volumetry in the Diagnostic Evaluation of Frontotemporal Dementia, Alzheimer's Disease and Mild Cognitive Impairment.

Background: Previous studies suggest that brain atrophy can not only be defined by its morphological extent, but also by the cerebral blood flow (CBF) within a certain area of the brain, including white and gray matter. The aim of this study is to investigate known atrophy patterns in different forms of dementia and to compare segmented brain volumetrics and pulsed arterial spin labeling (pASL) data to explore the correlation between brain maps with atrophy and this non-contrast-enhanced brain-perfusion method. Methods: Our study comprised 17 patients with diagnosed cognitive impairment (five Alzheimer's disease = AD, five frontotemporal dementia = FTD, seven mild cognitive impairment = MCI) and 19 healthy control subjects (CO). All patients and controls underwent 4D-pASL brain-perfusion MR imaging and T1w MPRAGE. The data were assessed regarding relative brain volume on the basis of 286 brain regions, and absolute and relative cerebral blood flow (CBF/rCBF) were derived from pASL data in the corresponding brain regions. Mini-Mental State Examination (MMSE) was performed to assess cognitive functions. Results: FTD patients demonstrated significant brain atrophy in 43 brain regions compared to CO. Patients with MCI showed significant brain atrophy in 18 brain regions compared to CO, whereas AD patients only showed six brain regions with significant brain atrophy compared to CO. There was good correlation of brain atrophy and pASL perfusion data in five brain regions of patients with diagnosed FTD, especially in the superior temporal gyrus (r = 0.900, p = 0.037), the inferior frontal white matter (pars orbitalis; r = 0.968, p = 0.007) and the thalami (r = 0.810, p = 0.015). Patients with MCI demonstrated a correlation in one brain region (left inferior fronto-occipital fasciculus; r = 0.786, p = 0.036), whereas patients with diagnosed AD revealed no correlation. Conclusions: pASL can detect affected brain regions in cognitive impairment and corresponds with brain atrophy, especially for patients suffering from FTD and MCI. However, there was no correlation of perfusion alterations and brain atrophy in AD. pASL perfusion might thus represent a promising tool for noninvasive brain-perfusion evaluation in specific dementia subtypes as a complimentary imaging-based bio marker in addition to brain volumetry.

Comparison of Two Automated Computed Tomography Perfusion Applications to Predict the Final Infarct Volume After Thrombolysis in Cerebral Infarction 3 Recanalization.

BACKGROUND: Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact. METHODS: Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences. RESULTS: Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings. CONCLUSIONS: By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.

"Virtual stent" - clinical evaluation and user experience of on-the-fly stent simulation in treatment of cerebral aneurysms.

BACKGROUND: Predicting final stent position can be challenging when treating cerebral aneurysms. Third-Party software proved helpful in selecting proper stents in treatment planning. Recent angiographic systems provide basic stent simulation capabilities integrated in the post-processing software to simulate stent position. Goal of this analysis was to evaluate the simulation process and correlation with definite stent position. MATERIALS AND METHODS: Thirty-three datasets with fusiform (n = 10) and saccular (n = 23) aneurysms, treated with stent or flow-diverter, were processed. A "virtual stent" of the same (nominal) size was simulated and its position was compared to the treatment result. Simulated length was rated in five grades (too short, shorter, equal, longer, too long), with regard to side-branches, anchoring zone etc. Simulation quality (centerline recognition/adherence to vessel margins) was rated in three grades (no, minor or major corrections required). RESULTS: Simulation was successful in 32/33 cases (97%), with one abortive attempt (3%). In 27/33 simulations (82%), there was no need for centerline refinement. Minor corrections were necessary in four and major corrections in two cases. Simulated nominal length was rated "equal" in 14/33 (42%) cases and "shorter" or "longer" - but within acceptable range - in each 9/33 (27%) cases. CONCLUSION: Basic stent simulation tools available with genuine angiographic workplace software can provide good simulation capabilities without need for third-party equipment. They can facilitate treatment planning and help to avoid shortage of devices. Yet, lack of calculation of foreshortening in large vessel diameters leaves the user to rely on their experience to account for device-specific properties.

IV-Thrombolysis in Ischemic Stroke With Unknown Time of Onset-Safety and Outcomes in Posterior vs. Anterior Circulation Stroke.

Background: rt-PA for ischemic stroke in the unknown or extended time window beyond the first 4. 5 h after symptom onset is safe and effective for certain patients after selection by multimodal neuroimaging. However, the evidence for this approach comes mainly from patients with anterior circulation stroke (ACS), while the data on posterior circulation stroke (PCS) are scarce. Methods: Ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window between January 2011 and May 2019 were identified from an institutional registry. The patients were categorized into PCS or ACS based on clinico-radiological findings. We analyzed the hemorrhagic complications, clinical and imaging efficacy outcomes, and mortality rates by comparing the PCS and ACS patient groups. Adjusted outcome analyses were performed after propensity score matching for the relevant factors. Results: Of the 182 patients included, 38 (20.9%) had PCS and 144 (79.1%) had ACS. Symptomatic acute large vessel occlusion (LVO) was present in 123 patients on admission [27 (22.0%) PCS and 96 (78.0%) ACS]. The score on the National Institutes of Health Stroke Scale (NIHSS), the time from last seen normal, and the door-to-needle times were similar in PCS and ACS. In patients with LVO, the NIHSS score was lower [8 (5-15) vs. 14 (9-18), p = 0.005], and infarction visible on follow-up imaging was less common [70.4 vs. 87.5%; aRD, -18.9% (-39.8 to -2.2%)] in the PCS patient group. There was a trend toward a lower risk for intracranial hemorrhage (ICH) following intravenous thrombolysis in PCS vs. ACS, without reaching a statistical significance [5.3 vs. 16.9%; aRD, -10.4% (-20.4 to 4.0%)]. The incidence of symptomatic ICH [according to the ECASS III criteria: 2.6 vs. 3.5%; aRD, -2.9% (-10.3 to 9.2%)], efficacy outcomes, and mortality rates were similar in PCS and ACS patients. Conclusions: In this real-world clinical cohort, the safety and the efficacy of rt-PA for ischemic stroke in the unknown or extended time window did not show relevant differences between PCS and ACS, with a trend toward less hemorrhagic complications in PCS. The findings reconfirm the clinician in the usage of rt-PA beyond the first 4.5 h also in selected patients with PCS.

Disability-Adjusted Life-Years Associated With Intracerebral Hemorrhage and Secondary Injury.

Importance: Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. Objective: To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. Design, Setting, and Participants: This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation-associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. Exposures: ICH occurrence and secondary injury. Main Outcomes and Measures: DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). Results: Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (< 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; >30 mL ICH: 12.42 [8.47] DALYs; P < .001) and ICH location (deep location: 10.60 [8.35] DALYs; lobar location: 8.18 [7.63] DALYs; cerebellum: 8.14 [6.80] DALYs; brainstem: 12.63 [9.21] DALYs; P < .001). Regarding population-level disease burden of secondary injuries after ICH, there was a statistically significant difference in mean (SD) by injury type, with 0.94 (3.19) DALYs for HE, 2.45 (4.16) DALYs for IVH, and 1.96 (2.66) DALYs for PHE (P < .001) among the entire ICH cohort. Regarding individual-level exposure to secondary injuries after ICH, there were a mean (SD) 7.14 (6.62) DALYs for HE, 4.58 (4.75) DALYs for IVH, and 3.35 (3.28) DALYs for PHE among patients with ICH affected by secondary injuries. Conclusions and Relevance: These findings suggest that there is a high burden of disability associated with ICH and secondary injuries, and the findings may guide public health strategies. The study findings further suggest that IVH and PHE may be relevant for the overall outcome of patients with ICH, that DALYs may represent a viable outcome parameter for studies to evaluate treatment outcomes in ICH research, and that IVH and PHE may represent potential treatment targets.

Beyond Functional Impairment: Redefining Favorable Outcome in Patients with Subarachnoid Hemorrhage.

BACKGROUND: For outcome assessment in patients surviving subarachnoid hemorrhage (SAH), the modified Rankin scale (mRS) represents the mostly established outcome tool, whereas other dimensions of outcome such as mood disorders and impairments in social life remain unattended so far. OBJECTIVE: The aim of our study was to correlate 12-month functional and subjective health outcomes in SAH survivors. METHODS: All SAH patients treated over a 5-year period received outcome assessment at 12 months, including functional scores (mRS and Barthel Index [BI]), subjective health measurement (EQ-5D), and whether they returned to work. Analyses - including utility-weighted mRS - were conducted to detect associations and correlations among different outcome measures, especially in patients achieving good functional outcome (i.e., mRS 0-2) at 12 months. RESULTS: Of 351 SAH survivors, 287 (81.2%) achieved favorable functional outcome at 12 months. Contrary to the BI, the EQ-5D visual analog scale (VAS) showed a strong association with different mRS grades, accentuated in patients with favorable functional outcome. Despite favorable functional outcome, patients reported a high rate of impairments in activities (24.0%), pain (33.4%), and anxiety/depression (42.5%). Further, multivariable analysis revealed (i) impairments in activities (odds ratio [OR] [95% confidence interval {CI}]: 0.872 [0.817-0.930]), (ii) presence of depression or anxiety (OR [95% CI]: 0.836 [0.760-0.920]), and (iii) return to work (OR [95% CI]: 1.102 [0.1.013-1.198]) to be independently associated with self-reported subjective health. CONCLUSION: Established stroke scores mainly focusing on functional outcomes do poorly reflect the high rate of subjective impairments reported in SAH survivors, specifically in those achieving good functional outcome. Further studies are needed to investigate whether psychoeducational approaches aiming at improving coping mechanisms and perceived self-efficacy may result in higher subjective health in these patients.

The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke.

PURPOSE: Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician's decision between GA and CS using voxel-based lesion symptom mapping (VLSM). METHODS: In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. RESULTS: One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. CONCLUSIONS: The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician's decision on using GA in EVT.

Neutrophil-to-lymphocyte ratio is associated with increased cerebral blood flow velocity in acute bacterial meningitis.

In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients' demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients', radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9-14] vs. 14 [11-15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4-30.2] vs. normal CBFv:13.5 [8.4-19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003-1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients' prognosis.

Influence of Early Enteral Nutrition on Clinical Outcomes in Neurocritical Care Patients With Intracerebral Hemorrhage.

Objective: Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU). Methods: This retrospective cohort study included patients admitted to the NICU with atraumatic ICH over a 4-year period. Nutritional data, demographic, clinical, radiological, and laboratory characteristics were assessed. EEN was defined as any enteral nutrition within 48 hours after admission. Comparisons were undertaken for patients with EEN vs. those without, further propensity score (PS) matching (caliper 0.2; one: many) was used to account for baseline imbalances. Primary outcome was the modified Rankin Scale (0-3 = favorable, 4-6 = unfavorable) at 12 months, secondary outcomes comprised perihemorrhagic edema (PHE) volume, infectious complications during the hospital stay, and mRS at 3 months, as well as mortality rates at 3 and 12 months. Results: Of 166 ICH-patients treated at the NICU, 51 (30.7%) patients received EEN, and 115 (69.3%) patients received no EEN (nEEN). After propensity score matching, calories delivered from enteral nutrition (EEN 161.4 [106.4-192.3] kcal/day vs. nEEN 0.0 [0.0-0.0], P < 0.001) and the total calories (EEN 190.0 [126.0-357.0] kcal/day vs. nEEN 33.6 [0.0-190.0] kcal/day, P < 0.001) were significantly different during the first 48 h admitted in NICU. Functional outcome at 12 months (mRS 4-6, EEN 33/43 [76.7%] vs. nEEN, 49/64 [76. 6%]; P = 1.00) was similar in the two groups. There were neither differences in mRS at 3 months, nor in mortality rates at 3 and 12 months between the two groups. EEN did not affect incidence of infective complications or gastrointestinal adverse events during the hospital stay; however, EEN was associated with significantly less extent of PHE evolution [maximum absolute PHE (OR 0.822, 95% CI 0.706-0.957, P = 0.012); maximum relative PHE (OR 0.784, 95% CI 0.646-0.952, P = 0.014)]. Conclusion: In our study, EEN was associated with reduced PHE in ICH-patients treated at a NICU. However, this observation did not translate into improved survival or functional outcome at 3 and 12 months.

Identification of anatomic risk factors for scalar translocation in cochlear implant patients.

AIM: Microanatomical evaluation of cochlear implant (CI) patients to identify anatomical risk factors for a scalar translocation. METHODS: CI patients with both a regular scala tympani spiralization (group A) and a scalar translocation (group B) were identified via postoperative flat-detector computed tomography (FD-CT). Then, the corresponding preoperative multislice computed tomography (MS-CT) and postoperative FD-CT datasets were assessed: First, the cochleae were separated in 6 segments of 45° each. Next, quantitative (cochlea height, length, depth, cochlear duct diameter [CD] per segment; percentual tapering of the CD per segment named cochlear geometry index [CGI]) and qualitative (identifiability of the CI model; CI-integrity; intracochlear array position) parameters were evaluated and compared for both groups. Receiver-operating-characteristics (ROC) analysis was performed for the CGI. RESULTS: In total, 40 preoperative MS-CT and postoperative FD-CT datasets (nA=20; nB=20) were analysed. Model "CI 512" was successfully identified and CI-integrity has been confirmed in all cases. Quantitative analysis showed a significant difference of both the CD at 0° (CDA0°= 2.06± 0.23mm; CDB0°= 2.19±0.18mm; p0°= 0.04) and the CGI of the first segment (CGIA0°-45°= 18.87±6.04%; CGIB0°-45°= 28.89±8.58%; p0°-45°= 0.0001). For all other 5 cochlear segments there was no significant difference of CD and CGI; there was no significant difference of external cochlea diameters. The area under the curve (AUC) of the CGI0-45° was 0.864 with 24.50° as the optimal cut-off value to discriminate patients with a scala tympani spiralization and a scalar translocation. CGI0-45° of> 24.50° allowed the correct identification of 85% of patients with a scalar translocation. CONCLUSION: CI insertion trauma is associated with a significantly higher narrowing of the proximal basal cochlea turn (BCT). The CGI as percentual tapering of the BCT turned out as reliable, clinically applicable parameter for identification of patients with an increased risk for a scalar translocation.