Impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion in patients with suspected stroke.

PURPOSE: CT perfusion of the brain is a powerful tool in stroke imaging, though the radiation dose is rather high. Several strategies for dose reduction have been proposed, including increasing the intervals between the dynamic scans. We determined the impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion from a large dataset of patients with suspected stroke. METHODS: We retrospectively included 3555 perfusion scans from our clinical routine dataset. All cases were processed using the perfusion software VEOcore with a standard sampling of 1.5 s, as well as simulated reduced temporal resolution of 3.0, 4.5, and 6.0 s by leaving out respective time points. The resulting perfusion maps and calculated volumes of infarct core and mismatch were compared quantitatively. Finally, hypothetical decisions for mechanical thrombectomy following the DEFUSE-3 criteria were compared. RESULTS: The agreement between calculated volumes for core (ICC = 0.99, 0.99, and 0.98) and hypoperfusion (ICC = 0.99, 0.99, and 0.97) was excellent for all temporal sampling schemes. Of the 1226 cases with vascular occlusion, 14 (1%) for 3.0 s sampling, 23 (2%) for 4.5 s sampling, and 63 (5%) for 6.0 s sampling would have been treated differently if the DEFUSE-3 criteria had been applied. Reduction of temporal resolution to 3.0 s, 4.5 s, and 6.0 s reduced the radiation dose by a factor of 2, 3, or 4. CONCLUSION: Reducing the temporal sampling of brain perfusion CT has only a minor impact on image quality and treatment decision, but significantly reduces the radiation dose to that of standard non-contrast CT.

Impact of Antiplatelet Therapy During Endovascular Therapy for Tandem Occlusions: A Collaborative Pooled Analysis.

Background and Purpose- Antiplatelet agents could be used in the setting of endovascular therapy for tandem occlusions to reduce the risk of de novo intracranial embolic migration, reocclusion of the extracranial internal carotid artery lesion, or in-stent thrombosis in case of carotid stent placement but have to be balanced with the intracerebral hemorrhagic transformation risk. In this study, we aim to investigate the impact of acute antiplatelet therapy administration on outcomes during endovascular therapy for anterior circulation tandem occlusions. Methods- This is a retrospective analysis of a collaborative pooled analysis of 11 prospective databases from the multicenter observational TITAN registry (Thrombectomy in Tandem Lesions). Patients were divided into groups based on the number of antiplatelet administered during endovascular therapy. The primary outcome was favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 90 days. Results- This study included a total of 369 patients; 145 (39.3%) did not receive any antiplatelet agent and 224 (60.7%) received at least 1 antiplatelet agent during the procedure. Rate of favorable outcome was nonsignificantly higher in patients treated with antiplatelet therapy (58.3%) compared with those treated without antiplatelet (46.0%; adjusted odds ratio, 1.38 [95% CI, 0.78-2.43]; P=0.26). Rate of 90-day mortality was significantly lower in patients treated with antiplatelet therapy (11.2% versus 18.7%; adjusted odds ratio, 0.47 [95% CI, 0.22-0.98]; P=0.042), without increasing the risk of any intracerebral hemorrhage. Successful reperfusion (modified Thrombolysis in Cerebral Ischemia score 2b-3) rate was significantly better in the antiplatelet therapy group (83.9% versus 71.0%; adjusted odds ratio, 1.89 [95% CI, 1.01-3.64]; P=0.045). Conclusions- Administration of antiplatelet therapy during endovascular therapy for anterior circulation tandem occlusions was safe and was associated with a lower 90-day mortality. Optimal antiplatelet therapy remains to be assessed, especially when emergent carotid artery stenting is performed. Further randomized controlled trials are needed.

Hemorrhagic Transformation After Thrombectomy for Tandem Occlusions.

Background and Purpose- Carotid artery stenting in tandem large vessel occlusion strokes is usually avoided because of the intracranial hemorrhagic risks induced by antiplatelet therapy during thrombectomy interventions. This study aimed to evaluate the incidence of hemorrhagic transformation following thrombectomy in large vessel occlusion strokes patients with atherosclerotic cervical carotid occlusion, associated factors, and clinical relevance. Methods- The TITAN (Thrombectomy in Tandem Lesions) collaboration pooled individual data of prospectively collected multicentric thrombectomy databases for consecutive anterior circulation tandem large vessel occlusion strokes patients who underwent thrombectomy. Hemorrhagic infarction (HI) and parenchymal hematoma (PH) were assessed within 24 hours. Results- Among 289 patients with atherosclerotic cause, 66 (24.7%) patients developed HI and 38 (14.2%) PH. Intracranial carotid occlusion, diabetes mellitus, absence of prior intravenous thrombolysis, and complete extracranial carotid occlusion were independent predictors of HI. Similar predictors were found for PH with addition of higher baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score <7. No detrimental effect of HI on 90-day clinical outcome was found. The occurrence of PH was associated with increased mortality rates (adjusted odds ratio, 2.63; 95% CI, 1.05-6.59; P=0.039) and had no detrimental effect on 90-day modified Rankin Scale 0 to 2 (adjusted odds ratio, 0.52; 95% CI, 0.20-1.28; P=0.25). Conclusions- Incidence of PH after tandem large vessel occlusion strokes thrombectomy is equivalent to those reported in the literature data for isolated occlusions. Similar predictors were found for PH and HI within 24 hours, whereas acute carotid artery stenting and antiplatelet therapy were not, suggesting an aggressive endovascular treatment of tandem occlusions.

Sirolimus-induced regression of a large orbital lymphangioma.

Microcystic lymphatic malformations are difficult to treat surgically, especially when located in the orbital apex. Recently, pharmacologic inhibition of the mTOR pathway by sirolimus was reported as a safe and efficacious treatment option for lymphatic malformations (also known as lymphangiomas). We report the case of a young male patient in which a unilateral, retrobulbar lymphatic malformation regressed to a large extent under treatment with 1 mg sirolimus given orally twice a day over a period of six months.

Second-Generation Hydrogel Coils for the Endovascular Treatment of Intracranial Aneurysms: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Endovascular embolization of intracranial aneurysms with hydrogel-coated coils lowers the risk of major recurrence, but technical limitations (coil stiffness and time restriction for placement) have prevented their wider clinical use. We aimed to assess the efficacy of softer, second-generation hydrogel coils. METHODS: A randomized controlled trial was conducted at 22 centers in France and Germany. Patients aged 18 to 75 years with untreated ruptured or unruptured intracranial aneurysms measuring 4 to 12 mm in diameter were eligible and randomized (1:1 using a web-based system, stratified by rupture status) to coiling with either second-generation hydrogel coils or bare platinum coils. Assist devices were allowed as clinically required. Independent imaging core laboratory was masked to allocation. Primary end point was a composite outcome measure including major aneurysm recurrence, aneurysm retreatment, morbidity that prevented angiographic controls, and any death during treatment and follow-up. Data were analyzed as randomized. RESULTS: Randomization began on October 15, 2009, and stopped on January 31, 2014, after 513 patients (hydrogel, n=256; bare platinum, n=257); 20 patients were excluded for missing informed consent and 9 for treatment-related criteria. Four hundred eighty-four patients (hydrogel, n=243; bare platinum, n=241) were included in the analysis; 208 (43%) were treated for ruptured aneurysms. Final end point data were available for 456 patients. Forty-five out of 226 (19.9%) patients in the hydrogel group and 66/230 (28.7%) in the control group had an unfavorable composite primary outcome, giving a statistically significant reduction in the proportion of an unfavorable composite primary outcome with hydrogel coils-adjusted for rupture status-of 8.4% (95% confidence interval, 0.5-16.2; P=0.036). Adverse and serious adverse events were evenly distributed between groups. CONCLUSIONS: Our results suggest that endovascular coil embolization with second-generation hydrogel coils may reduce the rate of unfavorable outcome events in patients with small- and medium-sized intracranial aneurysms. CLINICAL TRIAL REGISTRATION: URL: https://www.drks.de/drks_web/. Unique identifier: DRKS00003132.

Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause.

BACKGROUND AND PURPOSE: Tandem steno-occlusive lesions were poorly represented in randomized trials and represent a major challenge for endovascular thrombectomy in acute anterior circulation strokes. The impact of the cervical carotid lesion cause (ie, atherosclerotic versus dissection) on outcome of tandem patients endovascularly treated remains to be assessed. METHODS: We retrospectively analyzed individual data of prospectively collected consecutive tandem patients treated with endovascular thrombectomy. The primary outcome was favorable outcome at 90 days (modified Rankin Scale score of 0-2). Secondary efficacy outcomes included successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction scores of 2b-3), time to reperfusion, and safety outcomes encompassed procedural complications, symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Among the 295 included patients, 65 had cervical carotid dissection and 230 had cervical carotid atherosclerotic cause. The rate of favorable outcome was 56.3% in the dissection group versus 47.6% in the atherosclerotic arm (center-, age-, and admission National Institutes of Health Stroke Scale-adjusted odds ratio, 1.08; 95% confidence interval, 0.50-2.30; P=0.85). No significant differences were observed in secondary outcomes. The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and 90-day mortality were 78.5% versus 74.5% (P=0.13), 4.6% versus 5.2% (P=1.0), and 7.8% versus 15.3% (P=0.94) in the dissection versus atherosclerotic groups, respectively. The median procedural time was 76 minutes (interquartile range, 52-95 minutes) in the dissection group and 67 minutes (interquartile range, 45-98 minutes) in the atherosclerotic group (P=0.24). CONCLUSIONS: We found no differences in the outcomes of patients with anterior circulation tandem atherosclerotic and dissection lesions treated with endovascular thrombectomy. Further studies are warranted.

Early Vasospasm after Aneurysmal Subarachnoid Hemorrhage Predicts the Occurrence and Severity of Symptomatic Vasospasm and Delayed Cerebral Ischemia.

BACKGROUND: Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. METHODS: Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale >3) were evaluated in univariate and multivariate analyses. RESULTS: EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p < 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p < 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). CONCLUSIONS: In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA.

GREAT-a randomized controlled trial comparing HydroSoft/HydroFrame and bare platinum coils for endovascular aneurysm treatment: procedural safety and core-lab-assessedangiographic results.

INTRODUCTION: Hybrid hydrogel-platinum coils (HydroCoil) have proven effective for endovascular aneurysm treatment. To overcome technical limitations (coil stiffness, time restriction for placement), a second generation of softer hydrogel coils has been brought to clinical practice (HydroSoft, HydroFrame). We report on procedural safety and core-lab-assessed angiographic results from an open-label multicenter randomized controlled trial. METHODS: Web-based randomization occurred in 15 medical centers in France and seven in Germany between coil embolization with second-generation hydrogel coils and treatment with any bare platinum coil. Assist devices could be used as clinically required. Primary endpoint is a composite outcome including major aneurysm recurrence and poor clinical outcome at 18 months follow-up. RESULTS: Five hundred thirteen patients were randomized (hydrogel n = 256, bare platinum n = 257). Twenty patients were excluded for missing informed consent and nine patients for treatment related criteria. Four hundred eighty-four patients were analyzed as randomized (hydrogel n = 243, bare platinum n = 241). Two hundred eight had ruptured aneurysms (43 %). Prespecified procedural complications occurred in 58 subjects (hydrogel n = 28, bare platinum n = 30, p = 0.77). The 14-day mortality rate was 2.1 % in both arms of the study. The median calculated packing densities for aneurysms assigned to hydrogel and bare platinum were 39 and 31 % respectively (p < 0.001). No statistically significant differences were found between arms in the post procedural angiographic occlusion rate (p = 0.8). CONCLUSION: Second-generation hydrogel coils can be used in a wide spectrum of aneurysms with a risk profile equivalent to bare platinum. Packing density was significantly higher in aneurysms treated with hydrogel coils. TRIAL REGISTRATION: http://www.germanctr.de , DRKS00003132.

Endovascular Treatment versus Sonothrombolysis for Acute Ischemic Stroke.

BACKGROUND: Currently, there are 2 strategies to increase the effect of systemic thrombolysis with alteplase (rtPA) in acute major stroke: endovascular treatment via stent retrieval and ultrasound enhancement (sonothrombolysis). This study compares these 2 approaches in patients with proximal intracranial occlusion of the anterior circulation. METHODS: Consecutive data on the treatment outcome of acute middle cerebral artery (M1) or carotid T occlusion were collected from 2 stroke centers: one center used rtPA plus endovascular stent retrieval as standard treatment and the other rtPA plus ultrasound (sonothrombolysis). The primary outcome was functional independence (modified Rankin scale (mRS) 0-2) after neurorehabilitation. RESULTS: A total of 132 patients were assessed (n = 73 endovascular, n = 59 sonothrombolysis). The rate of functional independence was higher for endovascular treatment (adjusted OR 3.89 (95% CI 1.36-12.58)). Additionally, ordinal mRS analysis favored the endovascular strategy (adjusted common OR 1.70 (95% CI 0.88-3.31)). Subgroup analysis showed that endovascular treatment was superior for carotid T occlusion (adjusted common OR 5.61 (95% CI 1.60-20.93)), but not for middle cerebral artery occlusion (adjusted common OR 1.07 (95% CI 0.47-2.43)). Symptomatic intracerebral hemorrhage occurred in 3 patients from the endovascular group. CONCLUSIONS: This observational study suggests that endovascular treatment of acute major anterior circulation stroke is superior to sonothrombolysis in terms of functional outcome. This benefit seems to pertain primarily to patients with carotid T occlusion, whereas patients with M1 occlusion seem to profit in a similar way from both methods. ( CLINICAL TRIAL REGISTRATION: URL: http://www.germanctr.de. Unique identifier: DRKS0000x200B;5305.).

GREAT-a randomized aneurysm trial. Design of a randomized controlled multicenter study comparing HydroSoft/HydroFrame and bare platinum coils for endovascular aneurysm treatment.

The effectiveness of a hybrid hydrogel platinum detachable coil (HydroCoil; MicroVention Inc., Tustin, CA) for endovascular aneurysm treatment has been proven in a recently published RCT. Due to technical restrictions (coil stiffness, time restriction for placement), the HydroSoft coil as well as a corresponding 3D framing coil, the HydroFrame coil (MicroVention Inc., Tustin, CA), a class of new softer coils containing less hydrogel and swelling more slowly than the HydroCoil, have been developed and brought to clinical practice. The present study aims to compare the effectiveness of endovascular aneurysm treatment with coil embolization between patients allocated HydroSoft/HydroFrame versus bare platinum coiling. GREAT is a randomized, controlled, multicentre trial in patients bearing cerebral aneurysms to be treated by coil embolization. Eligible patients were randomized to either coil embolization with HydroSoft/HydroFrame coils (>50 % of administered coil length), or bare platinum coils. Inclusion criteria were as follows: age 18-75, ruptured aneurysm (WFNS 1-3) and unruptured aneurysm with a diameter between 4 and 12 mm. Anatomy such that endovascular coil occlusion deemed possible and willingness of the neurointerventionalist to use either HydroSoft/HydroFrame or bare platinum coils. Exclusion criteria were as follows: aneurysms previously treated by coiling or clipping. Primary endpoint is a composite of major aneurysm recurrence on follow-up angiography and poor clinical outcome (modified Rankin scale 3 or higher), both assessed at 18 months post treatment. Risk differences for poor outcomes will be estimated in a modified intention-to-treat analysis stratified by rupture status (DRKS-ID: DRKS00003132).

Clinical utility and cost-effectiveness of CT-angiography in the diagnosis of nontraumatic subarachnoid hemorrhage.

INTRODUCTION: CT-angiography gains an increasing role in the initial diagnosis of patients with nontraumatic subarachnoid hemorrhage (SAH). However, the implementation of CT-angiography does not always exclude the necessity of conventional angiography. Our objective was to determine the practical utility and cost-effectiveness of CT-angiography. METHODS: All patients with nontraumatic subarachnoid hemorrhage admitted to our university hospital after implementation of CT-angiography between June 1, 2011 and June 30, 2012 were retrospectively analyzed in regard to factors of treatment flow, radiation exposure, harms of contrast medium loading, and diagnostic costs. A control group of the same size was assembled from previously admitted SAH patients, who did not undergo pretreatment CT-angiography. Furthermore, cost-effectiveness analysis was performed. RESULTS: The final analysis consisted of 93 patients in each group. Of 93 patients with pretreatment CT-angiography, 74 had to undergo conventional angiography for diagnostic and/or therapeutic purposes. CT-angiography had significant impact on the reduction of collective effective radiation dose by 4.419 mSv per person (p = 0.0002) and was not associated with additional harms. Despite the significantly earlier detection of aneurysms with CT-angiography (p < 0.0001), there were no significant differences in the timing of aneurysm repair and duration of ICU and general hospital stay. There was an increase of diagnostic costs-the cost-effectiveness analysis showed, however, that benefits of CT-angiography in respect to radiation exposure and risk of conventional angiography-related complications justify the additional costs of CT-angiography. CONCLUSIONS: Although the implementation of CT-angiography in SAH diagnosis cannot completely replace conventional angiography, it can be approved in regard to radiation hygiene and cost-effectiveness.

Comparison of high-resolution X-ray and micro-CT for experimental evaluation of intracranial stent prototypes: quality evaluation beyond CE mark.

INTRODUCTION: As digital mammography and micro-computed tomography (CT) have been used for evaluation of stents deployed in experimental animal models, we compared the two methods regarding their sensitivity to detect abnormalities in three prototypes of intracranial stents. METHODS: Three different prototypes of intracranial stents (n = 84) were implanted in various animal models. Explanted stents were examined using digital mammography and micro-CT. The images were compared with respect to maintenance of material and form and the stents were compared to one another. Histological analysis was performed as well. RESULTS: In the open-cell stents, expansion of the stent cells was detected in the majority of cases (57.1 %) using micro-CT and less frequently using mammography (42.3 %). The closed-cell stent revealed kink stenoses in mammography as well as in micro-CT (3/7, 42.9 %). Detailed reconstructions of micro-CT images showed high-grade kink stenoses of the flow-diverter stent in two extremely curved vessels. Strut breaks were observed more frequently using micro-CT (6/84, 7.1 %) than by mammography (4/84, 4.8 %). Histology confirmed all changes of stent architecture. CONCLUSION: Significant changes of stent architecture can be observed and assessed even in the two-dimensional mammographic images. The use of micro-CT is recommended to detect subtle changes like single strut breaks and for three-dimensional information.

Parallel activation of helicopter and ground transportation after dispatcher identification of suspected anterior large vessel occlusion stroke in rural areas: a proof-of-concept case with modeling from the LESTOR trial.

BACKGROUND: When stroke patients with suspected anterior large vessel occlusion (aLVO) happen to live in rural areas, two main options exist for prehospital transport: (i) the drip-and-ship (DnS) strategy, which ensures rapid access to intravenous thrombolysis (IVT) at the nearest primary stroke center but requires time-consuming interhospital transfer for endovascular thrombectomy (EVT) because the latter is only available at comprehensive stroke centers (CSC); and (ii) the mothership (MS) strategy, which entails direct transport to a CSC and allows for faster access to EVT but carries the risk of IVT being delayed or even the time window being missed completely. The use of a helicopter might shorten the transport time to the CSC in rural areas. However, if the aLVO stroke is only recognized by the emergency service on site, the helicopter must be requested in addition, which extends the prehospital time and partially negates the time advantage. We hypothesized that parallel activation of ground and helicopter transportation in case of aLVO suspicion by the dispatcher (aLVO-guided dispatch strategy) could shorten the prehospital time in rural areas and enable faster treatment with IVT and EVT. METHODS: As a proof-of-concept, we report a case from the LESTOR trial where the dispatcher suspected an aLVO stroke during the emergency call and dispatched EMS and HEMS in parallel. Based on this case, we compare the provided aLVO-guided dispatch strategy to the DnS and MS strategies regarding the times to IVT and EVT using a highly realistic modeling approach. RESULTS: With the aLVO-guided dispatch strategy, the patient received IVT and EVT faster than with the DnS or MS strategies. IVT was administered 6 min faster than in the DnS strategy and 22 min faster than in the MS strategy, and EVT was started 47 min earlier than in the DnS strategy and 22 min earlier than in the MS strategy. CONCLUSION: In rural areas, parallel activation of ground and helicopter emergency services following dispatcher identification of stroke patients with suspected aLVO could provide rapid access to both IVT and EVT, thereby overcoming the limitations of the DnS and MS strategies.

Reducing False-Positives in CT Perfusion Infarct Core Segmentation Using Contralateral Local Normalization.

BACKGROUND AND PURPOSE: The established global threshold of rCBF <30% for infarct core segmentation can lead to false-positives, as it does not account for the differences in blood flow between GM and WM and patient-individual factors, such as microangiopathy. To mitigate this problem, we suggest normalizing each voxel not only with a global reference value (ie, the median value of normally perfused tissue) but also with its local contralateral counterpart. MATERIALS AND METHODS: We retrospectively enrolled 2830 CTP scans with suspected ischemic stroke, of which 335 showed obvious signs of microangiopathy. In addition to the conventional, global normalization, a local normalization was performed by dividing the rCBF maps with their mirrored and smoothed counterpart, which sets each voxel value in relation to the contralateral counterpart, intrinsically accounting for GM and WM differences and symmetric patient individual microangiopathy. Maps were visually assessed and core volumes were calculated for both methods. RESULTS: Cases with obvious microangiopathy showed a strong reduction in false-positives by using local normalization (mean 14.7 mL versus mean 3.7 mL in cases with and without microangiopathy). On average, core volumes were slightly smaller, indicating an improved segmentation that was more robust against naturally low blood flow values in the deep WM. CONCLUSIONS: The proposed method of local normalization can reduce overestimation of the infarct core, especially in the deep WM and in cases with obvious microangiopathy. False-positives in CTP infarct core segmentation might lead to less-than-optimal therapy decisions when not correctly interpreted. The proposed method might help mitigate this problem.

Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma.

Background: Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy. Methods: Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology. Results: We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all P < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all P < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all P < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples. Conclusions: Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.

The non-paretic-hand-to-opposite-ear test: A simple test to detect aphasia and neglect and an indicator of large anterior vessel occlusion in patients with suspected acute stroke.

INTRODUCTION: Aphasia and neglect in combination with hemiparesis are reliable indicators of large anterior vessel occlusion (LAVO). Prehospital identification of these symptoms is generally considered difficult by emergency medical service (EMS) personnel. Therefore, we evaluated the simple non-paretic-hand-to-opposite-ear (NPE) test to identify aphasia and neglect with a single test. As the NPE test includes a test for arm paresis, we also evaluated the diagnostic ability of the NPE test to detect LAVO in patients with suspected stroke. METHODS: In this prospective observational study, we performed the NPE test in 1042 patients with suspected acute stroke between May 2021 and May 2022. We analyzed the correlation between the NPE test and the aphasia/neglect items of the National Institutes of Health Stroke Scale. Additionally, the predictive values of the NPE test for LAVO detection were calculated. RESULTS: The NPE test showed a strong, significant correlation with both aphasia and neglect. A positive NPE test result predicted LAVO with a sensitivity of 0.70, a specificity of 0.88, and an accuracy of 0.85. Logistic regression analysis showed an odds ratio of 16.14 (95% confidence interval 10.82-24.44) for predicting LAVO. CONCLUSION: The NPE test is a simple test for the detection of both aphasia and neglect. With its predictive values for LAVO detection being comparable to the results of LAVO scores in the prehospital setting, this simple test might be a promising test for prehospital LAVO detection by EMS personnel. Further prospective prehospital validation is needed.

Non-ischemic cerebral enhancing (NICE) lesions after flow diversion for intracranial aneurysms: a multicenter study.

BACKGROUND: Non-ischemic cerebral enhancing (NICE) lesions have been reported as a rare complication of various neuroendovascular procedures, but information on their incidence after flow diversion is scant. It is unclear if specific devices or novel coating technologies may impact their occurrence. METHODS: We conducted a multicenter study on the incidence of NICE lesions after flow diverter (FD) implantation for cerebral aneurysm treatment. RESULTS: Eight centers identified 15 patients and provided detailed data. The clinical presentation ranged from asymptomatic to hemiplegia and cognitive impairment. The mean time to diagnosis after treatment was 65.1±101.5 days. Five centers disclosed information on all of their 1201 FD procedures during the inclusion period (2015-2022), during which 12 patients were diagnosed with NICE lesions in these institutions-that is, an incidence of 1%. FD coatings did not increase the incidence (6/591 patients (1%) treated with surface-modified FD vs 6/610 patients (1%) treated with bare FD; P=1.00). Significantly increased rates of 3.7% (6 cases in 161 procedures; P<0.01) and 3.3% (5 cases in 153 procedures; P<0.01) were found with stents of two specific product lines. The use of one product line was associated with a significantly lower incidence (0 cases in 499 procedures (0%); P<0.01). CONCLUSIONS: Novel stent coatings are not associated with an increased incidence of NICE lesions. The incidence rate of 1% suggests that these lesions may occur more often after flow diversion than after other endovascular treatments. We found a concerning accumulation of NICE lesion cases when FDs from two product families were used.

Immunohistochemical analysis of thrombi retrieved during treatment of acute ischemic stroke: does stent-retriever cause intimal damage?

BACKGROUND AND PURPOSE: To provide evidence whether mechanical thrombectomy with stent-retrievers in the treatment of acute ischemic stroke causes intimal damage. METHODS: This study analyzed thrombi retrieved by mechanical thrombectomy from cerebral arteries in 48 consecutive patients with acute ischemic stroke for the presence of endothelial cells using CD34 antibodies. RESULTS: Of 48 thrombi analyzed, CD34-positive cells were absent in 20, present as isolated cells in 21, and found in clusters in 7 thrombi. We did not find any subendothelial vessel wall structures. CONCLUSIONS: Our findings suggest that mechanical thrombectomy with stent-retrievers does not cause relevant intimal damage in acute ischemic stroke treatment. Clinical Trial Registration- URL: http://www.germanctr.de. Unique identifier: DRKS00004695.

Predictors of severity of cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is one of the leading causes of poor outcome after aneurysmal subarachnoid hemorrhage. The risk factors for the development of vasospasm have been evaluated in many clinical studies. However, it remains unclear if vasospasm severity can be predicted. The purpose of this study was to determine if different demographic and clinical factors that appear to be predictors of vasospasm can also prognosticate the severity of cerebral vasospasm. METHODS: We retrospectively analyzed consecutive patients with subarachnoid hemorrhage who underwent endovascular vasospasm treatment in a single center. In order to define predictors of vasospasm severity, we studied the demographic and clinical characteristics of these patients. Vasospasm severity was defined by cerebral angiography, transcranial Doppler ultrasound, and therapeutic response on endovascular treatment. Statistical analyses were performed to determine significant predictors. RESULTS: A total of 70 patients with vasospasm were included. Early onset of mean flow velocities>160 cm/second on transcranial Doppler ultrasound correlated with severity of angiographic vasospasm (P=.0469) and resistance against intra-arterial papaverine (P=.0277). Younger age (<51 years of age) was significantly associated with severity of vasospasm regarding extension on angiography (P=.0422), the need for repetitive endovascular treatment (P=.0084), persistence of transcranial Doppler ultrasound vasospasm after endovascular treatment (P=.0004), and resistance against intra-arterial papaverine (P=.0341). CONCLUSIONS: Younger age and early onset of vasospasm on transcranial Doppler ultrasound are important predictors for vasospasm severity. We recommend early and aggressive therapy in this subgroup.

COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke (COTTIS): a pilot study.

BACKGROUND: To evaluate the feasibility and safety of a fast initiation of cooling to a target temperature of 35°C by means of transnasal cooling in patients with anterior circulation large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT). METHODS: Patients with an LVO onset of <24 hour who had an indication for EVT were included in the study. Transnasal cooling (RhinoChill) was initiated immediately after the patient was intubated for EVT and continued until an oesophageal target temperature of 35°C was reached. Hypothermia was maintained with surface cooling for 6-hour postrecanalisation, followed by active rewarming (+0.2°C/hour). The primary outcome was defined as the time required to reach 35°C, while secondary outcomes comprised clinical, radiological and safety parameters. RESULTS: Twenty-two patients (median age, 77 years) were included in the study (14 received additional thrombolysis, 4 additional stenting of the proximal internal carotid artery). The median time intervals were 309 min for last-seen-normal-to-groin, 58 min for door-to-cooling-initiation, 65 min for door-to-groin and 123 min for door-to-recanalisation. The target temperature of 35°C was reached within 30 min (range 13-78 min), corresponding to a cooling rate of 2.6 °C/hour. On recanalisation, 86% of the patients had a body temperature of ≤35°C. The median National Institutes of Health Stroke Scale at admission was 15 and improved to 2 by day 7, and 68% of patients had a good outcome (modified Rankin Scale 0-2) at 3 months. Postprocedure complications included asymptomatic bradycardia (32%), pneumonia (18%) and asymptomatic haemorrhagic transformation (18%). CONCLUSION: The combined application of hypothermia and thrombectomy was found to be feasible in sedated and ventilated patents. Adverse events were comparable to those previously described for EVT in the absence of hypothermia. The effect of this procedure will next be evaluated in the randomised COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke-2 trial.