The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Flow diverter stents for endovascular treatment of aneurysms: a comparative study of efficacy and safety between FREDX and FRED.

BACKGROUND: The FRED X flow diverter (FREDX), as the second generation in the FRED series, aims to improve the treatment of cerebral aneurysms. This study compares the efficacy and safety of FREDX with its predecessor, FRED. METHODS: This prospective registry included patients treated with FRED and FREDX devices. Efficacy was assessed using digital subtraction angiography with 3D volumetric reconstruction at immediate and 1 year follow-ups. Safety was evaluated by recording complications, analyzed through univariate contrasts, generalized mixed models, and Bayesian network analyses. RESULTS: We treated 287 patients with 385 aneurysms, with 77.9% receiving FRED and 22.1% FREDX. The median age was 55 years (IQR 47-65) and 78.4% were women. The FREDX group showed a higher prevalence of saccular-like aneurysms (70.6% vs 52.7%, P=0.012) and a higher rate of complete occlusion compared with FRED interventions (79.4% vs 59.3%, P=0.022). After adjusting for confounders, these differences represented a 3.04-fold increased likelihood (95% CI 1.44 to 6.41, P=0.003) of achieving complete occlusion at 1 year with FREDX interventions. Regarding safety, two (3.5%) complications (both non-symptomatic) were observed in the FREDX group and 23 (10.4%) in the FRED group (P=0.166). Bayesian network analysis suggested a trend towards fewer complications for FREDX, with a median reduction of 5.5% in the posterior distribution of the prevalence of complications compared with FRED interventions. CONCLUSIONS: The FREDX device shows improved complete occlusion rates at 1 year compared with the FRED device while maintaining a favourable safety profile, indicating its potential advantage in the treatment of cerebral aneurysms.

Long-term vascular events after subarachnoid hemorrhage.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) long-term risk is not well known. Our aims are: describing long-term vascular event (VE) incidence rates in SAH survivors; describing VE: ischemic and/or hemorrhagic; identifying independent association of factors related to VE; and analyzing the usefulness of factors to increase predictive ability. METHODS: A prospective cohort study of consecutive patients admitted to Hospital del Mar with a diagnosis of SAH (n = 566) between January 2007 and January 2020 was carried out. They were followed up until January 2021. The study endpoint was a new VE in the follow-up. We calculated both incidence rates and cumulative rates at 5 years. Cox regression survival models including vascular risk factors with and without specific data of SAH disease were developed. We analyzed ROC curves of all multivariate models. RESULTS: The analyzed cohort included 423 non-fatal SAH cases. Total patient-years were 2468.16 years. The average follow-up was 70.03 ± 43.14; range: 1-180 months. There were 49 VE detected in 47 patients, as 2 of them had more than 1 VE. Incidence rate was 0.020 events_per_patient/year, cumulative incidence at 5 years was 11.11%. The more frequent VE that we found were cerebrovascular (28/49), mainly ischemic (21/28). Disability after SAH and the presence of multiple aneurysms were independently associated with a VE risk and improved the predictive capacity of multivariate models (AUC 0.679 vs 0.764; p = 0.0062). CONCLUSIONS: We reported a low vascular risk after SAH. We have shown the usefulness of SAH factors to identify patients with a higher risk of VE.

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

The Chemical Optimization of Cerebral Embolectomy trial: Study protocol.

RATIONALE: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. AIM: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. SAMPLE SIZE ESTIMATES: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). METHODS AND DESIGN: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). STUDY OUTCOME(S): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. DISCUSSION: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

On the Use of Digital Subtraction Angiography in Stereoelectroencephalography Surgical Planning to Prevent Collisions with Vessels.

OBJECTIVE: Stereoelectroencephalography (SEEG) consists of the implantation of microelectrodes for the electrophysiological characterization of epileptogenic networks. To reduce a possible risk of intracranial bleeding by vessel rupture during the electrode implantation, the stereotactic trajectories must follow avascular corridors. The use of digital subtraction angiography (DSA) for vascular visualization during planning is controversial due to the additional risk related to this procedure. Here we evaluate the utility of this technique for planning when the neurosurgeon has it available together with gadolinium-enhanced T1-weighted magnetic resonance sequence (T1-Gd) and computed tomography angiography (CTA). METHODS: Twenty-two implantation plans for SEEG were initially done using T1-Gd imaging (251 trajectories). DSA was only used later during the revision process. In 6 patients CTA was available at this point as well. We quantified the position of the closest vessel to the trajectory in each of the imaging modalities. RESULTS: Two thirds of the trajectories that appeared vessel free in the T1-Gd or CTA presented vessels in their proximity, as shown by DSA. Those modifications only required small shifts of both the entry and target point, so the diagnostic aims were preserved. CONCLUSIONS: T1-Gd and CTA, despite being the most commonly used techniques for SEEG planning, frequently fail to reveal vessels that are dangerously close to the trajectories. Higher-resolution vascular imaging techniques, such as DSA, can provide the neurosurgeon with crucial information about vascular anatomy, resulting in safer plans.

A new subtype of intracranial dural AVF according to the patterns of venous drainage.

BACKGROUND AND PURPOSE: A well-known classification of dural arteriovenous fistulas (DAVFs) according to the patterns of venous drainage was described in 1977 by Djindjian, Merland et al. and later revised by Cognard, Merland et al. in 1995. They described 5 types of DAVFs assuming that the type of venous drainage is directly correlated with neurologic symptoms and in particular with hemorrhagic risk. We present a series of cases that combines type IV (DAVF with cortical venous drainage associated with venous ectasia) and type V (DAVF with spinal venous drainage), which we named type IV + V. MATERIALS AND METHODS: A retrospective study between 2012 and 2020 in 2 Hospitals was performed on patients that met inclusion criteria for a diagnosis of this type of DAVF. Demographics, location, clinical presentation and outcomes of endovascular embolization were studied. RESULTS: Five (2,3%) patients out of 220 had a type IV + V DAVF. All cases had an aggressive presentation, either subarachnoid hemorrhage, myelopathy or both. All patients were treated with endovascular transarterial embolization achieving complete angiographic occlusion in one session and total remission of symptoms at 3 months. CONCLUSIONS: This rare type of DAVF, combines two aggressive venous drainage patterns. For that reason, patients with type IV+V DAVF probably have a more aggressive natural history and worst outcome due to risk of intracranial and/or spinal hemorrhage and myelopathy, thus requiring urgent diagnostic and treatment. Larger studies are needed to better understand this type of DAVF.

Short- and long-term outcome of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment. METHODS: In this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3-6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed. RESULTS: Of 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54-0.84]). CONCLUSIONS: Patients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.

Efficacy and safety of the dual-layer flow-diverting stent (FRED) for the treatment of intracranial aneurysms.

PURPOSE: To describe the efficacy and complications of treating cerebral aneurysms with the Flow Re-direction Endoluminal Device (FRED) and to identify predictors for aneurysm occlusion. METHODS: A prospective observational registry including all consecutive aneurysms treated with FRED between December 2015 and July 2018 was designed in one therapeutic neuroangiography department. The primary endpoint for treatment efficacy was complete or near-complete occlusion (O'Kelly-Marotta (OKM) C-D), assessed by three-dimensional digital subtraction angiography. Major (all symptomatics) and minor complications were described and those with modified Rankin Scale scores 3-6 were considered clinically relevant. Univariate and multivariate analyses were performed to identify predictors of efficacy. RESULTS: A total of 185 aneurysms were analyzed in 150 patients (mean age 54.3±11.5 years). Mean follow-up was 18.99±11.32 months (range 0-43). Efficacy was evaluated in 156 (84.32%) cases: 132 (84.6%) had OKM C-D occlusion, 31/47 (66%) within the first year and 101/109 (92.7%) later on. Major complications were observed in 12 (6.5%) cases: three strokes (one transient ischemic accident, two minor strokes), six intra-stent thrombosis, and three with bleeding, but only one (0.5%) was clinically relevant. Minor complications (all asymptomatic) were observed in 10 (5.4%) cases: three shortening/repositioning of stent; two arterial dissection, two arterial occlusion, and three intra-stent stenosis. Independent predictors of occlusion were immediate OKM grade B-C-D (OR 4.01, 95% CI 1.51 to 10.62), single aneurysm (OR 3.29, 95% CI 1.05 to 10.32), and small size aneurysm (OR 4.74, 95% CI 1.57 to 14.30). CONCLUSION: The FRED stent fully complied with efficacy and safety requirements for treatment of intracranial aneurysms. Three predictors of aneurysm occlusion were identified.

Misdiagnosis Worsens Prognosis in Subarachnoid Hemorrhage With Good Hunt and Hess Score.

Background and Purpose- Our aim was to describe variables associated with initial misdiagnosis of subarachnoid hemorrhage (SAH). We also analyzed the relationship of misdiagnosis with poor outcome and complications in good Hunt and Hess (HH) cases. Methods- In a prospective cohort of 401 patients with SAH, misdiagnosis was defined as failure to correctly identify, at first physician contact, a subsequently documented SAH; this meant no urgent radiological study and lumbar puncture was performed. Poor outcome was defined as modified Rankin Scale score 3 to 6 at 3-month follow-up. We recorded age, sex, hypertension, diabetes mellitus, current smoking, previous antithrombotic treatment, initial HH and radiological severity, presence of aneurysm, first therapeutic procedure, hydrocephalus, delayed cerebral ischemia (DCI), rebleeding, and procedure-related complications. Results- Misdiagnosis was confirmed in 104/401 (25.9%) patients, who also had a longer time-to-admission to hospital. Misdiagnosis was associated with less clinical and radiological severity, compared with a correct diagnosis; the 2 groups did not differ in age or cardiovascular risk factor profile. Poor outcome was registered in 167/401 patients (41.6%). Age, misdiagnosis, and greater clinical and radiological initial severity were independent predictors of poor outcome. In the 236 patients (58.8% of cohort) with HH 1-2, misdiagnosis was associated with poor outcome in univariate and multivariate analysis, respectively (odds ratio=3.89; 95% CI, 1.89-8.01). Delayed cerebral ischemia (odds ratio=2.47; 95% CI, 1.2-5.09) and procedure-related complications (odds ratio=2.27; 95% CI, 1.07-4.82) were independently associated with misdiagnosis. Conclusions- Misdiagnosis is an unresolved problem in SAH, and it is a missed opportunity for good outcome in patients with HH 1-2. The poor outcome is partially explained by a higher risk of delayed cerebral ischemia and procedure-related complications in misdiagnosed patients. There is a need to improve the diagnostic strategy in patients reporting only a headache (HH 1-2) after SAH.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. METHODS: Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. RESULTS: We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). CONCLUSIONS: This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

Angioseal™ as a hemostatic device for direct carotid puncture during endovascular procedures.

INTRODUCTION: Direct carotid artery puncture (DCP) is employed in patients with tortuous anatomy and peripheral vascular disease when the peripheral arteries are not available for vascular access. Manual compression is the only method of achieving hemostasis following DCP and, till date, the use of a closure device for DCP has been reported in only one patient. In this study we sought to analyze our experience with the use of closure device for DCP. METHODS: This is a retrospective study of patients in whom Angioseal™ was used following DCP for neuroendovascular procedures. Medical charts and imaging of these patients was reviewed for any abnormalities pertaining to the use of the closure device. RESULTS: A total of eight patients were included in the study. Angioseal™ was used in all the patients. There were no complications related to the use of the closure device in any of the eight patients. Immediate post-procedure angiography done in one patient did not show any structural or hemodynamic abnormalities within the carotid artery lumen. At 6 months follow-up imaging, there was no evidence stenosis or vascular wall abnormality in any of the patients. There were no adverse clinical reactions related to the use of closure device. CONCLUSION: In our experience, Angioseal™ may be a safe and off-label effective closure device for patients undergoing DCP for neuroendovascular procedures. It obviates the need for manual compression without causing any structural or hemodynamic changes within the carotid artery. Larger studies with longer follow-up are required to establish its safety in patients undergoing DCP.

Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms.

BACKGROUND AND PURPOSE: According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. The aim of the study was to assess whether AcoA aneurysms behave differently from other AC aneurysms. METHODS: Information about 932 patients newly diagnosed with intracranial aneurysms between November 1, 2006, and March 31, 2012, including aneurysm status at diagnosis, its location, size, and risk factors, was collected during the multicenter @neurIST project. For each location or location and size subgroup, the odds ratio (OR) of aneurysms being ruptured at diagnosis was calculated. RESULTS: The OR for aneurysms to be discovered ruptured was significantly higher for AcoA (OR, 3.5 [95% confidence interval, 2.6-4.5]) and posterior circulation (OR, 2.6 [95% confidence interval, 2.1-3.3]) than for AC excluding AcoA (OR, 0.5 [95% confidence interval, 0.4-0.6]). Although a threshold of 7 mm has been suggested by ISUIA as a threshold for aggressive treatment, AcoA aneurysms <7 mm were more frequently found ruptured (OR, 2.0 [95% confidence interval, 1.3-3.0]) than AC aneurysms of 7 to 12 mm diameter as defined in ISUIA. CONCLUSIONS: We found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Intervention should be recommended for this high-risk lesion group.

Hemorrhagic risk of emergent endovascular treatment plus stenting in patients with acute ischemic stroke.

BACKGROUND: Several endovascular revascularization strategies have been described for the treatment of acute ischemic stroke (AIS). One of them is stenting when a very narrow stenosis with high reocclusion risk remains after recanalization. This study describes the risk of symptomatic intracerebral hemorrhage (SICH) after emergent stenting in patients with AIS treated with endovascular therapies. METHODS: Consecutive patients who underwent endovascular treatment over a 37-month period were retrospectively analyzed. Patients were classified in 2 groups: (1) patients in whom a stent was deployed; and (2) patients without stenting. Double antiplatelet treatment with aspirin and clopidogrel was administered at the time of stenting. SICH was defined as any hemorrhagic transformation with National Institutes of Health Stroke Scale (NIHSS) score worsening 4 points or more (European-Australasian Acute Stroke Study II criteria). RESULTS: A total of 143 patients were included (mean age: 66.1±11.7 years, median NIHSS score: 18). Acute phase stenting was performed in 24 subjects (16.8%): 4 intracranial (3 in basilar artery, 1 in middle cerebral artery) and 20 extracranial (internal carotid artery). SICH occurred in 11 patients, 5 of 24 (20.8%) in patients with stenting and in 3 of 119 (2.5%) without (P=.008). No differences were found with respect to baseline NIHSS score or intravenous tissue plasminogen activator administration. Acute phase stenting emerged as an independent predictor of SICH after adjustment for potential confounders and procedure duration: odds ratio 7.3 (confidence interval 1.4-36.8, P=.016). CONCLUSIONS: Our findings suggest that emergent stenting in endovascular treatment of AIS is associated with SICH.

Three-dimensional morphological analysis of intracranial aneurysms: a fully automated method for aneurysm sac isolation and quantification.

PURPOSE: Morphological descriptors are practical and essential biomarkers for diagnosis and treatment selection for intracranial aneurysm management according to the current guidelines in use. Nevertheless, relatively little work has been dedicated to improve the three-dimensional quantification of aneurysmal morphology, to automate the analysis, and hence to reduce the inherent intra and interobserver variability of manual analysis. In this paper we propose a methodology for the automated isolation and morphological quantification of saccular intracranial aneurysms based on a 3D representation of the vascular anatomy. METHOD: This methodology is based on the analysis of the vasculature skeleton's topology and the subsequent application of concepts from deformable cylinders. These are expanded inside the parent vessel to identify different regions and discriminate the aneurysm sac from the parent vessel wall. The method renders as output the surface representation of the isolated aneurysm sac, which can then be quantified automatically. The proposed method provides the means for identifying the aneurysm neck in a deterministic way. The results obtained by the method were assessed in two ways: they were compared to manual measurements obtained by three independent clinicians as normally done during diagnosis and to automated measurements from manually isolated aneurysms by three independent operators, nonclinicians, experts in vascular image analysis. All the measurements were obtained using in-house tools. The results were qualitatively and quantitatively compared for a set of the saccular intracranial aneurysms (n = 26). RESULTS: Measurements performed on a synthetic phantom showed that the automated measurements obtained from manually isolated aneurysms where the most accurate. The differences between the measurements obtained by the clinicians and the manually isolated sacs were statistically significant (neck width: p <0.001, sac height: p = 0.002). When comparing clinicians' measurements to automatically isolated sacs, only the differences for the neck width were significant (neck width: p <0.001, sac height: p = 0.95). However, the correlation and agreement between the measurements obtained from manually and automatically isolated aneurysms for the neck width: p = 0.43 and sac height: p = 0.95 where found. CONCLUSIONS: The proposed method allows the automated isolation of intracranial aneurysms, eliminating the interobserver variability. In average, the computational cost of the automated method (2 min 36 s) was similar to the time required by a manual operator (measurement by clinicians: 2 min 51 s, manual isolation: 2 min 21 s) but eliminating human interaction. The automated measurements are irrespective of the viewing angle, eliminating any bias or difference between the observer criteria. Finally, the qualitative assessment of the results showed acceptable agreement between manually and automatically isolated aneurysms.

Feasibility of estimating regional mechanical properties of cerebral aneurysms in vivo.

PURPOSE: In this article, the authors studied the feasibility of estimating regional mechanical properties in cerebral aneurysms, integrating information extracted from imaging and physiological data with generic computational models of the arterial wall behavior. METHODS: A data assimilation framework was developed to incorporate patient-specific geometries into a given biomechanical model, whereas wall motion estimates were obtained from applying registration techniques to a pair of simulated MR images and guided the mechanical parameter estimation. A simple incompressible linear and isotropic Hookean model coupled with computational fluid-dynamics was employed as a first approximation for computational purposes. Additionally, an automatic clustering technique was developed to reduce the number of parameters to assimilate at the optimization stage and it considerably accelerated the convergence of the simulations. Several in silico experiments were designed to assess the influence of aneurysm geometrical characteristics and the accuracy of wall motion estimates on the mechanical property estimates. Hence, the proposed methodology was applied to six real cerebral aneurysms and tested against a varying number of regions with different elasticity, different mesh discretization, imaging resolution, and registration configurations. RESULTS: Several in silico experiments were conducted to investigate the feasibility of the proposed workflow, results found suggesting that the estimation of the mechanical properties was mainly influenced by the image spatial resolution and the chosen registration configuration. According to the in silico experiments, the minimal spatial resolution needed to extract wall pulsation measurements with enough accuracy to guide the proposed data assimilation framework was of 0.1 mm. CONCLUSIONS: Current routine imaging modalities do not have such a high spatial resolution and therefore the proposed data assimilation framework cannot currently be used on in vivo data to reliably estimate regional properties in cerebral aneurysms. Besides, it was observed that the incorporation of fluid-structure interaction in a biomechanical model with linear and isotropic material properties did not have a substantial influence in the final results.

Transient encephalopathy from angiographic contrast: a rare complication in neurointerventional procedures.

Neurotoxicity from contrast media used in angiography is a rare complication from these procedures. The infrequency with which it is encountered makes it a diagnostic challenge. We present the case of a 51-year-old male who, 30 min after successful angiography for treatment of a right carotid-ophthalmic fusiform aneurysm with a stent, developed psychomotor agitation, disorientation, and progressive left faciobrachial hemiparesis (4/5). An emergency nonenhanced CT showed marked cortical enhancement and edema in the right cerebral hemisphere. Cortical enhancement is thought to be secondary to contrast extravasation due to disruption of the blood-brain barrier. Angiography was performed immediately, without any pathologic findings. After this procedure there was an increase in the left faciobrachial hemiparesis (3/5), right gaze deviation, Gerstmann syndrome, and left anosognosia and left homonymous hemianopsia. Endovenous dexamethasone and mannitol were initiated. Twenty-four hours later an MRI showed no signs of acute infarct, just gyriform signal increase in the right cerebral hemisphere on FLAIR and a decrease in the edema observed before. The patient had progressive improvement of his neurological deficit. A control MRI done 5 days later was normal. The patient recovered completely and was discharged. This rare entity should be kept in mind but diagnosed only when all other causes have been ruled out, because more important and frequent causes, such as acute infarct, must be excluded promptly.

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations.

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.