Intracranial bypass for giant aneurysms treatment assessed by computational fluid dynamics (CFD) analysis.

Unruptured giant intracranial aneurysms (GIA) are those with diameters of 25 mm or greater. As aneurysm size is correlated with rupture risk, GIA natural history is poor. Parent artery occlusion or trapping plus bypass revascularization should be considered to encourage intra-aneurysmal thrombosis when other treatment options are contraindicated. The mechanistic background of these methods is poorly studied. Thus, we assessed the potential of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) analyses for clinical use in the preoperative stage. A CFD investigation in three patient-specific flexible models of whole arterial brain circulation was performed. A C6 ICA segment GIA model was created based on CT angiography. Two models were then constructed that simulated a virtual bypass in combination with proximal GIA occlusion, but with differing middle cerebral artery (MCA) recipient vessels for the anastomosis. FSI and CFD investigations were performed in three models to assess changes in flow pattern and haemodynamic parameters alternations (wall shear stress (WSS), oscillatory shear index (OSI), maximal time averaged WSS (TAWSS), and pressure). General flow splitting across the entire domain was affected by virtual bypass procedures, and any deficiency was partially compensated by a specific configuration of the circle of Willis. Following the implementation of bypass procedures, a reduction in haemodynamic parameters was observed within the aneurysm in both cases under analysis. In the case of the temporal MCA branch bypass, the decreases in the studied parameters were slightly greater than in the frontal MCA branch bypass. The reduction in the magnitude of the chosen area-averaged parameters (averaged over the aneurysm wall surface) was as follows: WSS 35.7%, OSI 19.0%, TAWSS 94.7%, and pressure 24.2%. FSI CFD investigation based on patient-specific anatomy models with subsequent stimulation of virtual proximal aneurysm occlusion in conjunction with bypass showed that this method creates a pro-thrombotic favourable environment whilst reducing intra-aneurysmal pressure leading to shrinking. MCA branch recipient selection for optimum haemodynamic conditions should be evaluated individually in the preoperative stage.

Computational fluid dynamics; a new diagnostic tool in giant intracerebral aneurysm treatment.

Giant intracerebral aneurysms (GIA) comprise up to 5 % of all intracranial aneurysms. The indirect surgical strategy, which leaves the GIA untouched but reverses the blood flow by performing a bypass in combination with proximal parent artery occlusion is a useful method to achieve spontaneous aneurysm occlusion. The goal of this study was to assess the utility of computational fluid dynamics (CFD) in preoperative GIA treatment planning. We hypothesise that CFD simulations will predict treatment results. A fluid-structure interaction (FSI) CFD investigation was performed for the entire arterial brain circulation. The analyses were performed in three patient-specific CT angiogram models. The first served as the reference geometry with a C6 internal carotid artery (ICA) GIA, the second a proximal parent artery occlusion (PAO) and virtual bypass to the frontal M2 branch of the middle cerebral artery (MCA), and the third a proximal PAO in combination with a temporal M2 branch bypass. The volume of "old blood", flow residence time (FRT), dynamic viscosity and haemodynamic changes were also analysed. The "old blood" within the aneurysm in the bypass models reached 41 % after 20 cardiac cycles while in the reference model it was fully washed out. In Bypass 2 "old blood" was also observed in the main trunk of the MCA after 20 cardiac cycles. Extrapolation of the results yielded a duration of 4 years required to replace the "old blood" inside the aneurysm after bypass revascularization. In both bypass models a 7-fold increase in mean blood viscosity in the aneurysm region was noted. Bypass revascularization combined with proximal PAO favours thrombosis. Areas prone to thrombus formation, and subsequently the treatment outcomes, were accurately identified in the preoperative model. Virtual surgical operations can give a remarkable insight into haemodynamics that could support operative decision-making.

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options. Objective: To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH. Design, Setting, and Participants: This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated. Intervention: During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group). Main Outcome and Measures: The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography. Results: Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups. Conclusions and Relevance: These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04269408.

Preoperatively-determined Red Distribution Width (RDW) predicts prolonged length of stay after single-level spinal fusion in elderly patients.

Introduction: Elderly patients receiving lumbar fusion surgeries present with a higher risk profile, which necessitates a robust predictor of postoperative outcomes. The Red Distribution Width (RDW) is a preoperative routinely determined parameter that reflects the degree of heterogeneity of red blood cells. Thereby, RDW is associated with frailty in hospital-admitted patients. Research question: This study aims to elucidate the potential of RDW as a frailty biomarker predictive of prolonged hospital stays following elective mono-segmental fusion surgery in elderly patients. Material and methods: In this retrospective study, we included all patients with age over 75 years that were treated via lumbar single-level spinal fusion from 2015 to 2022 at our tertiary medical center. Prolonged length of stay (pLOS) was defined as a length ≥ the 3rd quartile of LOS of all included patients. Classical correlation analysis, Receiver-operating characteristic (ROC) and new machine learning algorithms) were used. Results: A total of 208 patients were included in the present study. The median age was 77 (IQR 75-80) years. The median LOS of the patients was 6 (IQR 5-8) days. The data shows a significant positive correlation between RDW and LOS. RDW is significantly enhanced in the pLOS group. New machine learning approaches with the imputation of multiple variables can enhance the performance to an AUC of 71%. Discussion and conclusion: RDW may serve as a predictor for a pLOS in elderly. These results are compelling because the determination of this frailty biomarker is routinely performed at hospital admission. An improved prognostication of LOS could enable healthcare systems to distribute constrained hospital resources efficiently, fostering evidence-based decision-making processes.

Template-based target point localization for occlusion of the middle meningeal artery during evacuation of space-occupying chronic subdural hematoma.

OBJECTIVE: Endovascular middle meningeal artery (MMA) occlusion may help reduce the risk of recurrence after burr hole evacuation of chronic subdural hematoma (cSDH) but carries an additional periprocedural risk and remains hampered by logistical and financial requirements. In this study, the authors aimed to describe a simple and fast technique for preoperative MMA localization to permit burr hole cSDH evacuation and MMA occlusion through the same burr hole. METHODS: The authors performed a preclinical anatomical and prospective clinical study, followed by a retrospective feasibility analysis. An anatomical cadaver study with 33 adult human skulls (66 hemispheres) was used to localize a suitable frontal target point above the pterion, where the MMA can be accessed via burr hole trephination. Based on anatomical landmark measurements, the authors designed a template for projected localization of this target point onto the skin. Next, the validity of the template was tested using image guidance in 10 consecutive patients undergoing elective pterional craniotomy, and the feasibility of the target point localization for cSDH accessibility was determined based on hematoma localization in 237 patients who were treated for a space-occupying cSDH in the authors' department between 2014 and 2018. RESULTS: In the anatomical study, the mean perpendicular distance from the zygomatic process to the target point in the frontoparietal bone was 4.1 cm (95% CI 4-4.2 cm). The mean length along the upper margin of the zygomatic process from the middle of the external auditory canal to the point of the perpendicular distance was 2.3 cm (95% CI 2.2-2.4 cm). The template designed according to these measurements yielded high agreement between the template-based target point and the proximal MMA groove inside the frontoparietal bone (right 90.9%; left 93.6%). In the clinical validation, we noted a mean distance of 4 mm (95% CI 2.1-5.9 mm) from the template-based target point to the actual MMA localization. The feasibility analysis yielded that 95% of all cSDHs in this cohort would have been accessible by the new frontal burr hole localization. CONCLUSIONS: A template-based target point approach for MMA localization may serve as a simple, fast, reliable, and cost-effective technique for surgical evacuation of space-occupying cSDHs with MMA obliteration through the same burr hole in a single setting.

A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use. Research question: The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. Material and methods: In this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment. Results: Ten patients across four dose groups were treated with NicaPlant® (3-13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm. Discussion and conclusion: The placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies.

Comparison of intraoperative CT- and cone beam CT-based spinal navigation for the treatment of atlantoaxial instability.

BACKGROUND CONTEXT: Due to the complexity of neurovascular structures in the atlantoaxial region, spinal navigation for posterior C1-C2 instrumentation is nowadays a helpful tool to increase accuracy of surgery and safety of patients. Many available intraoperative navigation devices have proven their reliability in this part of the spine. Two main imaging techniques are used: intraoperative CT (iCT) and cone beam computed tomography (CBCT). PURPOSE: Comparison of iCT- and CBCT-based technologies for navigated posterior instrumentation in C1-C2 instability. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 81 consecutive patients from July 2014 to April 2020. OUTCOME MEASURES: Screw accuracy and operating time. METHODS: Patients with C1-C2 instability received posterior instrumentation using C2 pedicle screws, C1 lateral mass or pedicle screws. All screws were inserted using intraoperative imaging either using iCT or CBCT systems and spinal navigation with autoregistration technology. Following navigated screw insertion, a second intraoperative scan was performed to assess the accuracy of screw placement. Accuracy was defined as the percentage of correctly placed screws or with minor cortical breach (<2 mm) as graded by an independent observer compared to misplaced screws. RESULTS: A total of 81 patients with C1-C2 instability were retrospectively analyzed. Of these, 34 patients were operated with the use of iCT and 47 with CBCT. No significant demographic difference was found between groups. In the iCT group, 97.7% of the C1-C2 screws were correctly inserted; 2.3% showed a minor cortical breach (<2 mm); no misplacement (>2 mm). In the CBCT group, 98.9% of screws were correctly inserted; no minor pedicle breach; 1.1% showed misplacement >2 mm. Accuracy of screw placement demonstrated no significant difference between groups. Both technologies allowed sufficient identification of screw misplacement intraoperatively leading to two screw revisions in the iCT and three in the CBCT group. Median time of surgery was significantly shorter using CBCT technology (166.5 minutes [iCT] vs 122 minutes [CBCT]; p<.01). CONCLUSIONS: Spinal navigation using either iCT- or CBCT-based systems with autoregistration allows safe and reliable screw placement and intraoperative assessment of screw positioning. Using the herein presented procedural protocols, CBCT systems allow shorter operating time.

Oscillation analysis as a supporting element toward safe and reliable lumbar catheter intracranial pressure monitoring.

OBJECTIVE: Lumbar drainage of cerebrospinal fluid for treatment of refractory increased intracranial pressure (ICP) is associated with the risk of infratentorial herniation, but real-time biomarkers for signaling herniation at bedside are lacking. Here, the authors tested whether an alteration of pulsatile waveform conduction across the level of the foramen magnum could serve as an indicator of insufficient hydrostatic communication and impending herniation. METHODS: This prospective observational cohort study included patients with severe acute brain injury who underwent continuous external ventricular drain monitoring of ICP and lumbar drain pressure monitoring. Continuous recordings of ICP, lumbar pressure (LP), and arterial blood pressure (ABP) were screened throughout a recording period of 4-10 days. Pressure differences between ICP and LP > 5 mm Hg for 5 minutes were defined as a Δ-event, implicating nonsufficient hydrostatic communication. During this period, oscillation analysis of the ICP, LP, and ABP waveforms was performed by determining the eigenfrequencies (EFs) and their amplitudes (AEF) via Fourier transformation scripted in Python. RESULTS: Of 142 patients, 14 exhibited a Δ-event, with a median (range) ICP of 12.2 (10.7-18.8) mm Hg and LP of 5.6 (3.3-9.8) mm Hg during 2993 hours of recording time. The AEF ratio between ICP and LP (p < 0.01) and between ABP and LP (p = 0.032) increased significantly during Δ-events compared with the baseline values determined 3 hours prior to the event. The ratio between ICP and ABP remained unaffected. CONCLUSIONS: Oscillation behavior analysis of LP and ABP waveforms during controlled lumbar drainage may serve as a personalized, simple, and effective biomarker to signal impending infratentorial herniation in real time without the need for simultaneous ICP monitoring.

Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.

RATIONALE: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. AIM: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. METHODS AND DESIGN: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. SAMPLE SIZE ESTIMATES: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. STUDY OUTCOME: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). DISCUSSION: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

Decompression with or without fusion in degenerative adjacent segment stenosis after lumbar fusions.

Adjacent segment stenosis can occur after lumbar fusion surgery, leading to significant discomfort and pain. If further surgeries are required, the choice of the operative technique is an individual decision. In patients without over instability, it is still uncertain whether patients with adjacent spinal stenosis should be treated like primary lumbar spinal stenosis via decompressive surgery alone or with decompression and fusion. This is a retrospective analysis with prospective collected data. We included patients with adjacent segment stenosis after lumbar fusion. Patients with spinal deformity and/or obvious instability and/or significant neuroforaminal stenosis were excluded. All patients were divided into two groups according to the surgical technique that has been used: (a) treated via microsurgical decompression (MDG), (b) decompression and fusion of the adjacent segment (FG). Treatment decision was at discretion of the surgeon. Primary outcome was the need for further lumbar surgery after 1 year. In addition, patient reported outcome was measured via numerical rating scale (NRS), SF-36, Oswestry disability Index (ODI), Pittsburgh Sleep Quality Index (PSQI), and General Depression Scale before and after 1 year after surgery. In a further follow-up, need for additional lumbar surgery was redetermined. Total study population was 37 patients with a median age of 72 years. A total of 86.1% of patients suffered from a proximal adjacent segment stenosis and most common level was L3/4 (51.4%). A total of 61.1% of included patients developed adjacent segment stenosis after fusion of one single lumbar segment. Eighteen patients were included in MDG and 19 patients in FG. Both groups benefited from surgical interventions and there was no significant difference concerning pain, pain associated disability, sleeping, life quality, and mood after 1 year or the need of follow-up surgeries 1 year after primary fusion (5 in MDG vs. 5 in FG, p = 0.92) and at the second follow-up with a median time after surgery of 30 months (6 in MDG vs. 7 in FG, p = 0.823). Duration of surgery and hospital stay was significant shorter in MDG. There was no difference concerning operative complications rate. Both groups improved significantly in pain associated disability index, pain in motion, and concerning the sleeping quality. The present study indicates that decompression may not be inferior to decompression and fusion in patients suffering from degenerative adjacent segment stenosis without obvious signs of instability, deformation, and neuroforaminal stenosis after lumbar fusion in short-term follow-up. Due to significant shorter time of surgery, a pure microsurgical decompression may be a sufficient alternative to a decompression and fusion, particular regarding old age of this patient cohort.

Navigation accuracy and assessability of carbon fiber-reinforced PEEK instrumentation with multimodal intraoperative imaging in spinal oncology.

Radiolucent carbon-fiber reinforced PEEK (CFRP) implants have helped improve oncological follow-up and radiation therapy. Here, we investigated the performance of 3D intraoperative imaging and navigation systems for instrumentation and precision assessment of CFRP pedicle screws across the thoraco-lumbar spine. Thirty-three patients with spinal tumors underwent navigated CFRP instrumentation with intraoperative CT (iCT), robotic cone-beam CT (rCBCT) or cone-beam CT (CBCT) imaging. Two different navigation systems were used for iCT-/rCBCT- and CBCT-based navigation. Demographic, clinical and outcome data was assessed. Four blinded observers rated image quality, assessability and accuracy of CFRP pedicle screws. Inter-observer reliability was determined with Fleiss` Kappa analysis. Between 2018 and 2021, 243 CFRP screws were implanted (iCT:93, rCBCT: 99, CBCT: 51), of which 13 were non-assessable (iCT: 1, rCBCT: 9, CBCT: 3; *p = 0.0475; iCT vs. rCBCT). Navigation accuracy was highest using iCT (74%), followed by rCBCT (69%) and CBCT (49%) (*p = 0.0064; iCT vs. CBCT and rCBCT vs. CBCT). All observers rated iCT image quality higher than rCBCT/CBCT image quality (*p < 0.01) but relevant pedicle breaches were reliably identified with substantial agreement between all observers regardless of the imaging modality. Navigation accuracy for CFRP pedicle screws was considerably lower than expected from reports on titanium implants and CT may be best for reliable assessment of CFRP materials.

Development and Internal Validation of the ARISE Prediction Models for Rebleeding After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal rerupture is one of the most important determents for outcome after aneurysmal subarachnoid hemorrhage and still occurs frequently because individual risk assessment is challenging given the heterogeneity in patient characteristics and aneurysm morphology. OBJECTIVE: To develop and internally validate a practical prediction model to estimate the risk of aneurysmal rerupture before aneurysm closure. METHODS: We designed a multinational cohort study of 2 prospective hospital registries and 3 retrospective observational studies to predict the risk of computed tomography confirmed rebleeding within 24 and 72 hours after ictus. We assessed predictors with Cox proportional hazard regression analysis. RESULTS: Rerupture occurred in 269 of 2075 patients. The cumulative incidence equaled 7% and 11% at 24 and 72 hours, respectively. Our base model included hypertension, World Federation of Neurosurgical Societies scale, Fisher grade, aneurysm size, and cerebrospinal fluid drainage before aneurysm closure and showed good discrimination with an optimism corrected c-statistic of 0.77. When we extend the base model with aneurysm irregularity, the optimism-corrected c-statistic increased to 0.79. CONCLUSION: Our prediction models reliably estimate the risk of aneurysm rerupture after aneurysmal subarachnoid hemorrhage using predictor variables available upon hospital admission. An online prognostic calculator is accessible at https://www.evidencio.com/models/show/2626 .

Spinal alignment shift between supine and prone CT imaging occurs frequently and regardless of the anatomic region, risk factors, or pathology.

Computer-assisted spine surgery based on preoperative CT imaging may be hampered by sagittal alignment shifts due to an intraoperative switch from supine to prone. In the present study, we systematically analyzed the occurrence and pattern of sagittal spinal alignment shift between corresponding preoperative (supine) and intraoperative (prone) CT imaging in patients that underwent navigated posterior instrumentation between 2014 and 2017. Sagittal alignment across the levels of instrumentation was determined according to the C2 fracture gap (C2-F) and C2 translation (C2-T) in odontoid type 2 fractures, next to the modified Cobb angle (CA), plumbline (PL), and translation (T) in subaxial pathologies. One-hundred and twenty-one patients (C1/C2: n = 17; C3-S1: n = 104) with degenerative (39/121; 32%), oncologic (35/121; 29%), traumatic (34/121; 28%), or infectious (13/121; 11%) pathologies were identified. In the subaxial spine, significant shift occurred in 104/104 (100%) cases (CA: *p = .044; T: *p = .021) compared to only 10/17 (59%) cases that exhibited shift at the C1/C2 level (C2-F: **p = .002; C2-T: *p < .016). The degree of shift was not affected by the anatomic region or pathology but significantly greater in cases with an instrumentation length > 5 segments ("∆PL > 5 segments": 4.5 ± 1.8 mm; "∆PL ≤ 5 segments": 2 ± 0.6 mm; *p = .013) or in revision surgery with pre-existing instrumentation ("∆PL presence": 5 ± 2.6 mm; "∆PL absence": 2.4 ± 0.7 mm; **p = .007). Interestingly, typical morphological instability risk factors did not influence the degree of shift. In conclusion, intraoperative spinal alignment shift due to a change in patient position should be considered as a cause for inaccuracy during computer-assisted spine surgery and when correcting spinal alignment according to parameters that were planned in other patient positions.

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex.

Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion. Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP). Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP. Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.

Patients Receiving Extracranial to Intracranial Bypass for Atherosclerotic Vessel Occlusion Today Differ Significantly From the COSS Population.

Background and Purpose: Despite the findings reported in the COSS (Carotid Occlusion Surgery Study), patients with atherosclerotic cerebrovascular disease continue to be referred for superficial temporal artery to middle cerebral artery bypass surgery. Here, we determined how today's patients differ from the population reported in COSS. Methods: We retrospectively analyzed all patients that were referred to our Department for superficial temporal artery to middle cerebral artery bypass surgery of atherosclerotic cerebrovascular disease following the publication of COSS. Results: Between 2012 and 2019, 179 patients were referred for 186 bypass surgeries. Ninety-one (51%) patients suffered atherosclerotic, unilateral internal carotid occlusion and 88 (49%) atherosclerotic multivessel disease. All patients had received intensive medical management. A single transitory ischemic attack or ischemic stroke within the last 120 days according to the inclusion criteria of COSS occurred in only 36 out of 179 (20%) patients, whereas 27 out of 179 (15%) suffered >1 transitory ischemic attack within 120 days, 109 out of 179 (61%) had recurrent minor ischemic stroke, and 7 out of 179 (4%) were hemodynamically unstable and required blood pressure maintenance. The distribution of symptoms did not differ between atherosclerotic unilateral internal carotid artery occlusion and atherosclerotic multivessel disease (P=0.376) but hemodynamic impairment was significantly greater in atherosclerotic multivessel disease (P<0.001 for atherosclerotic multivessel disease versus atherosclerotic unilateral internal carotid artery occlusion). The overall perioperative stroke rate was 4.3%. Conclusions: Patients referred for flow augmentation surgery today appear to suffer more severe symptoms and vessel occlusion patterns than patients reported in COSS. A new, carefully designed randomized controlled trial appears warranted, considering the still poor prognosis of severe atherosclerotic cerebrovascular disease.

Complete or Partial Parent Artery Sacrifice: Effect of Vessel-Occlusion Strategies on Complete Obliteration of Complex Aneurysms.

OBJECTIVE/BACKGROUND: A small number of complex intracranial aneurysms are not amenable to direct clipping strategies or endovascular treatment. In these patients, parent artery sacrifice and bypass revascularization for aneurysm occlusion is an option. There are 3 strategies for parent artery sacrifice: trapping, complete occlusion of the inflow, and outflow segment; proximal occlusion of the inflow vessel; and distal occlusion of the outflow vessel(s). This study aimed to compare these techniques with regard to aneurysm occlusion rates. METHODS: We reviewed our database for cerebral revascularization before parent artery sacrifice to treat cerebral aneurysms. We assessed aneurysm occlusion rates 3 and 12 months after surgery, outcome, and postoperative aneurysm rupture. RESULTS: In total, 121 patients underwent parent artery sacrifice for complex aneurysms; 30% of the parent arteries were trapped, 58% proximally, and 12% distally occluded. Postoperative digital subtraction angiography revealed an aneurysm occlusion rate of 100% after trapping. Proximal occlusion led to early complete aneurysm occlusion in 71% of the cases, 21% occluded during follow-up. The complete occlusion rate was 96%, distal occlusion had an early aneurysm occlusion rate of 40%, 40% occluded during follow-up. Complete aneurysm occlusion rate was only 80%. All 3 techniques resulted in a volume reduction of more than 60% without a significant difference between the groups. The annual aneurysm rupture rate after distal parent artery sacrifice was 15%; there was no rupture after trapping or proximal parent artery sacrifice. CONCLUSIONS: Trapping and proximal parent artery sacrifice seem to be superior to distal parent artery sacrifice regarding occlusion and rupture rates.

Diagnostic reliability of the Berlin classification for complex MCA aneurysms-usability in a series of only giant aneurysms.

BACKGROUND AND OBJECTIVE: The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. METHODS: We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. RESULTS: We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. CONCLUSION: The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.

Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity.

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

The Comaneci Device for Entering an Acute-Angled Small Feeder during Cerebral Arteriovenous Malformation Embolization: A Novel Technique to Support Microcatheterization.

In this report, we describe the use of the Comaneci device to support microcatheterization in a small branch arising from a parent artery during embolization. In 2 cases, arteriovenous malformations presented with intracranial hemorrhage. A microcatheter was navigated into a small feeder while the Comaneci device was deployed just distal to the feeder with an acute angle from the parent artery. Our technical note represents an alternative option of catheterization in cases with difficult access to small feeders originating from higher flow arteries at a sharp angle while maintaining continuous flow in the parent artery.

Need for ensuring care for neuro-emergencies-lessons learned from the COVID-19 pandemic.

BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.