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.

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.

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.

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.

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.

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.

Association of Cerebrospinal Fluid Volume with Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Volumetric Analysis.

BACKGROUND: In aneurysmal subarachnoid hemorrhage (SAH), clot volume has been shown to correlate with the development of radiographic vasospasm (VS), while the role of cerebrospinal fluid (CSF) volume remains largely elusive in the literature. We evaluated CSF volume as a potential surrogate for VS in addition to SAH volume in this retrospective series. PATIENTS AND METHODS: From a consecutive cohort of aneurysmal SAH (n= 320), cases were included when angiographic evaluation for VS was performed (n= 125). SAH and CSF volumes were volumetrically quantified using an algorithm-assisted segmentation approach on initial computed tomography after ictus. Association with VS was analyzed using regression analysis. Receiver operating characteristic (ROC) curves were used to evaluate predictive accuracy of volumetric measures for VS and to identify cutoffs for risk stratification. RESULTS: Among 125 included cases, angiography showed VS in 101 (VS+), while no VS was observed in 24 (VS-) cases. In volumetric analysis, mean SAH volume was significantly larger (26.8 ± 21.1 ml vs. 12.6 ± 12.2 ml, p= 0.001), while mean CSF volume was significantly smaller (63.0 ± 31.2 ml vs. 85.7 ± 62.8, p= 0.03) in VS+ compared to VS- cases, respectively. The absence of correlation for SAH and CSF volumes (Pearson R - 0.05, p= 0.58) indicated independence of both measures of the subarachnoid compartment, which was a prerequisite for CSF to act as a new surrogate for VS not related to SAH. Regression analysis confirmed an increased risk of VS with increasing SAH (OR 1.06, 95% CI 1.02-1.11, p= 0.006), while CSF had a protective effect toward VS (OR 0.99, 95% CI 0.98-0.99, p= 0.02). SAH/CSF ratio was also associated with VS (OR 1.03, 95% CI 1.01-1.05, p= 0.015). ROC curves suggested cutoffs at 120 ml CSF and 20 ml SAH for VS stratification. Combination of variables improved stratification accuracy compared to use of SAH alone. CONCLUSION: This study provides a proof of concept for CSF correlating with angiographic VS after aneurysmal SAH. Quantification of CSF in conjunction with SAH might enhance risk stratification and exhibit advantages over traditional scores. The association of CSF has to be corroborated for delayed cerebral ischemia to further establish CSF as a surrogate parameter.

Bypass surgery of complex middle cerebral artery aneurysms-technical aspects and outcomes.

BACKGROUND: The main challenge of bypass surgery of complex MCA aneurysm is not the selection of the bypass type, but the initial decision making of how to exclude the affected vessel segment from circulation. The aim of our study was to review our experience with the treatment of complex MCA aneurysms using revascularization and parent artery sacrifice techniques. Based on this, we aimed at categorizing these aneurysms according to specific surgical aspects in order to facilitate preoperative planning for these challenging surgical pathologies. METHODS: We reviewed 50 patients with complex MCA aneurysms that were not clippable but required revascularization and parent artery sacrifice. We report the individual variations of surgical techniques, highlight the technical aspects, and categorize the aneurysms based on their location and orientation. RESULTS: Of the 50 aneurysms, 56% were giant, 16% large, and 28% < 10 mm, but fusiform. Fourteen percent were previously treated endovascular. Four percent presented with SAH. Ten percent were prebifurcational, 60% involved the bifurcation, and 30% were postbifurcational. Both parent artery sacrifice and bypass strategies were tailored to the individual localization and anatomical relationship of the aneurysm and inflow/outflow arteries (38% proximal inflow occlusion, 42% aneurysm trapping, 20% distal outflow occlusion; 14% STA-MCA bypass, 48% interposition graft, 36%, combined/complex revascularization with reimplantation/in situ techniques). Good outcome (mRS 0-2) rates at discharge and at follow-up were 64% and 84%. Based on our analysis of individual cases, we categorized complex MCA aneurysms into six types and provide individual recommendations for their surgical exploration and treatment by revascularization and parent artery sacrifice. CONCLUSION: Complex MCA aneurysms are among the most challenging vascular lesions and afford highly individualized treatment strategies. Revascularization and parent artery sacrifice provide durable results that are superior to the natural history. Our classification provides a tool for planning and pre-surgical assessment of the intraoperative anatomy of complex MCA aneurysms, helping to assume possible pitfalls.

Bypass strategies for common carotid artery occlusion.

BACKGROUND: Common carotid artery occlusion (CCA-occlusion) is a rare condition where standard revascularization is not feasible. Here, we analyzed our experience with surgical revascularization of CCA-occlusion to develop an algorithm for selection of the most suitable bypass strategy according to the Riles classification. METHODS: During a 10-year period, 16 out of 288 patients with cerebrovascular disease and compromised hemodynamic reserve underwent revascularization for unilateral CCA-occlusion. The utilized bypass strategies included (1) a saphenous vein graft from the subclavian artery (SA) to the internal carotid artery (ICA), (2) a radial artery graft from the V3 segment of the vertebral artery (VA) to a superficial branch of the middle cerebral artery (MCA), or (3) a saphenous vein graft from the SA to a deep branch of the MCA. RESULTS: In CCA-occlusion with maintained external carotid artery (ECA)/ICA patency (Riles type 1A), an SA-ICA bypass was performed (25%). In cases without ECA/ICA patency (Riles type 1B or 2) but suitable VA, a VA-MCA bypass was grafted (31%). In cases with unsuitable VA, a long SA-MCA interposition bypass was performed (38%). Transient postoperative neurological deficits occurred in 5 patients (31%) with 1 patient (6%) suffering permanent neurological worsening and 1 mortality (6%). Overall, no difference was found between the median preoperative mRS (2; range, 1-4) and the mRS at the time point of the last follow-up (2; range, 1-6; p = 0.75). The long-term graft patency was 94%. CONCLUSIONS: Although surgical revascularization for CCA-occlusion is feasible, it is associated with a higher risk than standard bypass grafting. Considering the poor natural history of CCA-occlusion, however, this risk may be justified in carefully selected patients.

Technical accuracy of the integration of an external ultrasonography system into a navigation platform: effects of ultrasonography probe registration and target detection.

BACKGROUND: Intraoperative navigated ultrasonography has reached clinical acceptance, while published data for the accuracy of some systems are missing. We technically quantified and optimised the accuracy of the integration of an external ultrasonography system into a BrainLab navigation system. METHODS: A high-end ultrasonography system (Elegra; Siemens, Erlangen, Germany) was linked to a navigation system (Vector Vision; BrainLab, Munich, Germany). In vitro accuracy and precision was calculated from differences between a real world target (high-precision crosshair phantom) and the ultrasonography image of this target in the navigation coordinate system. The influence of the intrinsic component of the calibration phantom (for ultrasonography probe registration), type of target definition (manual versus automatic) and orientation of the ultrasound probe in relation to the navigation tracking device on accuracy and precision were analysed in different settings (100 measurements for each setting) resembling clinically relevant scenarios in the neurosurgical operating theatre. RESULTS: Line-of-sight angles of 45°, 62° and 90° for the optical tracking of the navigated ultrasonography probe and a distance of 1.8 m revealed best accuracy and precision. Technical accuracy of the integration of ultrasonography into a standard navigation system is high [Euclidean error: median, 0.79 mm; mean, 0.89 ± 0.42 mm for 62° angle; median range: 1.16-1.46 mm; mean range (±SD): 1.22 ± 0.32 mm to 1.46 ± 0.55 mm for grouped analysis of all angles tested]. Software-based automatic target definition improved precision significantly (p < 0.001). CONCLUSIONS: Integration of an external ultrasonography system into the BrainLab navigation is accurate and precise. By modifying registration (and measurement conditions) via software modification, the in vitro accuracy and precision is improved and requirements for a clinical application are fully met.

Point-of-Care Testing in Neurosurgery.

Coagulation disorders can have a major impact on the outcome of neurosurgical patients. The central nervous system is located within the closed space of the skull, and therefore, intracranial hemorrhage can lead to intracranial hypertension. Acute brain injury has been associated with alterations of various hemostatic parameters. Point-of-care (POC) techniques such as rotational thromboelastometry are able to identify markers of coagulopathy which are not reflected by standard assessment of hemostasis (e.g., hyperfibrinolysis). In patients with acute brain injury, POC test results have been associated with important outcome parameters such as mortality and need for neurosurgical intervention. POC devices have also been used to rapidly identify and quantify the effects of antithrombotic medication. In cases of life-threatening intracranial hemorrhage, this information can be valuable when deciding over administration of prohemostatic substances or immediate neurosurgical intervention. In elective neurosurgical procedures, POC devices can provide important information when unexpected bleeding occurs or in cases of prolonged operative time with subsequent blood loss. Initial experiences with POC devices in neurosurgical care have shown promising results but further studies are needed to characterize their full potential and limitations.

Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes.

Chemosensory cells in the mucosal surface of the respiratory tract ("brush cells") use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis. Urethral brush cells express bitter and umami taste receptors and downstream components of the taste transduction cascade; respond to stimulation with bitter (denatonium), umami (monosodium glutamate), and uropathogenic Escherichia coli; and release acetylcholine to communicate with other cells. They are approached by sensory nerve fibers expressing nicotinic acetylcholine receptors, and intraurethral application of denatonium reflexively increases activity of the bladder detrusor muscle in anesthetized rats. We propose a concept of urinary bladder control involving a previously unidentified cholinergic chemosensory cell monitoring the chemical composition of the urethral luminal microenvironment for potential hazardous content.

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.

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.

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.

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.

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.

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.

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.