Effect of cranial entry site on the rate of proximal catheter misplacement in ventriculoperitoneal shunt insertion.

OBJECTIVE: The insertion of a ventriculoperitoneal shunt (VPS) is a common neurosurgical procedure, but the optimal entry site of the ventricular catheter is still under debate. In this study, the authors compare the parietal (Keen's) and frontal (Kocher's) entry sites in terms of the rate of revision surgery due to ventricular catheter misplacement, VPS dysfunction, and VPS infection. METHODS: The authors retrospectively analyzed the data on consecutive adults (age ≥ 18 years) who had undergone primary VPS insertion between 2010 and 2020 at two neurosurgical centers. One center regularly inserts the ventricular catheter frontally (frontal group); the other center, parietally (parietal group). The primary outcome of interest was the rate of ventricular catheter misplacement necessitating revision surgery. Secondary outcomes were functional outcome as measured by the modified Rankin Scale (mRS), rate of revision surgery for VPS dysfunction and infection, as well as early (≤ 30 days) and late (> 30 days) mortality rates. Propensity score matching was performed based on baseline variables, such as normal pressure hydrocephalus, postinfectious hydrocephalus, and idiopathic intracranial hypertension, which were identified as predictors of ventricular catheter misplacement using logistic regression analysis. RESULTS: Among 539 consecutive patients, 301 (55.8%) were in the frontal group and 238 (44.2%) in the parietal group. Postoperative rates of revision surgery due to misplacement were comparable in the two catheter entry site groups (frontal 14 [4.7%] vs parietal 11 [4.6%], p = 0.987). Rates of revision surgery for VPS dysfunction (14 [4.7%] vs 10 [4.2%], respectively, p = 0.802) and infection (22 [7.3%] vs 10 [4.2%], p = 0.13) exhibited no significant differences. Favorable functional outcomes (mRS score ≤ 2; 164 [76.3%] vs 174 [79.5%], respectively, p = 0.058) and early mortality rates (5 [1.7%] vs 6 [2.5%], p = 0.483) were similar between the groups. After propensity score matching, the primary and secondary outcome measures remained comparable between the groups. CONCLUSIONS: The entry site of the ventricular catheter in VPS surgery does not seem to affect proximal revision rates. Further, revision rates due to VPS dysfunction, VPS infection, and morbidity were comparable as well.

Aneurysm healing following treatment with biodegradable embolization materials: assessment in a rat sidewall aneurysm model.

BACKGROUND: Biodegradable materials that dissolve after aneurysm healing are promising techniques in the field of neurointerventional surgery. We investigated the effects of various bioabsorable materials in combination with degradable magnesium alloy stents and evaluated aneurysm healing in a rat aneurysm model. METHODS: Saccular aneurysms were created by end-to-side anastomosis in the abdominal aorta of Wistar rats. Untreated arterial grafts were immediately transplanted (vital aneurysms) whereas aneurysms with loss of mural cells were chemically decellularized before implantation. All aneurysms were treated with biodegradable magnesium stents. The animals were assigned to vital aneurysms treated with stent alone or decellularized aneurysms treated with stent alone, detachable coil, or long-term or short-term biodegradable thread. Aneurysm healing, rated microscopically and macroscopically at follow-up days 7 and 21, was defined by both neointima formation and absence of aneurysm volume increase over time. RESULTS: Of 56 animals included, significant increases in aneurysm volume 7 days after surgery were observed in aneurysms with vital and decellularized walls treated with a stent only (P=0.043 each group). Twenty-one days after surgery an increase in aneurysm volume was observed in decellularized aneurysms treated with long- and short-term biodegradable threads (P=0.027 and P=0.028, respectively). Histological changes associated with an increase in aneurysm volume were seen for aneurysm wall inflammation, periadventitial fibrosis, and luminal thrombus. CONCLUSIONS: An increase in aneurysm volume was associated with an absence of intrasaccular embolization material (early phase) and the breakdown of intrasaccular biodegradable material over time (late phase). Thrombus remnant and aneurysm wall inflammation promote aneurysm volume increase.

Safety and functional outcome analysis of ventriculoperitoneal shunt placement for hydrocephalus within the critical phase of possible delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Shunt-dependent hydrocephalus (HC) is a common sequela following aneurysmal subarachnoid hemorrhage (aSAH). However, there is still poor evidence regarding the optimal timing of ventriculoperitoneal shunt (VPS) placement, particularly in the context of early aSAH-associated complications such as delayed cerebral ischemia (DCI). The purpose of this study was to compare the impact of early (< 21 days after aSAH) versus late (≥ 21 days after aSAH) VPS placement on the functional clinical outcome. We retrospectively analyzed data from 82 patients with VPS placement after aSAH enrolled in our institutional database between 2011 and 2021. We compared two groups, early VPS placement (< 21 days after aSAH) versus late VPS placement (≥ 21 days after aSAH) in terms of demographics, SAH grading, radiological parameters, externalized cerebrospinal fluid diversions, DCI, VPS variables, and functional outcome. We identified 53 patients with early and 29 patients with late VPS implantation. Baseline variables, such as the modified Rankin Scale (mRS), the World Federation of Neurological Surgeons Scale, the Glasgow Coma Scale, and Fisher grade were not significantly different between the groups. Postoperatively, the mRS (p = 0.0037), the Glasgow Outcome Scale (p = 0.0037), and the extended Glasgow Outcome Scale (p = 0.0032) showed significantly better functional results in patients with early cerebrospinal fluid diversion. The rate of DCI did not differ significantly between the groups (p = 0.53). There was no difference in the rate of VPS placement associated complications (p = 0.44) or overall mortality (p = 0.39). Early shunt implantation, within 21 days after aSAH and therefore during the timeframe of possible DCI, might not be harmful in patients developing HC after aSAH.

Incidence, therapy, and outcome in the management of chronic subdural hematoma in Switzerland: a population-based multicenter cohort study.

Background: Chronic subdural hematoma (cSDH) is a disease affecting mainly elderly individuals. The reported incidence ranges from 2.0/100,000 to 58 per 100,000 person-years when only considering patients who are over 70 years old, with an overall incidence of 8.2-14.0 per 100,000 persons. Due to an estimated doubling of the population above 65 years old between 2000 and 2030, cSDH will become an even more significant concern. To gain an overview of cSDH hospital admission rates, treatment, and outcome, we performed this multicenter national cohort study of patients requiring surgical treatment of cSDH. Methods: A multicenter cohort study included patients treated in 2013 in a Swiss center accredited for residency. Demographics, medical history, symptoms, and medication were recorded. Imaging at admission was evaluated, and therapy was divided into burr hole craniostomy (BHC), twist drill craniostomy (TDC), and craniotomy. Patients' outcomes were dichotomized into good (mRS, 0-3) and poor (mRS, 4-6) outcomes. A two-sided t-test for unpaired variables was performed, while a chi-square test was performed for categorical variables, and a p-value of <0.05 was considered to be statistically significant. Results: A total of 663 patients were included. The median age was 76 years, and the overall incidence rate was 8.2/100,000. With age, the incidence rate increased to 64.2/100,000 in patients aged 80-89 years. The most prevalent symptoms were gait disturbance in 362 (58.6%) of patients, headache in 286 (46.4%), and focal neurological deficits in 252 (40.7%). CSDH distribution was unilateral in 478 (72.1%) patients, while 185 presented a bilateral hematoma with no difference in the outcome. BHC was the most performed procedure for 758 (97.3%) evacuations. CSDH recurrence was noted in 104 patients (20.1%). A good outcome was seen in almost 81% of patients. Factors associated with poor outcomes were age, GCS and mRS on admission, and the occurrence of multiple deficits present at the diagnosis of the cSDH. Conclusion: As the first multicenter national cohort-based study analyzing the disease burden of cSDH, our study reveals that the hospital admission rate of cSDH was 8.2/100,000, while with age, it rose to 64.2/100,000. A good outcome was seen in 81% of patients, who maintained the same quality of life as before the surgery. However, the mortality rate was 4%.

Topographic distribution of inflammation factors in a healing aneurysm.

BACKGROUND: Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. METHODS: Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. RESULTS: Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing. CONCLUSION: The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

IL-6 in spinal cord injury: could immunomodulation replace immunosuppression in the management of acute traumatic spinal cord injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Reducing morbidity associated with subdural drain placement after burr-hole drainage of unilateral chronic subdural hematomas: a retrospective series comparing conventional and modified Nelaton catheter techniques.

PURPOSE: Placement of a subdural drain after burr-hole drainage of chronic subdural hematoma (cSDH) significantly reduces risk of its recurrence and lowers mortality at 6 months. Nonetheless, measures to reduce morbidity related to drain placement are rarely addressed in the literature. Toward reducing drain-related morbidity, we compare outcomes achieved by conventional insertion and our proposed modification. METHODS: In this retrospective series from two institutions, 362 patients underwent burr-hole drainage of unilateral cSDH with subsequent subdural drain insertion by conventional technique or modified Nelaton catheter (NC) technique. Primary endpoints were iatrogenic brain contusion or new neurological deficit. Secondary endpoints were drain misplacement, indication for computed tomography (CT) scan, re-operation for hematoma recurrence, and favorable Glasgow Outcome Scale (GOS) score (≥ 4) at final follow-up. RESULTS: The 362 patients (63.8% male) in our final analysis included drains inserted in 56 patients by NC and 306 patients by conventional technique. Brain contusions or new neurological deficits occurred significantly less often in the NC (1.8%) than conventional group (10.5%) (P = .041). Compared with the conventional group, the NC group had no drain misplacement (3.6% versus 0%; P = .23) and significantly fewer non-routine CT imaging related to symptoms (36.5% versus 5.4%; P < .001). Re-operation rates and favorable GOS scores were comparable between groups. CONCLUSION: We propose the NC technique as an easy-to-use measure for accurate drain positioning within the subdural space that may yield meaningful benefits for patients undergoing treatment for cSDH and vulnerable to complication risks.

Anatomical Variations of the Common Carotid Arteries and Neck Structures of the New Zealand White Rabbit and Their Implications for the Development of Preclinical Extracranial Aneurysm Models.

BACKGROUND: Rabbit models involving neck arteries are of growing importance for the development of preclinical aneurysm models. An optimal understanding of the anatomy is primordial to allow the conception of models while minimizing mortality and morbidity. The aim of this study is to give reliable anatomical landmarks to allow a standardized approach to the neck vessels. METHODS: We performed a necropsy on nine specimens from ongoing experimental studies. We measured the distance between the origins of the right and left common carotid artery (rCCA/lCCA) and between the rCCA and the manubrium sterni (MS). The structures at risk were described. RESULTS: Female New Zealand White rabbits (NZWR) weighing 3.7 ± 0.3 kg and aged 25 ± 5 weeks were included. The rCCA origin was located 9.6 ± 1.2 mm laterally and 10.1 ± 3.3 mm caudally to the MS. In all specimens, the lCCA originated from the aortic arch, together with the brachiocephalic trunk (BCT), and 6.2 ± 3.1 mm proximally to the rCCA origin. The external and internal jugular veins, trachea and laryngeal nerve were the main structures at risk. CONCLUSIONS: The data help to localize both CCAs and their origin to guide surgical approaches with the manubrium sterni as a main landmark. Special attention has to be paid to the trachea, jugular veins and laryngeal nerves.

Usefulness and Reliability of the Bispectral Index during Balanced Anesthesia for Neurovascular Surgery in New Zealand White Rabbits.

Few data about the electroencephalogram and its calculated indices, such as the bispectral index (BIS), have been reported in rabbits. We aimed to evaluate whether a clinically stable anesthesia was mirrored by consistent and stable BIS values and to investigate the effects of modified cerebral blood supply, due to bilateral carotid clamping and re-opening, on BIS values. We also investigated the effects of fentanyl, as an antinociceptive drug, on the BIS. Sixty-eight rabbits undergoing general anesthesia for surgical creation of carotid bifurcation aneurysms were enrolled. The BIS values were recorded at nine selected time points (TPs) during each procedure and before and after fentanyl administration. The BIS values over time were compared with two-way repeated-measures analysis of variance followed by Tukey test, while the Wilcoxon signed rank test was performed to compare values at clamping and re-opening of the carotids as well as before and after fentanyl administration. The BIS values were significantly lower during anesthesia than at the end of anesthesia and at tracheal extubation; no significant differences were found among other TPs. Adequate depth of anesthesia was mirrored by consistent BIS values among rabbits, and alteration of cerebral blood supply did not modify BIS values, except once. Following fentanyl, BIS values did not change in a clinically relevant way.

Quality of Life After Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH. OBJECTIVE: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives. METHODS: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 & 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Rankin Scale. RESULTS: Two hundred-fifty patients were enrolled, of whom 237 were included in the analysis after 6 months and 223 after 12 months. After 6 months, 118 (49.8%) patients were alive, and after 12 months, 104 (46.6%) patients were alive. Of those, 95 (80.5%) and 89 (85.6%) reached a favorable outcome with mean EQ-5D-3L index values of 0.85 (±0.18) and 0.86 (±0.18). After 6 and 12 months, 23 (19.5%) and 15 (14.4%) of those alive had an unfavorable outcome with mean EQ-5D-3L index values of 0.27 (±0.25) and 0.19 (±0.14). CONCLUSION: Despite high initial mortality, the proportion of poor-grade aSAH survivors with good QoL is reasonably large. Only a minority of survivors reports poor QoL and requires permanent care.

Incidence and Outcome of Peri-interventional Vasospasm During Endovascular or Microsurgical Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Peri-interventional vasospasm (PIVS) is associated with high risk of delayed cerebral vasospasm (DCVS), delayed cerebral ischemia, and poor outcome after aneurysmal subarachnoid hemorrhage. However, the incidence rate associated with treatment of unruptured intracranial aneurysm (UIA) remains unclear. OBJECTIVE: To define the incidence and clinical significance of PIVS in UIA repair based on intraoperative/peri-interventional digital subtraction angiography. METHODS: A consecutive series of 205 patients who underwent UIA treatment by means of microsurgical clipping (n = 109) or endovascular coil embolization (n = 96) was assessed for the occurrence of PIVS. In all cases, PIVS was detected, measured, and classified using intraoperative/peri-interventional digital subtraction angiography. Severity of PIVS, association of PIVS with the development of DCVS, and neurological outcome were analyzed. RESULTS: Intraoperative PIVS was present in n = 14/109 (13%) patients with microsurgical clipping. Of these, caliber irregularities were mild (n = 10), moderate (n = 3), and severe (n = 1). In endovascularly treated patients, 6/96 (6%) developed PIVS, which were either mild (n = 3) or moderate (n = 3). Management in all cases included immediate intensive blood pressure management and application of topical papaverine or intra-arterial nimodipine immediately on detection of PIVS. No patient developed DCVS or lasting neurological deficits attributable to PIVS. CONCLUSION: This series revealed a relatively high overall incidence of PIVS (10%). However, no association of PIVS with the development of DCVS or poor outcome was found. In contrast to ruptured intracranial aneurysms, PIVS in unruptured intracranial aneurysms-if immediately and adequately addressed-seems to be benign and without sequelae for patient's functional outcome.

Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated. OBJECTIVE: To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge. METHODS: Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm. RESULTS: This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke. CONCLUSION: Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography.

OBJECTIVE: Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA-based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping. METHODS: Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models. RESULTS: The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence. CONCLUSIONS: The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

The Effect of Losartan on Neuroinflammation as Well as on Endothelin-1- and Serotonin-Induced Vasoconstriction in a Double-Haemorrhage Rat Model.

Poor patient outcome after aneurysmal subarachnoid haemorrhage (SAH) is due to a multifactorial process. Delayed cerebral vasospasm, ischemic neurological deficits, and infarction are the most feared acute sequelae triggered by enhanced synthesis of serotonin and endothelin-1 (ET-1). During the past decades, multiple drugs have been analysed for protective effects without resounding success. Therefore, the authors wanted to analyse the potential beneficial role of Losartan (LOS). Male Sprague Dawley rats were randomised into either a group receiving two injections of blood into the cisterna magna (SAH group) or a group receiving two injections of isotonic sodium chloride (sham group). The animals were culled on day five and basilar artery ring segments were used for in vitro tension studies. Sarafotoxin S6c caused a dose-dependent vasorelaxation in sham and SAH segments, which was more pronounced in sham segments. LOS, applied in a concentration of 10−3 M, was able to significantly reduce serotonin- (p < 0.01) and ET-1- (p < 0.05, p < 0.01) mediated vasoconstriction in sham segments. These findings, along with the well-known beneficial effects of LOS on restoring the impaired endothelin-B1-receptor function after SAH, as well as on the neuroprotectional and antiepileptogenic aspects, might be implemented in advancing tailored concepts to sufficiently ameliorate patients' functional outcome after SAH.

Using a Cell-Tracer Injection to Investigate the Origin of Neointima-Forming Cells in a Rat Saccular Side Wall Model.

Microsurgical clipping creates a subsequent barrier of blood flow into intracranial aneurysms, whereas endovascular treatment relies on neointima and thrombus formation. The source of endothelial cells covering the endoluminal layer of the neointima remains unclear. Therefore, the aim of the present study was to investigate the origin of neointima-forming cells after cell-tracer injection in the already well-established Helsinki rat microsurgical sidewall aneurysm model. Sidewall aneurysms were created by suturing decellularized or vital arterial pouches end-to-side to the aorta in male Lewis rats. Before arteriotomy with aneurysm suture, a cell-tracer injection containing CM-Dil dye was performed into the clamped aorta to label endothelial cells in the adjacent vessel and track their proliferation during follow-up (FU). Treatment followed by coiling (n = 16) or stenting (n = 15). At FU (7 days or 21 days), all rats underwent fluorescence angiography, followed by aneurysm harvesting and macroscopic and histological evaluation with immunohistological cell counts for specific regions of interest. None of the 31 aneurysms had ruptured upon follow-up. Four animals died prematurely. Macroscopically residual perfusion was observed in 75.0% coiled and 7.0% of stented rats. The amount of cell-tracer-positive cells was significantly elevated in decellularized stented compared to coiled aneurysms with respect to thrombus on day 7 (p = 0.01) and neointima on day 21 (p = 0.04). No significant differences were found in thrombus or neointima in vital aneurysms. These findings confirm worse healing patterns in coiled compared to stented aneurysms. Neointima formation seems particularly dependent on the parent artery in decellularized aneurysms, whereas it is supported by the recruitment from aneurysm wall cells in vital cell-rich walls. In terms of translation, stent treatment might be more appropriate for highly degenerated aneurysms, whereas coiling alone might be adequate for aneurysms with mostly healthy vessel walls.

Interrater and intrarater agreement superior for three-dimensional digital subtraction angiography (3D-DSA) over 2D-DSA classification for detecting remnants after intracranial aneurysm clipping, a GRRAS Reliability and Agreement Study.

BACKGROUND: Growing evidence suggests that three-dimensional digital subtraction angiography (3D-DSA) is superior to 2D-DSA in detection of intracranial aneurysm (IA) remnants after clipping. With a simple, practical quantitative scale proposed to measure maximal remnant dimension on 3D-DSA, this study provides a rigorous interrater and intrarater reliability and agreement study comparing this newly established scale with a commonly used (Sindou) 2D-DSA scale. METHOD: Records of 43 patients with clipped IAs harboring various sized remnants who underwent 2D- and 3D-DSA between 2012 and 2018 were evaluated. Using the 2D and 3D scales, six raters scored these remnants and repeated the scoring task 8 weeks later. Interrater and intrarater agreement for both grading schemes were calculated using kappa (κ) statistics. RESULTS: Interrater agreement was highly significant, yielding κ-values at 95% CI (p = 0.000) of 0.225 for the first [0.185; 0.265] and 0.368 s [0.328; 0.408] time points for 2D-DSA and values of 0.700 for the first [0.654; 0.745] and 0.776 s [0.729; 0.822] time points for 3D-DSA. Intrarater agreement demonstrated κ-values between 0.139 and 0.512 for 2D-DSA and between 0.487 and 0.813 for 3D-DSA scores. CONCLUSION: Interrater and intrarater agreement was minimal or weak for 2D-DSA scores, but strong for 3D-DSA scores. We propose that baseline 3D-DSA characterization may prove more reliable when categorizing clipped IA remnants for purposes of risk stratification and lifelong follow-up.

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Hemodynamic response and clinical outcome following intravenous milrinone plus norepinephrine-based hyperdynamic hypertensive therapy in patients suffering secondary cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PURPOSE: Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH. METHODS: Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters. RESULTS: The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months. CONCLUSION: The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine-based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset.