Unruptured Cerebral Aneurysms Research Articles

Microsurgical Clipping of Unruptured Middle Cerebral Artery Bifurcation Aneurysms: A Single-Center Experience

Background/Objectives: Microsurgical clipping has traditionally been considered a standard treatment for middle cerebral artery (MCA) aneurysms. Recently, a caseload reduction related to improved endovascular treatment options has occurred in cerebrovascular neurosurgery. Therefore, studies that report the clinical and radiological outcomes after clipping are highly warranted. Methods: Patients with an unruptured MCA bifurcation aneurysm, who were surgically treated at the Department of Neurosurgery in Linz between 2002 and 2019, were included in this study. Clinical and radiological outcome parameters were evaluated for each patient. Results: Overall, 272 patients were eligible for inclusion. Complete aneurysm occlusion was demonstrated in 266 (99.3%) of the 268 (98.5%) patients who underwent postoperative digital subtraction angiography. In six (2.2%) patients, a permanent new neurological deficit (pNND) persisted after treatment. Intraoperative aneurysm rupture was a significant factor (p = 0.0049) in the logistic regression. At the last follow-up, only two patients (0.7%) had an unfavorable outcome (mRS > 2). More recent surgeries were associated with fewer cases of pNND (p = 0.009). A transient new neurological deficit occurred in 13 patients (4.8%), with aneurysm size being a significant risk factor (p = 0.009). Surgical site infections were reported in four patients (1.5%), with patient age (p = 0.039) and time (p = 0.001) being significant factors. Two patients died (0.7%) perioperatively and two patients (0.7%) needed a retreatment in the long-term follow-up. Conclusions: The findings indicate that microsurgical clipping is a safe procedure with minimal need for retreatment. It achieves a high occlusion rate while maintaining a very low rate of adverse outcomes. Continuous intraoperative enhancements over time have contributed to a progressive improvement in clinical outcomes in recent years. This trend is exemplified by the absence of detectable pNND in the era of ICG angiography. Consequently, these data support the conclusion that microsurgical clipping should still be considered an appropriate treatment option for unruptured MCA bifurcation aneurysms.

Application of computational fluid dynamic simulation of parent blood flow in the embolization of unruptured A1 aneurysms

To investigate the effect of microcatheter shaping based on the parent artery mainstream line of blood flow simulated using the computational fluid dynamics (CFD) technique on embolization of unruptured aneurysms on the posterior wall of the anterior cerebral artery (ACA) A1 segment. Patients with unruptured cerebral aneurysms on the posterior wall of the ACA A1 segment were retrospectively enrolled and treated with endovascular embolization after microcatheter shaping. The clinical, embolization and follow-up data were analyzed. Eight patients were enrolled and treated with endovascular embolization. Eight microcatheters were steam shaped in vitro and were all successfully navigated to the right location in the in vitro experiment. During the embolization procedure, seven microcatheters were successfully navigated to the right location for embolization. In the remaining one patient who had tortuous cerebral arteries, reshaping of the microcatheter based on the parent artery mainstream of blood flow made successful navigation of the microcatheter to the right place. Complete occlusion was obtained in seven (87.5%) aneurysms and residual aneurysm neck in the remaining one (12.5%). At angiographic follow-up in 6 (75%) patients, the Raymond grade was I in 5 (83.3%) and II in the rest one (16.7%). Use of CFD simulation of parent artery blood flow for microcatheter shaping in the embolization of unruptured aneurysms on the posterior wall of the ACA A1 segment is safe and effective in navigating the microcatheter to the right location for embolization, resulting in good stability and support for the embolization.

Visualization of “subclinical consequence” after successful and uneventful surgical intervention for unruptured cerebral aneurysms

There are many studies on post-operative cognitive function after surgical clipping (SC) and endovascular coiling (EC) for unruptured cerebral aneurysms, but few reports focusing on possible subclinical damage. The aim of the present study was to detect the subclinical damage after surgical intervention. Patients with anterior circulation aneurysms who underwent either SC (SC group) or EC (EC group) were recruited. Imaging studies and evaluation of cognitive function were performed within 1 month preoperatively and at 6 months and 2 years postoperatively. The ipsilateral/contralateral cerebral blood flow (CBF) ratio (I/C ratio) calculated from values in four regions of interest (ROIs) placed on N-isopropyl-p-[123I] iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) was used to detect "subclinical consequence". "Subclinical consequence" was defined as post-operative CBF reduction without abnormality in other radiological examinations and cognitive tests. There were 14 patients in the SC group (mean age, 60.6±11.7 years) and 33 patients in the EC group (mean age, 67.5±7.2 years). All cognitive assessment results showed no significant reduction through the survey period. However, I/C ratios were restored by 2 years in the EC group not but in the SC group. I/C ratios at 6 months and 2 years were significantly lower in the SC group than the EC group (P<0.01). 123IMP-SPECT revealed a statistically significant reduction in ipsilateral CBF in patients who had an uneventful clinical course and no cognitive problems. The subclinical consequence could persist for at least 2 years following SC, and was less pronounced following EC.

Evaluating the Safety of Stent-Assisted Endovascular Treatment for Unruptured Cerebral Aneurysms in Older Adults: Emphasizing the Role of Antiplatelet Therapy.

This study aimed to compare the outcomes and safety in patients aged ≥75 years and those aged &lt;75 years who underwent stent-assisted endovascular treatment for unruptured cerebral aneurysms, specifically focusing on perioperative antiplatelet therapy (APT). This multicenter retrospective study comprised patients who underwent stent-assisted coiling (SAC) or flow diverter stent (FDS) placement for unruptured cerebral aneurysms. The primary outcome was defined as the composite outcomes of perioperative thromboembolic events, bleeding events, or death. Among 632 patients, 533 (84.3%) were aged &lt;75 years and 99 (15.6%) were aged ≥75 years. No significant differences were observed in the dual APT duration. The primary outcome occurred in 14.3% of patients aged &lt;75 years and in 14.1% of those aged ≥75 years, with no significant difference (P=1.0). The composites of the primary outcome, including thromboembolic events, bleeding events, and death differed insignificantly. Similar findings were observed when the primary outcomes for SAC (12.7% vs. 11.5%, P=0.95) and FDS (17.5% vs. 18.4%, P=1.0) were analyzed. The 30-day, 1-year, and 2-year cumulative event-free survival rates for the primary outcome were 89.5, 87.2%, and 85.2%, respectively, in patients aged &lt;75 years, and 90.9%, 88.7%, and 87.0%, respectively, in those aged ≥75 years. These trends were similar (log-rank test, P=0.92). No significant differences were observed in the rates of the primary outcomes between patients aged &lt;75 years and those aged ≥75 years. Therefore, refraining from stent-assisted treatment for unruptured aneurysms based solely on age might be inappropriate.

Hemodynamic analysis of a thrombosed bleb in an unruptured cerebral aneurysm

Hemodynamic analysis of a thrombosed bleb in an unruptured cerebral aneurysm

Effects of paroxetine, a P2X4 inhibitor, on cerebral aneurysm growth and recanalization after coil embolization: the NHO Drug for Aneurysm Study.

Rupture of cerebral aneurysms has a poor prognosis, and growing aneurysms are prone to rupture. Although the number of coil embolization procedures is increasing worldwide, they are more prone to recurrence than clipping surgeries. However, there is still no drug that prevents aneurysm growth or recanalization after coil embolization. The authors have previously focused on the role of hemodynamics in cerebral aneurysm development and reported that inhibition of the P2X4 purinoceptor, by which vascular endothelial cells sense blood flow, reduced the induction and growth of aneurysms in an animal model. In this study, the authors investigated the effects of paroxetine, a P2X4 inhibitor also used as an antidepressant, on aneurysm growth and recanalization after endovascular coiling. Using the J-ASPECT Study registry, the largest comprehensive reimbursement database system for acute stroke inpatient care in Japan, the authors searched for patients incidentally taking paroxetine who were registered in the decade 2010-2019 with an unruptured cerebral aneurysm or who underwent aneurysm coiling. They calculated the growth incidence and growth rate by the person-year method and the odds ratio for recanalization within 1 year after coiling and statistically compared to controls. Seventy-eight stroke facilities participated, and 275 patients were identified as potentially eligible. Thirty-seven patients with unruptured aneurysms and 38 after coil embolization met all eligibility criteria. They were compared with 396 control cases of unruptured aneurysms and 308 coil-placement controls. Multivariate analysis showed that paroxetine significantly reduced the incidence of aneurysm growth (number of cases with growth/person/year; incidence rate ratio [IRR] 0.24, 95% CI 0.05-0.66; p = 0.003) and the growth rate (total increase in maximum diameter in millimeters/person/year; IRR 0.57, 95% CI 0.28-0.98; p = 0.04). Paroxetine also significantly reduced the odds of recanalization in the year after coiling (OR 0.21, 95% CI 0.05-0.95; p = 0.04). The authors then performed propensity score matching to reduce bias due to imbalances in patient characteristics between the two groups; the outcome confirmed that paroxetine significantly reduced aneurysm growth incidence (IRR 0.02, 95% CI 0.008-0.05; p < 0.0001) and growth rate (IRR 0.03, 95% CI 0.01-0.06; p < 0.0001) and the 1-year recanalization (OR 0.18, 95% CI 0.03-0.99; p = 0.04). This observational cohort study suggests that P2X4 inhibitors such as paroxetine may be clinically applicable as prophylaxis against aneurysm rupture and postoperative recanalization.

Letter to the Editor: "Influence of Perioperative Three-Dimensional Computed Tomography (CT) Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease"

Letter to the Editor: "Influence of Perioperative Three-Dimensional Computed Tomography (CT) Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease"

In Reply to the Letter to the Editor Regarding: “Influence of Perioperative Three-Dimensional Computed Tomography (CT) Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

In Reply to the Letter to the Editor Regarding: “Influence of Perioperative Three-Dimensional Computed Tomography (CT) Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

Letter to the Editor Regarding “Influence of Perioperative Three-Dimensional Computed Tomography Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

Letter to the Editor Regarding “Influence of Perioperative Three-Dimensional Computed Tomography Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

In Reply to the Letter to the Editor Regarding “Influence of Perioperative Three-Dimensional CT Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

In Reply to the Letter to the Editor Regarding “Influence of Perioperative Three-Dimensional CT Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease”

The value of IL-6 in cerebrospinal fluid for determining the development of cerebral vasospasm after subarachnoid hemorrhage

An inflammatory response following aneurysmal SubArachnoid Hemorrhage (aSAH) plays a significant role in the development of cerebral vasospasm. This study analyzes the correlation between the level of InterLeukin-6 (IL-6) in CerebroSpinal Fluid (CSF) after aSAH and the occurrence of cerebral vasospasm. We analyzed clinical manifestations, laboratory data, and instrumental examination methods in 45 patients who were treated for intracranial aSAH within 21 days, studying the relationship between the development of cerebral angiospasm and the concentration of the inflammatory factor. We found the potential significance of IL-6 in predicting vasospasm, confirmed by cerebral angiography. As a control, we analyzed the CSF samples of 15 patients treated for unruptured cerebral aneurysms. According to the study results, vasospasm developed in 44% of patients, on average on the 6th day from the onset of the disease. Patients with aSAH demonstrated statistically significant (p&lt;0.05) higher mean IL-6 values in CSF on the 3rd, 7th, and 10th days compared to the control group. Patients with vasospasm showed statistically significant (p&lt;0.05) higher mean IL-6 values in CSF on the 3rd day, while the differences on the 7th and 10th days (p&lt;0.05) were not statistically significant. The threshold value for predicting the formation of cerebral vasospasm was determined to be 325 pg/ml on the 3rd day from the onset of the disease. We concluded that IL-6 in cerebrospinal fluid is a potential early marker for predicting vascular spasm after subarachnoid hemorrhage on the 3rd day of the disease, before the onset of clinical manifestations. We concluded that monitoring the value of IL-6 in the cerebrospinal fluid on the third day after aneurysm rupture is potentially significant for the early diagnosis of vasospasm. Keywords: intracranial aneurysm, vasospasm, stroke, cytokines.

Fluid-Structure Interaction Simulations of the Initiation Process of Cerebral Aneurysms.

Background: Hemodynamics during the growth process of cerebral aneurysms are incompletely understood. We developed a novel fluid-structure interaction analysis method for the identification of relevant scenarios of aneurysm onset. Method: This method integrates both fluid dynamics and structural mechanics, as well as their mutual interaction, for a comprehensive analysis. Patients with a single unruptured cerebral aneurysm were included. Results: Overall, three scenarios were identified. In scenario A, wall shear stress (WSS) was low, and the oscillatory shear index (OSI) was high in large areas within the region of aneurysm onset (RAO). In scenario B, the quantities indicated a reversed behavior, where WSS was high and OSI was low. In the last scenario C, a behavior in-between was found, with scenarios A and B coexisting simultaneously in the RAO. Structural mechanics demonstrated a similar but independent trend. Further, we analyzed the change in hemodynamics between the onset and a fully developed aneurysm. While scenarios A and C remained unchanged during aneurysm growth, 47% of aneurysms in scenario B changed into scenario A and 20% into scenario C. Conclusions: In conclusion, these findings suggest that WSS and the OSI are reciprocally regulated, and both low and high WSS/OSI conditions can lead to aneurysm onset.

Efficacy of pCONUS Devices in the Management of Intracranial Aneurysms: Outcomes of 190 Patients.

Intracranial aneurysms (IAs) pose a significant health concern, necessitating effective treatment modalities. The pCONUS device has emerged as a promising option for managing complex IAs, particularly wide-necked bifurcation aneurysms. Evaluating its efficacy across multiple studies is essential for establishing therapeutic guidelines.A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies assessing the efficacy of pCONUS devices in treating cerebral aneurysms. PubMed, Google Scholar, and Scopus were searched for relevant articles published from January 1, 2000, to December 31, 2021. Inclusion criteria encompassed clinical trials examining pCONUS device benefits for ruptured or unruptured cerebral aneurysms. Data extraction and quality assessment were performed independently by two reviewers.Out of 390 initially identified articles, eight studies met the inclusion criteria. These studies collectively involved 190 participants with intracranial aneurysms. The sample sizes ranged from seven to 40 patients, predominantly in retrospective designs. Complete occlusion rates varied from 46.8% to 100%, with a mean diameter of treated aneurysms ranging from 2.5 mm to 8.83 mm. This systematic review suggests that pCONUS devices are feasible and effective for treating complex bifurcation cerebral aneurysms, with acceptable complication rates. Despite limitations such as retrospective study designs and limited follow-up durations, the findings support the beneficial role of pCONUS devices in managing challenging intracranial aneurysms. Larger collaborative efforts with longer follow-up durations are warranted to validate these findings and establish wider therapeutic guidelines.

Letter to Editor, “Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Letter to Editor, “Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Association Between Intracranial Aneurysms and Genes

Ruptured intracranial aneurysm(IA) leads to aneurysmal subarachnoid hemorrhage(aSAH), which is the most severe type of stroke. Besides age, sex, and alcohol consumption, family history is considered an important risk factor. Approximately 5% of the Japanese population is affected by unruptured cerebral aneurysms. However, their developmental processes and pathologies remain unclear. Familial cerebral aneurysms account for 10% of all cerebral aneurysm cases, and somatic gene mutations are believed to be involved in their development. This review summarizes the recent findings from family-based, genome-wide association, sequencing, and somatic gene mutation studies on IA.

Trends in Hospitalization and Mortality Rates Associated with Subarachnoid Hemorrhage and Unruptured Cerebral Aneurysms in Brazil

PurposeSpontaneous subarachnoid haemorrhage (SAH) and unruptured intracranial aneurysm (UIA) epidemiology is valuable for determining neurosurgical and general healthcare effectiveness· There is an information gap regarding these conditions in middle- and low-income countries· Therefore, we aimed to investigate their hospitalisation and mortality rates in Brazil from 2011-2019· MethodsThis observational, population-based study used hospital admission and mortality data and included all SAH- and UIA-related public hospitalisations and deaths occurring from 2011-2019· Data were obtained from the Ministry of Health’s National Hospitalisation and Mortality Information Systems· Population data were obtained from the Brazilian Institute of Geography and Statistics· Simple linear regression models with normal responses were adjusted to explain the temporal evolution of variables· Joinpoint regression models were adjusted to detect moments of significant change in variable behaviour· Graduated choropleth maps were generated using georeferencing and geospatial analyses· ResultsThe annual SAH hospitalisation and mortality coefficients were 4·81 and 2·49/100,000 persons, respectively· The unruptured intracranial aneurysm hospitalisation and mortality coefficients were 1·21 and 0·24/100,000 persons, respectively· In addition to regional differences, we found a stable SAH hospitalisation trend and an increasing mortality rate of 0·062 cases/100,000 inhabitants annually· The UIA hospitalisation rate increased by 0·074 cases/100,000 inhabitants annually and mortality decreased by 0·07 deaths/100,000 inhabitants annually· ConclusionIn Brazil, the SAH hospitalisation trend is stable, while there is a worrisome increasing SAH-related mortality trend· A better scenario was observed for an UIA, with an increase in hospitalisations and decrease in mortality·

Adenosine-induced cardiac standstill in intracranial aneurysm surgery: A case report

Surgical clipping of complex intracranial aneurysms can pose intraoperative challenges due to difficulty in anatomic exposure and uncontrolled intraoperative rupture, leading to significant morbidities or mortalities. This report presents a case of a 61-year-old Asian male with an unruptured saccular basilar tip aneurysm and an unruptured right middle cerebral artery aneurysm. The patient underwent a left temporal craniotomy and clipping of an unruptured basilar tip aneurysm, successfully achieved through adenosine-induced cardiac standstill. This technique reduces perfusion pressure and decreases the turgor of the aneurysm, thereby facilitating clip ligation. Our experience demonstrated that thorough, careful patient selection, optimal anesthetic management, and proper communication between neurosurgeon and anesthesiologist are important for achieving successful surgical outcomes.

Preliminary Experience With Novel Straight 3-Fr Guiding Sheath for Transradial Access in Endovascular Treatment: Feasibility and Safety.

Radial artery diameter may limit whether a guiding sheath (GS) can be used via transradial artery access (TRA). A smaller GS may reduce the risk of access site-related complications. This study investigated the feasibility and safety of endovascular treatment (EVT) using a straight-shaped 3-Fr GS (Axcelguide; Medikit). Patients who underwent EVT with a straight-shaped 3-Fr GS at 3 institutions between April 2022 and March 2024 were retrospectively reviewed. Patient background, anatomic and procedural factors, and complications were recorded. Twenty-six pathologies were treated with EVT using a 3-Fr GS. Median radial artery diameter was 1.9 mm, and distal TRA (73.1%) was selected more often than TRA (26.9%) as the access site. The breakdown of target pathologies and the role of the 3-Fr GS were as follows: 12 unruptured cerebral aneurysms for intra-aneurysmal coiling, with 5 dural arteriovenous fistulas, 5 brain or head and neck tumors, 2 chronic subdural hematoma, 1 arteriovenous malformation, and 1 hereditary hemorrhagic telangiectasia for transarterial embolization. A success rate of 96.2% was achieved, with no access site- or non-access site-related complications observed within 30 days. The straight-shaped 3-Fr GS may be applicable for selected pathologies, allowing access even with RAs <2 mm in diameter and facilitating EVT without complications. Preliminary experience with the 3-Fr GS via TRA demonstrated excellent feasibility and safety.

Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Our study aimed to evaluate the postoperative outcome of patients with unruptured giant middle cerebral artery (MCA) aneurysm revealed by intracranial hypertension associated to midline brain shift. From 2012 to 2022, among the 954 patients treated by a microsurgical procedure for an intracranial aneurysm, our study included 9 consecutive patients with giant MCA aneurysm associated to intracranial hypertension with a midline brain shift. Deep hypothermic circulatory flow reduction (DHCFR) with vascular reconstruction was performed in 4 patients and cerebral revascularization with aneurysm trapping was the therapeutic strategy in 5 patients. Early (< 7 days) and long term clinical and radiological monitoring was done. Good functional outcome was considered as mRS score ≤ 2 at 3 months. The mean age at treatment was 44 yo (ranged from 17 to 70 yo). The mean maximal diameter of the aneurysm was 49 mm (ranged from 33 to 70 mm). The mean midline brain shift was 8.6 mm (ranged from 5 to 13 mm). Distal MCA territory hypoperfusion was noted in 6 patients. Diffuse postoperative cerebral edema occurred in the 9 patients with a mean delay of 59 h and conducted to a postoperative neurological deterioration in 7 of them. Postoperative death was noted in 3 patients. Among the 6 survivors, early postoperative decompressive hemicraniotomy was required in 4 patients. Good functional outcome was noted in 4 patients. Complete aneurysm occlusion was noted in each patient at last follow-up. We suggest to discuss a systematic decompressive hemicraniotomy at the end of the surgical procedure and/or a partial temporal lobe resection at its beginning to reduce the consequences of the edema reaction and to improve the postoperative outcome of this specific subgroup of patients. A better intraoperative assessment of the blood flow might also reduce the occurrence of the reperfusion syndrome.

Role of aneurysmal hemodynamic changes in pathogenesis of headaches associated with unruptured cerebral aneurysms.

One symptom commonly associated with the presence of unruptured intracranial aneurysms is headache. In this study, the authors aimed to analyze factors associated with headaches among patients with intracranial aneurysms, with special consideration of hemodynamic parameters. The authors prospectively included 96 patients with 122 unruptured intracranial aneurysms. The authors obtained detailed medical history including current diseases and medications, as well as blood pressure values taken during hospitalization from the patients' medical records. The short-form McGill Pain Questionnaire was administered to each patient at admission and 3-6 months after the procedure to assess type and severity of headache. Based on imaging data, the authors obtained 3D reconstruction of each patients' aneurysm dome with feeding artery. The authors performed computational fluid dynamics analysis of blood flow through prepared models using OpenFOAM. Blood was modeled as Newtonian fluid, using the incompressible transient solver. Patient-specific internal carotid artery (ICA) blood velocity waves obtained with Doppler ultrasound were set as inlet boundary conditions. After performing simulation, the authors calculated the hemodynamic parameters of the aneurysm dome. A total of 30 patients (31.25%) reported having headaches. In multivariate logistic regression analysis, female sex (OR 2.81, 95% CI 2.51-4.86; p < 0.01), ICA aneurysm location (OR 7.93, 95% CI 5.51-8.52; p < 0.01), multiple aneurysms (OR 6.05, 95% CI 1.83-11.83; p = 0.02), mean dome blood velocity (OR 3.10, 95% CI 2.01-3.30; p < 0.01) and time-averaged wall shear stress (OR 1.18, 95% CI 1.47-2.72; p = 0.04) were independently associated with the presence of headache. Additionally, 17 patients (56.67%) reported complete relief of symptoms after the procedure. In multivariate logistic regression analysis, the mean blood flow in the ICA was independently associated with complete resolution of headaches after aneurysm treatment (OR 2.32, 95% CI 1.57-3.28; p < 0.01). Hemodynamic parameters of intracranial aneurysms might be associated with headaches and their relief after aneurysm treatment.