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The clinical presentation is varied, ranging from asymptomatic lesions to those presenting with major rupture
Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.
Patients from a prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.
The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).
Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification 1).
Tobacco cigarette smoking is an independent risk factor for ruptured intracranial aneurysm, and the rupture risk in current smokers is 3× higher than that of nonsmokers 2).
A dose-response relationship has been noted for the intensity and duration of smoking consumption and increased risk of IAR. As smoking is modifiable, this finding is important to managing patients with IAs to quit or reduce smoking prior to life-threatening subarachnoid hemorrhage 3)
Current cigarette smoking, smoking intensity, and smoking duration are significantly associated with ruptured IAs at presentation. However, the significantly increased risk persists after smoking cessation, and smoking cessation does not confer a reduced risk of aneurysmal subarachnoid hemorrhage beyond that of reducing the cumulative dose 4).
Intravenous thrombolysis-treated stroke patients with unruptured intracranial aneurysms were more often current smokers and had higher systolic blood pressure than the matched patients without UIAs. They were as likely to have unfavorable outcomes at 3 months but seemed less likely to achieve excellent outcomes and were more likely to have higher mRS in shift analysis 5).
Until now, the exact etiology of intracranial aneurysms formation remains unclear.
Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysm rupture 1).
Miyata et al. proposed the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs 2).
Intracranial aneurysm risk factors.
Saccular intracranial aneurysm rupture leads to subarachnoid hemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the Saccular intracranial aneurysm wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in saccular intracranial aneurysm (sIAs) has remained unexplored. Huuska et al. studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for Lymphatic endothelial cells (LEC)markers. Of these LEC-markers, both extracellular and intracellular LYVE1, podoplanin, VEGFR-3, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and α-smooth muscle actin (αSMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and αSMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the saccular intracranial aneurysm pathogenesis 3).
see Intracranial aneurysm genetics.
see Intracranial aneurysm pathophysiology.
see Intracranial aneurysm hemodynamics.
In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage.
Data suggest that macrophage-derived Matrix metalloproteinase 2 and Matrix metalloproteinase 9, may play an important role in the progression of intracranial aneurysms. The findings will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease 4).
Investigations strongly suggest that the pathophysiology is closely associated with chronic inflammation in vascular walls. Nuclear factor kappaB (NF-kappaB) has a key role in the formation and progression.
Children with Sickle Cell Disease (SCD) are at risk for developing multiple intracranial aneurysms, and a high index of suspicion must be maintained during the interpretation of routine magnetic resonance imaging or angiography of the brain 5).
Dental bacterial DNA can be found using a quantitative polymerase chain reaction in both ruptured and unruptured aneurysm walls, suggesting that bacterial DNA plays a role in the pathogenesis of cerebral aneurysms in general, rather than only in ruptured aneurysms 6).
Thrombospondin type-1 domain-containing protein 1 is a protein that in humans is encoded by the THSD1 gene.
The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in thrombospondin, a number of proteins involved in the complement pathway, as well as extracellular matrix proteins. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
As illustrated by THSD1 research, cell adhesion may play a significant role in IA 7).
A study discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models 8).
A report identified THSD1 mutations in familial and sporadic IA patients and shows that THSD1 loss results in cerebral bleeding in 2 animal models. This finding provides new insight into IA and subarachnoid hemorrhage pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion 9).
Toll‑like receptor (TLR) 2/4 serves an important regulatory role in nerve tissue injury. However, the downstream and potential mechanisms remain to be elucidated. The present study was designed to investigate the roles of the TLR2/4‑major myeloid differentiation response gene 88 (MyD88)‑NF‑κB signaling pathway in the development of an intracranial aneurysm. The expression of TLR2, TLR4, and MyD88 in the blood of normal controls and patients with intracranial aneurysms were detected by quantitative PCR and ELISA. Human brain vascular smooth muscle cells were treated by Angiotensin II (Ang II) to evaluate the involvement of the TLR2/4‑MyD88‑NF‑κB signaling pathway in the process. The in vitro experiment was divided into four groups: The control group, an Ang Ⅱ group, an Ang Ⅱ + small interfering (si)RNA control group, and an Ang Ⅱ + TLR2‑group. Cell viability, migration, apoptosis, and expression of TLR2, TLR4, MyD88, NF‑κB, and phosphorylated (p‑)p65 expression was detected. The results demonstrated that the expression of TLR2, TLR4, MyD88, and NF‑κB at mRNA and protein levels in patients with an intracranial aneurysm was significantly higher compared with corresponding protein in normal controls (P<0.05). <em>In vitro</em> experiments demonstrated that Ang Ⅱ treatment increased the cell proliferation and migration rate but reduced the apoptotic rate compared with the control (P<0.05). The expression of TLR2, TLR4, MyD88, NF‑κB, and p‑p65 was significantly increased in the Ang II group (vs. control; P<0.05). By contrast, TLR2‑short interfering RNA reduced the cell proliferation and migration rate and reduced the expression of TLR2, TLR4, MyD88, NF‑κB, and p‑p65 (vs. Ang Ⅱ + short interfering RNA control; P<0.05). In conclusion, the data of the present study indicated that the TLR2/4‑MyD88‑NF‑κB signaling pathway is involved in the intracranial aneurysm pathogenesis 10).
Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the intracranial aneurysm pathogenesis (IA). Circular RNAs (circRNAs) have been implicated by reducing microRNA (miRNA) activity. Qin et al. investigated the precise roles of circRNA ADP ribosylation factor interacting protein 2 (circ-ARFIP2, circ_0021001) in VSMC dysfunction. The levels of circ-ARFIP2, miR-338-3p and kinase insert domain receptor (KDR) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease (RNase) R and subcellular fractionation assays were used to assess the stability and localization of circ-ARFIP2, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell invasion was measured by transwell assay. Cell proliferation was gauged by 5-Ethynyl-2′-Deoxyuridine (EdU) assay. Cell migration was evaluated by transwell and wound-healing assays. Targeted correlations among circ-ARFIP2, miR-338-3p and KDR were validated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ-ARFIP2 and KDR were underexpressed and miR-338-3p was overexpressed in the arterial wall tissues of IA patients. Overexpression of circ-ARFIP2 in human umbilical artery smooth muscle cells (HUASMCs) showed a significant promotion in cell proliferation, migration and invasion. Mechanistically, circ-ARFIP2 targeted miR-338-3p, and circ-ARFIP2 regulated cell behaviors by miR-338-3p. KDR was a direct and functional target of miR-338-3p. Moreover, KDR was a downstream effector of circ-ARFIP2 function. Circ-ARFIP2 regulated KDR expression by targeting miR-338-3p.The findings demonstrated that the increased level of circ-ARFIP2 enhanced HUASMC proliferation, migration and invasion at least in part by the miR-338-3p/KDR axis 11).
Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-β, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3- subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation 12).
Intraprocedural aneurysm rupture and thrombus formation are serious complications during coiling of ruptured intracranial aneurysms, and they more often occur in patients with anterior communicating artery aneurysms.
It is associated with a high rate of complete angiographic occlusion. However, the procedure-related permanent morbidity and mortality are not negligible for aneurysms in this location 1).
Delgado Acosta et al. from Hospital Universitario Reina Sofía aimed to report the characteristics of patients suffering intra- or peri-procedural ruptures during embolization of cerebral aneurysms.
Between March 1994 and October 2021, 648 consecutive cerebral aneurysms were treated by the endovascular procedure. Medical records were reviewed retrospectively with emphasis on procedure description, potential risk factors, and clinical outcomes related to intra- or peri-procedural rupture.
Of the 648 patients, 17 (2.6%) suffered an intra- or peri-procedural hemorrhagic event. The most common location was the anterior communicating artery. There was no significant difference between previously ruptured and unruptured aneurysms in the incidence of bleeding. In four patients, bleeding was evident within 24 h after the procedure. The clinical evolution at three months was poor and only four patients presented a positive evolution. There were 11 deaths (64.71%). Balloon remodeling was associated with an increased frequency of ruptures, while stenting was a safer treatment.
Aneurysm rupture during endovascular therapy is unpredictable, and its occurrence can be devastating. The incidence is quite low although the outcome is frequently poor. Early detection and proper management, including prompt occlusion of the aneurysm, are important to achieve a positive outcome. Anterior communicating artery aneurysms and those treated with balloon catheters have a higher incidence of rupture. A small number of ruptures of uncertain origin occur that go unnoticed in digital subtraction angiograms 2).
The immediate and long-term outcomes, complications, recurrences and the need for retreatment were analyzed in a series of 280 consecutive patients with anterior communicating artery aneurysms treated with the endovascular technique. From October 1992 to October 2001 280 patients with 282 anterior communicating artery aneurysms were addressed to our center. For the analysis, the population was divided into two major groups: group 1, comprising 239 (85%) patients with ruptured aneurysms and group 2 comprising of 42 (15%) patients with unruptured aneurysms. In group 1, 185 (77.4%) patients had a good initial pre-treatment Hunt and Hess grade of I-III. Aneurysm size was divided into three categories according to the larger diameter: less than 4 mm, between 4 and 10 mm and larger than 10 mm. The sizes of aneurysms in groups 1 and 2 were identical but a less favorable neck to depth ratio of 0.5 was more frequent in group 2. Endovascular treatment was finally performed in 234 patients in group 1 and 34 patients in group 2. Complete obliteration was more frequently obtained in group 2 unlike a residual neck or opacification of the sac that were more frequently seen in group 1. No peri-treatment complications were recorded in group 2. In group 1 the peri-treatment mortality and overall peri-treatment morbidity were 5.1% and 8.1% respectively. Eight patients (3.4%) in group 1 presented early post treatment rebleeding with a mortality of 88%. The mean time to follow-up was 3.09 years. In group 1, 51 (21.7%) recurrences occurred of which 14 were minor and 37 major. In group 2, eight (23.5%) recurrences occurred, five minor and three major. Two patients (0.8%) presented late rebleeding in group 1. Twenty-seven second endovascular retreatments were performed, 24 (10.2%) in group 1 and three (8.8%) in group 2, seven third endovascular retreatments and two surgical clippings in group 1 only. There was no additional morbidity related to retreatments. Endovascular treatment is an effective method for the treatment of anterior communicating artery aneurysms allowing late rebleeding prevention. Peri-treatment rebleeding warrants caution in anticoagulation management. This is a single center experience and the follow-up period is limited. Patients should be followed-up in the long-term as recurrences may occur and warrant additional treatment 3).
Prolonged anterograde amnesia and disorientation after anterior communicating artery aneurysm coil embolization 4)
LVIS stent-assisted coiling for ruptured wide-necked ACoA aneurysms was safe and effective, with a relatively low rate of perioperative complications and a high rate of complete occlusion at follow-up 5)
Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages 1) 2) 3).
A dose-response relationship has been noted between intensity and duration of smoking consumption and increased risk of intracranial aneurysm rupture. As smoking is modifiable, this finding is important to managing patients with IAs to quit or reduce smoking prior to life-threatening subarachnoid hemorrhage 4).
Current cigarette smoking, smoking intensity, and smoking duration are significantly associated with ruptured IAs at presentation. However, the significantly increased risk persists after smoking cessation, and smoking cessation does not confer a reduced risk of aneurysmal subarachnoid hemorrhage beyond that of reducing the cumulative dose 5)
Data suggest that smoking, independent of hypertension, plays a critical role in aneurysm development, especially in younger patients, but that physiological mechanism exists for the repair of the damage induced by this toxic insult if cessation is possible 6)
Results suggest that high cotinine levels in smokers with brain aneurysms are significantly associated with high rupture risk, independently of smoker status, age, and sex 7)
The prevalence of smoking in patients who have suffered from SAH is higher than that in general adult population 8) 9).
Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling.
To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, Brinjikji et al. studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling.
All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed.
In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61-1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31-1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46-1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21-0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33-1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60-1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23-1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46-1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers.
The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors’ institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking 10).
Tobacco use were not significantly associated with poor outcome after aneurysmal subarachnoid hemorrhage 11).
Previously established risk factors such as hypertension and smoking were identified as the most prevalent comorbidities, with disparity between subgroups, particularly women and African Americans 12).
The duration and timing of tobacco use, rather than the dose of tobacco per se, seem to be risk factors for delayed neurological deterioration after aneurysmal subarachnoid hemorrhage (aSAH). Although Krishnamurthy et al. did not find an association between tobacco use and overall clinical outcome after aneurysmal SAH, these results suggest that the distribution of various patterns of tobacco use within a given data set may influence the overall result 13).
Only 8 studies have investigated the incidence and epidemiology of aneurysmal subarachnoid hemorrhage (aSAH) in the United States. This is the first investigation in Indiana, which has some of the highest rates of tobacco smoking and obesity in the nation. The authors prospectively identified 441 consecutive patients with aSAH from 2005 to 2010 at 2 hospitals where the majority of cases are treated. Incidence calculations were based on US Census populations. Epidemiologic variables included demography; risk factors; Hunt and Hess scale; Fisher grade; number, location, and size of aneurysms; treatment type; and complications. Overall incidence was 21.8 per 100,000 population. Incidence was higher in women, increased with age, and did not vary by race. One third to half of patients were hypertensive and/or smoked cigarettes at the time of ictus. Variations by count were partially explained by Health Factor and Morbidity Rankings. Complications varied by treatment. These findings deviate from estimates that 6-16 per 100,000 people in the United States will develop aSAH and are double the incidence in a Minnesota population between 1945 and 1974. The results also deviate from the worldwide estimate of 9.0 aSAHs per 100,000 person-years. The predictive value of variations in Health Factor and Morbidity Rankings implicates the importance of future research on multivariate biopsychosocial causation of aSAH 14).
Observational evidence identified multiple clinical and anatomic risk factors for the formation of de novo IAs, including female sex, age <40 yr, family history, smoking history, multiple intracranial aneurysms at first diagnosis, and IC as the initial site. More aggressive long-term angiographic follow-up with digital subtraction angiography, computed tomography angiography, or magnetic resonance angiography is recommended for these patients 1).
Genetically determined HDL-C and LDL-C reduce the risk of intracranial aneurysm and ruptured intracranial aneurysm. The effects of different lipid-modifying drugs on IA need to be further investigated 2).
Although some previous reports have demonstrated an association between lipid accumulation and degenerative changes in aneurysm walls in humans, epidemiological studies have failed to identify dyslipidemia as a risk factor for intracranial aneurysm pathogenesis. Thus, Shimizu et al. examined whether an increase in serum cholesterol levels facilitates the progression of intracranial aneurysms in a rat model. Rats were given a high-fat diet (HFD) and subjected to an intracranial aneurysm model. The HFD elevated their serum cholesterol levels. The intracranial aneurysms induced at the anterior cerebral artery-olfactory artery bifurcation were significantly larger in the high-fat group than in the normal-chow group. Histological analysis demonstrated that the loss of medial smooth muscle layers was exacerbated in the high-fat group and indicated the presence of macrophage-derived foam cells in the lesions. In in vitro experiments, the expression levels of the pro-inflammatory genes induced by LPS in RAW264.7-derived foam cells were significantly higher than those in RAW264.7 cells. The combination of these results suggests that increased serum cholesterol levels facilitate degenerative changes in the media and the progression of intracranial aneurysms presumably through foam cell transformation 3).
Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.
METHODS: Patients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.
RESULTS: The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).
CONCLUSIONS: Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification 4).
Intracranial aneurysms after radiotherapy (RT) have previously been reported. However, the majority of studies were case reports. Therefore, we performed a nationwide study to explore the risk of radiation-induced intracranial aneurysms.
METHODS: This study included patients diagnosed with head and neck cancer (ICD9: 140-149, 161). Intracranial aneurysms formation was identified using the following ICD9 codes: nonruptured cerebral aneurysm (ICD9:4373), aneurysm clipping (ICD9:3951). Patients who did not receive curative treatment and those with intracranial aneurysms before the diagnosis of head and neck cancer were excluded.
RESULTS: In total, 70,691 patients were included in the final analysis; they were categorized into the following three groups: nasopharyngeal carcinoma (NPC) with RT, non-NPC with RT, and non-NPC without RT. Patients in the NPC with RT group had the highest risk of developing intracranial aneurysms (hazard ratio (HR) 2.57; P < 0.001). In addition, hypertension was also a risk factor of developing intracranial aneurysms (HR 2.14; P < 0.01). The mean time interval from cancer diagnosis to intracranial aneurysm formation in the NPC with RT group was 4.3 ± 3.1 years.
CONCLUSIONS: Compared with the non-NPC with RT and the non-NPC without RT groups, patients with NPC who received RT had a higher risk of developing intracranial aneurysms 5).
Middle cerebral artery aneurysms, are mainly found in the proximal and bifurcation tracts and only in the 1.1-1.7% of cases they are located in the M4 segment of the middle cerebral artery 1) 2) 3).
Generally, these aneurysms are secondary to traumatic brain injury and inflammatory or infectious diseases and only rarely they have idiopathic origin 4).
At present, only nine cases of ruptured cortical middle cerebral artery aneurysms have been described in literature 5) 6) 7) 8) 9) 10).
The patients are all males, except the case of Ricci et al. 11). The average age of the reported patients is 40 years. The size of the aneurysms is between 1 mm and 10 mm and, in most cases, they are saccular intracranial aneurysms or fusiform morphology. In five patients, the aneurysms present infectious etiology. Usually, they occur with ICH, sometimes associated with subarachnoid hemorrhage (SAH).
The endovascular treatment (EVT) has been performed in four cases, while the surgical treatment has been performed in three cases (two of trapping and one of clipping). In one patient, the infectious aneurysm has resolved spontaneously after antibiotic therapy. In all treatments performed, the patients have improved the neurologic symptoms and no residual aneurysms have been observed in the subsequent neuroradiology follow-up 12). Although surgery remains the main choice in the M4 aneurysms, because of the extremely distal location of them over the motor/somatosensory cortices, 13) Lv et al. 14) propose the use of the EVT in all types of the M4 aneurysms, especially after the surgery, when it is impossible to locate the small ruptured aneurysm.
The main difficulty of the surgery is the precise surgical localization of the small M4 aneurysms 15). An inaccurate localization of these vascular lesions may result in larger craniotomies and unnecessary arachnoid and pial dissections with possible resultant permanent neurological injuries 16).
In cases of aneurysms or arteriovenous malformations located at the sylvian point or at the posterior superior aspect of the insula, especially in dominant hemisphere, to reduce the dissection and open easily sylvian fissure, a logical path would follow the angular artery in the sylvian fissure cutting the arachnoid fibers and retracting only the tissues which are necessary to gain more exposure of the lesion 17).
A case of a ruptured dissecting pseudoaneurysm in the distal Middle cerebral artery (distal M3/proximal M4) prefrontal division in an healthy young patient (<60 years) successfully treated with a Pipeline Embolization Device. The PED was chosen both as the only vessel sparing option in the young patient as well as for its potential as a vessel sacrifice tool if the pseudoaneurysm was felt to be incompletely treated, which in this case was not necessary-though would have leveraged the thrombogenicity of the device as a therapeutic advantage 18).
A 53-year-old female was admitted with a sudden severe headache, nausea, vomiting, and a slight left hemiparesis. The computed tomography (CT) scan showed subarachnoid hemorrhage (SAH) in the left sylvian fissure and intracerebral hemorrhage (ICH) in the left posterior parietal area. The CT angiography (CTA) reconstructed with 3D imaging showed a small saccular aneurysm in the M4 segment in proximity of the angular area. A left parieto-temporal craniotomy was performed, the aneurysm was clipped and the ICH evacuated. The motor deficit was progressively recovered. At 3-month follow-up examination, the patient was asymptomatic and feeling well.
Surgery is the best choice for the treatment of ruptured M4 aneurysms with ICH in the opinion of Ricci et al., because it allows to evacuate the hematoma and to exclude the aneurysm from the intracranial circulation. In addition, we suggest both the use of the neuronavigation technique and of the indocyanine green videoangiography (ICGV) for the aneurismal surgery 19).
A 41-year-old man presented with an infarction manifesting as left-sided weakness and dysarthria. Magnetic resonance angiography revealed a subacute stage infarction in the right MCA territory and complete occlusion of the right ICA. Angiography demonstrated aneurysmal dilatation of the M4 segment of the right MCA. Surgery was performed to prevent hemorrhage from the aneurysm. The aneurysm was proximally clipped guided by Navigation-CT angiography and flow to the distal MCA was restored by superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis 20).
A 20-year-old man with an intracerebral haemorrhage due to a ruptured aneurysm, which arose from a penetrating artery of the distal middle cerebral artery (MCA; M4 segment). Excision of the aneurysm was successfully achieved via a right pterional approach. The follow-up angiogram demonstrated filling of the parent vessel and no residual aneurysm. This report illustrates the angiographical finding of a penetrating artery aneurysm of the distal MCA and summarizes the previous reports to discuss their pathological and clinical characteristics 21).
see also PHASES score.
The unruptured intracranial aneurysm treatment score (UIATS) was published in April 2015 as a multidisciplinary consensus regarding the treatment of unruptured intracranial aneurysms (UIA).
Etminan et al. endeavored to develop an unruptured intracranial aneurysm treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in Unruptured intracranial aneurysm (UIA) management and research.
An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39-panel members involved in the identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr) (vr = 0 indicating excellent agreement and vr* = 1 indicating poor agreement).
The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033).
This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA 1) 
The Unruptured Intracranial Aneurysm Treatment Score (UIATS) offers support for clinical decision making and has been shown to correlate with real-life decisions in clinical practice. However, there is no data concerning the correlation of patient Unruptured intracranial aneurysm outcome and UIATS. Patients presenting to the Department of Neurosurgery,University Hospital Leipzig, outpatient clinic between January 1st, 2014, and December 31st, 2017 were retrospectively analyzed. They recorded the Extended Glasgow Outcome Scale (GOS-E) for the longest possible follow-up, the choice of treatment, complications, and UIATS recommendation. They included 221 patients with 322 UIA. 124 (38.5 %) UIA were observed and 198 (61.5 %) were occluded, of which 62 (31.3 %) underwent open surgery and 136 (68.7 %) were treated endovascularly. Spearman’s rank correlation between the treatment choice and conclusive UIATS recommendation was 0.362 (p < 0.001). If UIATS was inconclusive, there were significantly more treatment-associated deteriorations (10/66 versus 7/132, p = 0.020). Otherwise, UIATS was not significantly associated with outcome. Therefore, the treatment choice for UIA remains an individual decision. However, inconclusive UIATS must trigger vigilance and may be a negative prognostic marker for complications 2).
A tertiary center with focus on vascular neurosurgery, aimed to investigate whether there treatment decision-making in patients with UIA has been in accordance with the published UIATS. A retrospective analysis of patients admitted to the center with UIA was performed. UIATS was applied to all identified UIA. Three decision groups were defined: (a) UIATS favoring treatment, (b) UIATS favoring observation, and © UIATS inconclusive. These results were then compared to our clinical decisions. Spearman’s rank-order correlation (ρ) was run to determine the relationship between the UIATS and our clinical decisions. Cases of discrepancies between UIATS and our clinical decisions were then examined for complications, defined as periprocedural adverse events in treated aneurysms, or aneurysm rupture in untreated aneurysms. Ninety-three patients with 147 UIA were included. A total of 118/147 (80.3%) UIA were treated. In 70/118 (59.3%), UIATS favored treatment, in 18/118 (15.3%), it was inconclusive, and in 30/118 (25.4%), it favored observation. A total of 29/147 (19.7%) UIA were not treated. In 15/29 (51.7%), UIATS favored observation, in 9/29 (31%), it favored treatment, and in 5/29 (17.2%), it was inconclusive (ρ = 0.366, p < 0.01). Discrepancies between UIATS and our clinical decisions did not correlate with complications (ρ = 0.034, p = 0.714). Our analysis shows that our more intuitive clinical decision-making has been in line with UIATS. Our treatment decisions did not correlate with an increased rate of complications 3).
The purpose of the study of Ravindra et al. was to compare the unruptured intracranial aneurysm treatment score (UIATS) recommendations with the real-world experience in a quaternary academic medical center with a high volume of patients with unruptured intracranial aneurysms (UIAs).
All patients with UIAs evaluated during a 3-year period were included. All factors included in the UIATS were abstracted, and patients were scored using the UIATS. Patients were categorized in a contingency table assessing UIATS recommendation versus real-world treatment decision. The authors calculated the percentage of misclassification, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. RESULTS A total of 221 consecutive patients with UIAs met the inclusion criteria: 69 (31%) patients underwent treatment and 152 (69%) did not. Fifty-nine (27%) patients had a UIATS between -2 and 2, which does not offer a treatment recommendation, leaving 162 (73%) patients with a UIATS treatment recommendation. The UIATS was significantly associated with treatment (p < 0.001); however, the sensitivity, specificity, and percentage of misclassification were 49%, 80%, and 28%, respectively. Notably, 51% of patients for whom treatment would be recommended by the UIATS did not undergo treatment in the real-world cohort and 20% of patients for whom conservative management would be recommended by UIATS had intervention. The area under the ROC curve was 0.646.
Compared with the authors’ experience, the UIATS recommended overtreatment of UIAs. Although the UIATS could be used as a screening tool, individualized treatment recommendations based on consultation with a cerebrovascular specialist are necessary. Further validation with longitudinal data on rupture rates of UIAs is needed before widespread use 4).
Although the research on the risk factors of anterior communicating artery aneurysm has made great progress, the independent effect of each risk factor on the rupture of AComA aneurysm is controversial among different studies. For this answer Xie et al. will present the results employing the random effects model. Quality assessment of the included studies will be evaluated using the Newcastle–Ottawa Scale. Statistical analyses will be performed using Stata16 (Stata Corporation, College Station, TX, USA) software.The findings of this study will be submitted to peer-reviewed journals for publication. This systematic review will provide evidence to determine the risk factors that affect the rupture of the AComA aneurysm and quantify their independent effects 1).
Ma et al. found that larger size, greater size ratio, larger flow angle, irregular shape, and smoking of the patient were associated with the rupture of ACoA aneurysms based on univariate analysis. Size ratio (OR = 3.890, P = 0.003), irregular shape (OR = 1.068, P = 0.001), flow angle (OR = 1.054, P = 0.001), and current smoking (OR = 4.435, P = 0.009) were the strongest factors related to ruptured ACoA aneurysms based on multivariate logistic regression analysis. The areas under the curves for the flow angle and size ratio were 0.742 (95% CI 0.646-0.838; P = 0.001) and 0.736 (95% CI 0.621-0.796; P = 0.001), respectively. The strongest risk factors for rupture include size ratio, irregular shape, flow angle, and current smoking. These features should be taken into consideration to aid in the prediction of the rupture risk of ACoA aneurysms 2).
Multiple logistic regression model revealed that A1 dominance [odds ratio (OR) 3.034], an irregular shape (OR 3.358), and an aspect ratio ≥1.19 (AR; OR 3.163) increased the risk of rupture, while cerebral atherosclerosis (OR 0.080), and mean diameters ≥2.48 mm (OR 0.474) were negatively correlated with ACoAA rupture. Incorporating these five factors, the ROC analysis revealed that the threshold value of the multifactors was one, the sensitivity was 88.3%, and the specificity was 66.0%. The scoring model is a simple method that is based on A1 dominance, irregular shape, aspect ratio, cerebral atherosclerosis, and mean diameters from CTA and is of great value in the prediction of the rupture risk of ACoAAs 3).
According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. Bijlenga et al. found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Intervention should be recommended for this high-risk lesion group 4).
For Matsukawa et al. the anterior projection of an ACoA aneurysm may be related to rupturing. The authors would perhaps recommend treatment to patients with unruptured ACoA aneurysms that have an anterior dome projection, a bleb(s), and a size ≥ 5 mm 5).
Aneurysms found unruptured in the ACoA show a risk of rupture twice as high as that of other intracranial aneurysms (95% confidence interval, 1.29-3.12). It is the first time this fact has been demonstrated based on the follow-up of unruptured aneurysms.
When deciding whether to operate on UIAs located in the ACoA, surgeons should consider their higher risk of rupture 6).
Evolution in the surgical treatment of intracranial aneurysms is driven by the need to refine and innovate. From an early application of the Hunterian carotid ligation to modern-day sophisticated aneurysm clip designs, progress was made through dedication and technical maturation of the cerebrovascular neurosurgeons to overcome challenges in their practices. The global expansion of endovascular services has challenged the existence of aneurysm surgery, changing the complexity of aneurysm case mix and volume that are presently referred for surgical repair. Concepts of how to best treat intracranial aneurysms have evolved over generations, and will continue to do so with further technological innovations. As with the evolution of any type of surgery, innovations frequently arise from the criticism of currently available techniques 1).
Intracranial Aneurysm treatment with surgery remains the recommended form of treatment in high-grade SAH patients with intracerebral space occupying hematomas, where the surgical decompression of the mass effect may be warranted, and along with it the clipping of the bleeding aneurysm.
Less invasive surgical approaches for intracranial aneurysm clipping may reduce length of hospital stay, surgical morbidity, treatment cost, and improve patient outcomes.
In the US, a number of training programs are including endovascular exposure to residents during their training, assuming the endovascular suite as a regular OR room.
The training of surgeons in both techniques seems promising and the right way to go, regardless of whether a dually trained neurosurgeon will end up opting for the use of one technique over the other. The important is that we guarantee the ability to deliver our patients the best possible care by providing them with a choice that is not born out of a turf war but based on evidence both on a general, but similarly important, local one 2).
Time from rupture to treatment is a crucial factor in determining outcome.
Practice of delayed surgery to avoid edematous brain has been replaced by early surgery to minimize risk from rebleeding and vasospasm. Mahaney et al. in their analysis of intraoperative hypothermia for aneurysm surgery trial (IHAST) data observed that patients operated early (day 0-2) or late (day 7-14) fared significantly better than those operated during intermediate phase (day 3-6). Change in surgical strategy has posed challenge to the anesthesiologists as increasing number of patients are operated during off-work hours in inadequately optimized state with less expert help.
Nieuwkamp et al., performed a retrospective observational study on the timing of intracranial aneurysm surgery in The Netherlands over a two-year period.
In eight hospitals they identified 1,500 patients with an aneurysmal subarachnoid hemorrhage. They were subjected to predefined inclusion criteria. They included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage.
They included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT
Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition.
In this observational study they found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling 3).
The guidelines relevant to the anesthesiologists in the day-to-day perioperative management of patients with ruptured intracranial aneurysm given by various societies are:
Diringer MN, Bleck TP, Claude Hemphill J, 3rd, Menon D, Shutter L, Vespa P, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.
Bederson JB, Connolly ES, Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40:994–1025.
Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G, et al. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35:93–112.
Both intravenous and inhalational anesthetic technique may be used for maintenance keeping in mind the objectives of stable intraoperative hemodynamics, early smooth recovery and effect on special monitoring techniques. Cerebral perfusion increases with isoflurane when compared with propofol without increase in ICP in aSAH.
Hypocapnia is not essential in good grade patients as it can reduce ICP and increase transmural pressure within aneurysmal sac predisposing it to rupture. In poor grade patients, hyperventilation however is beneficial to reduce ICP and provide lax brain.
Brain laxity is crucial to obtain good surgical access to the aneurysm without causing IOAR or compromising underlying brain from excessive retractor pressure. This is important as early surgery risks a tense/full brain and dissection without adequate exposure can result in IOAR. Both 20% mannitol and 3% hypertonic saline are suitable osmotic agents for intraoperative brain relaxation in the dose of 2-4 ml/kg. Head end elevation, avoiding jugular venous compression, avoiding high concentration of inhalational agents and nitrous-oxide and mild hyperventilation are other measures to achieve a lax brain. If full brain persists, additional measures like moderate hyperventilation, switching to intravenous anesthetic maintenance and release of cerebrospinal fluid might be helpful. 4).
Intracranial aneurysm surgery by clipping requires meticulous technique and is usually performed through open approaches. Endoscopic endonasal clipping of intracranial aneurysms may use the same techniques through an alternative corridor.
To enhance visual confirmation of regional anatomy, endoscopy was introduced.
see Endoscopic endonasal approach for intracranial aneurysm
see Surgical clipping versus endovascular coiling for intracranial aneurysm
Clipping is an important technique for intracranial aneurysm surgery. Although clip mechanisms and features have been refined, little attention has been paid to clip appliers. Clip closure is traditionally achieved by opening the grip of the clip applier. Sato et al.. reconsidered this motion and identified an important drawback, namely that the standard applier holding power decreased at the moment of clip release, which could lead to unstable clip application develop a forceps to address this clip applier design flaw.The new clip applier has a non–cross-type fulcrum that is closed at the time of clip release, with an action similar to that of a bipolar forceps or scissors. Thus, a surgeon can steadily apply the clip from various angles. They successfully used the clip applier to treat 103 aneurysms. Although training was required to ensure smooth applier use, no difficulties associated with applier use were noted. This clip applier can improve clipping surgery safety because it offers additional stability during clip release. 5).
Pterional approach via standard frontotemporal craniotomy and interhemispheric approach via bifrontal craniotomy is the gold standard for clipping of cerebral aneurysms in the anterior circulation. Endovascular treatment is now widely used, but subsets of aneurysms are still indicated for surgical clipping. Modern technological advances allow less invasive clipping techniques such as the keyhole approach. Mori and Watanabe discussed the surgical indications, preoperative simulation, surgical techniques, and pros and cons of keyhole (supraorbital) clipping. Selection of standard craniotomy or keyhole craniotomy should be uncontroversial, but keyhole clipping requires definite surgical indications based on the characteristics of the target aneurysm for safe clipping 6).
see Intracranial aneurysm clipping complications.
A challenge is to ensure noninclusion of normal vessel/perforators within the clip and perform complete aneurysmal isolation. This is done with either intraoperative microvascular Doppler sonography (IMD) or Indocyanine green videoangiography (ICG-VA) as they are simple and safe. Anesthesiologists administer ICG and also help perform IMD. ICG-VA appropriately assessed vessel patency and aneurysm obliteration in 93.5% of 109 aneurysms clipped 7) However, ICG can cause transient oxygen desaturation 8). IMD use confirms aneurysm isolation and patency of parent vessel and branching arteries. Hui et al. observed that clip repositioning was required based on IMD findings in 24% of aneurysms clipped in 91 patients and concluded that IMD could reduce the rate of residual aneurysm and unanticipated vessel stenosis 9).
The complete clipping of a cerebral aneurysm usually warrants its sustained occlusion, while clip remnants may have far-reaching consequences. The aim of this study is to identify the risk factors for clip remnants requiring retreatment and/or exhibiting growth. METHODS All consecutive patients with primary aneurysm clipping performed at University Hospital of Essen between January 1, 2003, and December 31, 2013, were eligible for this study. Aneurysm occlusion was judged on obligatory postoperative digital subtraction angiography and the need for repeated vascular control. The identified clip remnants were correlated with various demographic and clinical characteristics of the patients, aneurysm features, and surgery-related aspects. RESULTS Of 616 primarily clipped aneurysms, postoperative angiography revealed 112 aneurysms (18%) with clip remnants requiring further control (n = 91) or direct retreatment (n = 21). Seven remnants exhibited growth during follow-up, whereas 2 cases were associated with aneurysmal bleeding. Therefore, a total of 28 aneurysms (4.5%) were retreated as clip remnants (range 1 day to 67 months after clipping). In the multivariate analysis, the need for retreatment of clip remnant was correlated with the aneurysm’s initial size (> 12 mm; OR 3.22; p = 0.035) and location (anterior cerebral artery > internal carotid artery > posterior circulation > middle cerebral artery; OR 1.85; p = 0.003). Younger age with a cutoff at 45 years (OR 33.31; p = 0.004) was the only independent predictor for remnant growth. CONCLUSIONS The size and location of the aneurysm are the main risk factors for clip remnants requiring retreatment. Because of the risk for growth, younger individuals (< 45 years old) with clip remnants require a long-term (> 5 years) vascular follow-up. Clinical trial registration no: DRKS00008749 (Deutsches Register Klinischer Studien) 10).
Total index hospitalization costs for clipping are lower than for coiling. Costs of clipping and coiling are driven by different clinical variables. The cost of coils and devices is the predominant contributor to the higher total costs of coiling 11).
The mechanisms underlying neurocognitive changes after surgical clipping of unruptured intracranial aneurysms (UIAs) are poorly understood.
Minimal structural damage visualized on T2-weighted images at 6 months as a result of factors such as pial/microvascular injury and excessive retraction during surgical manipulation could cause subtle but significant negative effects on postoperative neurocognitive function after surgical clipping of a UIA. However, this detrimental effect was small, and based on the group-rate analysis
Successful and meticulous surgical clipping of a UIA does not adversely affect postoperative cognitive function 12).
Results of treatment after clipping and coiling do not differ in total for all patients, but differ depending on the presence of bleeding. Patients with bleeding aneurysms achieve better outcomes after coiling, and patients with non-bleeding aneurysms achieve better outcomes after clipping 13).
Risk of ischemia during intracranial aneurysm surgery is significantly related to temporary clipping time and final clipping that might incorporate a perforator.
Abdulrauf et al. attempted to assess the potential added benefit to patient outcomes of “awake” neurological testing when compared with standard neurophysiological testing performed under general anesthesia. The procedure is performed after the induction of conscious sedation, and for the neurological testing, the patient is fully awake.
They conducted an institutional review board-approved prospective study of clipping unruptured intracranial aneurysms (UIAs) in 30 consecutive adult patients who underwent awake clipping. The end points were the incidence of stroke/cerebrovascular accident (CVA), death, discharge to a long-term facility, length of stay, and 30-day modified Rankin Scale score. All clinical and neurophysiological intraoperative monitoring data were recorded.
The median patient age was 52 years (range 27-63 years); 19 (63%) female and 11 (37%) male patients were included. Twenty-seven (90%) aneurysms were anterior, and 3 (10%) were posterior circulation aneurysms. Five (17%) had been coiled previously, 3 (10%) had been clipped previously, 2 (7%) were partially calcified, and 2 (7%) were fusiform aneurysms. Three patients developed synchronous clinical neurological and neurophysiological changes during temporary clipping with consequent removal of the temporary clip and reversal of those clinical and neurophysiological changes. Three patients developed asynchronous clinical neurological and neurophysiological changes. These 3 patients developed hemiparesis without changes in neurophysiological monitoring results. One patient developed linked clinical neurological and neurophysiological changes during final clipping that were not reversed by reapplication of the clip, and the patient had a CVA. Four patients with internal carotid artery ophthalmic segment aneurysms underwent visual testing with final clipping, and 1 of these patients required repositioning of the clip. Three patients who required permanent occlusion of a vessel as part of their aneurysm treatment underwent a 10-minute intraoperative clinical respective-vessel test occlusion. The median length of stay was 3 days (range 1-5 days). The median modified Rankin Scale score was 1 (range 0-3). All of the patients were discharged to home from the hospital except for 1 who developed a CVA and was discharged to a rehabilitation facility. There were no deaths in this series.
The 3 patients who developed neurological deterioration without a concomitant neurophysiological finding during temporary clipping revealed a potential advantage of awake aneurysm surgery (i.e., in decreasing the risk of ischemic injury) 14).
see Virtual reality simulator for aneurysmal clipping surgery.
A total of 53 patients from Phoenix and San Francisco, who initially presented with a subarachnoid hemorrhage and underwent surgical clipping of a previously coiled intracranial aneurysm between December 1997 and December 2014 were studied. Clinical features, hospital course, and preoperative and most recent functional status (Glasgow Outcome Scale score) were reviewed retrospectively.
The mean time interval from coiling to clipping was 2.6 years, and mean follow-up was 5.5 years (range, 0.1-14.7 years). Five patients (9.8%) presented with rebleed prior to clipping. Most patients (79.3%, 42/53) experienced good neurologic outcomes. Most showed no change (81%, 43/53) or improvement (13%, 7/53) in functional status after microsurgical clipping. One patient (2%) deteriorated clinically, and there were 2 mortalities (4%).
Microsurgical clipping of previously ruptured, coiled aneurysms is a promising treatment method with favorable clinical outcomes 15).
Retrospective review of the medical records of 320 patients with 416 aneurysms treated with microsurgical clipping from 2008 to 2016 in a single neurosurgical center in Brazil. This study evaluated postoperative outcome, using the modified Rankin Scale (mRS) on hospital discharge, treatment efficacy, assessed by digital subtraction angiography (DSA) performed postoperatively, and mortality.
Among 320 patients with aneurysms, 228 patients presented with ruptured aneurysms and 92 patients with unruptured aneurysms. Overall, 81 (26,3%) presented poor outcome (mRs>2) while 227 (73,4%) showed good outcome. The presence of a ruptured aneurysm was a statistically significant factor for poor outcome (p<0,001) and mortality (p<0,015). Giant and large aneurysms were also associated with poor outcome (p=0,004). When we analyze separately, unruptured aneurysms with poor outcome were only associated with aneurysms size. Among the patients with ruptured aneurysms, those with Hunt Hess (HH) > 2 on hospital admission showed unfavorable outcomes (p<0,0001). Among patients submitted to postoperative DSA, 207 (89,8%) had complete occlusion of the aneurysms and 24 (10,2%) presented residual aneurysms, with reoperation required in eight cases.
Microsurgical treatment of intracranial aneurysms is an effective and safe method 16).