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Blood blister-like aneurysms in Tibetans: A retrospective observational study
Clinical Neurology and Neurosurgery 156 (2017) 18–23
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Blood blister-like aneurysms in Tibetans: A retrospective observational study Ruiqi Chen 1 , Anqi Xiao 1 , Hao Li, Lu Ma, Sen Lin, Chao You ∗ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Article history: Received 29 December 2016 Received in revised form 7 February 2017 Accepted 4 March 2017 Available online 6 March 2017 Keywords: Blood blister-like aneurysms Cerebral aneurysm Tibetan Han Endovascular treatment Surgical treatment
a b s t r a c t Object: Although research on blood blister-like aneurysms (BLAs) in different population is well documented, studies of that in the plateau area remain elusive. This study aimed to develop a better understanding of BLAs in Tibetan population, which is a typical representation of people in plateau area. Methods: In this retrospective observational study, the hospital information system (HIS) was used to search for consecutive patients with BLAs by using the discharge diagnoses. A total of 19 Tibetan patients and 34 Han patients were recruited from January 2012 to January 2016. Intra-hospital and follow-up data were collected and compared between two races. Results: Compared with Han group, Tibetan group got significantly higher ratio of BLAs among aneurysmal subarachnoid hemorrhages (aSAHs) (19.6% (19/97) vs 3.2% (34/1071), p < 0.001), higher Incidence of atypical located BLAs (26.3% vs 2.9%, p = 0.034), higher risk of cerebral infarction (63.2% vs 11.8%, p < 0.001), and greater number of patients with unfavorable outcomes at 6 months after ictus (57.9% vs 23.5%, p = 0.028). In Tibetan group, patients underwent endovascular treatment presented with significantly lower cerebral infarction rate (p = 0.019) and better neurological functional recovery outcome (p = 0.048) compared with surgical group. Conclusions: Compared with Han patients, Tibetan BLA patients presented with high risk of occurrence with atypical locations and high incidence of cerebral infarctions with poor prognoses. Endovascular treatment benefits more for Tibetan BLA patients in reducing cerebral infarctions and improving neurological functional recovery prognosis. © 2017 Published by Elsevier B.V.
1. Introduction Blood blister-like aneurysms (BLAs) are a high-risk neurovascular disease with high morbidity and mortality. First described in 1988, BLAs account for only 0.3%–6.6% of all intracranial aneurysms [8,11,12,17]. Their typical characteristics are fully understood as a thin hemispherical wall with a predilection to a non-branching dorsal part of the internal carotid artery (ICA) [18,27]. Due to their extremely fragile thin walls [17,28,29], severe perioperative rebleeding (33%–80%) has been a great challenge for neurosurgeons [22]. Although research on neurovascular diseases in different population is well documented, studies of patients living in the plateau
∗ Corresponding author at: No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China. E-mail address: huaxi [email protected] (C. You). 1 These authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.clineuro.2017.03.004 0303-8467/© 2017 Published by Elsevier B.V.
area remain elusive. In China, the majority of Tibetan people live in the southwest area, which is characterized by its special plateau atmosphere with low barometric pressure and oxygen-thin air. Moreover, the diet in this area is generally composed of high-fat, high-salt foods, which refer to the factors for hemorrhagic stroke [4,6,26]. Currently, there is no study on BLAs in Tibetan people. Since our previous study revealed high infarction and rebleeding incidences in Tibetan aneurysmal subarachnoid hemorrhage (aSAH) patients, and among which BLAs account for a significantly higher ratio (19%, 19/97) than among Han aSAH patients, we here for the first time address the question of whether BLAs in Tibetans present any different clinical characterizations. As the largest and leading medical center in the western part of China, the West China Hospital of Sichuan University (WCH) accepts a substantial number of aSAH patients from different regions covering the Tibet plateau. In this retrospective observational study, we compared the medical data between Tibetan and Han groups of patients with BLAs recruited from WCH from January 2012 to January 2016, aimed to develop a better understanding of
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on CTA examination. Upon the confirmation of BLAs by DSA, meetings with the patients and their relatives were arranged to select a craniotomy surgery or an endovascular treatment. Patients would be sent to intensive care unit (ICU) for standard post-interventional treatment, including the management of cerebral vasospasm, hydrocephalus, seizures and other complications according to the least guideline [2]. 2.3. Outcomes
Fig 1. Typical figure of BLAs, In DSA, BLAs often present as an aneurysm at a nonbranching site of the supraclinoid ICA, as a small hemispheric appearance.
the clinical patterns, treatment options, and prognoses of Tibetan BLAs. 2. Material and methods 2.1. Study design and data collection This was a retrospective observational study which was approved by the institutional review board (IRB) of WCH. The hospital information system (HIS) was used to search for consecutive patients with BLAs from January 2012 to January 2016. The inclusion criteria were the patients identified by the discharge diagnoses in the HIS database using the key words “Tibetan”; “Han”; “subarachnoid hemorrhage” and “blood blister-like aneurysm”. The typical image of BLAs in DSA was shown in Fig 1. The diagnoses of the selected patients were confirmed by two neurosurgeons and one neuroradiologist based on reviews of their inpatient medical records; follow-up information and imaging data. Those with the incorrect diagnosis or incomplete medical or follow-up data were excluded. In total; 19 Tibetan BLAs from 97 Tibetan aSAHs and 34 Han BLAs out of 1071 Han aSAHs were enrolled. The medical information included the following: Baseline information: age, gender, hypertension, diabetes mellitus, hypercholesterolemia, hemoglobin, prior hemorrhagic stroke, current smoking, and current drinking Aneurysm information: location of the aneurysm, and Hunt and Hess grade and Fisher grade. Complications: rebleeding (preoperative, intraoperative and postoperative), vasospasm, cerebral infarction, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding. Follow-ups: Modified Rankin Scale score at 6 months after ictus, intra-hospital mortality (IHM), and mortalities at 1, 3 and 6 months after ictus. 2.2. Treatment The patients were sent to the emergency unit to initiate standard medical treatment and care. CT and CTA scans, routine blood tests, biochemical examinations (e.g., hepatic and renal function, and electrolytes), and routine coagulation studies were immediately performed. The medical history and neurologic physical examination were also recorded simultaneously following hospitalization in the neurosurgery unit. All patients had their vital signs monitored and were simultaneously given supportive treatment. Digital subtraction angiography (DSA) was scheduled when suspicious SAH was found on a CT scan or aneurysms were found
The patients were followed for at least 6 months. The primary outcome was neurological functional status at 6 months post-ictus as evaluated with the modified Rankin Scale (mRS). Favorable outcomes were defined by mRSs between 0 and 2 points, and unfavorable outcomes were defined by mRSs between 3 and 6 points. The secondary outcomes included mortalities at different follow-up time-points post ictus (IHM, 1 month, 3 months and 6 months), complications such as bleeding (preoperative, intraoperative and postoperative), vasospasm, cerebral infarction, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding. Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction, which was confirmed by computed tomography angiogram (CTA) or digital subtraction angiography (DSA) during hospitalization. Cerebral infarction was defined as radiographic evidence of stroke due to any cause during hospitalization. Cerebral infarction was confirmed by head CT or diffusion-weighted magnetic resonance imaging (MRI) during the patient’s hospitalization. 2.4. Statistical analysis Univariable analyses were conducted using Chi-square test or Fisher exact tests, Studentt tests, and Mann–Whitney U tests as appropriate. Student t tests, Chi-square test or Fisher exact tests were used to compare the neurological functional status, mortality and complications between Tibetan and Han BLA patients. Significance was defined as P < 0.05 and 95% confidence intervals (CI) was used. All the statistical analysis was done by SPSS 19.0 (IBM, Armonk, New York, USA). 3. Results A total of 19 Tibetan BLA patients and 34 Han BLA patients were enrolled in this study. The mean ages of the two groups were 40.5 ± 11.6 and 41.9 ± 10.9, respectively. The occurrence of BLAs exhibited a female predominance in both groups, 68.4% (n = 13) in the Tibetans and 73.5% (n = 25) in the Hans. Significantly larger number of patients in the Tibetan group had hypertension (p < 0.001), and the Tibetan group presented a significantly higher mean hemoglobin value than the Han group (160.2 ± 23.0 vs 139.3 ± 16.1, respectively, p < 0.001). The two groups did not differ significantly (p > 0.05) in age, gender, diabetes mellitus, coronary artery disease, hypercholesterolemia, prior hemorrhagic stroke, current drinking, smoking, admission delay in hours, Hunt and Hess grade and Fisher grade on admission (Table 1). There was also a significant difference (p < 0.001) in the location of the BLAs between the two groups. The location of the aneurysmal lesions in the Han group seemed relatively consistent. Among the 34 Han patients, 33 patients exhibited BLAs in the typical location of the dorsal wall of the ICA, and only 1 patient had an aneurysmal lesion located in the atypical position of the middle cerebral artery (MCA). In contrast, among the 19 Tibetan BLA patients, 14 (73.7%) had the aneurysmal lesions in the typical location of the dorsal wall of the ICA at non-branching sites. Among the remaining 5 BLA patients, 1 was located in the anterior cerebral artery (ACA), 2 in the posterior communicating artery (PCA), 1 was found
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Table 1 Comparison of Tibetan and Han BLA patients.
Mean age years(SD) Sex (male:femal) Hypertension, n (%) Diabetes mellitus, n (%) Coronary artery disease, n (%) Hypercholesterolemia, n (%) Prior hemorrhagic stroke, n (%) Current smoking, n (%) Current drinking, n (%) Mean hemoglobin, g(SD) Admission delay in hours Hunt and Hess grade, n (%) I II III IV Fisher grade, n (%) I II III IV
Tibetan BLAs (n = 19)
Han BLAs (n = 34)
P value
40.5(11.6) 6:13 12(63.2) 5(26.3) 2(10.5) 8(42.1) 0,0 8(42.1) 5(26.3) 160.2(23.0) 16.4 ± 12.3
41.9(10.9) 9:25 11(32.4) 7(20.6) 1(2.9) 10(29.4) 1(2.9) 11(32.4) 9(26.5) 139.3(16.1) 13.2 ± 14.6
0.663 0.938 <0.001 0.892 0.580 0.527 0.766 0.681 0.755 <0.001 0.423
3(15.8) 13(68.4) 2(10.5) 1(5.3)
4(11.8) 25(73.5) 3(8.8) 2(5.9)
0.994 0.938 0.774 0.617
0(0) 3(15.8) 14(73.7) 2(10.5)
1(2.9) 5(14.7) 27(79.4) 1(2.9)
0.766 0.768 0.892 0.599
BLAs indicates Blood blister-like aneurysms.
in middle cerebral artery and the other 1 in the lacerum segment (C3) of the ICA. Atypical aneurysmal lesions were significantly more frequent in the Tibetan group than in the Han group (26.3% vs 2.9%, p = 0.034). Regarding complications, the ratio of vasospasm was similar in two groups, with 31.2% in Tibetan group and 29.6% in Han groups. However, the incidence of cerebral infarction in the Tibetan group was significantly higher than that in the Han group (63.2% vs 11.8%, p < 0.001). The incidences of postoperative bleeding in the Tibetan group were greater than those in the Han group, although the difference was not significant (p > 0.05). Meanwhile, no significant differences (p > 0.05) were found in the risks of the other complications, i.e., preoperative and intraoperative bleeding, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding between the two groups. (Table 2, part 1). In terms of their neurological functional status at 6 months after ictus as measured with the mRS, there was a significant difference (p = 0.028) between the two groups. A significantly greater proportion of the patients in Han group exhibited favorable outcomes compared with the Tibetan group, which included more patients who displayed unfavorable outcomes. Furthermore, Tibetan group had higher mortality rates than those of the Han group at different follow-up time points (i.e., IHM, 1 month, 3 months and 6 months, Table 2, part 2), although the differences were not significant (p > 0.05). Moreover, the two groups exhibited a significant difference in the 6-month survival curve (Fig. 2). Among the 19 Tibetan BLA patients, 13 (68.4%) patients underwent craniotomy aneurysm clipping surgery, and the other 6 patients chose endovascular treatments (5 patients underwent endovascular coiling, and 1 underwent stent-associated coiling). Regarding the 34 Han BLA patients, 21 (61.8%) underwent craniotomy aneurysm clipping surgery, and the remaining 13 patients underwent endovascular treatments (11 underwent endovascular coiling, and 2 underwent stent-associated coiling). Two groups did not differ significantly in treatment method (p > 0.05). We performed subgroup analyses to compare the risks of complications associated with the different treatments in the Tibetan and Han groups. In the Tibetan cohort, the risk of cerebral infarction in the surgical group was significantly higher than that in the endovascular group (84.6% vs 16.7%, p = 0.019). Though did not show significant difference (p > 0.05), the risk of intraoperative
Fig. 2. Survival curve of Tibetan and Han group, two groups exhibited a significant difference in the 6-month survival curve, Han group got a significantly higher survival rate compared with Tibetan group (p = 0.027).
bleeding in surgical group was much higher than that in endovascular group (76.9% vs 33.3%). The two groups did not significantly differ (p > 0.05) in the risks of other complications, including preoperative and postoperative bleeding, vasospasm, hydrocephalus, seizures, pulmonary infection and gastrointestinal bleeding. In the Han cohort, though similar tendency of higher risk of intraoperative bleeding in surgical group was observed, the difference was not significantly different (61.9% vs 23.1%, p > 0.05). Additionally, two treatment groups did not show significant differences in the risk of other complications (P > 0.05). (Table 3, part 1). Regarding the prognoses associated with the different treatments, in the Tibetan cohort, the endovascular group had significantly more patients with favorable neurological functional statuses at 6 months after ictus than the surgical group (p = 0.048). Additionally, the mortality rates in the surgical group at all followup time points were higher than those in the endovascular group, but these differences did not reach statistical significance (p > 0.05). In the Han cohort, although the endovascular patients presented trends toward better neurological functional recovery, the difference between the two groups was not statistically significant (p > 0.05).Additionally, two groups did not differ significantly in mortality rate. (Table 3, part 2).
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Table 2 comparison of complications and prognosis between Tibetan and Han BLA patients.
Part 1 Complications Rebleeding, n (%) Preoperative Intraoperative Postoperative Vasospasm, n (%)) Infarction, n (%) Hydrocephalus, n (%) Seizures, n (%) Pulmonary infection, n (%) Gastrointestinal bleeding, n (%) Part 2 Follow-ups NFS at 6 months, n (%) Favorable Unfavorable Mortality, n (%) IHM 1 month 3 months 6 months
Tibetan BLAs (n = 19)
Han BLAs (n = 34)
P value
2(10.5) 12(63.2) 3(15.8) 6(31.6) 12(63.2) 2(10.5) 1(5.3) 5(26.3) 1(5.3)
3(8.8) 16(47.1) 2(5.9) 10(29.4) 4(11.8) 3(8.8) 2(5.9) 7(20.6) 1(2.9)
0.774 0.414 0.488 0.883 <0.001 0.774 0.599 0.892 0.744
8(42.1) 11(57.9)
26(76.5)) 8(23.5)
4(21.1) 6(31.6) 8(31.6) 8(42.1)
3(8.8) 4(11.8) 5(14.7) 5(14.7)
0.028
0.402 0.161 0.058 0.058
BLAs indicate Blood blister-like aneurysms; Favorable neurological functional status indicates mRS between 0 and 2 points; IHM indicates intra-hospital mortality; NFS indicates neurological functional status; Unfavorable neurological functional status indicates mRS between 3 and 6 points.
Table 3 subgroup analysis between surgical and endovascular patients in Tibetan and Han cohort. Tibetan N = 19
Part 1 Complications Bleeding, n (%) Preoperative Intraoperative Postoperative Vasospasm, n (%) Infarction, n (%) Hydrocephalus, n (%) Seizures, n (%) Pulmonary infection, n (%) Gastrointestinal bleeding, n (%) Part 2 Follow-ups NFS at 6 months, n (%) Favorable Unfavorable Mortality, n (%) IHM 1 month 3 months 6 months
Han N = 34
Surgery (n = 13)
endovascular (n = 6)
P value
Surgery (n = 21)
endovascular (n = 13)
P value
1(7.7) 10(76.9) 3(23.1) 4(30.8) 11(84.6) 1(7.7) 1(7.7) 4(30.8) 1(7.7)
1(16.7) 2(33.3) 0(0) 2(33.3) 1(16.7) 1(16.7) 0(0) 1(16.7) 0(0)
0.832 0.187 0.545 0.675 0.019 0.832 0.684 0.929 0.684
2(9.5) 13(61.9) 1(4.8) 7(33.3) 3(14.3) 2(9.5) 2(9.5) 5(23.8) 1(4.8)
1(7.7) 3(23.1) 1(7.7) 3(23.1) 1(7.7) 1(7.7) 0(0) 2((15.4) 0(0)
0.661 0.064 0.691 0.802 0.974 0.661 0.691 0.878 0.805
3(23.1) 10(76.9)
5(83.3) 1(16.7)
15(71.4) 6(28.6)
11(84.6) 2(15.4)
3(23.1) 5(38.5) 6(46.2) 6(46.2)
1(16.7) 1(16.7) 2(33.3) 2(33.3)
2(9.5) 2(9.5) 3(14.3) 3(14.3)
1(7.7) 2(15.4) 2(15.4) 2(15.4)
0.048
0.774 0.675 0.979 0.979
0.642
0.661 0.974 0.682 0.682
Favorable neurological functional status indicates mRS between 0 and 2 points; IHM indicates intra-hospital mortality; NFS indicates neurological functional status; Unfavorable neurological functional status indicates mRS between 3 and 6 points.
4. Discussion This is the first retrospective observational study of the differences in the clinical characteristics of BLAs between Tibetans and Hans. We found that the Tibetan aneurysm patients had a greater risk of BLA, more frequent occurrences at atypical sites, more infarctions and complications and poorer prognoses. Besides, endovascular treatment was the more effective therapy for the Tibetan BLA patients. The results of our study may help neurosurgeons to obtain a better understanding of BLAs in Tibetan populations. In previous studies, BLAs have been reported to account only for 0.3%–6.6% of all intracranial aneurysms [11,12]. In our study, among 97 Tibetan aSAH patients there were 19 BLA patients, and this ratio was significantly higher than that observed in the Han patients and in the previously reported data. Based on the high ratio
of BLAs among Tibetan aSAHs, we speculate that the Tibetan population is more susceptible to BLAs. Currently, the mechanism of BLA formation remains unclear. Some research has revealed several risk factors that include atherosclerosis, hemodynamic changes, hypertension and dissection of the cerebral artery [8]. In our study, significant differences were found between the two groups in the baseline information, including hypertension and hemoglobin level, suggesting that these factors may contribute to the greater risk of BLAs in the Tibetan population. In our study, the proportion of BLAs that were located in atypical sites of the cerebral circulation system was significantly greater in the Tibetan group than in the Han group (26.3% vs 2.9%, p < 0.001). Although BLAs are generally located in the dorsal wall of the ICA, more recent cases of atypically located BLAs have been reported [1,3,21,22,24] and have revealed other locations at which BLAs occur. According to a meta-analysis, atypically
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located BLAs account for 7.8%–8.6% of cases [23], and this value is significantly lower than that was found in our study in the Tibetan group. Therefore, it is reasonable to believe that BLAs are more likely to occur in atypical sites among Tibetan people than other populations. Although this phenomenon currently lacks an explanation, we suggest clinicians pay attention to suspected BLA when a Tibetan patient presents an aneurysm at an atypical site. Our study also found a higher ratio of Tibetan BLA patients with intraoperative bleeding and cerebral infarction than the Han group. Moreover, the Tibetan patients exhibited significantly poorer prognoses (i.e., unfavorable neurological functional statuses at 6 months after ictus and in the 6-month survival curves) than did the Han patients. We believe that the greater risk of intraoperative bleeding observed in the Tibetan group might be related to the greater proportion of surgical compared with endovascular treatments. In our Tibetan group, the incidence of intraoperative rebleeding in the surgical group was significantly higher than that in the endovascular group. In addition to intraoperative rebleeding, greater concern should be placed on the risk of cerebral infarction in Tibetan groups because Tibetan patients also presented with a significantly increased susceptibility compared with the results of several previous studies [10,17,20,32]. Based on the results of this research and our previous study, we believe that a high incidence of cerebral infarction should be considered one of the most common characteristics of Tibetan primary hemorrhagic neurovascular diseases (PHNVDs). Regarding the potential mechanisms responsible for the high incidence of cerebral infarction in BLAs, some studies have indicated that vasospasm after SAH should be the most important factor [10,32]. According to the research previously, approximately half of aSAH patients who suffer from vasospasm would present with cerebral infarction [31]. Interestingly, it is worth noting that the incidence of cerebral infarction in our Tibetan group was much higher than that of vasospasm. As for other factors that contribute to the incidence of cerebral infarction in Tibetan BLAs, addition related research should be performed. Although the mechanisms of the poor neurological functional recovery and high mortality rate observed in the Tibetan BLA patients still lack accurate explanations, the high risk of cerebral infarction may be among the leading causes of its poor prognosis. Based on the high incidence of cerebral infarction and the high level of hemoglobin in the Tibetan group, we propose the “hemoglobin, blood viscosity, tiny thrombosis-based cerebral infarction” hypothesis as a possible mechanism of cerebral infarction in Tibetan BLA cases. Specifically, the compensatorily high hemoglobin level caused by the oxygen-thin atmosphere of the plateau area functions as the initial basis in the transduction axis and then contributes to an increase in blood viscosity. This subsequently leads to the development of tiny thromboses inside the cerebral circulation system, which ultimately results to cerebral infarction formation. Several previous studies have provided evidence for an increase of blood viscosity due to high hemoglobin levels [7,14,15]. Moreover, other studies have reported a relationship between high blood viscosity and infarction in which tiny thrombosis formation in the cerebral circulation system may play an important role [5,9,13,19]. Although supported by the literature mentioned above, additional research is still needed to definitely prove this hypothesis. Although many studies have discussed the treatment of BLAs, the debate over whether surgical or endovascular treatment is more beneficial continues. Our subgroup analysis revealed several interesting points. In the Tibetan cohort, the risks of intraoperative bleeding and cerebral infarction in the surgical group were significantly greater than those in the endovascular group. Moreover, significantly poorer neurological functional prognoses was observed in the surgical group (p < 0.05). Regarding the Han cohort, no differences were found in the incidences of complications or
neurological functional prognoses between the two treatment groups with the exceptions of the significantly higher rate of intraoperative bleeding in the surgical group. Theoretically, BLAs present treatment challenges due to their unfavorable morphology, small size, fragile walls, ill-defined necks and high intra-operative risk of rupture [23]. To date, various surgical approaches have been proposed, including wrapping of the ICA and aneurysm clipping. However, high rates of intra- and post-operative rebleeding have been reported, and these conditions subsequently lead to cerebral infarcts during the period of vasospasm and very poor outcomes [32]. Compared with surgical approaches, endovascular treatment presents a lower risk of complications and has been suggested to be a definitive and safer approach to the treatment of BLAs. Moreover, patients who undergo endovascular treatments tend to achieve better short-term prognoses in terms of neurological functional recovery and mortality [16]. Furthermore, with the introduction of new technologies, such as multilayer flowdiverting devices, endovascular treatment will become safer and more efficient [25]. However, it was reported that aSAH patients who undergo endovascular treatment exhibit a higher recurrence rate, which makes the long-term prognosis unclear [30]. Based on our results, we assume that endovascular treatment is more beneficial in terms of decreasing the incidence of complications during hospitalization and improving the neurological functional recovery prognosis compared with surgical treatment. However, due to the lack of additional relevant follow-up data, further studies are needed to compare the long-term prognoses and recurrence rates between the two treatment methods. Our study has some limitations. First, the study design was a nonrandomized retrospective observational study performed only in a single center. Second, all of the data we collected were based on inpatient records and short-term follow-ups; thus, the long-term prognoses remained uncertain. Third, the baseline information was not considered in the subgroup analyses. Thus, there might be some bias factors that influenced the risk of complications and prognoses other than the treatment difference. 5. Conclusions To date, research on BLAs in the Tibetan population remains nonexistent. As the first retrospective observational study focusing on the clinical characteristics of Tibetan BLAs, our research revealed Tibetan BLAs had a high risk of occurrence and atypical locations in the cerebral vascular system. They presented with high incidence of cerebral infarctions with poor prognosis. Endovascular treatment is more beneficial for Tibetan BLA patients in terms of reducing complications during hospitalization and improving the neurological functional recovery prognosis. Funding This work was supported by the National Key Technology R&D Program for the 12th Five-year Plan of P.R China (grant numbers:2011BAI08B05). Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Acknowledgment Authors would like to express our sincere appreciation to Dr. Xie Hong for her valuable comments on our paper.
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Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Blood blister-like aneurysms in Tibetans: A retrospective observational study Ruiqi Chen 1 , Anqi Xiao 1 , Hao Li, Lu Ma, Sen Lin, Chao You ∗ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
a r t i c l e
i n f o
Article history: Received 29 December 2016 Received in revised form 7 February 2017 Accepted 4 March 2017 Available online 6 March 2017 Keywords: Blood blister-like aneurysms Cerebral aneurysm Tibetan Han Endovascular treatment Surgical treatment
a b s t r a c t Object: Although research on blood blister-like aneurysms (BLAs) in different population is well documented, studies of that in the plateau area remain elusive. This study aimed to develop a better understanding of BLAs in Tibetan population, which is a typical representation of people in plateau area. Methods: In this retrospective observational study, the hospital information system (HIS) was used to search for consecutive patients with BLAs by using the discharge diagnoses. A total of 19 Tibetan patients and 34 Han patients were recruited from January 2012 to January 2016. Intra-hospital and follow-up data were collected and compared between two races. Results: Compared with Han group, Tibetan group got significantly higher ratio of BLAs among aneurysmal subarachnoid hemorrhages (aSAHs) (19.6% (19/97) vs 3.2% (34/1071), p < 0.001), higher Incidence of atypical located BLAs (26.3% vs 2.9%, p = 0.034), higher risk of cerebral infarction (63.2% vs 11.8%, p < 0.001), and greater number of patients with unfavorable outcomes at 6 months after ictus (57.9% vs 23.5%, p = 0.028). In Tibetan group, patients underwent endovascular treatment presented with significantly lower cerebral infarction rate (p = 0.019) and better neurological functional recovery outcome (p = 0.048) compared with surgical group. Conclusions: Compared with Han patients, Tibetan BLA patients presented with high risk of occurrence with atypical locations and high incidence of cerebral infarctions with poor prognoses. Endovascular treatment benefits more for Tibetan BLA patients in reducing cerebral infarctions and improving neurological functional recovery prognosis. © 2017 Published by Elsevier B.V.
1. Introduction Blood blister-like aneurysms (BLAs) are a high-risk neurovascular disease with high morbidity and mortality. First described in 1988, BLAs account for only 0.3%–6.6% of all intracranial aneurysms [8,11,12,17]. Their typical characteristics are fully understood as a thin hemispherical wall with a predilection to a non-branching dorsal part of the internal carotid artery (ICA) [18,27]. Due to their extremely fragile thin walls [17,28,29], severe perioperative rebleeding (33%–80%) has been a great challenge for neurosurgeons [22]. Although research on neurovascular diseases in different population is well documented, studies of patients living in the plateau
∗ Corresponding author at: No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China. E-mail address: huaxi [email protected] (C. You). 1 These authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.clineuro.2017.03.004 0303-8467/© 2017 Published by Elsevier B.V.
area remain elusive. In China, the majority of Tibetan people live in the southwest area, which is characterized by its special plateau atmosphere with low barometric pressure and oxygen-thin air. Moreover, the diet in this area is generally composed of high-fat, high-salt foods, which refer to the factors for hemorrhagic stroke [4,6,26]. Currently, there is no study on BLAs in Tibetan people. Since our previous study revealed high infarction and rebleeding incidences in Tibetan aneurysmal subarachnoid hemorrhage (aSAH) patients, and among which BLAs account for a significantly higher ratio (19%, 19/97) than among Han aSAH patients, we here for the first time address the question of whether BLAs in Tibetans present any different clinical characterizations. As the largest and leading medical center in the western part of China, the West China Hospital of Sichuan University (WCH) accepts a substantial number of aSAH patients from different regions covering the Tibet plateau. In this retrospective observational study, we compared the medical data between Tibetan and Han groups of patients with BLAs recruited from WCH from January 2012 to January 2016, aimed to develop a better understanding of
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on CTA examination. Upon the confirmation of BLAs by DSA, meetings with the patients and their relatives were arranged to select a craniotomy surgery or an endovascular treatment. Patients would be sent to intensive care unit (ICU) for standard post-interventional treatment, including the management of cerebral vasospasm, hydrocephalus, seizures and other complications according to the least guideline [2]. 2.3. Outcomes
Fig 1. Typical figure of BLAs, In DSA, BLAs often present as an aneurysm at a nonbranching site of the supraclinoid ICA, as a small hemispheric appearance.
the clinical patterns, treatment options, and prognoses of Tibetan BLAs. 2. Material and methods 2.1. Study design and data collection This was a retrospective observational study which was approved by the institutional review board (IRB) of WCH. The hospital information system (HIS) was used to search for consecutive patients with BLAs from January 2012 to January 2016. The inclusion criteria were the patients identified by the discharge diagnoses in the HIS database using the key words “Tibetan”; “Han”; “subarachnoid hemorrhage” and “blood blister-like aneurysm”. The typical image of BLAs in DSA was shown in Fig 1. The diagnoses of the selected patients were confirmed by two neurosurgeons and one neuroradiologist based on reviews of their inpatient medical records; follow-up information and imaging data. Those with the incorrect diagnosis or incomplete medical or follow-up data were excluded. In total; 19 Tibetan BLAs from 97 Tibetan aSAHs and 34 Han BLAs out of 1071 Han aSAHs were enrolled. The medical information included the following: Baseline information: age, gender, hypertension, diabetes mellitus, hypercholesterolemia, hemoglobin, prior hemorrhagic stroke, current smoking, and current drinking Aneurysm information: location of the aneurysm, and Hunt and Hess grade and Fisher grade. Complications: rebleeding (preoperative, intraoperative and postoperative), vasospasm, cerebral infarction, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding. Follow-ups: Modified Rankin Scale score at 6 months after ictus, intra-hospital mortality (IHM), and mortalities at 1, 3 and 6 months after ictus. 2.2. Treatment The patients were sent to the emergency unit to initiate standard medical treatment and care. CT and CTA scans, routine blood tests, biochemical examinations (e.g., hepatic and renal function, and electrolytes), and routine coagulation studies were immediately performed. The medical history and neurologic physical examination were also recorded simultaneously following hospitalization in the neurosurgery unit. All patients had their vital signs monitored and were simultaneously given supportive treatment. Digital subtraction angiography (DSA) was scheduled when suspicious SAH was found on a CT scan or aneurysms were found
The patients were followed for at least 6 months. The primary outcome was neurological functional status at 6 months post-ictus as evaluated with the modified Rankin Scale (mRS). Favorable outcomes were defined by mRSs between 0 and 2 points, and unfavorable outcomes were defined by mRSs between 3 and 6 points. The secondary outcomes included mortalities at different follow-up time-points post ictus (IHM, 1 month, 3 months and 6 months), complications such as bleeding (preoperative, intraoperative and postoperative), vasospasm, cerebral infarction, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding. Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction, which was confirmed by computed tomography angiogram (CTA) or digital subtraction angiography (DSA) during hospitalization. Cerebral infarction was defined as radiographic evidence of stroke due to any cause during hospitalization. Cerebral infarction was confirmed by head CT or diffusion-weighted magnetic resonance imaging (MRI) during the patient’s hospitalization. 2.4. Statistical analysis Univariable analyses were conducted using Chi-square test or Fisher exact tests, Studentt tests, and Mann–Whitney U tests as appropriate. Student t tests, Chi-square test or Fisher exact tests were used to compare the neurological functional status, mortality and complications between Tibetan and Han BLA patients. Significance was defined as P < 0.05 and 95% confidence intervals (CI) was used. All the statistical analysis was done by SPSS 19.0 (IBM, Armonk, New York, USA). 3. Results A total of 19 Tibetan BLA patients and 34 Han BLA patients were enrolled in this study. The mean ages of the two groups were 40.5 ± 11.6 and 41.9 ± 10.9, respectively. The occurrence of BLAs exhibited a female predominance in both groups, 68.4% (n = 13) in the Tibetans and 73.5% (n = 25) in the Hans. Significantly larger number of patients in the Tibetan group had hypertension (p < 0.001), and the Tibetan group presented a significantly higher mean hemoglobin value than the Han group (160.2 ± 23.0 vs 139.3 ± 16.1, respectively, p < 0.001). The two groups did not differ significantly (p > 0.05) in age, gender, diabetes mellitus, coronary artery disease, hypercholesterolemia, prior hemorrhagic stroke, current drinking, smoking, admission delay in hours, Hunt and Hess grade and Fisher grade on admission (Table 1). There was also a significant difference (p < 0.001) in the location of the BLAs between the two groups. The location of the aneurysmal lesions in the Han group seemed relatively consistent. Among the 34 Han patients, 33 patients exhibited BLAs in the typical location of the dorsal wall of the ICA, and only 1 patient had an aneurysmal lesion located in the atypical position of the middle cerebral artery (MCA). In contrast, among the 19 Tibetan BLA patients, 14 (73.7%) had the aneurysmal lesions in the typical location of the dorsal wall of the ICA at non-branching sites. Among the remaining 5 BLA patients, 1 was located in the anterior cerebral artery (ACA), 2 in the posterior communicating artery (PCA), 1 was found
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Table 1 Comparison of Tibetan and Han BLA patients.
Mean age years(SD) Sex (male:femal) Hypertension, n (%) Diabetes mellitus, n (%) Coronary artery disease, n (%) Hypercholesterolemia, n (%) Prior hemorrhagic stroke, n (%) Current smoking, n (%) Current drinking, n (%) Mean hemoglobin, g(SD) Admission delay in hours Hunt and Hess grade, n (%) I II III IV Fisher grade, n (%) I II III IV
Tibetan BLAs (n = 19)
Han BLAs (n = 34)
P value
40.5(11.6) 6:13 12(63.2) 5(26.3) 2(10.5) 8(42.1) 0,0 8(42.1) 5(26.3) 160.2(23.0) 16.4 ± 12.3
41.9(10.9) 9:25 11(32.4) 7(20.6) 1(2.9) 10(29.4) 1(2.9) 11(32.4) 9(26.5) 139.3(16.1) 13.2 ± 14.6
0.663 0.938 <0.001 0.892 0.580 0.527 0.766 0.681 0.755 <0.001 0.423
3(15.8) 13(68.4) 2(10.5) 1(5.3)
4(11.8) 25(73.5) 3(8.8) 2(5.9)
0.994 0.938 0.774 0.617
0(0) 3(15.8) 14(73.7) 2(10.5)
1(2.9) 5(14.7) 27(79.4) 1(2.9)
0.766 0.768 0.892 0.599
BLAs indicates Blood blister-like aneurysms.
in middle cerebral artery and the other 1 in the lacerum segment (C3) of the ICA. Atypical aneurysmal lesions were significantly more frequent in the Tibetan group than in the Han group (26.3% vs 2.9%, p = 0.034). Regarding complications, the ratio of vasospasm was similar in two groups, with 31.2% in Tibetan group and 29.6% in Han groups. However, the incidence of cerebral infarction in the Tibetan group was significantly higher than that in the Han group (63.2% vs 11.8%, p < 0.001). The incidences of postoperative bleeding in the Tibetan group were greater than those in the Han group, although the difference was not significant (p > 0.05). Meanwhile, no significant differences (p > 0.05) were found in the risks of the other complications, i.e., preoperative and intraoperative bleeding, hydrocephalus, seizures, pulmonary infection, and gastrointestinal bleeding between the two groups. (Table 2, part 1). In terms of their neurological functional status at 6 months after ictus as measured with the mRS, there was a significant difference (p = 0.028) between the two groups. A significantly greater proportion of the patients in Han group exhibited favorable outcomes compared with the Tibetan group, which included more patients who displayed unfavorable outcomes. Furthermore, Tibetan group had higher mortality rates than those of the Han group at different follow-up time points (i.e., IHM, 1 month, 3 months and 6 months, Table 2, part 2), although the differences were not significant (p > 0.05). Moreover, the two groups exhibited a significant difference in the 6-month survival curve (Fig. 2). Among the 19 Tibetan BLA patients, 13 (68.4%) patients underwent craniotomy aneurysm clipping surgery, and the other 6 patients chose endovascular treatments (5 patients underwent endovascular coiling, and 1 underwent stent-associated coiling). Regarding the 34 Han BLA patients, 21 (61.8%) underwent craniotomy aneurysm clipping surgery, and the remaining 13 patients underwent endovascular treatments (11 underwent endovascular coiling, and 2 underwent stent-associated coiling). Two groups did not differ significantly in treatment method (p > 0.05). We performed subgroup analyses to compare the risks of complications associated with the different treatments in the Tibetan and Han groups. In the Tibetan cohort, the risk of cerebral infarction in the surgical group was significantly higher than that in the endovascular group (84.6% vs 16.7%, p = 0.019). Though did not show significant difference (p > 0.05), the risk of intraoperative
Fig. 2. Survival curve of Tibetan and Han group, two groups exhibited a significant difference in the 6-month survival curve, Han group got a significantly higher survival rate compared with Tibetan group (p = 0.027).
bleeding in surgical group was much higher than that in endovascular group (76.9% vs 33.3%). The two groups did not significantly differ (p > 0.05) in the risks of other complications, including preoperative and postoperative bleeding, vasospasm, hydrocephalus, seizures, pulmonary infection and gastrointestinal bleeding. In the Han cohort, though similar tendency of higher risk of intraoperative bleeding in surgical group was observed, the difference was not significantly different (61.9% vs 23.1%, p > 0.05). Additionally, two treatment groups did not show significant differences in the risk of other complications (P > 0.05). (Table 3, part 1). Regarding the prognoses associated with the different treatments, in the Tibetan cohort, the endovascular group had significantly more patients with favorable neurological functional statuses at 6 months after ictus than the surgical group (p = 0.048). Additionally, the mortality rates in the surgical group at all followup time points were higher than those in the endovascular group, but these differences did not reach statistical significance (p > 0.05). In the Han cohort, although the endovascular patients presented trends toward better neurological functional recovery, the difference between the two groups was not statistically significant (p > 0.05).Additionally, two groups did not differ significantly in mortality rate. (Table 3, part 2).
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Table 2 comparison of complications and prognosis between Tibetan and Han BLA patients.
Part 1 Complications Rebleeding, n (%) Preoperative Intraoperative Postoperative Vasospasm, n (%)) Infarction, n (%) Hydrocephalus, n (%) Seizures, n (%) Pulmonary infection, n (%) Gastrointestinal bleeding, n (%) Part 2 Follow-ups NFS at 6 months, n (%) Favorable Unfavorable Mortality, n (%) IHM 1 month 3 months 6 months
Tibetan BLAs (n = 19)
Han BLAs (n = 34)
P value
2(10.5) 12(63.2) 3(15.8) 6(31.6) 12(63.2) 2(10.5) 1(5.3) 5(26.3) 1(5.3)
3(8.8) 16(47.1) 2(5.9) 10(29.4) 4(11.8) 3(8.8) 2(5.9) 7(20.6) 1(2.9)
0.774 0.414 0.488 0.883 <0.001 0.774 0.599 0.892 0.744
8(42.1) 11(57.9)
26(76.5)) 8(23.5)
4(21.1) 6(31.6) 8(31.6) 8(42.1)
3(8.8) 4(11.8) 5(14.7) 5(14.7)
0.028
0.402 0.161 0.058 0.058
BLAs indicate Blood blister-like aneurysms; Favorable neurological functional status indicates mRS between 0 and 2 points; IHM indicates intra-hospital mortality; NFS indicates neurological functional status; Unfavorable neurological functional status indicates mRS between 3 and 6 points.
Table 3 subgroup analysis between surgical and endovascular patients in Tibetan and Han cohort. Tibetan N = 19
Part 1 Complications Bleeding, n (%) Preoperative Intraoperative Postoperative Vasospasm, n (%) Infarction, n (%) Hydrocephalus, n (%) Seizures, n (%) Pulmonary infection, n (%) Gastrointestinal bleeding, n (%) Part 2 Follow-ups NFS at 6 months, n (%) Favorable Unfavorable Mortality, n (%) IHM 1 month 3 months 6 months
Han N = 34
Surgery (n = 13)
endovascular (n = 6)
P value
Surgery (n = 21)
endovascular (n = 13)
P value
1(7.7) 10(76.9) 3(23.1) 4(30.8) 11(84.6) 1(7.7) 1(7.7) 4(30.8) 1(7.7)
1(16.7) 2(33.3) 0(0) 2(33.3) 1(16.7) 1(16.7) 0(0) 1(16.7) 0(0)
0.832 0.187 0.545 0.675 0.019 0.832 0.684 0.929 0.684
2(9.5) 13(61.9) 1(4.8) 7(33.3) 3(14.3) 2(9.5) 2(9.5) 5(23.8) 1(4.8)
1(7.7) 3(23.1) 1(7.7) 3(23.1) 1(7.7) 1(7.7) 0(0) 2((15.4) 0(0)
0.661 0.064 0.691 0.802 0.974 0.661 0.691 0.878 0.805
3(23.1) 10(76.9)
5(83.3) 1(16.7)
15(71.4) 6(28.6)
11(84.6) 2(15.4)
3(23.1) 5(38.5) 6(46.2) 6(46.2)
1(16.7) 1(16.7) 2(33.3) 2(33.3)
2(9.5) 2(9.5) 3(14.3) 3(14.3)
1(7.7) 2(15.4) 2(15.4) 2(15.4)
0.048
0.774 0.675 0.979 0.979
0.642
0.661 0.974 0.682 0.682
Favorable neurological functional status indicates mRS between 0 and 2 points; IHM indicates intra-hospital mortality; NFS indicates neurological functional status; Unfavorable neurological functional status indicates mRS between 3 and 6 points.
4. Discussion This is the first retrospective observational study of the differences in the clinical characteristics of BLAs between Tibetans and Hans. We found that the Tibetan aneurysm patients had a greater risk of BLA, more frequent occurrences at atypical sites, more infarctions and complications and poorer prognoses. Besides, endovascular treatment was the more effective therapy for the Tibetan BLA patients. The results of our study may help neurosurgeons to obtain a better understanding of BLAs in Tibetan populations. In previous studies, BLAs have been reported to account only for 0.3%–6.6% of all intracranial aneurysms [11,12]. In our study, among 97 Tibetan aSAH patients there were 19 BLA patients, and this ratio was significantly higher than that observed in the Han patients and in the previously reported data. Based on the high ratio
of BLAs among Tibetan aSAHs, we speculate that the Tibetan population is more susceptible to BLAs. Currently, the mechanism of BLA formation remains unclear. Some research has revealed several risk factors that include atherosclerosis, hemodynamic changes, hypertension and dissection of the cerebral artery [8]. In our study, significant differences were found between the two groups in the baseline information, including hypertension and hemoglobin level, suggesting that these factors may contribute to the greater risk of BLAs in the Tibetan population. In our study, the proportion of BLAs that were located in atypical sites of the cerebral circulation system was significantly greater in the Tibetan group than in the Han group (26.3% vs 2.9%, p < 0.001). Although BLAs are generally located in the dorsal wall of the ICA, more recent cases of atypically located BLAs have been reported [1,3,21,22,24] and have revealed other locations at which BLAs occur. According to a meta-analysis, atypically
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located BLAs account for 7.8%–8.6% of cases [23], and this value is significantly lower than that was found in our study in the Tibetan group. Therefore, it is reasonable to believe that BLAs are more likely to occur in atypical sites among Tibetan people than other populations. Although this phenomenon currently lacks an explanation, we suggest clinicians pay attention to suspected BLA when a Tibetan patient presents an aneurysm at an atypical site. Our study also found a higher ratio of Tibetan BLA patients with intraoperative bleeding and cerebral infarction than the Han group. Moreover, the Tibetan patients exhibited significantly poorer prognoses (i.e., unfavorable neurological functional statuses at 6 months after ictus and in the 6-month survival curves) than did the Han patients. We believe that the greater risk of intraoperative bleeding observed in the Tibetan group might be related to the greater proportion of surgical compared with endovascular treatments. In our Tibetan group, the incidence of intraoperative rebleeding in the surgical group was significantly higher than that in the endovascular group. In addition to intraoperative rebleeding, greater concern should be placed on the risk of cerebral infarction in Tibetan groups because Tibetan patients also presented with a significantly increased susceptibility compared with the results of several previous studies [10,17,20,32]. Based on the results of this research and our previous study, we believe that a high incidence of cerebral infarction should be considered one of the most common characteristics of Tibetan primary hemorrhagic neurovascular diseases (PHNVDs). Regarding the potential mechanisms responsible for the high incidence of cerebral infarction in BLAs, some studies have indicated that vasospasm after SAH should be the most important factor [10,32]. According to the research previously, approximately half of aSAH patients who suffer from vasospasm would present with cerebral infarction [31]. Interestingly, it is worth noting that the incidence of cerebral infarction in our Tibetan group was much higher than that of vasospasm. As for other factors that contribute to the incidence of cerebral infarction in Tibetan BLAs, addition related research should be performed. Although the mechanisms of the poor neurological functional recovery and high mortality rate observed in the Tibetan BLA patients still lack accurate explanations, the high risk of cerebral infarction may be among the leading causes of its poor prognosis. Based on the high incidence of cerebral infarction and the high level of hemoglobin in the Tibetan group, we propose the “hemoglobin, blood viscosity, tiny thrombosis-based cerebral infarction” hypothesis as a possible mechanism of cerebral infarction in Tibetan BLA cases. Specifically, the compensatorily high hemoglobin level caused by the oxygen-thin atmosphere of the plateau area functions as the initial basis in the transduction axis and then contributes to an increase in blood viscosity. This subsequently leads to the development of tiny thromboses inside the cerebral circulation system, which ultimately results to cerebral infarction formation. Several previous studies have provided evidence for an increase of blood viscosity due to high hemoglobin levels [7,14,15]. Moreover, other studies have reported a relationship between high blood viscosity and infarction in which tiny thrombosis formation in the cerebral circulation system may play an important role [5,9,13,19]. Although supported by the literature mentioned above, additional research is still needed to definitely prove this hypothesis. Although many studies have discussed the treatment of BLAs, the debate over whether surgical or endovascular treatment is more beneficial continues. Our subgroup analysis revealed several interesting points. In the Tibetan cohort, the risks of intraoperative bleeding and cerebral infarction in the surgical group were significantly greater than those in the endovascular group. Moreover, significantly poorer neurological functional prognoses was observed in the surgical group (p < 0.05). Regarding the Han cohort, no differences were found in the incidences of complications or
neurological functional prognoses between the two treatment groups with the exceptions of the significantly higher rate of intraoperative bleeding in the surgical group. Theoretically, BLAs present treatment challenges due to their unfavorable morphology, small size, fragile walls, ill-defined necks and high intra-operative risk of rupture [23]. To date, various surgical approaches have been proposed, including wrapping of the ICA and aneurysm clipping. However, high rates of intra- and post-operative rebleeding have been reported, and these conditions subsequently lead to cerebral infarcts during the period of vasospasm and very poor outcomes [32]. Compared with surgical approaches, endovascular treatment presents a lower risk of complications and has been suggested to be a definitive and safer approach to the treatment of BLAs. Moreover, patients who undergo endovascular treatments tend to achieve better short-term prognoses in terms of neurological functional recovery and mortality [16]. Furthermore, with the introduction of new technologies, such as multilayer flowdiverting devices, endovascular treatment will become safer and more efficient [25]. However, it was reported that aSAH patients who undergo endovascular treatment exhibit a higher recurrence rate, which makes the long-term prognosis unclear [30]. Based on our results, we assume that endovascular treatment is more beneficial in terms of decreasing the incidence of complications during hospitalization and improving the neurological functional recovery prognosis compared with surgical treatment. However, due to the lack of additional relevant follow-up data, further studies are needed to compare the long-term prognoses and recurrence rates between the two treatment methods. Our study has some limitations. First, the study design was a nonrandomized retrospective observational study performed only in a single center. Second, all of the data we collected were based on inpatient records and short-term follow-ups; thus, the long-term prognoses remained uncertain. Third, the baseline information was not considered in the subgroup analyses. Thus, there might be some bias factors that influenced the risk of complications and prognoses other than the treatment difference. 5. Conclusions To date, research on BLAs in the Tibetan population remains nonexistent. As the first retrospective observational study focusing on the clinical characteristics of Tibetan BLAs, our research revealed Tibetan BLAs had a high risk of occurrence and atypical locations in the cerebral vascular system. They presented with high incidence of cerebral infarctions with poor prognosis. Endovascular treatment is more beneficial for Tibetan BLA patients in terms of reducing complications during hospitalization and improving the neurological functional recovery prognosis. Funding This work was supported by the National Key Technology R&D Program for the 12th Five-year Plan of P.R China (grant numbers:2011BAI08B05). Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Acknowledgment Authors would like to express our sincere appreciation to Dr. Xie Hong for her valuable comments on our paper.
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