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Number of cerebral microbleeds after intracranial/extracranial stenting and dual antiplatelet therapy

Hsu, Huan-Minga,b; Lu, Yueh-Hsunb,c,d,*; Su, I-Changd,e,f; Chan, Lungd,g,h

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Journal of the Chinese Medical Association: June 2022 - Volume 85 - Issue 6 - p 704-708
doi: 10.1097/JCMA.0000000000000718
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Cerebral microbleeds (CMBs) are small perivascular hemosiderin deposits (usually with macrophages) resulting from leakage through cerebral small vessels. They can be visualized as small, rounded, homogeneous, and hypointense lesions on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging (SWI) in magnetic resonance imaging (MRI).1 They are almost <1 cm in diameter.

Microbleeds indicate a previous small perivascular hemorrhage and are a marker of microangiopathy.2 Studies have demonstrated that CMB formation can occur in different cerebrovascular events.3,4 The number of CMBs may be a risk factor for intracranial hemorrhage or hemorrhagic transformation.5

Carotid and intracranial stentings are well-developed methods to treat the stenotic artery, improve blood flow, and prevent major stroke. Dual antiplatelet therapy (DAPT) is essential to prevent stent-associated ischemic complications following stenting.6,7 DAPT is routinely used in pre- and poststenting conditions. CMB has been observed after stenting.8,9 The objective of the current study was to evaluate and observe changes before and after DAPT and the stenting of various vessels. The observation was focused on changes in CMB numbers in different cases and brain territories.


2.1. Included cases

In this retrospective study, from 2018 to 2020, patients receiving extracranial or intracranial stenting were enrolled. All the patients received DAPT before and after stenting. This study was approved by our institutional review board (N202106014). The image data were obtained from the PACs system.

2.2. Stenting and medications

The stented arteries included the cervical internal carotid artery (ICA), intracranial ICA, middle cerebral artery (MCA), extracranial vertebral artery (VA), intracranial VA, basilar artery (BA), and subclavian artery. The indications for stenting were symptomatic arterial stenosis ≥60% or asymptomatic stenosis ≥70%. Symptomatic arterial stenosis was defined as ipsilateral ischemic events or transient ischemic attack within 3 months before stenting. Stenting for arterial dissection was also included. DAPT included aspirin (100 mg/d) and clopidogrel (75 mg/d) from 3 days before stenting to 6 months after stenting.

2.3. MRI protocols

MRI examinations were performed 1 day before and 3 months after stenting. All the patients were scanned using a 3T MR system (Discovery MR750; GE Healthcare). Imaging parameters for SWI were as follows: repetition time, minimum; echo time, 24.7 ms; flip angle, 15°; matrix, 418 × 288; field of view, 23.0 × 0.75; section thickness, 2.0 mm; bandwidth, 83.33 kHz; and acquisition time, 3 minutes 36 seconds.

2.4. Imaging analysis methods

Initial number of CMBs and CMBs at the 3-month follow-up MRI were recorded. CMBs were classified into deep (basal ganglia, thalamus, internal capsule, external capsule, corpus callosum, and deep and periventricular white matter), lobar (frontal, parietal, temporal, occipital, and insular), and infratentorial regions (brain stem and cerebellum). The locations of CMBs were also classified according to the stented artery supplying territory and other territories. The degree of small vessel disease (SVD) was evaluated using the Fazekas scale. All images were reviewed by two radiologists independently. A consensus was achieved after discussion. Differences in the initial number of CMBs were compared. The differences in the increased number of CMBs between stented arteries supplying territory and other territories, as well as extracranial and intracranial stentings were also compared.

2.5. Statistical analysis

Student’s t test and one-way analysis of variance were used to analyze patient baseline characteristics, initial CMB numbers, and increased CMB numbers between stented arteries supplying territory and other territories, as well as extracranial and intracranial stentings. A p value of <0.05 was considered statistically significant. SPSS, version 24, was used for all statistical analyses.


Overall, 99 patients underwent extracranial or intracranial stenting at the hospital during the study period; 24 who did not undergo SWI before or after stenting were excluded. A total of 75 patients (50 male and 25 female patients) were included in the final analysis. Overall, 84 stentings were performed, namely 25 cervical ICA stentings, 10 intracranial ICA stentings, 26 MCA stentings, 8 extracranial VA stentings, 2 intracranial VA stentings, 7 BA stentings, and 6 subclavian artery stentings. The average patient age was 65.37 years ± 11.53; 55 patients had hypertension, 39 had diabetes mellitus, 35 had both hypertension and diabetes mellitus, 28 had acute ischemic stroke, and 37 had old lacunar infarctions (Table 1). In patients with acute ischemic stroke, they received stenting at least 2 weeks after initial events. None of the patients had underlying atrial fibrillation and received anticoagulants.

Table 1 - Patient baseline characteristics
Initial 0 CMBs (n=52) Initial 1-5 CMBs (n=20) Initial ≥6 CMBs (n=3) p
Age, y; mean ± SD 65.8 ± 11.8 63.4 ± 11.1 70.7 ± 11 0.446
Women, n (%) 19 (36.5%) 6 (30%) 0 (0%) 0.403
Medical history
 Hypertension, n (%) 48 (92.3%) 11 (55%) 3 (100%) 0.904
 Diabetes mellitus, n (%) 26 (50%) 13 (65%) 1 (33.4%) 0.448
 Both hypertension and diabetes mellitus, n (%) 25 (48.1%) 9 (45%) 1 (33.4%) 0.875
 Acute ischemic stroke, n (%) 21 (40.4%) 5 (25%) 2 (66.7%) 0.279
 Old lacunar infarctions, n (%) 22 (42.3%) 15 (75%) 1 (33.4%) 0.232
Stenting area
 Cervical ICA, n (%) 20 (38.5%) 5 (25%) 0 (0%) 0.262
 Intracranial ICA, n (%) 7 (13.5%) 3 (15%) 0 (0%) 0.782
 MCA, n (%) 19 (36.5%) 5 (25%) 2 (66.7%) 0.332
 Extracranial VA, n (%) 5 (9.6%) 2 (10%) 1 (33.4%) 0.441
 Intracranial VA, n (%) 1 (1.9%) 1 (5%) 0 (0%) 0.744
 BA, n (%) 6 (11.5%) 1 (5%) 0 (0%) 0.602
 Subclavian artery, n (%) 2 (3.8%) 4 (20%) 0 (0%) 0.068
MRI findings
Fazekas scale, n (%)
 0 6 (11.5%) 1 (5%) 0 (0%) 0.602
 1 33 (11.5%) 10 (50%) 1 (33.4%) 0.396
 2 10 (11.5%) 7 (35%) 0 (0%) 0.234
 3 3 (11.5%) 2 (10%) 2 (66.7%) 0.001 a
BA = basilar artery; CMB = cerebral microbleed; ICA = internal carotid artery; MCA = middle cerebral artery; MRI = magnetic resonance imaging; VA = vertebral artery.
aStatistical significance.

The 75 patients were divided into three groups according to the number of CMBs on initial SWI: 52 patients with no CMBs, 20 patients with 1-5 CMBs, and 3 patients with ≥6 CMBs. In the initial 1-5 CMB group, deep CMBs were present in 5 patients (25%), lobar CMBs in 14 patients (70%), and infratentorial CMBs in 6 patients (30%). In the initial ≥6 CMB group, deep and lobar CMBs were present in all three patients, and infratentorial CMBs were present in one patient. Overall, 28 patients (37.3%) had additional CMBs in 3-month follow-up MRI. The average increase in CMBs was 0.56 ± 1.06, 1.45 ± 3.32, and 7 ± 3.6, respectively, in each group. Significantly more CMBs developed in the initial ≥6 CMB group than in the other groups (7 ± 3.6 vs 0.56 ± 1.06, 1.45 ± 3.32, p < 0.001). No significant difference in the increase in CMB numbers was observed between the initial no CMB and 1-5 CMB groups (0.56 ± 1.06 vs 1.45 ± 3.32, p = 0.218; Table 2). A representative case with new CMB formation after stenting is shown in the Fig. 1. In the initial 0 CMB group, new deep CMBs were present in 4 patients (7.7%), new lobar CMBs in 14 patients (26.9%), and new infratentorial CMBs in 1 patient (1.9%). In the initial 1-5 CMB group, no deep CMBs developed (0%), new lobar CMBs were present in eight patients (40%), and new infratentorial CMBs in two patients (10%). In the initial ≥6 CMB group, new deep and lobar CMBs were present in all three patients, and new infratentorial CMBs were present in two patients. More new CMB development was found in the lobar area (p < 0.05). Significantly more CMBs developed in the stented arterial supplying territory than in other territories (0.6 ± 0.13 vs 0.44 ± 0.17, p < 0.05). No significant difference in the increase in CMB numbers was observed between patients with and without acute ischemic stroke (0.72 ± 1.81 vs 1.6 ± 3.03, p = 0.12). We also compared the initial CMB numbers and the degree of SVD. The average Fazekas scale score of each group was 1.19 ± 0.72, 1.61 ± 0.76, and 2.33 ± 1.15. The initial ≥6 CMB group had a significantly more severe degree of SVD. No significant difference in the degree of SVD was observed between the initial no CMB and the 1-5 CMB groups (Table 2). No intracerebral hemorrhage (ICH) was noted in all cases.

Table 2 - Comparison of increased CMBs at 3-month follow-up and baseline Fazekas scale
Initial 0 CMBs (n=52) Initial 1-5 CMBs (n=20) Initial ≥6 CMBs (n=3) p
Increased CMBs 0.56 ± 1.06 1.45 ± 3.32 7 ± 3.6 0.000 a
Fazekas scale 1.19 ± 0.72 1.61 ± 0.76 2.33 ± 1.15 0.011 a
CMB = cerebral microbleed.
aStatistical significance.

Fig. 1:
A 70-y-old man received right MCA stenting. Pretreatment SWI (A) indicated a CMB at the right thalamus (arrow). SWI at 3-mo follow-up (B) indicated increased number of CMBs at the right frontal lobe, right putamen, and left thalamus (arrowheads). Axial fluid-attenuated inversion recovery image (C) indicated confluent periventricular white matter hyperintensity. Prestenting MR angiography (D) indicated severe stenosis at right M1 segment of MCA (arrow) and decreased right MCA ramifications. MR angiography at 3-mo follow-up (E) indicated increasing right MCA ramifications. CMB = cerebral microbleed; MCA = middle cerebral artery; MR = magnetic resonance; SWI = susceptibility-weighted imaging.

In total, 39 extracranial stentings and 45 intracranial stentings were performed; two patients underwent both extracranial and intracranial stenting (one patient with cervical ICA and MCA stentings and one with cervical ICA and intracranial ICA stentings); four patients underwent two intracranial stentings (two with intracranial ICA and MCA stentings, one with intracranial ICA and BA stentings, and one with MCA and BA stentings); and three patients underwent two extracranial stentings (two with cervical ICA and extracranial VA stentings and one with extracranial VA and subclavian artery stentings). The average increase in CMBs in patients who underwent extracranial and intracranial stentings were 0.82 ± 1.55 and 1.59 ± 5.07, respectively. After the patients who underwent both extracranial and intracranial stenting were excluded, no significant difference in the increased number of CMBs was observed between extracranial and intracranial stentings (p = 0.37). Although MCA was the most common stented artery in this series, there were no significant differences in the increased CMBs between MCA stentings and other stentings (1.23 ± 2.49 vs 0.96 ± 2.32, p = 0.64).


In this study, the following was observed: (1) CMBs can develop after stenting whether in the operative territory or elsewhere; (2) preexisting CMBs before treatment was an independent risk factor for new lesion development; (3) the stenting-related territory had larger increase in CMBs than other territories; (4) no significant difference was noted in CMB formation among different arterial stentings; and (5) more new CMB developments were found in the lobar area. The Figure demonstrates CMB formation in the right MCA territory after right MCA M1 segment stenting. Intracranial atherosclerosis is more prevalent in the eastern hemisphere than in the western hemisphere,10 and 48% of stentings in our series were intracranial. In our case, new CMBs were observed with both intracranial and extracranial stents. New-onset CMBs were found in 47 cases (62.67%). No difference was observed in the increasing tendency between intracranial and extracranial stenting.

CMBs may be seen in 3.1%-17% of the healthy population. The number of CMBs increases with age.11 In a series, 36 of 187 patients with acute stroke undergoing mechanical thrombectomy presented with CMBs in pretreatment brain MRI.12 Risk factors for CMBs include hypertension and male sex.3,13 In our case series, 30.7% of patients had preexisting CMBs, which is much higher than the ratio in other series. The high prevalence in our case series is perhaps related to the high hypertension ratio (73.3%) and male predominance (67%).

Our case series demonstrated different CMB increase in number in different initial brain condition. With more CMBs in the pretreatment brain, a trend of increasing CMB number post-treatment (after stenting and medications) was revealed. According to previous research,14 we divided preexisting CMB numbers into three groups. The result indicated that ≥6 preexisting CMBs caused significantly more CMB formation post-treatment. Some studies15 have concluded that newly developed CMBs in patients with intracranial and/or extracranial stents were associated with increasing systolic blood pressure but not with the number of baseline CMBs; our findings are compatible with other studies,8,9,16,17 which show preexisting CMBs as the risk factor.

When we compared the stenting-related territory with nonrelated territories, the increase in the number of CMBs in the stenting-related territory was significantly higher. Even if we controlled for the posttreatment blood pressure well, significantly increasing blood flow was observed in the poststenting territory. The formation of CMBs might be the result of tiny atherosclerotic plaque migration, fat embolism, or a shower of cholesterol microemboli produced from the injured intimal layer of postballoon angioplasty and stenting arteries.4 Significantly increasing flow after treatment was also found in the treatment-related territory proved by brain perfusion study. Increasing flow and transient asymptomatic hyperperfusion conditions might cause asymptomatic microhemorrhage of brain parenchyma. In our results, CMB formation in stenting supplying territories was compatible with these possible CMB formation mechanisms. More new CMB developments found in the lobar area were compatible with the theory. Various microemboli during the procedure flowed into the lobar area and caused the formation of CMBs.

In our results, formation of new CMBs was not only in stenting arterial supplying territory but also in other territories. Gao et al15 described the formation of new CMBs was related to hypertension. In our case series, high incidence of hypertension (73.3%) was observed. Poststenting DAPT was routinely used in our case series. Both the factors affected the formation of new CMBs. Kakumoto et al9 described rapid formation of new CMBs after carotid stenting in 88 cases whether in ipsilateral or contralateral side. Therefore, there were multiple factors affecting the formation of new CMBs.4,8,9,14–17 Some factors remained unclear, and further large case-control studies were necessary. But the results state that relatively high incidence of new CMB formation is found at the stenting-related territory in our case series. Thus, some uncommon causes of CMB formation were not uncovered in our case series, such as amyloid angiopathy, anemia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or Fabry’s disease.4

In previous research,18–23 a trend of the increased risk of symptomatic ICH after thrombolysis for ischemic stroke was noted if CMBs were present in pretreatment MRI. In our study, no new symptomatic acute stroke or ICH occurred, even with new CMB development. Ogawa Ito et al8 demonstrated seven new CMBs following the onset of symptomatic ICH after carotid artery stenting. A previous meta-analysis review21 reported a trend for a higher ICH risk in patients with CMBs. Therefore, even if DAPT6,24 and stenting are safe for use in cerebrovascular disease treatment, routine posttreatment blood pressure control and caution regarding hyperperfusion syndrome are necessary, especially in high baseline CMB patients.

In our case series, 90.3% had various degrees of SVD. The number of CMBs exhibited a positive correlation with the degree of SVD. This result is in line with previous research.17,22,25 Pathologically, CMBs generally correspond to hemosiderin-laden macrophages close to arterioles affected by SVD.1,2 Therefore, baseline CMB numbers could reflect the brain condition as related by the SVD degree.

This study used the unitary protocol to follow up the patients. The same DAPT medication treatment was also arranged in all cases. The imaging follow-up was performed using the same 3T MRI. This standardized method could increase the power of this research. However, the study had limitations: (1) this was a retrospective study, with the potential risk of selection bias; (2) small case number, especially cases with a high baseline number of CMBs, would decrease the strength of this study; (3) no brain perfusion study was routinely arranged to evaluate the perfusion change effect by stenting; (4) the follow-up period was only 3 months, long-term follow-up should be necessary in further study; (5) the study lacked of noninterventional group to compare between nature course of CMB formation and poststenting effect.

In conclusion, preexisting CMBs were risk factors for the onset of new CMBs post-treatment. Poststenting and DAPT were associated with statistically significant increase in the number of CMBs in stented artery supplying territories at short-term follow-up. Poststenting care for patients with CMBs requires close attention.


This work received no financial support. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All protocols were under the supervision of the Institutional Review Board of the Taipei Medical University–Shuang-Ho Hospital (N202106014). This article was edited by Wallace Academic Editing.


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Cerebral microbleeds; Dual antiplatelet therapy; Extracranial stenting; Intracranial stenting; Small vessel disease

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