Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease

doi:10.21203/rs.3.rs-4692455/v1

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Research Article

Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease

https://doi.org/10.21203/rs.3.rs-4692455/v1

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Objective

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. In the present study, we evaluated the change of EPVSs after surgical revascularization in adult patients with MMD.

Methods

This was a single-center study. We counted the EPVSs in the basal ganglia (BG) and centrum semiovale (CSO) in each hemisphere on T2-weighted MRI performed upon admission. EPVSs were also quantified three months and two years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs.

Results

This study included 120 hemispheres of 65 adults with MMD. Older age (P = 0.04) and hypertension (P = 0.04) were significantly associated with a larger baseline number of EPVSs in the BG. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs in the CSO. The number of EPVSs only in the CSO markedly decreased at three months and two years after surgery compared with that before surgery (P < 0.01).

Conclusions

The number of EPVSs in the CSO was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

moyamoya disease

enlarged perivascular space

combined bypass surgery

MRI

Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the terminal segments of the internal carotid artery (ICA) and its main branches within the circle of Willis. Disease progression impairs cerebral hemodynamics, which causes transient ischemic attack (TIA) and/or ischemic stroke.[1, 2] In response to cerebral ischemia, perforating arteries dilate and function as collateral circulation. The fragile perforating arteries readily rupture, causing intracranial hemorrhage.[2] Surgical revascularization including direct, indirect, and combined bypass procedures improve cerebral hemodynamics and contribute to prevent future stroke risk in MMD patients.[2–5]

The diagnosis of MMD is based on cerebral angiography or magnetic resonance angiography. The severity of the cerebral ischemia is evaluated using single-photon emission computed tomography (SPECT), positron emission tomography, and perfusion magnetic resonance imaging (MRI). In contrast, previous studies also focused on the parenchymal abnormalities in MMD using MRI.² Several imaging markers of cerebral small vessel disease, including lacunes, cerebral microbleeds, enlarged perivascular spaces (EPVSs), and white matter hyperintensities, have been frequently found in MMD patients.[6–9] Among them, EPVSs, which are also known as Virchow-Robin space and detected as dot-like or linear hyperintensity in the basal ganglia (BG) and the centrum semiovale (CSO) on T2-weighted MRI, are more numerous in patients with older age, hypertension (HT), cognitive impairment, and lacunar stroke.[10–13] EPVS has also been associated with decreased cerebral blood flow (CBF) and ischemic events in MMD, which suggests EPVS as a potential radiological marker of cerebral ischemia in MMD.[9] Furthermore, a previous report has also indicated an association between EPVS and dysfunction of the glymphatic system in patients with MMD.[8] However, no previous report has elucidated the postoperative change in EPVSs in surgically treated patients diagnosed with MMD.

The present study aimed to clarify the number of EPVSs in adult patients with MMD before and after surgical revascularization and to elucidate the postoperative changes in EPVSs, as well as the clinical and radiological factors affecting the number of EPVSs and the degree of postoperative changes.

Patients

Seventy-four adult patients with MMD were admitted to our hospital between 2012 and 2019. They were diagnosed with MMD based on the findings of cerebral angiography according to the guideline for the diagnosis of MMD set by the Research Committee on Moyamoya Disease of the Ministry of Health, Welfare, and Labor of Japan.[14] In total, of 148 hemispheres of 74 patients, the study included hemispheres that met the following criteria: (1) no or, if any, minor brain damage due to ischemic and hemorrhagic stroke on MRI and (2) no history of surgical treatment. Therefore, we excluded cerebral hemispheres with significant brain damage due to ischemic or hemorrhagic stroke, and those that had previously undergone surgical revascularization. Therefore, this study included 120 hemispheres from 65 patients (25 men and 40 women) with MMD. Their mean age was 43.1 ± 10.1 years. Seventeen patients (26.2%) were diagnosed with HT, 14 (21.5%) had hyperlipidemia (HL), seven (10.8%) had diabetes mellitus (DM), 15 (23.1%) had a smoking history, and nine (13.8%) had a drinking habit. Clinical diagnoses included ischemic stroke in 18 patients (27.7%), TIA in 26 (40.0%), intracranial hemorrhage in 11 (16.9%), and asymptomatic stroke in 10 (15.4%). The baseline characteristics are summarized in Table 1.

Table 1

Clinical characteristics and radiological findings of patients on admission
Number of patients	65
Number of hemispheres	120
Age	43.1 ± 10.1
Sex (male:female)	25:65
Comorbidity
Hypertension	17 (26.2)
Hyperlipidemia	14 (21.5)
Diabetes mellitus	7 (10.8)
Smoking history	15 (23.1)
Drinking habit	9 (13.8)
Onset type
Ischemic stroke	18 (27.7)
Transient ischemic attack	26 (40.0)
Intracranial hemorrhage	11 (16.9)
Asymptomatic	10 (15.4)
Disease stage
0	19 (15.8)
1	0
2	6 (5.0)
3	42 (35.0)
4	28 (23.3)
5	22 (18.3)
6	3 (2.5)
PCA involvement	26 (21.7)
SPECT
CBF impairment	41 (35.0)
CVR impairment	84 (70.0)
PCA, posterior cerebral artery; SPECT, single photon emission computed tomography; CBF, cerebral blood flow; CVR, cerebrovascular reactivity

Radiological Examination

MRI was performed in all 65 patients on admission and at three months and two years after combined bypass surgery in surgically treated patients. MRI was performed using a clinical 1.5T MRI unit (Magnetom Avanto [Siemens AG, Erlangen, Germany]) equipped with a standard 12-channel head coil. T1-weighted, T2-weighted, T2*-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted images were obtained to locate the ischemic and hemorrhagic lesions in the brain parenchyma. EPVS was defined as small (< 3 mm) punctate or linear hyperintensities on T2-weighted imaging with corresponding hypointensities on FLAIR imaging according to the previous studies (Fig. 1).[8, 15] In the present study, two neurosurgeons counted the number of EPVS in each hemisphere in BG and CSO levels.[9] In all patients, the number of EPVS at baseline was counted. In surgically treated patients, the number of EPVS at three months and two years after surgery was also counted. The T2-weighted imaging evaluation used the following parameters: repetition time, 4,000 ms; echo time, 109 ms; flip angle, 160°; matrix size, 235 × 384; slice thickness, 6 mm; field of view, 220 mm; voxel size, 0.8 × 0.6 × 6 mm; number of excitations, 1; and scan time, 56 seconds. The FLAIR-weighted imaging evaluation used the following parameters: repetition time, 9,000 ms; echo time, 109 ms; flip angle, 170°; matrix size, 202 × 256; slice thickness, 6 mm; field of view, 220 mm; voxel size, 1 × 0.9 × 6 mm; number of excitations, 2; and scan time, 2 min 42 s.

Before surgery, the disease was categorized into six stages according to Suzuki’s classification based on cerebral angiography.[1] Involvement of the posterior cerebral artery (PCA) was also assessed. PCA was judged as involved when stenosis was > 50% in the P1-P3 segments with a decreased signal in the cortical arteries.[16] Quantitative ¹²³I-IMP single-photon emission computed tomography (SPECT) with an acetazolamide test was performed on admission.

Surgical Treatment and Postoperative Analysis

Symptomatic patients with impaired CBF and cerebrovascular reactivity (CVR) to acetazolamide on SPECT were surgically treated. Symptomatic patients with impaired cerebrovascular reactivity also underwent surgical revascularization even if their cerebral blood flow was not impaired. Antiplatelet agents were not used in any patient before or after surgery. All surgically treated patients in this study underwent superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis and encephaloduro-myo-arterio-pericranial synangiosis (EDMAPS).[4, 17] The precise procedures have been described previously in detail.[4, 18] Briefly, a frontotemporal craniotomy extending into the frontal area was performed. In an end-to-side fashion, one or two branches of the STA were anastomosed to the cortical branches of the MCA. Finally, the brain surface was covered with the temporal muscle, dura mater, and a pericranial flap.

Postoperative analysis was also conducted, including the hemispheres that met the following criteria: (1) underwent STA-MCA bypass combined with EDMAPS in our hospital and (2) underwent MRI three months and two years after combined bypass surgery. Therefore, the postoperative analysis excluded patients who did not complete the 2-year follow-up using MRI.

Statistical Analysis

In the present study, we defined ΔEPVS as follows: (ΔEPVS) = (the number of EPVS two years after surgery) - (the number of EPVS before surgery). Clinical and radiological factors affecting the number of EPVSs and ΔEPVS were statistically evaluated. Continuous variables including age, number of EPVSs, and ΔEPVS were expressed as mean ± standard deviation (SD). Variables were compared using a t-test or one-factor analysis of variance (ANOVA), followed by Tukey’s post-hoc analysis, as appropriate. A multiple regression model was used to estimate the clinical and radiological factors affecting the number of EPVSs and ΔEPVS. A stepwise forward method was used in model building with the interrogated parameters, using P < 0.10, achieved by univariate analysis, as the cut-off value. Differences were considered statistically significant when the P-value was < 0.05. In this study, the intraclass correlation coefficient (ICC) was evaluated for the number of EPVS, which is a measure of the consistency of quantitative measurements made by two different observers and ranged from 0 (no association between two measurements) to 1 (perfect agreement between two measurements).

Radiological Findings at Baseline

Using T2-weighted MRI, the number of EPVS was quantified in all 120 hemispheres. The ICC was 0.89, indicating an excellent agreement between the two observers. At baseline, the number of EPVSs in the BG and the CSO was 4.8 ± 3.2 and 18.7 ± 16.6, respectively, in 120 hemispheres. The Suzuki angiographic stage was 0 in 19 (15.8%), 2 in six (5.0%), 3 in 42 (35.0%), 4 in 28 (23.3%), 5 in 22 (18.3%), and 6 in 3 (2.5%). PCA involvement was observed in 26 (21.7%) hemispheres. On ¹²³I-IMP SPECT, CBF and CVR for acetazolamide decreased in 41 hemispheres (34.2%). In 43 hemispheres (35.8%), the CVR for acetazolamide decreased, whereas the CBF remained normal. The radiological findings on admission are summarized in Table 1.

First, we compared the number of EPVSs between non-involved and involved hemispheres in patients diagnosed with unilateral MMD (n = 19). There was no difference in the number of EPVSs in the BG between the non-involved and involved hemispheres (4.8 ± 3.4 and 6.8 ± 3.0, P = 0.14). The number of EPVSs in the CSO was 16.7 ± 12.4 in the involved hemispheres, which was significantly greater than in the non-involved hemispheres (9.6 ± 12.1, P = 0.03).

In the 101 involved hemispheres, univariate analysis revealed that age was positively correlated with the number of EPVSs in the BG (P < 0.01, R² = 0.08). Furthermore, female sex (P = 0.02), HT (P < 0.01), DM (P = 0.02), and smoking history (P = 0.04) were associated with a large number of EPVSs in the BG. In multiple regression analysis, age (β = 0.20, P = 0.04) and HT (β = 0.21, P = 0.04) were independent predictors of a large number of EPVSs in the BG (Table 2). In contrast, univariate analysis showed that age was positively correlated with the number of EPVSs in CSO (P < 0.01, R² = 0.08). Additionally, HT (P < 0.01), DM (P < 0.01), PCA involvement (P < 0.01), and CBF impairment (P = 0.01) were associated with a large number of EPVSs in CSO. Multiple regression analysis showed that age (β = 0.28, P < 0.01), PCA involvement (β = 0.30, P < 0.01), and CBF impairment (β = 0.21, P = 0.02) were independent predictors of the number of EPVSs in the CSO (Table 3).

Table 2

Multivariate regression model for the number of EPVS in the basal ganglia
Variable		Number of hemispheres	Number of EPVSs	Crude	Multivariate Adjustment
Variable		Number of hemispheres	Number of EPVSs	P-value	β	P-value
Age (continuous variable)				< 0.01	0.20	0.04
Sex	Female	60	5.4 ± 3.4	0.02	0.15	0.14
	Male	41	3.9 ± 2.8
Hypertension	Yes	28	6.3 ± 3.3	< 0.01	0.21	0.04
	No	73	4.3 ± 3.1
Hyperlipidemia	Yes	23	5.5 ± 3.1	0.24
	No	78	4.6 ± 3.3
Diabetes mellitus	Yes	11	6.9 ± 2.3	0.02	0.08	0.43
	No	90	4.6 ± 3.3
Smoking	Yes	23	3.6 ± 2.5	0.04	0.11	0.29
	No	78	5.2 ± 3.4
Drinking habit	Yes	16	4.6 ± 2.6	0.73
	No	85	4.9 ± 3.4
Onset type	Ischemic stroke	18	4.9 ± 2.8	0.66
	Transient ischmic attack	29	4.3 ± 3.1
	Intracranial hemorrhage	11	4.6 ± 3.8
	Asymptmatic	42	5.3 ± 3.4
Disease stage	1–3	48	4.8 ± 3.6	0.93
	4–6	53	4.8 ± 2.9
PCA involvement	Yes	26	5.3 ± 3.8	0.34
	No	75	4.6 ± 3.0
CBF impairment	Yes	41	5.3 ± 3.5	0.15
	No	58	4.3 ± 2.9
EPVS, enlarged perivascular space; PCA, posterior cerebral artery; CBF, cerebral blood flow

Table 3

Multivariate regression model for the number of EPVSs in the centrum semiovale
Variable		Number of hemispheres	Number of EPVSs	Crude	Multivariate Adjustment
Variable		Number of hemispheres	Number of EPVSs	P-value	β	P-value
Age (continuous variable)				< 0.01	0.28	< 0.01
Sex	Female	60	20.7 ± 17.4	0.85
	Male	41	20.0 ± 16.3
Hypertension	Yes	28	27.8 ± 19.7	< 0.01	0.16	0.09
	No	73	17.6 ± 14.8
Hyperlipidemia	Yes	23	23.8 ± 19.7	0.28
	No	78	19.4 ± 15.9
Diabetes mellitus	Yes	11	33.9 ± 24.2	< 0.01	0.13	0.16
	No	90	18.8 ± 15.1
Smoking	Yes	23	17.0 ± 11.5	0.27
	No	78	21.4 ± 18.1
Drinking habit	Yes	16	17.3 ± 10.3	0.41
	No	85	21.0 ± 17.8
Onset type	Ischemic stroke	18	22.3 ± 21.5	0.38
	Transient ischmic attack	29	18.8 ± 12.6
	Intracranial hemorrhage	11	13.5 ± 10.9
	Asymptmatic	42	22.8 ± 18.4
Disease stage	1–3	48	18.5 ± 14.0	0.27
	4–6	53	22.2 ± 19.0
PCA involvement	Yes	26	32.2 ± 21.9	< 0.01	0.30	< 0.01
	No	75	16.3 ± 12.5
CBF impairment	Yes	41	25.9 ± 16.7	0.01	0.21	0.02
	No	58	17.2 ± 16.1
EPVS, enlarged perivascular space; PCA, posterior cerebral artery; CBF, cerebral blood flow

Change of the Number of EPVS after Surgery

We performed STA-MCA bypass and EDMAPS in 73 hemispheres of 42 patients. Among them, 2-year follow-up using MRI was completed in 67 hemispheres of 37 patients. The number of EPVSs in the BG before, three months after, and two years after surgery were 4.8 ± 3.3, 4.0 ± 2.9, and 3.7 ± 2.8, respectively. There were no significant differences among the three time points (P = 0.09). On the other hand, the number of EPVSs in the CSO three months and two years after surgery were 11.8 ± 9.8 and 9.8 ± 8.6, respectively, which was a significant decrease compared with before surgery (21.1 ± 6.7; both P < 0.01, Fig. 2). An illustrative case in which EPVSs in the CSO decreased after surgery is shown in Fig. 3.

ΔEPVS was calculated at the CSO level because the EPVSs decreased after surgery only in the CSO. As a result, ΔEPVS in the CSO was − 11.3 ± 11.1 in 67 surgically treated hemispheres. In the univariate analysis, age was negatively correlated with ΔEPVS in the CSO (P = 0.02, R² = 0.08). Furthermore, HT (P < 0.01), HL (P = 0.02), DM (P = 0.01), PCA involvement (P < 0.01), and CBF impairment (P < 0.01) were associated with ΔEPVS in the CSO. Multiple regression analysis revealed that PCA involvement (β = 0.23, P = 0.04) and CBF impairment (β = 0.30, P = 0.02) were independent predictors of ΔEPVS (Table 4).

Table 4

Multivariate regression model for the number of EPVS in the centrum semiovale
Δ
Variable		Number of hemispheres	ΔEPVS	Crude	Multivariate Adjustment
Variable		Number of hemispheres	ΔEPVS	P-value	β	P-value
Age (continuous variable)				< 0.01	0.20	0.14
Female sex	Yes	49	-12.1 ± 11.9	0.30
	No	18	-8.9 ± 8.1
Hypertension	Yes	19	-19.3 ± 13.3	< 0.01	0.24	0.09
	No	48	-8.1 ± 8.2
Hyperlipidemia	Yes	18	-16.6 ± 11.4	0.02	0.05	0.73
	No	49	-9.3 ± 10.4
Diabetes mellitus	Yes	7	-21.6 ± 14.9	0.01	0.15	0.23
	No	60	-10.1 ± 10.0
Smoking	Yes	14	-9.2 ± 8.0	0.44
	No	53	-11.8 ± 11.7
Drinking habit	Yes	8	-9.6 ± 6.3	0.65
	No	59	-11.5 ± 11.6
Onset type	Ischemic stroke	13	-14.5 ± 15.7	0.13
	Transient ischmic attack	27	-9.8 ± 9.7
	Intracranial hemorrhage	10	-4.8 ± 4.4
	Asymptmatic	16	-15.3 ± 10.5
Disease stage	1–3	35	-9.6 ± 10.5	0.20
	4–6	32	-13.1 ± 11.5
PCA involvement	Yes	18	-17.4 ± 13.9	< 0.01	0.23	0.04
	No	49	-9.0 ± 9.0
CBF impairment	Yes	33	-16.0 ± 12.2	< 0.01	0.30	0.02
	No	34	-6.7 ± 7.5
EPVS, enlarged perivascular space; PCA, posterior cerebral artery; CBF, cerebral blood flow

This is the first study to demonstrate that EPVSs decrease after surgical revascularization in adult MMD, which showed that EPVSs in the CSO significantly regress after STA-MCA bypass combined with EDMAPS. According to previous reports on patients with lacunar stroke or cortical stroke, EPVSs are more numerous in patients with older age and HT.[10–12] Furthermore, a population-based study showed that EPVSs are associated with greater age, male sex, and HT in stroke- and dementia-free patients.[13] In patients with MMD, in contrast, the significance of EPVSs differs from that in stroke patients or healthy participants. According to previous reports, EPVS in the CSO are more frequently observed in female patients, those with HT, flow voids in the BG, more advanced disease stage, and decreased CBF in MMD patients.[8, 9] Furthermore, Sun et al. (2022) reported that the number of EPVS in the CSO is an independent predictor of good postoperative collateral formation in MMD.[9] Most recently, Han et al. (2023) showed a clear correlation between MCA stenosis and EPVSs in the CSO. [19] These reports suggested that EPVSs in the CSO are closely associated with chronic cerebral ischemia in patients with MMD. In the present study, older age, PCA involvement, and impaired CBF were independent predictors of a large number of EPVSs in patients with CSO (Table 3). PCA involvement is well known to promote cerebral ischemia because the PCAs function as essential collaterals in the ACA and MCA areas in MMD. Therefore, these results suggest a close relationship between EPVSs in the CSO and cerebral ischemia, supporting the results of a previous report.[9] In the present study, EPVSs in the BG were correlated with greater age and HT (Table 2), similar to reports that included patients with lacunar/cortical stroke or healthy participants.[10–13] Therefore, In MMD patients, the pathophysiology may differ between EPVS in the CSO and that in the BG. Thus, EPVSs in the CSO are more closely related to cerebral ischemia, while EPVSs in the BG may reflect aging or atherosclerosis. This is strongly supported by the finding that only the EPVSs in the CSO regressed postoperatively.

As described above, the present study clearly demonstrates that EPVSs in the CSO significantly regress after combined bypass surgery. The regression was more marked in hemispheres with PCA involvement and decreased CBF (Table 4). This result is acceptable because baseline EPVSs were more numerous in cerebral hemispheres with PCA involvement and decreased CBF. Previously, Kazumata et al. (2019) evaluated the structural and functional alterations in the brain following surgical revascularization.[20] They demonstrated the volume reduction in the subcortical nuclei and cortical thinning in the prefrontal cortex after STA-MCA anastomosis combined with EDMAPS in adult patients with MMD. The regression of EPVSs due to surgical revascularization may have been associated with this phenomenon because reduction of the perivascular space leads to a decrease in the volume of the brain.

Perivascular spaces are thought to be the spaces of extracerebral fluid surrounding the walls of perforating arterioles and venules as they course from the brain surface through the parenchyma.[8, 15] Perivascular spaces have been thought to be pathways for the clearance of interstitial solutes from the brain parenchyma.[21–24] Previous studies reported that cerebrospinal fluid (CSF) enters the brain along perivascular spaces surrounding cerebral arteries and exchanges with surrounding interstitial fluid (ISF).[25, 26] A large proportion of subarachnoid CSF enters the brain along perivascular pathways surrounding penetrating arteries, reaching the terminal capillary beds, and exchanging with ISF throughout the brain. This perivascular CSF-ISF exchange is facilitated by astroglial water transport via the aquaporin-4 water channel, supporting the clearance of interstitial solutes, such as soluble amyloid-beta, from the brain parenchyma.[27] This is known as the “glymphatic system” because of its similarity in function to the peripheral lymphatic system and its dependence upon astroglial water flux.[28] Furthermore, a previous study demonstrated that reducing cerebral arterial pulsation slows perivascular CSF–ISF exchange in the brain, whereas increasing pulsation accelerates the rate of perivascular CSF influx into the brain, indicating that cerebral arterial pulsation is a significant driver of perivascular CSF–ISF exchange in the brain.[29] In MMD, chronic progressive stenosis of the terminal portion of ICA and its main branches may result in the reduction of arterial pulsations, which impairs cerebral hemodynamics and functionally disturbs the glymphatic system.[8, 30, 31] The fact that combined bypass surgery regressed EPVSs suggests the possibility that surgical revascularization may increase cerebral arterial pulsation and improve the glymphatic system function. Further studies exploring the relationship between EPVSs and the glymphatic system are warranted.

The present study has some limitations. First, we plan to conduct a prospective study to more accurately evaluate the regressive effect of surgical revascularization on EPVSs. Second, the association between cognitive function and serial changes in EPVSs should be assessed because the present study evaluated only radiological findings. Third, changes in EPVSs after surgical revascularization should be assessed in pediatric cases. To resolve these issues, we plan to conduct a more extensive multi-center prospective study.

The number of EPVSs in the CSO was associated with age, PCA involvement, and CBF impairment, which markedly regressed after STA-MCA bypass combined with EDMAPS in adult patients with MMD. Furthermore, the postoperative changes were more remarkable in patients with PCA involvement and CBF impairment. These results strongly suggest that EPVSs are reversible structural changes that are closely correlated with cerebral ischemia in adult patients diagnosed with MMD. Furthermore, radiological changes may be associated with the functional improvement of the glymphatic system. Further multi-center prospective cohort studies are required.

MMD

moyamoya disease

ICA

internal carotid artery

TIA

transient ischemic attack

SPECT

single-photon emission computed tomography

MRI

magnetic resonance imaging

EPVS

enlarged perivascular space

basal ganglia

CSO

centrum semiovale

hypertension

CBF

cerebral blood flow

hyperlipidemia

diabetes mellitus

FLAIR

fluid-attenuated inversion recovery

PCA

posterior cerebral artery

CVR

cerebrovascular reactivity

STA

superficial temporal artery

MCA

middle cerebral artery

EDMAPS

encephaloduro-myo-arterio-pericranial synangiosis

ANOVA

analysis of variance

ICC

intraclass correlation coefficient

ISF

interstitial fluid

Ethical Approval

This study was approved by the Institutional Review Board of our hospital (R2019057). Informed consent was obtained using an opt-out method on our institutional website. In accordance with the ethical standards of the institutional research committees, this non-invasive study did not require formal consent. Instead, the outline of the study was open to the public on our institutional homepage and provided an opportunity for patients and their guardians to decline inclusion in the research.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Funding

No funding was received to assist with the preparation of this manuscript.

Author Contribution

S. Y. wrote the main manuscript text and prepared all figures and tables. S. Y., K. M., and D. K. conducted data analysis. T. A., K. N., and S. K. supervised the study. All authors reviewed the manuscript.

Availability of data and materials

The data supporting the findings of this study are available from the corresponding author upon reasonable request from any investigator.

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No competing interests reported.

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Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease

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Introduction

Methods

Patients

Radiological Examination

Surgical Treatment and Postoperative Analysis

Statistical Analysis

Results

Radiological Findings at Baseline

Change of the Number of EPVS after Surgery

Discussion

Conclusion

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