Indirect Revascularization Surgery Research Articles

Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS. Adults with MMD and T2DM who underwent EDAS between June 2004 and December 2018 were included in the analysis. In total, 126 patients (213 hemispheres) with MMD and T2DM from the Fifth Medical Centre of the Chinese PLA General Hospital were included and randomly divided into training (152 hemispheres) and internal validation (61 hemispheres) cohorts at a ratio of 7:3. Univariate logistic and least absolute shrinkage and selection operator regression analyses were used to identify the significant factors associated with good neoangiogenesis, which were used to develop a nomogram. The discrimination, calibration, and clinical utility were assessed. A total of 213 hemispheres in 126 patients were reviewed, including 152 (71.36%) hemispheres with good postoperative collateral formation and 61 (28.64%) with poor postoperative collateral formation. The authors selected 4 predictors (FGD5 rs11128722, VEGFA rs9472135, Suzuki stage, and internal carotid artery [ICA] moyamoya vessels) for nomogram development. The C-indices of the nomogram in the training and internal validation cohorts were 0.873 and 0.841, respectively. The nomogram exhibited a sensitivity of 84.5% and specificity of 81.0%. The positive and negative predictive values were 92.1% and 66.7%, respectively. The calibration curves indicated high predictive accuracy, and receiver operating characteristic curve analysis showed the superiority of the nomogram. The decision-making analysis validated the fitness and clinical application value of this nomogram. Then a web-based calculator to facilitate clinical application was generated. The nomogram developed in this study accurately predicted neoangiogenesis in patients with MMD and T2DM after EDAS and may assist neurosurgeons in identifying suitable candidates for indirect revascularization surgery.

Development of the external carotid artery system including the middle temporal artery after direct-indirect revascularization surgery for moyamoya disease

BackgroundThe aim of this study was to clarify when and from which blood vessels indirect revascularization develops after combined revascularization surgery for moyamoya disease and how the donor vessels that undergo direct revascularization change in the medium to long term. In particular, we focused on the middle temporal artery (MTA), which has not received much attention in indirect revascularization surgery for moyamoya disease until now. MethodsWe targeted 20 sides that were suitable for evaluating the diameter of the external carotid artery system involved in combined revascularization surgery among moyamoya disease patients who underwent a composite revascularization procedure utilizing a 'U'-shaped skin incision encircling the parietal branch of the superficial temporal artery (STA) at our institution from 2018 to 2023. We identified the STA parietal branch, MMA, DTA, and MTA in the TOF source MR images acquired preoperatively and three and six months after surgery; measured the long and short diameters of each blood vessel; approximated the blood vessel shape as an ellipse, and calculated its cross-sectional area. ResultsThe cross-sectional areas of the MMA, DTA, and MTA involved in indirect revascularization significantly increased compared to presurgery three months after surgery, and this trend continued six months after surgery, but no significant change was observed between three and six months after surgery. There were no cases in which the MTA was clearly confirmed before surgery in the TOF reconstructed images, but the MTA was clearly confirmed in 55% (11/20 cases) of hemispheres three months after surgery and in 85% (17/20 cases) of hemispheres six months after surgery. The crosssectional area of the STA parietal branch, which was the donor for direct revascularization, had increased by more than 150% compared to before surgery in 55% (11/20 cases) of hemispheres three months after surgery. ConclusionsIndirect revascularization can be expected three months after combined revascularization surgery for moyamoya disease. The MTA, which has not received much attention in terms of indirect revascularization for moyamoya disease patients thus far, was found to be a useful blood flow source for indirect revascularization in combined revascularization surgery for patients with moyamoya disease. Whether or not the cross-sectional area of the superficial temporal artery used as a donor for direct revascularization increased in the medium to long term varied on a case-by-case basis.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4h before and 24h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24h, hourly neurologic assessments for at least 12h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Nomogram to Predict Good Neoangiogenesis After Indirect Revascularization Surgery in Patients with Moyamoya Disease: a Case-control Study.

Indirect bypass surgery is an effective treatment for moyamoya disease (MMD), but the success of the surgery depends on the formation of spontaneous collateral vessels, which cannot be accurately predicted before surgery. Developing a prediction nomogram model for neoangiogenesis in patients after indirect revascularization surgery can aid surgeons in identifying suitable candidates for indirect revascularization surgery. This retrospective observational study enrolled patients with MMD who underwent indirect bypass surgery from a multicenter cohort between December 2010 and December 2018. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis identifying potential predictors of good neoangiogenesis. A total of 263 hemispheres of 241 patients (mean ± SD age 24.38 ± 15.78years, range 1-61years) were reviewed, including 168 (63.9%) hemispheres with good postoperative collateral formation and 95 (36.1%) with poor postoperative collateral formation. Based on multivariate analysis, a nomogram was formulated incorporating four predictors, including age at operation, abundance of ICA moyamoya vessels, onset type, and Suzuki stage. The C-index for this nomogram was 0.80. Calibration curve and decision-making analysis validated the fitness and clinical application value of this nomogram. The nomogram developed in this study exhibits high accuracy in predicting good neoangiogenesis after indirect revascularization surgery in MMD patients. This model can be very helpful for clinicians when making decisions about surgical strategies for MMD patients in clinical practice.

Surgical outcomes following encephaloduroarteriosynangiosis in moyamoya disease associated with hyperhomocysteinemia.

This study investigated the effect of indirect revascularization surgery in adult patients with moyamoya disease (MMD) complicated with hyperhomocysteinemia (HHcy), and the effect of HHcy on the progression of adult MMD. A retrospective case-control study was conducted in patients with MMD, with or without HHcy (n=123). Postoperative collateral angiogenesis was evaluated using the Matsushima grading system and disease progression using the Suzuki staging system. Cerebral blood flow was evaluated before and after surgery using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and neurological function prognosis using the improved Rankin score (mRS). Univariate and multivariate logistic regression analyses were performed to determine risk factors for the clinical outcomes. There was no significant difference in the Suzuki stage composition ratios between the HHcy group and the non-HHcy group before and after surgery. Non-HHcy patients were more likely to grow new collateral circulating vessels after encephaloduroarteriosynangiosis (EDAS). Moreover, postoperative DSC-MRI indicated that the time to peak significantly improved. HHcy level may be a specific predictor of adverse clinical outcomes after EDAS in patients with MMD and a risk factor for poor collateral circulation and poor prognosis. Patients with MMD complicated with HHcy need to strictly control homocysteine levels before EDAS surgery.

ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease

PurposeMoyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients.MethodsEleven MM patients (initial age 6–50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7–21 (mean 12) months after surgery.ResultsBefore surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events.ConclusionUsing ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.

Disappearance of hemichorea as the initial presentation of moyamoya disease after revascularization surgery regardless of residual hypoperfusion evaluated by quantitative N-isopropyl-p-123I-iodoamphetamine SPECT

Background and importanceAlthough hypoperfusion of the basal ganglia or the frontal subcortical matter is suspected, the pathology of chorea in moyamoya disease remains unclarified. Herein, we report a case of moyamoya disease presenting with hemichorea and evaluate pre- and postoperative perfusion using single photon emission computed tomography with N-isopropyl-p-123I-iodoamphetamine (123I-IMP SPECT). Clinical presentationAn 18-year-old woman presented with choreic movement of her left limbs. Magnetic resonance imaging revealed an ivy sign, and 123I-IMP SPECT demonstrated decreased cerebral blood flow (CBF) and cerebral vascular reserve (CVR) values in the right hemisphere. The patient underwent direct and indirect revascularization surgery to improve cerebral hemodynamic impairment. The choreic movements entirely resolved immediately after surgery. Although CBF and CVR values in the ipsilateral hemisphere demonstrated by quantitative SPECT increased, these did not reach the normal values threshold. ConclusionChoreic movement in moyamoya disease may be related to cerebral hemodynamic impairment. Further studies are required to elucidate its pathophysiological mechanisms.

Delta-Like Factor 1 Negatively Regulates Angiogenesis as a Target Gene of MIR-126-5P after Indirect Revascularization Surgery in Patients with Moyamoya Disease

Introduction: Moyamoya disease (MMD) is a chronic cerebral hypoperfusion state with increased narrowing of the intracranial internal carotid artery. Objectives: The main objective of the study is to analyses the delta-like factor 1 negatively regulates angiogenesis as a target gene of miR-126-5p after indirect revascularization surgery in patients with moyamoya disease. Material and methods: This retrospective study was conducted in Akhtar Saeed Medical College Lahore during 2020 to 2021. First, we compared the DLK1 expression in DM tissues from patient with moyamoya disease (n = 8) and unruptured aneurysms (n = 8, control group). DM samples (1.0 × 0.5 cm) were collected from patients with moyamoya disease during revascularization procedures. DM samples were harvested from the temporal part of the head and stored for further use. Results: EPC markers CD31, VE-cadherin, and VEGFR-2 were strongly expressed in cultured cells, while hematopoietic marker CD133 did not display remarkable expression, suggesting highly purified EPC isolation. Practical implication: This study will be helpful in EC proliferation and angiogenesis. Conclusion: It is concluded that DLK1, a target gene of miR-126-5p, negatively regulates EC proliferation and angiogenesis and that downregulating DLK1 expression potentially promotes angiogenesis in chronically ischaemic brains. Keywords: DLK1, EC, Proliferation, Angiogenesis

Headache in Pediatric Moyamoya Disease after Revascularization Surgery

Introduction: Patients with moyamoya disease (MMD) often have headaches after successful revascularization surgery. We aimed to characterize headache in surgically treated MMD patients and elucidate its clinical meaning and pathophysiology. Methods: Headache and related symptoms were surveyed using structured questionnaires in pediatric MMD patients with follow-up for 6 months or longer after indirect revascularization surgery. Clinical information including initial presentation, surgical method, and outcome was collected from medical records. Surgical outcomes were assessed clinically and by perfusion imaging. We defined “headache associated with MMD” as the headache accompanied by a transient ischemic attack or provoked by hyperventilation. Other headaches were further classified based on the diagnostic criteria of the International Headache Society-3. We analyzed the characteristics of “headache associated with MMD” and newly developed headache after surgery. Results: Among 90 participants, 65 (72.2%) had headaches within the last year before survey, including 28 (43.1%) with “headaches associated with MMD,” 10 (15.3%) with probable migraines, 2 (3.1%) with infrequent episodic tension-type headaches, and 4 (6.2%) with probable tension-type headaches. Headache quality was pulsatile in 27 (41.5%) patients and pressing or tightening in 27 (41.5%) patients. Nausea or vomiting was accompanied in 30 (46.2%) patients. Headache upon awakening was reported in 37 (57.8%) patients. Headache disturbed daily life in 12 (18.5%) patients. Among the 32 (35.6%) patients who suffered headache during both the pre- and postoperative period, the headache quality was similar in 27 (84.4%) patients, and its severity decreased in 24 (75.0%) and did not change in 8 (25.0%) patients. Twelve (13.3%) patients experienced newly developed headaches after surgery. Among them, six (50.0%) were classified as having “headaches associated with MMD.” They were predominantly electric shock-like or stabbing in 5 (45.6%) patients and nondisturbing in all patients. All 90 patients achieved improvement of ischemic symptoms after surgery. Conclusion: Headaches often persist or newly develop after revascularization surgery in MMD patients. Accompanying nausea or vomiting and occurrence upon awakening are characteristic features. Postoperative headache does not necessarily imply insufficient disease control.

Practice variability in the perioperative management of pediatric moyamoya disease in North America

BackgroundRevascularization surgery decreases the long-term risk of stroke in children with moyamoya but carries an increased risk of perioperative ischemic events. Evidence-based approaches to safe perioperative management of children with moyamoya are limited. We aimed to understand practice variability in perioperative moyamoya care. MethodsNeurologists, neurosurgeons, and intensivists practicing in North America with expertise in perioperative pediatric moyamoya care participated in a 138-item anonymous survey focused on interdisciplinary perioperative care surrounding indirect revascularization surgery. ResultsMany perioperative care practices vary substantially between participants. Timing of resumption of antiplatelet therapy postoperatively, choice of sedative agents and vasopressors, goal blood pressures, rate and duration of intravenous fluid administration, and red blood cell transfusion thresholds are among the most variable practices. ConclusionsThis practice variability survey highlights several important knowledge gaps and areas of equipoise that should be targets for future investigation and consensus-building efforts.

Effect of combined Japanese traditional medicines, keishibukuryogan and jidabokuippo, on postoperative soft tissue swelling in adult patients undergoing revascularization surgery for ischemic moyamoya disease: A comparison of two prospective cohort studies

AbstractAimIndirect revascularization surgery for moyamoya disease (MMD) sometimes results in swelling of the soft tissues (including the temporalis muscle) compressing the cerebral hemispheres postoperatively. The present supplementary analysis of two prospective cohorts aimed to elucidate the effects of Japanese traditional medicines, keishibukuryogan and jidabokuippo, on postoperative soft tissue swelling in adult patients undergoing revascularization surgery for ischemic MMD.MethodsThirty‐two patients treated using direct revascularization surgery alone without Japanese traditional medicine (the first original study) and another 22 patients treated using indirect revascularization surgery alone with perioperative administration of keishibukuryogan and jidabokuippo (the second original study) underwent computed tomography of the head before and 3 days after surgery. The postoperative swelling rate of soft tissues in the head ipsilateral to the surgery was calculated.ResultsThe postoperative swelling rate of the soft tissues was significantly lower in patients participating in the second original study (88.8 ± 31.6%) than in those participating in the first original study (127.1 ± 31.1%) (p = 0.0002). When postoperative swelling rates of soft tissues in all 54 patients were arranged in descending order and divided into tertiles (186.7–132.0%, 130.0–92.4%, 92.3–44.3%), logistic regression analysis revealed that participation in the second original study was significantly associated with the bottom tertile of postoperative swelling rate of soft tissues (95% confidence interval, 4.90–100.12; p = 0.0098).ConclusionCombined administration of Japanese traditional medicines, keishibukuryogan and jidabokuippo, can reduce postoperative soft tissue swelling in adult patients undergoing revascularization surgery for ischemic MMD.

Cerebrovascular Reserve Impairment in the Anterior Cerebral Artery Territory Predicts Deep Temporal Artery Enlargement After Combined Revascularization Surgery in Moyamoya Disease.

A combined surgery of direct and indirect revascularization has been frequently performed in patients with moyamoya disease, though the efficacy of indirect revascularization surgery in adult patients with moyamoya disease has not been established. This study aimed to evaluate superficial temporal artery (STA) and deep temporal artery (DTA) diameters 1day and 3months after combined revascularization surgery in patients with moyamoya disease. We also investigated clinical factors related to DTA enlargement after surgery. We examined 78 cerebral hemispheres in 57 adult and pediatric patients with moyamoya disease who underwent combined revascularization surgery [STA-MCA bypass and encephalo-duro-myo-synangiosis] in our institution. STA and DTA diameters were measured on axial magnetic resonance angiography images at 1day and 3months after surgery. DTA diameter increased in 64 hemispheres (82.1%). DTA diameter increase in association with STA diameter decrease was found in 39 hemispheres (50%). The proportion of hemispheres with a reduction in STA diameter was significantly higher in hemispheres with DTA enlargement than in hemispheres with DTA reduction (P=0.0088). Among the 64 hemispheres with DTA enlargement, 51 (79.7%) showed cerebrovascular reserve (CVR) impairment in the anterior cerebral artery (ACA) territory before surgery. CVR impairment in the ACA territory was the only clinical factor related to DTA enlargement (P<0.001). The DTA frequently enlarges after combined revascularization surgery, even in adult patients with moyamoya disease. In patients with impaired CVR in the ACA territory, blood supply from the DTA to the ACA territory can be expected after combined revascularization surgery.

Transient ischemic attack after indirect revascularization surgery for pediatric patients with moyamoya disease: A retrospective study of intraoperative blood pressure

BackgroundThis study aimed to investigate the association between intraoperative blood pressure and postoperative transient ischemic attacks (TIAs) in pediatric patients with moyamoya disease after indirect revascularization surgery. MethodsWe retrospectively reviewed the medical records of patients with moyamoya disease younger than 15 years who underwent indirect revascularizations under general anesthesia from 2013 to 2019. Perioperative clinical factors and intraoperative blood pressure data were collected and analyzed. Univariate and multivariable mixed-effect logistic regressions were used to identify predictors of postoperative TIA and symptom progression. ResultsAmong 444 hemispheres in 296 pediatric patients, 70 cases (16%) experienced postoperative TIAs within 2 weeks after surgery, and 34 cases (7.7%) developed postoperative symptom progression. Baseline mean blood pressure (MBP) (adjusted odds ratio, 1.261; 95% confidence interval, 1.037−1.528; P < 0.001), Average mean arterial pressure (MAP) (adjusted odds ratio, 1.137; 95% confidence interval, 1.052−1.228; P = 0.006), and Ipsilateral magnetic resonance angiography (MRA) score (adjusted odds ratio, 1.464; 95% confidence interval, 0.886−2.419; P = 0.012) were statistically significant risk factors for postoperative TIA. Average real variability of MAP (ARV-MAP), which were measures of intraoperative MAP variability (adjusted odds ratio, 4.731; 95% confidence interval, 1.419−15.257; P = 0.003) and maximum MAP declination (MaxD-MAP) (adjusted odds ratio, 1.271; 95% confidence interval, 1.013−1.520; P = 0.010) were statistically significant risk factors for postoperative symptom progression. ConclusionHigher pre-induction baseline blood pressure and ipsilateral MRA score were independent risk factors predicting postoperative TIA in pediatric patients with moyamoya disease after indirect revascularization. The high variability and drastic decline in intraoperative MAP showed predictive value in postoperative symptom progression.

Changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic moyamoya disease.

Periventricular anastomosis in moyamoya disease (MMD) is an unusual angiographic finding that arises from perforating arteries such as the lenticulostriate artery (LSA), thalamic artery (THA), and anterior choroidal artery (AChA). This anastomosis is associated with increased hemorrhagic risk in MMD and can be corrected by direct revascularization surgery. The present supplementary analysis on a prospective cohort aimed to elucidate changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Twenty-two patients with misery perfusion in the symptomatic cerebral hemisphere who underwent indirect revascularization surgery alone also underwent six-vessel cerebral angiography via arterial catheterization before and at 6months after surgery. Before surgery, two patients (9%) had positive periventricular anastomosis from the LSA and another (5%) from the AChA; all three of these periventricular anastomoses regressed after surgery, but these changes were not statistically significant (p = 0.0833). The degree of formation of collateral vessels from the LSA significantly decreased after surgery (p = 0.0143), but the degree of collateral vessels from the THA or AChA did not differ between pre- and postoperative conditions. Eight patients with postoperative regression of the collateral vessels from any perforating artery exhibited postoperative rich collateral flow from indirect revascularization. Periventricular anastomosis tended to regress after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Collateral vessels formed from the LSA likely regressed after indirect revascularization surgery alone for such patients, but those vessels from the THA or AChA seldom changed.

Postoperative vascular event prediction using angiography and ultrasonography in patients with Moyamoya disease

ObjectiveIndirect revascularization surgery reduce the risk of recurrent vascular events in patients with moyamoya disease (MMD), but the roles of postoperative angiography and ultrasonography in predicting these events remain unclear. MethodsThis prospective study enrolled patients with MMD who would undergo their first unilateral indirect revascularization surgery. They received preoperative and postoperative ultrasound examination at 1, 3, and 6 months and conventional cerebral angiography. On ultrasonography, postoperative emerging flow (PEF) in an intracranial artery was defined as emerging flow postoperatively with absence of flow preoperatively. Predictors of vascular event frequency reduction were identified from angiographic and ultrasonographic parameters. ResultsIn total, 52 patients (including 24 pediatric and 24 male patients), who underwent 52 preoperative and 82 postoperative ultrasound examinations, were enrolled. Significant postoperative changes were noted in all the ultrasonographic parameters of ipsilateral superficial temporal artery (STA) and the end-diastolic velocity and flow volume in contralateral STA. During a median follow-up of 5.3 years, indirect revascularization surgery significantly reduced the occurrence of ipsilateral vascular events. Predictors of vascular event frequency reduction included Matsushima grade A or B on the ipsilateral side on angiography (odds ratio [OR] = 22.00, P = 0.002) and lower resistance index (RI) in ipsilateral STA (OR = 0.0001, P = 0.012) but no PEF pattern in ipsilateral middle cerebral artery (OR = 0.14, P = 0.029) on ultrasonography performed within 6 months. ConclusionsReduction of long-term vascular event frequency probably can be predicted through postoperative angiography and ultrasonography within 6 months after indirect revascularization surgery.

Delta-like factor 1 negatively regulates angiogenesis as a target gene of miR-126-5p after indirect revascularization surgery in patients with moyamoya disease

Promoting endothelial cell (EC) proliferation and angiogenesis after indirect revascularization surgery is crucial for decreasing the stroke rate in moyamoya patients. However, the role of delta-like factor 1 (DLK1) in regulating EC proliferation in chronically ischaemic brains and the specific mechanisms remain unclear. Therefore, we compared the expression levels of DLK1 in the dura mater (DM) tissues of patients with moyamoya disease and patients with aneurysms, and dual luciferase reporter and RNA binding protein immunoprecipitation assays were conducted to determine whether DLK1 is a target gene of miR-126-5p. The effect of DLK1 on EC proliferation and the interaction between DLK1 and miR-126-5p were explored in vitro. Then, we established an animal model of two-vessel occlusion together with encephalo-myo-synangiosis (2VO+EMS). The temporalis muscles (TMs) of the animals were transfected with DLK1 lentiviral RNA (Lv-DLK1) and short hairpin RNA (sh-DLK1) to compare the DLK1 expression, angiogenesis (CD31 count), and numbers of vacuoles and impaired tight junctions in the ECs of TM-covered chronically ischaemic brains as well as the cognitive improvement in each group. DLK1 expression was lower in the DM tissues of moyamoya patients than in those of the aneurysm patients, and DLK1 was identified as a target gene of miR-126-5p. In vitro, DLK1 inhibited EC proliferation, migration and angiogenesis and exerted effects opposite those of miR-126-5p. In 2VO+EMS rats, compared to the control transfection, the TM transfection of Lv-DLK1 induced significantly higher DLK1 expression and worse angiogenesis in the TM-covered ischaemic brain as well as less extensive cognitive improvement, while the transfection of sh-DLK1 into the TM had the opposite effects. In summary, DLK1, a target gene of miR-126-5p, negatively regulates angiogenesis in chronically ischaemic brains and is expected to be a new target to improve the efficacy of indirect revascularization surgery and the prognosis of moyamoya patients.

Indirect Revascularization Surgery for Chronic Ischemia in Moyamoya Disease

Indirect revascularization is a surgical procedure to reduce cerebral ischemia, using subcutaneous tissues or dura mater supplied by extracranial arteries as grafts. The perfusion pressure gradient between the cortex and the graft, if present, induces arteriogenesis and develops extracranial-intracranial anastomoses to supply blood flow to the cerebral cortex underneath the graft. Therefore, it is essential to perform the craniotomy over the site of the cerebral ischemia to induce functional anastomoses. The details of the indirect revascularization procedure vary among institutes in terms of the grafts used(skin arteries, such as the superficial temporal artery; temporal muscle, galea, or pericranium), dura mater incisions(removal and replacement with the grafts, linear incision, or multiple small incisions), and the location and size of the craniotomy. Indirect revascularization is especially effective in patients with moyamoya disease because the pathophysiology of the disease itself is related to intracranial to extracranial carotid system conversion. Generally, indirect revascularization was considered ineffective in patients with atherosclerotic steno-occlusive cerebrovascular disease; however, recent clinical trials suggested that it may also be effective in these patients. If a future clinical trial demonstrates a positive outcome, indirect revascularization may become a possible treatment for atherosclerotic patients.

Recovery of Cortical Neurotransmitter Receptor Function and Its Impact on Cognitive Improvement after Indirect Revascularization Surgery Alone for Adult Patients with Ischemic Moyamoya Disease: 123I-Iomazenil Single-Photon Emission Computed Tomography Study

Brain 123I-iomazenil single-photon emission computed tomography (SPECT) can assess the distribution of the binding potential of central benzodiazepine receptors in the cerebral cortex. This binding potential may reflect neuronal function in viable tissues. The present prospective study using brain 123I-iomazenil SPECT aimed to determine whether improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in neurotransmitter receptor function in the affected cerebral hemisphere among adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion. Twenty-two patients who underwent indirect revascularization surgery alone also underwent brain SPECT scanning at 180minutes after 123I-iomazenil administration and neuropsychological testing before and at 6months after surgery. The affected-to-contralateral cerebral hemispheric asymmetry of tracer uptake before and after surgery was then calculated. The asymmetry of tracer uptake was significantly increased after surgery (P<0.0001). A significant difference between the preoperative and postoperative asymmetry of tracer uptake was seen in patients with improved cognition compared with those with unchanged cognition (P=0.0001). The area under the receiver operating characteristic curve was 0.99 for the difference between the preoperative and postoperative asymmetry of tracer uptake to assess the ability to discriminate patients with improved cognition from those with unchanged cognition. Improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in the binding potential of central benzodiazepine receptors in the affected cerebral hemisphere in adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion.

Angiographic, Cerebral Hemodynamic, and Cognitive Outcomes of Indirect Revascularization Surgery Alone for Adult Patients With Misery Perfusion due to Ischemic Moyamoya Disease.

Revascularization surgery for adult patients with ischemic moyamoya disease (MMD) may improve both cognitive function and cerebral perfusion. To determine angiographic, cerebral hemodynamic, and cognitive outcomes of indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD (IDR group) and to test the superiority of indirect revascularization surgery for cognitive improvement by conducting comparisons with historical control patients who had undergone direct revascularization surgery (DR group) through prospective cohort study with historical controls. Twenty adult patients with cerebral misery perfusion underwent encephalo-duro-myo-arterio-pericranial-synangiosis alone. Cerebral angiography through arterial catheterization, brain perfusion single-photon emission computed tomography, and neuropsychological testing were performed preoperatively and at 6 months postoperatively. In 17 patients of the IDR group, collateral flows that were newly formed after surgery on angiograms fed more than one-third of the middle cerebral artery (MCA) cortical territory. In the IDR group, perfusion in the MCA territory was significantly increased after surgery (P < .0001), and the difference in MCA perfusion between before and after surgery was significantly greater (P = .0493) compared with the DR group. Improved cognition was significantly more frequent in the IDR group (65%) than in the DR group (31%, P = .0233). Indirect revascularization surgery alone forms sufficient collateral circulation, improves cerebral hemodynamics, and recovers cognitive function in adult patients with misery perfusion due to ischemic MMD. The latter 2 beneficial effects may be higher when compared with patients undergoing direct revascularization surgery.

Imaging Pattern and the Mechanisms of Postoperative Infarction After Indirect Revascularization in Patients with Moyamoya Disease

To develop preventive strategies against postoperative infarction after indirect revascularization surgery in patients with moyamoya disease (MMD), we evaluated clinical information, with a specific focus on the imaging pattern of postoperative infarction. We retrospectively evaluated 421 surgical procedures performed in 354 (262 pediatric and 159 adult) patients with MMD from April 1991 to March 2021 at our institute. In addition to clinical information, raw images of postoperative infarction were collected and categorized into subtypes by the location of the infarction. Symptomatic and asymptomatic postoperative infarction occurred in 47 and 12 patients (11.1% and 2.6%), respectively, and more than half (51.7%) of these cases of postoperative infarction occurred immediately or the day after the surgery. Cortical infarction around the craniotomy site was the most frequent pattern observed (50/59, 84.8%), and some of these cases seemed to occur under local compression from epidural or subdural hematomas (15/50, 30.0%). Ipsilateral white matter infarctions located in the watershed area (9/59, 15.3%) and contralateral infarctions (3/59, 5.1%) were also observed. Four patients (1.0%) showed sudden occlusions of ipsilateral or contralateral large intracranial arteries immediately after surgery. Postoperative infarction caused permanent neurologic deficits in 7 patients (1.7%), and all included the cortex outside the craniotomy site. Local cortical irritation, hemodynamic fluctuation, and thromboembolic events were suggested as possible mechanisms of postoperative infarction after indirect revascularization in patients with MMD. Minimizing cortical irritation, maintaining adequate cerebral blood flow, and perioperative antiplatelet agents might decrease the incidence of postoperative infarction.