Clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease: Longitudinal and Cross-Sectional Study.

Objective: This study aimed to explore the long-term outcome of unilateral moyamoya disease and predict the clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease. Methods: We retrospectively recruited unilateral moyamoya disease patients with available genetic data who underwent encephaloduroarteriosynangiosis (EDAS) surgery at our institution from January 2009 to November 2017. Long-term follow-up data, including clinical outcomes, angiographic features, and genetic information, were analyzed. Results: A total of 83 unilateral moyamoya disease patients with available genetic data were enrolled in our study. The mean duration of clinical follow-up was 7.9 ± 2.0 years. Among all patients, 19 patients demonstrated contralateral progression to bilateral disease. Heterozygous Ring Finger Protein 213 p.R4810K mutations occurred significantly more frequently in unilateral moyamoya disease patients with contralateral progression. Furthermore, patients with contralateral progression typically demonstrated an earlier age of onset than those with non-progressing unilateral moyamoya disease. In the contralateral progression group, posterior circulation involvement was observed in 11 (11/19, 57.9%) patients compared to 12 (12/64, 18.8%) in the non-contralateral progression group (P = 0.001). The time to peak of cerebral perfusion and neurological status showed significant postoperative improvement. Conclusion: Long-term follow-up revealed that the EDAS procedure might provide benefits for unilateral moyamoya disease patients. Ring Finger Protein 213 p.R4810K mutations, younger age, and posterior circulation involvement might predict the contralateral progression of unilateral moyamoya disease.

A long-term study of posterior circulation changes after revascularization in patients with moyamoya disease.

OBJECTIVE: This study aimed to explore the long-term course of posterior circulation changes and predictors in patients with moyamoya disease (MMD). METHODS: The authors retrospectively enrolled patients who were diagnosed with MMD and underwent encephaloduroarteriosynangiosis (EDAS) surgery at the authors' department from December 2002 to September 2011. A comparative study between short-term (6-12 months) and long-term (≥ 9 years) follow-up angiography was conducted. The progression of lesions was defined from lower to higher stages of the posterior cerebral artery (PCA). RESULTS: Eighty-eight patients who received indirect EDAS were enrolled in the study. The mean age at first surgery was 28.1 ± 15.0 years. Among these 88 patients with MMD, 39 (44.3%) exhibited transient ischemic attack and 27 (30.7%) exhibited infarction, comprising 5 with occipital lobe infarction, 14 (15.9%) with hemorrhagic symptoms, and 8 (9.1%) with atypical symptoms as the initial symptoms. Heterozygous mutations occurred significantly more frequently in the cases that presented with PCA involvement. During follow-up, stage progression of PCA was observed in 21 patients (28 hemispheres). At short-term follow-up, 21/176 (11.9%) hemispheres had progression of steno-occlusive lesions in the PCA. At long-term follow-up, 7 (4.0%) hemispheres had progression of steno-occlusive lesions in the PCA. At short-term follow-up, the progression of steno-occlusive lesions in the PCA was associated with progression of the internal carotid artery. Stage progression of PCA occurred significantly more frequently in the cases with PCA involvement on preoperative angiography. Nine strokes (10.2%) occurred in 88 patients during long-term follow-up. Four patients (4.5%) presented with ischemic stroke, including 2 with occipital lobe infarctions. CONCLUSIONS: Progression of PCA stenosis is common in patients with MMD, even if the PCA is normal initially. Mutations of RNF213 p.R4810K may predict PCA involvement or progression. Follow-up of the PCA in MMD patients should be conducted, and timely surgical revascularization is needed.

Natural course and risk factors of moyamoya disease with unruptured intracranial aneurysm.

Background and objective: The natural course and risk factors of moyamoya disease (MMD) associated with unruptured intracranial aneurysms involving stenosed parental arteries are scarcely studied. This study aimed to elucidate the natural course of MMD and its associated risk factors in patients with MMD with unruptured aneurysms. Methods: Between September 2006 and October 2021, patients with MMD with intracranial aneurysms at our center were examined. The natural course, clinical features, radiological features, and follow-up outcomes after revascularization were analyzed. Results: This study included 42 patients with MMD with intracranial aneurysms (42 aneurysms). The age distribution of MMD cases ranged from 6 to 69 years, with four children (9.5%) and 38 adults (90.5%). A total of 17 male and 25 female subjects were included (male-to-female ratio: 1:1.47). The first symptom was cerebral ischemia in 28 cases, and cerebral hemorrhage occurred in 14 cases. There were 35 trunk aneurysms and seven peripheral aneurysms. There were 34 small aneurysms (<5 mm) and eight medium aneurysms (5-15 mm). During the average clinical follow-up period of 37.90 ± 32.53 months, there was no rupture or bleeding from aneurysms. Twenty-seven of these patients underwent a cerebral angiography review, in which it was found that one aneurysm had enlarged, 16 had remained unchanged, and 10 had shrunk or disappeared. A correlation exists between the reduction or disappearance of aneurysms and the progression of the Suzuki stages of MMD (P = 0.015). Nineteen patients underwent EDAS on the aneurysm side, and nine aneurysms disappeared, while eight patients did not undergo EDAS on the aneurysm side and one aneurysm disappeared. Conclusion: The risk of rupture and hemorrhage of unruptured intracranial aneurysms is low when the parent artery already has stenotic lesions, thus, direct intervention may not be necessary for such aneurysms. The progression of the Suzuki stage of moyamoya disease may play a role in the shrinkage or disappearance of the aneurysms, thereby decreasing the risk of rupture and hemorrhage. Encephaloduroarteriosynangiosis (EDAS) surgery may also help promote atrophy or even the disappearance of the aneurysm, thus reducing the risk of further rupture and bleeding.

Recognition of the Effect of Indirect Revascularization for Moyamoya Disease: The Balance Between the Stage Progression and Neoangiogenesis.

Objective: To explore the long-term progression of neoangiogenesis after indirect revascularization for moyamoya disease (MMD). Methods: We enrolled patients who were diagnosed with MMD and treated by encephaloduroarteriosynangiosis (EDAS) surgery at our center from December 2002 through September 2009. A comparative study between short-term (6-12 months) and long-term (duration ≥ 8 years) follow-up angiographies was performed. The development of collateral circulation through EDAS was graded according to the system described by the Matsushima grade system. Results: A total of 78 patients who received indirect EDAS were enrolled in the study. The mean age at the first operation was 26.9 ± 15.0 years. The Matsushima grades of the same hemisphere were higher at the long-term follow-up compared with the short-term follow-up. Importantly, no attenuation was observed in any hemisphere during the long-term follow-up. In total, 51 hemispheres (32.7%) and 26 hemispheres (16.6%) had progression during the short-term and the long-term follow-up, respectively. The ipsilateral Suzuki stage showed a significant negative correlation with progression pace. Furthermore, higher Suzuki stages were significantly correlated with the postsurgical Matsushima grade at both time points. A total of nine strokes (11.5%) occurred in 78 patients was reported at the long-term follow-up. The annual incidence rate of recurrent strokes was higher for the stage progression group than for the stable group. Conclusion: For patients with MMD, postsurgical neoangiogenesis after indirect bypass continuously improved with time. The short-term progression of the internal carotid artery (ICA) might be attributed to cerebral revascularization, while the long-term progression should be attributed to the natural progression of the disease.

The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya.

Background and Purpose: To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD). Methods: An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated. Results: Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group. Conclusions: These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.

Dynamic Changes of Collateral Vessels After Encephaloduroarteriosynangiosis in Moyamoya Disease: Childhood to Adulthood.

BACKGROUND: Moyamoya disease (MMD) often presents as ischemic stroke in pediatric patients and hemorrhage in adults. This situation raises questions as to whether the phenotype of moyamoya disease changes with age. OBJECTIVE: We performed self-precontrol and postcontrol observation monitoring until adulthood on abnormal collateral vessels (ACVs) with the potential risk of bleeding to evaluate the chance of further hemorrhage. METHODS: Fifteen pediatric patients with >10 years angiography-based follow-up were analyzed. The Matsushima grades were divided into 2 groups (good group, representing Matsushima stage A; and mild group, representing Matsushima stages B and C) to investigate the relationship between Matsushima grades and ACVs derived from vessels likely to cause intracranial hemorrhage. RESULTS: Four patients (26.7%) had infarction type and 11 (73.3%) patients had transient ischemic attack type. No patient experienced late-onset cerebral hemorrhagic events. One patient experienced recurrent ischemic stroke 6 months after the second surgery and recovered completely after the third surgery. The angiography-based follow-up was conducted at least 10 years after the encephaloduroarteriosynangiosis (EDAS). The good Matsushima group showed a significant positive correlation with the reduction of the anterior choroidal artery (odds ratio, 56.00; P = 0.003), whereas the posterior communicating artery showed no significant decrease before and after the EDAS procedure (odds ratio, 2.00; P = 1.00). CONCLUSIONS: The EDAS procedure can effectively attenuate the dilation and ACVs of the anterior choroidal artery, which may reduce the incidence of further hemorrhage in adulthood.