Paradoxical symptomatic cerebral blood flow decreases after combined revascularization surgery for patients with pediatric moyamoya disease: illustrative case

BACKGROUND Transient neurological deficits (TNDs) develop after cerebral revascularization in patients with moyamoya disease (MMD). The authors report a rare pediatric MMD case with extensive decreased cerebral blood flow (CBF) and prolonged TNDs after combined revascularization. OBSERVATIONS A 9-year-old boy presented with transient left upper limb weakness, and MMD was diagnosed. A right-sided combined surgery was performed. Two years after the surgery, frequent but transient facial (right-sided) and upper limb weakness appeared. The left internal carotid artery terminal stenosis had progressed. Therefore, a left combined revascularization was performed. The patient’s motor aphasia and right upper limb weakness persisted for approximately 10 days after surgery. Magnetic resonance angiography showed that the direct bypass was patent, but extensive decreases in left CBF were observed using single photon emission tomography. With adequate fluid therapy and blood pressure control, the neurological symptoms eventually disappeared, and CBF improved. LESSONS The environment of cerebral hemodynamics is heterogeneous after cerebral revascularization for MMD, and the exact mechanism of CBF decreases was not identified. TNDs are significantly associated with the onset of stroke during the early postoperative period. Therefore, appropriate treatment is desired after determining complex cerebral hemodynamics using CBF studies.

Moyamoya Disease Susceptibility Gene RNF213 Regulates Endothelial Barrier Function

Background: Variants in the ring finger protein 213 ( RNF213 ) gene are known to be associated with increased predisposition to cerebrovascular diseases development. Genomic studies have identified RNF213 as a major risk factor of Moyamoya disease in East Asian descendants. However, little is known about the RNF213 (ring finger protein 213) biological functions or its associated pathogenic mechanisms underlying Moyamoya disease. Methods: To investigate RNF213 loss-of-function effect in endothelial cell, stable RNF213-deficient human cerebral endothelial cells were generated using the CRISPR-Cas9 genome editing technology. Results: In vitro assays, using RNF213 knockout brain endothelial cells, showed clear morphological changes and increased blood-brain barrier permeability. Downregulation and delocalization of essential interendothelial junction proteins involved in the blood-brain barrier maintenance, such as PECAM-1 (platelet endothelial cell adhesion molecule-1), was also observed. Brain endothelial RNF213-deficient cells also showed an abnormal potential to transmigration of leukocytes and secreted high amounts of proinflammatory cytokines. Conclusions: Taken together, these results indicate that RNF213 could be a key regulator of cerebral endothelium integrity, whose disruption could be an early pathological mechanism leading to Moyamoya disease. This study also further reinforces the importance of blood-brain barrier integrity in the development of Moyamoya disease and other RNF213-associated diseases.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research

Objective To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels. Methods The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction. Results In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]). Conclusions Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Structural Equation Model for Evaluating Factors Affecting Health-related Quality of Life in Adolescents With Moyamoya Disease: Based on Salutogenesis Theory

BackgroundMoyamoya disease is a cerebrovascular disorder and a significant chronic health concern requiring regular monitoring to control the disease and its related complications.ObjectiveTo develop a structural model based on the salutogenesis theory, and to identify how social support, sense of coherence, and stress contribute to health behaviors, subjective health status, and quality of life in adolescents with moyamoya disease.MethodsWe examined a hypothetical model by integrating the concepts of a structural health-related quality-of-life model based on the salutogenesis theory among 239 adolescents with moyamoya disease in Korea. Data on health-related quality of life of adolescents with moyamoya disease were collected using the following scales: social support rating scale, sense of coherence scale, stress scale, health behavior scale, subjective health status scale, and quality-of-life scale. A structural equation model was used to analyze the data.ResultsThe final model demonstrated goodness-of-fit. A sense of coherence directly influenced quality of life (β = 0.504, p < 0.01) and indirectly influenced quality of life (β = 0.299, p < 0.05) through health behavior. Stress (β = -0.414, p < 0.001) and health behavior (β = -0.085, p < 0.01) directly influenced quality of life. Social support directly influenced health behavior (β = 0.321, p < 0.01) and subjective health status (β = 0.112, p < 0.01).DiscussionSince moyamoya disease, a chronic disease, is progressive, it is very important to identify factors for health promotion.This study found that sense of coherence and social support were significant factors contributing to lower stress, improved health, and quality of life in adolescents with moyamoya disease. This paper is intended to help health experts to develop an intervention strategy based on theory as an approach for chronic disease management.

INDIRECT CEREBRAL REVASCULARIZATION ON OPTHALMIC ARTERY BY USING A DRUG-ELUTING BALLON FOR SUSPECTED MOYAMOYA DISEASE

Moyamoya disease (MMD) is a rare idiopathic progressive vaso-occlusive disease causing multiple occlusion of cerebral vessels lead to ischemic stroke. Asian population is the most common race to be affected. We present a male patient 33-years old with suspected MMD with right hemiparesis and neurocognitive changes. On digital substraction angiography (DSA) there was appearance of ‘puff of smoke’ on his right hemisphere, stenosis middle cerebral arteries M1 bilaterally, stenosis of right opthalmic artery (OA), stenosis of left anterior cerebral artery (ACA) and aplasia of right ACA. Ballon angioplasty was performed on right OA that supply the contralateral symptomatic stenosis area (left A1) indirectly through anterior ethmoidal artery and anterior falcine artery (OA-ACA collateral). While no guidelines for the management of MMD, cerebral revascularization by using drug-eluting ballon (DEB) in right opthalmica artery is potentially effective treatment that could allow the brain to have good blood supply (gives good collateral to both ACA), reduces burden of the fragile moya-moya vessels to be ruptured followed by improvement of clinical results. Patient’s selection by understanding the stage, its progressivity and collateral formation are crucial before decision is made.