A rare case of pituitary dysfunction with Moyamoya disease.

Moyamoya disease is an idiopathic chronic and progressive vaso-occlusive disease ofthe bilateral intracranial branches of the internal carotid artery. Growth hormone failure, thyroid dysfunction, and low cortisol hormones are consequences of hypopituitarism. A 14-year-old girl with short stature presented with right-sided weakness associated with dysarthria. Ahormonal assay test showed abnormality ofthe anterior pituitary hormones. Magnetic resonance imaging of the brain and pituitary gland showed a reduction in the size of the adenohypophysis. A cerebral vessel angiogram showed multiple areas of stenosis in the right internal carotid artery. Magnetic resonance angiography demonstrated stenosis at the suprasellar region of the bilateral internal carotid artery. Pituitary dysfunction associated with moyamoya disease is rare but must be considered as adifferential diagnosis for any patient with hypopituitarism. Hypothalamopituitary dysfunction as result of carotid ischemia might be associated with moyamoya disease. Such patients require close follow-up and hormonal assay tests.

"Navigating moyamoya: bridging gaps in neurocognitive outcomes through STA-ACA bypass".

With its bimodal age distribution, higher prevalence in Far East Asian populations, and significant risk of ischemic stroke, Moyamoya disease (MMD) poses a distinctive clinical challenge. In a recently published study by Sho Tsunoda et al., the neurocognitive results of patients with MMD undergoing revascularization surgery were assessed, highlighting the potential advantages of superficial temporal artery to anterior cerebral artery (STA-ACA) direct bypass in ameliorating neuropsychological impairment. Despite its propitious findings, the study's limitations-including a small sample size, single-center design, and lack of long-term follow-up-underscore the need for further research. Future multicenter, prospective trials with larger patient cohorts and comprehensive neurocognitive assessments are essential to validate these results and enhance the generalizability of the findings. This letter emphasizes the importance of robust study designs in advancing our understanding of MMD treatment and ensuring better patient outcomes.

Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome.

Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

Glymphatic System Impairment in the Advanced Stage of Moyamoya Disease.

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis.

Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships.

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

Endovascular Therapy of Ruptured Aneurysms on Moyamoya Collateral Vessels: Two Cases.

Background: Using two case reports of adult women with moyamoya disease presenting with intracranial hemorrhage from ruptured aneurysms on moyamoya collateral vessels, we aim to demonstrate the potential for effective endovascular treatment navigated by CT angiography, digital subtraction angiography, and flat panel CT. Case 1 Presentation: A 45-year-old female patient with sudden onset of headache, followed by somnolency. CT scan showed a four-ventricle hematocephalus caused by a 27 × 31 × 17 mm hematoma located in the left basal ganglia. Angiography revealed a 3 mm aneurysm on hypertrophic lenticulostriate artery bridging the M1 occlusion. Selective catheterization and distal embolisation with acrylic glue was done. Case 2 Presentation: A 47-year-old woman was admitted for a sudden onset of severe headache, CT scan showed four-ventricle hematocephalus. A 4 mm aneurysm on the collateral vessel-anterior chorioidal artery bridging the closure of the terminal segment of the internal carotid artery was diagnosed as the source of bleeding. Selective catheterization and distal embolisation with acrylic glue was done. Conclusions: Selective embolisation of ruptured aneurysms on moya moya collaterals is a simple, effective, and safe procedure when relevant microcatheters are used with imaging software navigation such as 3D DSA, 3D road map and flat-panel CT.

Exploring the Impact of Hemoglobin on Cerebral Blood Flow in Arterial Territories and Surgical Outcomes: Potential Implications for Moyamoya Disease Treatment.

BACKGROUND: Changes in levels of hemoglobin would result in alterations of cerebral blood flow (CBF). However, the impact of hemoglobin on CBF in moyamoya disease (MMD) remains largely unknown. This study sought to determine whether CBF would be influenced by hemoglobin before surgical revascularization and to analyze the relationships between hemoglobin and CBF with clinical outcome after surgery in patients with MMD. METHODS AND RESULTS: We prospectively enrolled adult patients with MMD undergoing surgical revascularization between June 2020 and December 2022. Preoperative CBF was measured in the territories of anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA, respectively) using 3-dimensional pseudo-continuous arterial spin labeling magnetic resonance imaging. Clinical outcome at 1 year after surgery was evaluated using the modified Rankin Scale. A total of 60 patients with MMD were included, with 25% (n=15) experiencing unfavorable outcomes. Patients with MMD exhibited lower CBF (ACA: P=0.007; MCA: P<0.001; PCA: P=0.014), compared with healthy controls (n=40). Hemoglobin was negatively and significantly associated with CBF (ACA: ß=-0.45, P<0.001; MCA: ß=-0.38, P<0.001; PCA: ß=-0.54, P<0.001). CBF rather than hemoglobin was significantly related with clinical outcome (ACA: P<0.001; MCA: P<0.001; PCA: P=0.001), and CBF showed high discrimination in predicting clinical outcome (ACA: area under the curve, 0.84; MCA: area under the curve, 0.84; PCA: area under the curve, 0.80). CONCLUSIONS: Our findings demonstrate that hemoglobin significantly influences CBF, and CBF has a high predictive value for clinical outcome in MMD. The optimal hemoglobin level before surgical revascularization should be further investigated.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Proteomics and digital subtraction angiography approaches reveal CDH18 as a potential target for therapy of moyamoya disease.

Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease.

Clinical Features and Treatment Outcomes in Patients in Their Twenties with Ischemic Moyamoya Disease.

INTRODUCTION: Revascularization surgery is recommended for all pediatric patients with moyamoya disease (MMD) with ischemic symptoms because the brains of such patients are still developing. By contrast, no clear guidelines for selective revascularization surgery in adult patients (30 years or more) with ischemic presentation have been established. Regarding the age of initial onset of ischemic MMD, patients in their 20s are at the bottom of the distribution and this age group may share features with both adult and pediatric patients. The present prospective study aimed to clarify the clinical features and treatment outcomes of patients in their 20s (younger patients) with ischemic MMD compared with patients aged 30-60 years (older patients). METHODS: While patients with misery perfusion in the symptomatic cerebral hemisphere on 15O-positron emission tomography underwent combined surgery including direct and indirect revascularizations in the first study period and indirect revascularization alone in the second study period, patients without misery perfusion in that hemisphere received pharmacotherapy alone through the two study periods. Cerebral angiography via arterial catheterization and neuropsychological testing were performed before and after surgery. RESULTS: During 12 years, 12 younger patients were included and comprised 6% of all adult patients (194 patients). The incidence of misery perfusion in the affected hemisphere was significantly higher in younger (12/12 [100%]) than in older patients (57/182 [31%]) (p < 0.0001). No difference in the incidence of cerebral hyperperfusion syndrome and postoperatively declined cognition was seen between younger (2/5 [40%] and 2/5 [40%], respectively) and older (11/36 [31%] and 15/36 [42%], respectively) cerebral hemispheres undergoing combined revascularization surgery. No difference in the incidence of postoperatively formed collateral flows feeding more than one-third of the middle cerebral artery cortical territory on angiograms and postoperatively improved cognition was seen between younger (9/10 [90%] and 6/10 [60%], respectively) and older (18/22 [83%] and 14/22 [64%], respectively) cerebral hemispheres undergoing indirect revascularization surgery alone. CONCLUSION: Patients in their 20s with ischemic MMD always exhibit misery perfusion in the affected hemisphere, unlike older patients, and sometimes develop cerebral hyperperfusion syndrome after combined revascularization surgery, leading to cognitive decline, similar to older patients. Moreover, indirect revascularization surgery alone forms sufficient collateral circulation and restores cognitive function in patients in their 20s, similar to older patients.

Prevalence of RNF213 rs112735431 Genetic Polymorphism in Non-Cardioembolic Ischemic Cerebrovascular Disease: A Cross-Sectional Study in Thai Patients.

INTRODUCTION: Moyamoya disease (MMD) and non-MMD intracranial cerebral artery stenosis (ICAS) have been linked to the RNF213 rs112735431 gene in Korean and Japanese populations. This cross-sectional study investigates the prevalence of the RNF213 rs112735431 gene in non-cardioembolic ischemic stroke (NCIS) among Thai patients. METHODS: A cross-sectional investigation was conducted on patients aged 18 years or older admitted to King Chulalongkorn Memorial Hospital between June 2015 and March 2016 with acute NCIS. ICAS and extracranial carotid artery stenosis (ECAS) were assessed through computer tomography angiography or magnetic resonance angiography. Blood samples were collected, and Sanger sequencing was performed. RESULTS: Among 234 acute NCIS cases, 113 exhibited ICAS, 12 had ECAS, 20 had both, and 89 had neither. The RNF213 rs112735431 gene variant was detected in 2 patients, both heterozygous A/G. The frequency of the RNF213 rs112735431 variant was 0.9% (2/234; 95% CI: 0-2.1%) in acute NCIS patients and 1.8% (2/113; 95% CI: 0-4.2%) in ICAS. All individuals with the RNF213 variant were males with hypertension, diabetes mellitus, dyslipidemia, and ICAS, without a family history of ischemic stroke. CONCLUSION: This study reveals that the RNF213 rs112735431 gene variant is uncommon among Thai NCIS patients, suggesting a discrepancy in the prevalence of this genetic variation between Thai and other Eastern Asian populations.

Ultrasonographic Predictors for Post-operative Ischemic Events After Indirect Revascularization Surgeries in Patients with Moyamoya Disease.

OBJECTIVE: Recurrent stroke after revascularization surgeries predicts poor outcome in patients with moyamoya disease (MMD). Early identification of patients with stroke risk paves the way for rescue intervention. This study aimed to investigate the role of ultrasound in identifying patients at risk of post-operative ischemic events (PIEs). METHODS: This prospective study enrolled patients with symptomatic MMD who underwent indirect revascularization surgeries. Ultrasound examinations were performed preoperatively and at 3 mo post-operatively to evaluate the hemodynamic changes in extracranial and intracranial arteries on the operated side. PIE was defined as ischemic stroke or transient ischemic attack in the operated hemisphere within 1 y. The areas under receiver operating characteristic curves were compared between models for prediction of PIE. RESULTS: A total of 56 operated hemispheres from 36 patients (mean age, 23.0 ± 18.5 y) were enrolled in this study, and 27% developed PIE. In multivariate logistic regression models, PIE was associated with lower end-diastolic velocity and flow volume (FV) of the ipsilateral external carotid artery (ECA), and lower FV of ipsilateral superficial temporal artery and occipital artery at 3 mo post-operatively (all p < 0.05). Moreover, the post-operative FV of the ipsilateral ECA was the only one factor that significantly increased the areas under receiver operating characteristic curves from 0.727 to 0.932 when adding to a clinical-angiographic model for prediction of PIE (p = 0.017). This parameter was significantly lower in hemispheres with PIE, both in adult and pediatric patients. CONCLUSION: After indirect revascularization, surgeries in patients with symptomatic MMD, FV of ipsilateral ECA at 3 mo helps clinicians to identify patients at risk of PIE.

Influence of an improvement in frontal lobe hemodynamics on neurocognitive function in adult patients with moyamoya disease.

BACKGROUND: In adults, moyamoya disease (MMD) often presents with slight neurocognitive impairment, which may result from frontal lobe hemodynamic insufficiency. METHODS: In this study, we performed revascularization surgery by superficial temporal artery-anterior cerebral artery (ACA) direct bypass in 20 adults with MMD with poor anterograde ACA flow (Group M). The pre- and postoperative neurocognitive test results of these patients were retrospectively analyzed. The comparative group (Group C) included 23 patients with unruptured aneurysms or brain tumors who underwent craniotomy, as well as the same neurocognitive tests as Group M. We calculated the compositive frontal lobe function index (CFFI) based on the results of seven neurocognitive tests for each patient, and the difference between the pre- and postoperative CFFI values (CFFI Post - Pre) was compared between the two groups. RESULTS: Frontal perfusion improved postoperatively in all patients in Group M. The CFFI Post - Pre was significantly higher in Group M than in Group C (0.23 ± 0.44 vs. - 0.20 ± 0.32; p < 0.001). After adjusting for postoperative age, sex, preoperative non-verbal intelligence quotient, and preoperative period of stress, Group M had a significantly higher CFFI Post - Pre than Group C in the multiple regression analysis (t value = 4.01; p < 0.001). CONCLUSION: Improving frontal lobe hemodynamics might be the key for improving neurocognitive dysfunction in adults with MMD. The surgical indication and method should be considered from the perspective of both stroke prevention and neurocognitive improvement or protection.

Moyamoya Disease: A Rare Presentation and Literature Review.

Moyamoya disease is a rare vasculopathy involving the vessels of the central nervous system, predominantly the internal carotid arteries. A 21-year-old female patient from the Murshidabad district of West Bengal presented to us with an altered sensorium. She was referred to us from another hospital in Kolkata, where she was diagnosed and being treated as a case of ischemic stroke 2 weeks prior to the presentation. There was a significant past history of excruciating headaches, which would be more at night, and did not have any other obvious aggravating or relieving factors. On examination, the plantar was bilaterally extensor, and the patient was afebrile with no signs of meningeal irritation. Neuroimaging with noncontrast computed tomography (CT) head revealed a large right-sided middle cerebral artery (MCA) territory infarct along with acute hemorrhage in the left basal ganglia region. Upon a thorough perusal of the course of treatment at the previous hospital, it was ascertained that there was no usage of antiplatelet or anticoagulant agents there. A magnetic resonance (MR) angiogram of the intracranial blood vessels was therefore ordered, which was suggestive of moyamoya disease. Therefore, it was concluded that the spontaneous and near-simultaneous occurrence of infarct and hemorrhage was due to the vascular anomalies induced by moyamoya disease, making this case an uncommon presentation of a very rare disease.

Magnetic Resonance Angiography Alone Is Insufficient for Diagnosis and Surgical Planning in Children With Moyamoya.

BACKGROUND: The gold standard for evaluation of the severity of moyamoya vasculopathy is the Suzuki grade determined with cerebral catheter angiography (CA). With greater use of magnetic resonance angiography (MRA) it is important to understand if MRA is truly comparable to CA. METHODS: Children with moyamoya were evaluated using the Suzuki score for CA and the modified MRA six-stage Suzuki score to describe the angiographic findings in moyamoya from initial narrowing of the distal internal carotid artery to the "puff of smoke" appearance of the lenticulostriate collaterals and finally to the disappearance of this network of collaterals. Using Cohen kappa we compared Suzuki grade based on CA with MRA in the same patients. RESULTS: A total of 27 children with moyamoya were reviewed. We calculated a weighted Cohen kappa of 0.49 (P < 0.0001), which is a moderate correlation. CONCLUSIONS: We suggest caution in the reliance on MRA for the diagnosis and evaluation of severity of moyamoya in children.