Exploring the impact of pre-anastomosis cerebral microcirculation on cerebral hyperperfusion syndrome in superficial temporal artery-middle cerebral artery bypass surgery of moyamoya disease.

Significance: Cerebral hyperperfusion syndrome (CHS), characterized by neurologic deficits due to postoperative high cerebral perfusion, is a serious complication of superficial temporal artery-middle cerebral artery (STA-MCA) surgery for moyamoya disease (MMD). Aim: We aim to clarify the importance of assessing pre-anastomosis cerebral microcirculation levels by linking the onset of CHS to pre- and post-anastomosis hemodynamics. Approach: Intraoperative laser speckle contrast imaging (LSCI) measured changes in regional cerebral blood flow (rCBF) and regional blood flow structuring (rBFS) within the cerebral cortical microcirculation of 48 adults with MMD. Results: Following anastomosis, all MMD patients exhibited a significant increase in rCBF ( 279.60 % ± 120.00 % , p < 0.001 ). Changes in rCBF and rBFS showed a negative correlation with their respective baseline levels (rCBF, p < 0.001 ; rBFS, p = 0.005 ). Baseline rCBF differed significantly between CHS and non-CHS groups ( p = 0.0049 ). The areas under the receiver operating characteristic (ROC) curve for baseline rCBF was 0.753. Hemorrhagic MMD patients showed higher baseline rCBF than ischemic patients ( p = 0.036 ), with a marked correlation between pre- and post-anastomosis rCBF in hemorrhagic cases ( p = 0.003 ), whereas ischemic MMD patients did not. Conclusion: Patients with low levels of pre-anastomosis baseline CBF induce a dramatic increase in post-anastomosis and show a high risk of postoperative CHS.

Prediction of contralateral progression in patients with bilateral nonhemorrhagic moyamoya disease following unilateral revascularization surgery.

OBJECTIVE: This study was designed to identify predictive factors associated with substantial contralateral progression in adult patients with bilateral nonhemorrhagic moyamoya disease (MMD) who undergo revascularization surgery (RS) on one hemisphere. METHODS: The authors retrospectively analyzed 174 contralateral hemispheres of patients with bilateral nonhemorrhagic MMD (non-hMMD) who underwent RS on one side. The primary endpoint was defined as substantial contralateral progression requiring additional RS 6 months after the initial RS. The annual risk and predictive factors for contralateral progression were also analyzed. RESULTS: Of 174 patients included in the study, 57 (32.8%) experienced contralateral progression over a mean follow-up of 45.3 ± 31.6 months (range 12-196 months). The annual risk for contralateral progression after initial unilateral RS was 7.7% per person-year. Multivariable analysis revealed that age (HR 0.967, 95% CI 0.944-0.992; p = 0.009) and a BMI ≥ 25 (HR 1.946, 95% CI 1.126-3.362; p = 0.017) were significant predictors of contralateral progression. Specifically, the annual risk of contralateral progression was 12.1% in the higher BMI (≥ 25) group and 4.0% in the lower BMI (< 25) group per person-year. CONCLUSIONS: The study revealed a 7.7% per person-year rate of contralateral progression in patients with bilateral non-hMMD following unilateral RS. Younger age and a BMI ≥ 25 were identified as significant risk factors. For these patients, careful weight management and the use of antilipid agents may be crucial strategies for reducing the risk of contralateral progression after unilateral RS.

Pseudo-continuous and territorial arterial spin labeling MRI for assessment of cerebral perfusion in moyamoya disease after revascularization: A comparative study with digital subtraction angiography.

Purpose: To evaluate if pseudo-continuous arterial spin labeling (pcASL) and territorial ASL (tASL) can assess cerebral perfusion post-revascularization in Moyamoya disease and compare with digital subtraction angiography (DSA) outcomes. Materials and methods: Patients diagnosed with Moyamoya disease who underwent pcASL using two post-labeling delays (short ASL, 1,525 ms; delayed ASL, 2,525 ms), tASL, and DSA 3 months after surgery at a single institution were retrospectively evaluated. Manual delineation on pcASL cerebral blood flow (CBF) maps covered middle cerebral artery (MCA) territory on both sides, and cerebellum. Normalized CBF (nCBF) was calculated. Revascularization in the MCA territory was evaluated with external carotid angiography and tASL, graded on a three-point scale. Intermodality agreement was analyzed with weighted κ statistics. Correlation between pcASL-derived nCBF and tASL-measured revascularization, and revascularization grade from direct angiography, was determined. Diagnostic performance of pcASL and tASL was evaluated using DSA as a reference via receiver operating characteristic (ROC) curve analysis. Results: A total of 32 hemispheres from 31 patients were assessed. On the operated side, sASL and dASL had nCBF values of 1.00 ± 0.30 and 1.31 ± 0.31, respectively. Revascularization area grading showed substantial intermodality agreement (weighted κ = 0.68; 95 % CI: 0.49, 0.87). DSA revascularization moderately correlated with sASL and dASL nCBF values (r = 0.56 and 0.47) and strongly correlated with tASL revascularization area (r = 0.73). ROC analysis revealed that sASL and dASL nCBF values reflected revascularization (area under the curve (AUC) = 0.86 and 0.77) and tASL revascularization area (AUC = 0.91). Combined pcASL and tASL had an AUC of 0.93, comparable to tASL alone, improving diagnostic performance. The diagnostic accuracy of nCBF for sASL was 87.5 %, superior to 75 % for dASL. The diagnostic accuracy of tASL external carotid artery revascularization area was 87.5 %, with sensitivity and specificity of 88 % and 85.7 %, respectively. Conclusion: The combination of pcASL and tASL outperformed pcASL alone in assessing cerebral perfusion post-Moyamoya disease revascularization.

Does disease etiology matter in long-term patency in extracranial-intracranial bypass?

OBJECTIVE: Extracranial-intracranial (EC-IC) bypass has been well described in chronic vaso-occlusive cerebrovascular diseases, including both moyamoya disease (MMD) and atherosclerotic disease (AD). This study aimed to compare factors associated with bypass occlusion between these two diseases. METHODS: An institutional database of 357 patients with intracranial bypass procedures performed between August 2001 and May 2022 was retrospectively reviewed. Patients with MMD and AD were selected for study. Baseline characteristics, surgical technique, and flow-related measurements were compared in relation to the outcome of bypass occlusion. RESULTS: A total of 232 patients met inclusion criteria (AD, n = 108; MMD, n = 124). The average age and sex differed significantly between groups (AD 57.2 years, 56.5% male; MMD 36.6 years, 31.5% male; p < 0.001). The modified Rankin Scale scores at surgery and at follow-up were higher in the AD group (p = 0.004 and p < 0.001, respectively), showing a slightly worse baseline functional status, and higher rates of stroke were observed in the AD group by last follow-up (p = 0.005). Patients with AD also were more likely to require an interpositional graft (p < 0.001). At last follow-up, rates of occlusion did not differ between AD and MMD groups (25.2% vs 25.4%, respectively). Of occluded bypasses, the AD group had more occlusions within 1 week compared to MMD (51.9% vs 35.5%, p = 0.176), although the difference was not significant. In patients with more than 1 year of follow-up and in those with more than 2 years of follow-up, MMD tended to have higher rates of occlusion (31.2% vs 26.1% [p = 0.558], and 26.4% vs 20.7% [p = 0.564]). Flow measurements did not differ between AD and MMD groups, but in subgroup analyses of patients with AD and those with MMD, both bypass flow and cut flow index predicted occlusion in both groups. CONCLUSIONS: Despite different disease etiologies treated with bypass, rates of occlusion at last follow-up did not vary between groups, although short-term follow-up would suggest earlier bypass failure in AD, and extended follow-up trended toward higher occlusion rates in MMD. Additionally, patients with AD were more likely to have further occurrences of stroke by last follow-up. Importantly, the bypass flow and cut flow index at the time of surgery predicted occlusion in both AD and MMD.

Long-term Clinical Outcomes after Cerebral Revascularization in Moyamoya disease with extra-cranial Internal Carotid Artery Occlusion.

OBJECTIVE: The aim of this study is to evaluate the efficacy of cerebral revascularization for Moyamoya disease (MMD) with extra-cranial internal carotid artery occlusion (ICAO). METHODS: This study retrospectively analyzed 37 patients diagnosed with MMD with extra-cranial ICAO who underwent cerebral revascularization surgery. We conducted propensity score matching for MMD patients without extra-cranial ICAO from database of 932 MMD patients. Outcome data, recurrent strokes and modified Rankin Scale (mRS) were collected during follow-up. RESULTS: A total of 37 MMD patients with extra-cranial ICAO were included in the study. The average follow-up time of MMD patients with extra-cranial ICAO included in the study was 74 months. During the follow-up period, there were 15 hemispheres recurred stroke events. All hemispheres underwent surgery, and the follow-up mRS score was significantly reduced (P <0.001). Kaplan-Meier analysis showed no significant statistical difference in stroke events between the indirect bypass (IB), direct bypass (DB), and combined bypass (CB) groups (P = 0.131). After propensity matching, 48 hemispheres of MMD patients without extra-cranial ICAO were identified from a review of 932 MMD patients. There was no significant statistical difference in stroke events between the MMD patients with extra-cranial ICAO group and the MMD group (P = 0.271). CONCLUSIONS: Cerebral revascularization can prevent recurrent ischemic and hemorrhagic stroke events for MMD patients with extra-cranial ICAO. There was no difference on long-term clinical outcomes after CB, DB, and IB surgery. The cerebral revascularization has similar effect on the MMD patients with extra-cranial ICAO and MMD patients without.

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.

Characterizing Revascularization after Encephalo-Duro-Arterio-Synangiosis (EDAS) in Adult Patients with Moyamoya Disease Using the Orbital Grading System.

BACKGROUND: The Matsushima Grade has traditionally been used to evaluate vessel ingrowth from the STA after EDAS for MMD-patients. However, this grading is subjective and prone to measurement variability. Herein, we propose the orbital grading system quantifying leptomeningeal and burr hole-related vessel-ingrowth from the STA and/or MMA to the middle and anterior cerebral arteries post-EDAS in MMD patients. METHODS: An anatomical classification was developed by reference to two parallel vertical lines from the bony landmarks of the orbit, categorized from Grade 0-3. Regression models were used to compare clinical and functional outcomes of our grading system with the Matsushima scale. RESULTS: Forty MMD patients, with median age of 48 years, mostly females (72.5%), were included. Presentation included ischemic events (65.0%), hemorrhage (22.5%), and seizures (7.5%). Most patients were categorized as Suzuki ≥ IV (69.5%). Fifty EDAS (89.9%) had concurrent burr holes placed (parietal and frontal regions). At a median follow-up of 13.7 months, collateral growth was graded as follows: grade 0 (6;10.8%), grade 1 (12;21.4%), grade 2 (23;41.1%) and grade 3 (15;26.8%). Linear regression showed similarities in the distribution between the orbital grading system and Matsushima grading (r=0.86;p<0.01). Ischemic events were fewer in hemispheres categorized as grade 2-3 compared to grade 0-1 (p=0.047) as well as in Matsushima grading A or B compared to C (p=0.047). CONCLUSION: The orbital grading system demonstrated agreement in identifying postoperative ischemic events as the Matsushima grade and provides a more practical and objective evaluation of collateral vessel ingrowth after EDAS with and without burr-holes.

HAPLN3 p.T34A contributes to incomplete penetrance of moyamoya disease in Chinese carrying RNF213 p.R4810K.

BACKGROUND AND PURPOSE: The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150-1/300. However, the factors affecting its penetrance remain unclear. Therefore, our study aims to identify modifier genes associated with the incomplete penetrance of this founder mutation. METHODS: Whole-exome sequencing (WES) was performed on 36 participants, including 22 MMD patients and 14 non-MMD controls with RNF213 p.R4810K mutation. Fisher's exact test was used to assess the presence of genetic variants that differed significantly between MMD patients and non-MMD controls. In order to exclude false-positive results, another 55 carriers were included to perform Fisher's exact test for the selected sites in the WES discovery stage. Subsequently, human brain microvascular endothelial cells were transfected with wild-type and mutant HAPLN3 for tube formation assays and western blotting to explore the impact of candidate genes on angiogenesis. RESULTS: Analysis of variants from WES data revealed a total of 12 non-synonymous variants. Through bioinformatics analysis, the focus was on the HAPLN3 p.T34A variant with a significant p value of 0.00731 in Fisher's exact test. Validation through Sanger sequencing confirmed the presence of this variant in the WES data. In vitro experiments revealed that silencing HAPLN3 and transfecting HAPLN3 p.T34A significantly enhanced tube formation and increased the relative protein expression of vascular endothelial growth factor in endothelial cells. CONCLUSIONS: These results suggest that HAPLN3 may function as a modifier gene of RNF213 p.R4810K, promoting the development of MMD and contributing to the incomplete penetrance of MMD founder mutations.

Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

Background: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Methods: Twelve MMD patients-six children and six adults-along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms.

Systemic immune-inflammatory markers and long-term prognosis after revascularization in Moyamoya disease: a retrospective study.

Background: Systemic immune-inflammatory markers combine various individual inflammatory cell parameters to comprehensively explore their relationship with the development and long-term outcomes of cardiovascular, cerebrovascular, and oncological disorders. The systemic immune-inflammatory marker index has not been extensively studied in terms of its impact on the long-term prognosis following cerebral revascularization in MMD patients. Our research aims to address this gap and improve the prediction of long-term outcomes for these patients. Methods: We included 851 patients with Moyamoya disease who underwent cerebral revascularization at our medical center from 2009 to 2021. Systemic immune-inflammatory markers were calculated based on routine blood test results at admission, and follow-up was conducted for over 6 months after surgery. During monitoring and upon release, we evaluated patient neurological condition by utilizing the modified Rankin Scale (mRS). We examined the correlation between alterations in mRS ratings and systemic immune-inflammatory markers. Results: Comparing the unfavorable long-term prognosis group to the favorable long-term prognosis group, it was found that the NLR level was markedly higher (p = 0.037), while the LMR was lower in the unfavorable long-term prognosis group (p = 0.004). Results from logistic regression analysis revealed that the high-level LMR group had a lower risk of unfavorable long-term prognosis compared to the low-level group (T3: OR = 0.433, 95% CI [0.204-0.859], p = 0.026). The AUC of the model was 0.750 (95% CI [0.693-0.806]). Conclusion: Lymphocyte-to-monocyte ratio levels are independently linked to an increased risk of unfavorable long-term prognosis, highlighting LMR as a new and effective predictor for postoperative Moyamoya patients.

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.

Primitive proatlantal intersegmental artery associated with moyamoya disease: A case report.

Primitive proatlantal intersegmental artery (PPIA) is rare and can be divided into types I and II. PPIAs can be associated with some anatomical variations and vascular diseases. However, no case of PPIA combined with moyamoya disease (MMD) has been reported. Here, we reported such a case. A 54-year-old man experienced headache for 1 month. The results of the neurological examinations were unremarkable. Magnetic resonance angiography and digital subtraction angiography revealed a right type I PPIA with MMD. The PPIA serves as an important collateral path for MMD patients. Because the patient only experienced headache, he was discharged and underwent follow-up observation. This case indicates that, rarely, PPIA can be associated with MMD and serve as a collateral vessel for MMD patients.

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.

Case Report: A rare presentation of rapidly progressive moyamoya disease refractory to unilateral surgical revascularization.

Moyamoya disease (MMD) is a chronic, occlusive cerebrovasculopathy typified by progressive steno-occlusive disease of the intracranial internal carotid arteries (ICAs) and their proximal branches. Moyamoya syndrome (MMS) categorizes patients with characteristic MMD plus associated conditions. As such, the most usual presentations are those that occur with cerebral ischemia, specifically transient ischemic attack, acute ischemic stroke, and seizures. Hemorrhagic stroke, headaches, and migraines can also occur secondary to the compensatory growth of fragile collateral vessels propagated by chronic cerebral ischemia. While the pathophysiology of MMD is unknown, there remain numerous clinical associations including radiation therapy to the brain, inherited genetic syndromes, hematologic disorders, and autoimmune conditions. We describe the case of a 31-year-old woman who presented with recurrent ischemic cerebral infarcts secondary to rapidly progressive, bilateral MMD despite undergoing early unilateral surgical revascularization with direct arterial bypass. She had numerous metabolic conditions and rapidly decompensated, ultimately passing away despite intensive and aggressive interventions. The present case highlights that progression of moyamoya disease to bilateral involvement can occur very rapidly, within a mere 6 weeks, a phenomenon which has not been documented in the literature to our knowledge.

Intersecting Pathologies: A Case Report on the Co-presentation of Quasi-Moyamoya Disease and Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Plasma Cell Disorder, and Skin Changes (POEMS) Syndrome.

Moyamoya disease (MMD) is a rare chronic vasculopathy characterized by progressive stenosis of the internal carotid arteries and the formation of fragile collateral vessels in the brain. Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome with a complex presentation that includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. Here, we report a unique case of a 54-year-old male with MMD presenting with recurrent speech loss and mumbling, later diagnosed with POEMS syndrome. Initial imaging revealed Moyamoya vasculopathy, confirmed by computed tomographic angiography (CTA) and magnetic resonance imaging (MRI). Further examination revealed polyneuropathy, organomegaly, and elevated vascular endothelial growth factor (VEGF), meeting the diagnostic criteria for POEMS syndrome. The patient was treated with a cyclophosphamide-bortezomib-dexamethasone regimen, followed by the addition of daratumumab, resulting in clinical improvement. This case highlights the importance of thorough diagnostics and a multidisciplinary treatment approach for patients with complex comorbidities, emphasizing the need for early detection and targeted therapy in managing dual pathologies of MMD and POEMS syndrome.

Pregnancy Risk Assessment, Management, and Delivery Plan for Pregnant Women with Moyamoya Disease Using a Multidisciplinary Collaborative Approach: A Case Series.

Purpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan. Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto's thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived. Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.

Association of rare variants in RNF213 with severe progression of intracranial artery stenosis in quasi-moyamoya disease.

OBJECTIVE: The genetic basis underlying the pathophysiology of quasi-moyamoya disease (qMMD) is unclear. Herein, the authors aimed to comprehensively analyze genetic variants in qMMD and investigate their association with clinical phenotypes, focusing on RNF213 and other moyamoya angiopathy (MMA)-related genes. METHODS: The authors evaluated 14 consecutive cases of qMMD, whose underlying conditions included autoimmune disease, head irradiation, meningitis/pachymeningitis, and Turner syndrome, and 9 cases of hyperthyroidism-associated MMD (hMMD). The frequencies of RNF213 p.Arg4810Lys in qMMD and hMMD were each compared to those in healthy controls and in patients with MMD. Whole-exome sequencing was performed, and rare variants (RVs) or damaging variants were analyzed in RNF213 and 36 MMA-related genes. RESULTS: The frequencies of p.Arg4810Lys were significantly higher in patients with qMMD (28.6%) and hMMD (33.3%) than in controls (1.1%; p < 0.001) and lower in the two former groups than in the MMD group (67.6%; p = 0.003 and 0.065, respectively). In qMMD, no significant clinical differences were observed based on the presence of p.Arg4810Lys. A novel RNF213 RV was identified in four cases with qMMD. These same cases also presented with significant worsening of intracranial main artery stenosis, which suggests a possible association between RNF213 RVs and the severe progression of qMMD. Among the 36 MMA-related genes, no variants correlated with specific phenotypes. CONCLUSIONS: While the clinical implications of p.Arg4810Lys in cases with qMMD were not identified, the study findings suggest a potential association between RNF213 RVs and the significant progression of intracranial artery stenosis. Genetic analysis should not focus solely on p.Arg4810Lys but instead consider a comprehensive analysis of RNF213 for more accurate clinical prognostication of qMMD.

Is initial unilateral revascularization acceptable in pediatric patients with bilateral moyamoya disease with mild contralateral hemodynamic disturbance?

OBJECTIVE: Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment. METHODS: The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up. RESULTS: Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008). CONCLUSIONS: In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.

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.

Hemorrhagic Moyamoya Angiopathy in European Patients.

BACKGROUND: Moyamoya angiopathy (MMA) is an important cause of juvenile stroke but an overall rare disease among European populations compared with East Asian cohorts. Consecutively, hemorrhagic MMA is described well in East Asian cohorts, but knowledge in non-Asian patients is limited. Literature suggests that disease presentation may vary between those cohorts, also including hemorrhage frequencies. Hence, this article aims to analyze hemorrhagic MMA in European patients. METHODS: We screened for patients of European origin with MMA from a single-center consecutive database of a German hospital specialized on MMA. Those who had a record of intracranial hemorrhage were analyzed individually regarding the type of hemorrhage and use of antiplatelet therapy before and after bleeding onset. To identify associated factors of intracranial hemorrhage, an age- and sex-matched control group was identified from the pool of patients without a history of hemorrhage. Both groups had a comparable follow-up time and were compared in terms of disease presentation, therapeutic interventions, and imaging characteristics, using both univariate tests and multivariate logistic regression analysis. RESULTS: From a pool of 332 patients with MMA we identified 288 of European ancestry. From those, 36 had a record of intracranial hemorrhage (12.5%). Thirty-three patients presenting with 37 events were included for further analysis and case-control-comparison. Most events were intracerebral hemorrhage (n=20; 54%) and subarachnoid hemorrhage (n=11; 30%). 78% developed hemorrhage although no antiplatelet therapy was in use (n=29). Seven patients developed intracranial hemorrhage ipsilateral to prior bypass surgery (21%), while 29 of the control patients had a bypass surgery (88%; P=0.0001). There was no significant difference in terms of unilateral or bilateral disease type, history of hypertension, as well as imaging characteristics (high Suzuki stage and the presence of collateral pathways in conventional angiography, as well as ischemic defects and the presence of microbleeds on cerebral magnetic resonance imaging; P>0.05 in multivariate analysis, respectively). CONCLUSIONS: Bypass surgery was negatively associated with the development of intracranial hemorrhage in MMA in European patients. There was no difference in terms of a history of hypertension between groups, indicating that blood pressure is not the major contributor for rupture of fragile collateral vessels. The investigated imaging characteristics were not associated to hemorrhage onset and, therefore, are not suitable as a tool of screening for patients at risk.