Association of RNF213 polymorphism and cortical hyperintensity sign on fluid-attenuated inversion recovery images after revascularization surgery for moyamoya disease: possible involvement of intrinsic vascular vulnerability.

A cortical hyperintensity on fluid-attenuated inversion recovery images (FLAIR cortical hyperintensity (FCH)) is an abnormal finding after revascularization surgery for moyamoya disease. This study aimed to investigate the pathophysiology of FCH through genetic analyses of RNF213 p.R4810K polymorphism and perioperative hemodynamic studies using single-photon emission computed tomography. We studied 96 hemispheres in 65 adults and 47 hemispheres in 27 children, who underwent combined direct and indirect revascularization. Early or late FCH was defined when it was observed on postoperative days 0-2 and 6-9, respectively. FCH scores (range: 0-6) were evaluated according to the extent of FCH in the operated hemisphere. FCHs were significantly more prevalent in adult patients than pediatric patients (early: 94% vs. 78%; late: 97% vs. 59%). In pediatric patients, FCH scores were significantly improved from the early to late phase regardless of the RNF213 genotype (mutant median [IQR]: 2 [1-5] vs. 1 [0-2]; wild-type median: 4 [0.5-6] vs. 0.5 [0-1.75]). In adults, FCH scores were significantly improved in patients with the wild-type RNF213 allele (median: 4 [2-5.25] vs. 2 [2, 3]); however, they showed no significant improvement in patients with the RNF213 mutation. FCH scores were significantly higher in patients with symptomatic cerebral hyperperfusion than those without it (early median: 5 [4, 5] vs. 4 [2-5]; late median: 4 [3-5] vs. 3 [2-4]). In conclusion, the RNF213 p.R4810K polymorphism was associated with prolonged FCH, and extensive FCH was associated with symptomatic cerebral hyperperfusion in adult patients with moyamoya disease.

Impact of RNF213 c.14576G>A Variant on the Development of Direct and Indirect Revascularization in Pediatric Moyamoya Disease.

BACKGROUND: Superficial temporal artery (direct) and encephalomyosynangiosis (indirect) revascularization may develop after combined bypass surgery in pediatric patients with moyamoya disease (MMD). However, arterial development varies widely among patients, and the underlying mechanisms remain unknown. OBJECTIVES: We evaluated the relationship between the development of donor arteries after bypass surgery in pediatric patients with MMD and the MMD-susceptibility gene variant c.14576G>A of ring finger protein (RNF) 213. METHODS: The data of pediatric patients with MMD (age <16 years at the time of surgery) treated with combined bypass surgery between September 2013 and April 2019 were consecutively analyzed. Quantitative measurements of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) diameters with magnetic resonance angiography (MRA) source imaging were performed preoperatively and at 6-12 months postoperatively. The postoperative caliber change ratios (CCRs) were calculated. The relationship between CCRs and RNF213 c.14576G>A status was examined. RESULTS: Forty-eight hemispheres from 28 pediatric patients with MMD were examined. Three hemispheres belonged to patients with the AA genotype; 33 to patients with the AG genotype (AA/AG group); and 12 to patients with the GG genotype (GG group; wild type). The CCRs for the DTA were significantly higher in patients with RNF213 variant (AA/AG group; 2.5 ± 0.1) than in the GG group (2.0 ± 0.2) (p = 0.03), whereas the CCRs for the STA were significantly higher in the GG (1.6 ± 0.1) than in the AA/AG group (1.3 ± 0.6) (p = 0.02). There was no significant difference in the CCRs for the MMA and basilar artery between the groups. Other factors, including sex, age, and MRA grading, were not associated with the development of specific bypass development. CONCLUSIONS: The extent of collateral development associated with direct or indirect bypass was found to differ between the genotypes of the RNF213 c.14576G>A associated with pediatric MMD. This genetic variant correlates with the development of the disease and affects revascularization after bypass surgery in pediatric patients with MMD.

Outcomes of Combined Revascularization Surgery for Moyamoya Disease without Preoperative Cerebral Angiography.

OBJECTIVE: Cerebral angiography is the gold standard for diagnosing moyamoya disease (MMD), whereas magnetic resonance (MR) imaging/angiography is becoming more popular in the field of cerebrovascular disease due to its low invasiveness. Although there are concerns about using only MR imaging/angiography for preoperative analysis of MMD, considering the underestimation of pre-existing transdural collateral circulations and dangerous collaterals related to the risk of hemorrhage, we retrospectively reviewed our 10-year experience of MR imaging-first diagnosis and analyzed the perioperative outcomes. METHODS: We analyzed 160 consecutive direct/indirect combined revascularization procedures for MMD preoperatively assessed using MR imaging/angiography alone. Perioperative complications were assessed for up to 2 weeks after surgery. Locations of the lesions responsible for complications were further classified into the surgical field, the ipsilateral hemisphere outside the surgical field, and the contralateral hemisphere. RESULTS: Sixty-four revascularization procedures were performed in 38 children, and 96 procedures were performed in 68 adults. There was no difference in the incidence of perioperative ischemic complications between adults (6.3%) and pediatric patients (4.7%), but hemorrhagic complications were more frequently observed in adults (7.3%) than in children (0%) (P < 0.05). There was no specific lesion deviation for ischemic complications; however, hemorrhagic complications predominantly occurred in the surgical field. CONCLUSIONS: Direct/indirect combined revascularization surgery based on our preoperative diagnostic protocol with the MR-first strategy resulted in favorable outcomes in pediatric MMD patients with relatively low complication rates. However, the validity of the MR-first diagnostic protocol should be further evaluated in adult patients with MMD.

Impact of RNF213 founder polymorphism (p.R4810K) on the postoperative development of indirect pial synangiosis after direct/indirect combined revascularization surgery for adult Moyamoya disease.

Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral. Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2-16), advanced MR angiographic stage (OR9.5; 95%CI 1.7-73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8-35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03-0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37-2.4).In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis.

Use of magnetic resonance venography for inferior petrosal sinus sampling.

BACKGROUND: Inferior petrosal sinus (IPS) sampling (IPSS) is a transvenous interventional procedure performed to diagnose Cushing's disease. The reported IPSS failure rate is approximately 10% because IPS catheter delivery is conducted blindly and is challenging because of IPS anatomical variations. This study aimed to evaluate the usefulness of preprocedural magnetic resonance venography (MRV) for assessing IPS access routes before IPSS. METHODS: Nineteen consecutive patients who underwent IPSS at a single university hospital in Japan were retrospectively studied. A preprocedural MRV protocol optimized to visualize the IPS before IPSS was established and utilized in the eight most recent cases. An IPSS procedure was considered successful when bilateral IPS catheterization was accomplished. Patient demographics, IPSS success rate, and radiation dose required during IPSS were compared between two groups: MRV group (N = 8) and no-MRV group (N = 11) before IPSS. RESULTS: There were no significant differences in age, sex, and IPSS success rates between the groups. The average radiation dose was 663.6 ± 246.8 (SD) mGy and 981.7 ± 389.5 (SD) mGy in the MRV group and no-MRV group, respectively. Thus, there was a significant reduction in radiation exposure in the MRV group (p = 0.044). Catheterization of the left IPS was unsuccessful in only one patient in the MRV group owing to IPS hypoplasty, as found on the MRV. CONCLUSIONS: Hypoplastic IPSs occur in patients and can complicate IPSS. Preprocedural MRV assessment is useful for understanding venous anatomy and preventing unnecessary intravenous catheter manipulation during IPSS, which involves blind manipulation around the IPS.

The mechanobiological theory: a unifying hypothesis on the pathogenesis of moyamoya disease based on a systematic review.

OBJECTIVE: Moyamoya angiopathy (MMA) affects the distal internal carotid artery and is designated as moyamoya disease (MMD) when predisposing conditions are absent, or moyamoya syndrome (MMS) when it occurs secondary to other causes. The authors aimed to investigate the reason for this anatomical site predilection of MMA. There is compelling evidence to suggest that MMA is a phenomenon that occurs due to stereotyped mechanobiological processes. Literature regarding MMD and MMS was systematically reviewed to decipher a common pattern relating to the development of MMA. METHODS: A systematic review was conducted to understand the pathogenesis of MMA in accordance with PRISMA guidelines. PubMed MEDLINE and Scopus were searched using "moyamoya" and "pathogenesis" as common keywords and specific keywords related to six identified key factors. Additionally, a literature search was performed for MMS using "moyamoya" and "pathogenesis" combined with reported associations. A progressive search of the literature was also performed using the keywords "matrix metalloprotease," "tissue inhibitor of matrix metalloprotease," "endothelial cell," "smooth muscle cell," "cytokines," "endothelin," and "transforming growth factor" to infer the missing links in molecular pathogenesis of MMA. Studies conforming to the inclusion criteria were reviewed. RESULTS: The literature search yielded 44 published articles on MMD by using keywords classified under the six key factors, namely arterial tortuosity, vascular angles, wall shear stress, molecular factors, blood rheology/viscosity, and blood vessel wall strength, and 477 published articles on MMS associations. Information obtained from 51 articles that matched the inclusion criteria and additional information derived from the progressive search mentioned above were used to connect the key factors to derive a network pattern of pathogenesis. CONCLUSIONS: Based on the available literature, the authors have proposed a unifying theory for the pathogenesis of MMA. The moyamoya phenomenon appears to be the culmination of an interplay of vascular anatomy, hemodynamics, rheology, blood vessel wall strength, and a plethora of intricately linked mechanobiological molecular mediators that ultimately results in the mechanical process of occlusion of the blood vessel, stimulating angiogenesis and collateral blood supply in an attempt to perfuse the compromised brain.

Efficacy of Carotid Artery Stenting Performed under General Anesthesia with Somatosensory Evoked Potential Monitoring.

OBJECTIVES: During carotid artery stenting (CAS), hemodynamics may be affected by the carotid sinus reflex in some cases. Although general anesthesia has been reported to stabilize intraoperative hemodynamics, the patient's neurological condition must be assessed indirectly. Therefore, we investigated the changes in intraoperative hemodynamics and perioperative complications of CAS under general anesthesia and evaluated the efficacy of somatosensory evoked potential (SEP) monitoring in detecting a reduction in perfusion during CAS. MATERIALS AND METHODS: From April 2011 to August 2016,57 consecutive patients who underwent CAS under general anesthesia were evaluated. The follow-up period ranged from 3 to 8 years. During CAS, anesthesiologists monitored and managed the hemodynamics. SEP monitoring was performed during the CAS procedure in all patients. RESULTS: Intraoperative hypotension (systolic blood pressure ≤ 100 mmHg) was evident in 16 patients (28.1%), and 13 patients (22.8%) experienced intraoperative bradycardia; however, all of these cases were promptly managed under general anesthesia. None of the patients showed systolic blood pressure < 50 mmHg from baseline. Regarding perioperative complications, none of the patients exhibited myocardial infarction or postoperative hyperperfusion symptoms, and there was no mortality. Among 21 patients (36.8%) with a decrease in the intraoperative SEP, 3 (5.3%) exhibited transient ischemic symptoms and 1 (1.8%) had postoperative infarction. CONCLUSIONS: CAS under general anesthesia is a safe and effective management option in terms of intraoperative hemodynamic stability. In addition, our findings indicate that SEP monitoring could be helpful in evaluating transient postoperative cerebral ischemia or cerebral infarction after CAS.

[Familial Mediterranean Fever-Associated Lenticulostriate Artery Aneurysm Presenting with Intracranial Hemorrhage and Disappearing Spontaneously: A Case Report].

Lenticulostriate artery (LSA) aneurysm is relatively rare, and the need for surgical intervention is controversial. Here, we report a case of ruptured LSA aneurysm which was accompanied by familial Mediterranean fever (FMF). A 45-year-old woman with a history of FMF presented with sudden onset of headache and vertigo. Computed tomography revealed hemorrhage in the right caudate nucleus and lateral ventricles. Digital subtraction angiography revealed a fusiform aneurysm (3mm) at the distal site of medial LSA. Observation was selected, and the aneurysm gradually decreased and eventually disappeared on the 105th day from the onset. This was the first report describing an LSA aneurysm associated with FMF. It suggests that such aneurysms could be treated conservatively with close radiological follow-up.

Complication rate, cure rate, and long-term outcomes of microsurgery for intracranial dural arteriovenous fistulae: a multicenter series and systematic review.

Although microsurgery is an established treatment modality for intracranial dural arteriovenous fistula (dAVF), data regarding the perioperative complication rate, cure rate, and long-term outcomes remain scarce. The aims of this study were to describe our original experience with microsurgery, including the surgical complications and pitfalls, and conduct a systematic review of the relevant literature. A multicenter cohort of patients with dAVF treated by microsurgery was retrospectively assessed. In addition, the PubMed database was searched for published studies involving microsurgery for dAVF, and the complication rate, cure rate, and long-term outcomes were estimated. The total number of patients in our multicenter series and published articles was 553 (593 surgeries). The overall rates of transient complications, permanent complications, death, and incomplete treatment were 11.4, 4.0, 1.2, and 6.5%, respectively. A favorable outcome was achieved for 90.1% patients, even though almost half of the patients presented with intracranial hemorrhage. Of note, the incidence of recurrence was only one per 8241 patient-months of postoperative follow-up. Surgeries for anterior cranial fossa dAVF were associated with a lower complication rate, whereas those for tentorial dAVF were associated with higher complication and incomplete treatment rates. The complication and incomplete treatment rates were lower with simple disconnection of cortical venous drainage than with radical occlusion/resection of dural shunts. Our findings suggest that the cure rate, complication rates, and outcomes of microsurgery for dAVF are acceptable; thus, it could be a feasible second-line treatment option for dAVF. However, surgeons should be aware of the specific adverse events of microsurgery.

Crossed cerebellar diaschisis as an indicator of severe cerebral hyperperfusion after direct bypass for moyamoya disease.

Cerebral hyperperfusion (HP) complicates the postoperative course of patients with moyamoya disease (MMD) after direct revascularization surgery. Crossed cerebellar diaschisis (CCD) has been considered to be rarely associated with HP after revascularization surgery. This study aimed to describe the clinical features and factors associated with CCD secondary to cerebral HP after revascularization surgery for MMD. We analyzed 150 consecutive hemispheres including 101 in adults and 49 in pediatric patients who underwent combined direct and indirect bypass for MMD. Using single-photon emission computed tomography (SPECT), serial cerebral blood flow (CBF) was measured immediately after the surgery and on postoperative days 2 and 7. Pre- and postoperative voxel-based analysis of SPECT findings was performed to compare the changes in regional CBF. Multivariate logistic regression analysis was performed to test the effect of multiple variables on CCD. Asymptomatic and symptomatic HP was observed in 41.3% (62/150) and 16.7% (25/150) of the operated hemispheres, respectively. CCD was observed in 18.4% (16/87) of these hemispheres with radiological HP. Multivariate analysis revealed that the occurrence of CCD was significantly associated with symptomatic HP (p = 0.0015). Voxel-based analysis showed that the CBF increase in the operated frontal cortex, and the CBF reduction in the contralateral cerebellar hemisphere on day 7 were significantly larger in symptomatic HP than in asymptomatic HP (median 11.3% vs 7.5%; - 6.0% vs - 1.7%, respectively). CCD secondary to postoperative HP is more common than anticipated in MMD. CCD could potentially be used as an indicator of severe postoperative HP in patients with MMD.

Immersive 3-Dimensional Virtual Reality Modeling for Case-Specific Presurgical Discussions in Cerebrovascular Neurosurgery.

BACKGROUND: Adequate surgical planning includes a precise understanding of patient-specific anatomy and is a necessity for neurosurgeons. Although the use of virtual reality (VR) technology is emerging in surgical planning and education, few studies have examined the effectiveness of immersive VR during surgical planning using a modern head-mounted display. OBJECTIVE: To investigate if and how immersive VR aids presurgical discussions of cerebrovascular surgery. METHODS: A multiuser immersive VR system, BananaVisionTM, was developed and used during presurgical discussions in a prospective patient cohort undergoing cerebrovascular surgery. A questionnaire/interview was administered to multiple surgeons after the surgeries to evaluate the effectiveness of the VR system compared to conventional imaging modalities. An objective assessment of the surgeon's knowledge of patient-specific anatomy was also conducted by rating surgeons' hand-drawn presurgical illustrations. RESULTS: The VR session effectively enhanced surgeons' understanding of patient-specific anatomy in the majority of cases (83.3%). An objective assessment of surgeons' presurgical illustrations was consistent with this result. The VR session also effectively improved the decision-making process regarding minor surgical techniques in 61.1% of cases and even aided surgeons in making critical surgical decisions about cases involving complex and challenging anatomy. The utility of the VR system was rated significantly higher by trainees than by experts. CONCLUSION: Although rated as more useful by trainees than by experts, immersive 3D VR modeling increased surgeons' understanding of patient-specific anatomy and improved surgical strategy in certain cases involving challenging anatomy.

Vascular Smooth Muscle Cell Derived from IPS Cell of Moyamoya Disease - Comparative Characterization with Endothelial Cell Transcriptome.

BACKGROUND: Moyamoya disease (MMD) is an occlusive cerebrovascular disease, causing stroke in children and young adults with unknown etiology. The fundamental pathology is fibrocellular intimal thickening of cerebral arteries, in which vascular smooth muscle cells (VSMCs) are observed as one of the major cell types. Although the characteristics of circulating smooth muscle progenitor cells have been previously reported, the VSMCs are poorly characterized in MMD. We aimed to characterize VSMCs in MMD using induced pluripotent stem cell (iPSC)-technology. METHODS: We differentiated VSMCs from neural crest stem cells (NCSCs) using peripheral blood mononuclear cell-derived iPSCs and compared biological and transcriptome features under naïve culture conditions between three independent healthy control (HC) subjects and three MMD patients. VSMC transcriptome profiles were also compared to those of endothelial cells (ECs) differentiated from the same iPSCs. RESULTS: Homogeneous spindle-shaped cells differentiated from iPSCs exhibited smooth muscle cell marker expressions, including α-smooth muscle actin (αSMA, 82.3 ± 6.7% and 81.0 ± 6.7%); calponin (91.3 ± 2.1% and 90.9 ± 1.3%); myosin heavy chain-11 (MYH11, 96.9 ± 0.7% and 97.1 ± 0.3%) without significance of differences between the two groups. Real-time PCR showed few PECAM1 and CD34 gene expressions in both groups, indicating features of differentiated VSMCs. There were no significant differences in cellular proliferation (p = 0.45), migration (p = 0.60), and contractile abilities (p = 0.96) between the two groups. Transcriptome analysis demonstrated similar gene expression profiles of VSMCs in HC subjects and MMD patients with six differentially expressed genes (DEGs); while ECs showed a distinct transcriptome profile in MMD patients with 120 DEGs. The Wnt-signaling pathway was a significant pathway in VSMCs. CONCLUSIONS: This is the first study that established VSMCs from NCSCs using MMD patient-derived iPSCs and demonstrated similar biological function and transcriptome profile of iPSC-derived VMSCs in MMD patients and HC subjects under naïve single culture condition. Comparative transcriptome features between iPSC-derived VSMCs and ECs, displaying distinct transcriptome in the ECs, suggested that pathological traits can be driven by naïve ECs predominantly and VSMCs may require specific environmental factors in MMD, which provides novel insight into the pathophysiology of MMD. Our iPSC derived VSMC model can contribute to further investigations of diagnostic and therapeutic target of MMD in addition to the current iPSC derived EC model.

Neuroprotective effects of combination therapy of regional cold perfusion and hemoglobin-based oxygen carrier administration on rat transient cerebral ischemia.

Regional cold perfusion and hemoglobin-based oxygen carrier administration both exert neuroprotective effects against cerebral ischemia reperfusion injury. We herein investigated whether the combination of these two therapies leads to stronger neuroprotective effects. Combination therapy was performed with the regional perfusion of cold HemoAct, a core-shell structured hemoglobin-albumin cluster, in a rat transient middle cerebral artery occlusion model. The effects of combination therapy, the intra-arterial administration of 10 °C HemoAct (10H) initiated at the onset of reperfusion, were compared with those of monotherapies, the intra-arterial administration of 10 °C saline (10S) and 37 °C HemoAct (37H), and an untreated control under the condition of 2-hour ischemia/24-hour reperfusion. The durability of therapeutic effects and the therapeutic time window of combination therapy were assessed based on comparisons with the 10H and control groups. Significantly better neurological findings and smaller infarct volumes were observed in the three treated (10S, 37H, and 10H) groups than in the control group. Among the 3 treated groups, only the 10H group showed significant improvements over the control group in the other items examined, including cerebral blood flow reduction, brain edema, and protein extravasation. The significant therapeutic effects of combination therapy on neurological disabilities and infarct volumes were confirmed at least until 7 days after reperfusion. Furthermore, combination therapy ameliorated neurological disabilities and hemorrhagic transformation in rats subjected to 4- and 5-hour ischemia/24-hour reperfusion. Since therapeutic effects may be expected until at least 5 h of complete ischemia and reperfusion, this combination therapy is a promising neuroprotective strategy against severe ischemic stroke.

Microsurgical Findings of Pial Arterial Feeders in Intracranial Dural Arteriovenous Fistulae: A Case Series.

BACKGROUND: Pial arterial feeders in an intracranial dural arteriovenous fistula (dAVF) are risk factors for both ischemic and hemorrhagic complications during endovascular embolization. Microsurgery in dAVF with pial arterial feeders has rarely been reported. OBJECTIVE: To assess our original experience with microsurgery for dAVF with pial arterial feeders by investigating surgical findings and outcomes. METHODS: In 40 patients with intracranial dAVF who underwent microsurgery, we found 8 patients who had pial arterial feeders. A retrospective review was conducted. RESULTS: The locations of the dAVFs were as follows: tentorium, 2 patients; Galenic system, 1; straight sinus, 1; torcula, 1; transverse sinus, 1; ethmoid, 1; and convexity, 1. Preoperative angiography revealed that the pial arterial feeders originated from the middle cerebral artery in 2 patients, the anterior cerebral artery in 1, the posterior cerebral artery in 2, and the posterior medial choroidal artery in 1. Of note, in 2 patients (6.7%), feeders from the superior cerebellar artery were determined to be angiographically occult during preoperative examination and were detected through careful intraoperative observation and arachnoid dissection. In 5 cases, the additional obliteration of the pial arterial feeders and/or more distal cortical venous drainers after the simple disconnection of proximal cortical drainers was necessary to cure the dAVF. Finally, all shunts were cured with only 1 minor complication. CONCLUSION: Although microsurgical results were acceptable, the surgeon should be aware of the presence of pial arterial feeders even after the simple disconnection of cortical venous drainage. Angiographically occult feeders may also exist.

Neuroendoscope-Assisted Aneurysm Trapping for Ruptured Intraventricular Aneurysms in Moyamoya Disease Patients.

BACKGROUND: Intracranial hematomas associated with abnormal collateral vessels are observed in certain populations of adult patients with moyamoya disease (MMD). Of these, intraventricular hematomas resulting from rupture of intraventricular aneurysms, which are formed along an abnormal peripheral choroidal artery, are sometimes detected and could be severe. No appropriate treatment option for these ruptured aneurysms has been well established to date. Therefore in this report, we describe the case of an MMD patient with an intraventricular hematoma resulting from a ruptured intraventricular aneurysm arising along the abnormal collateral vessels near the lateral ventricular wall, which was successfully treated using a neuroendoscope. CASE DESCRIPTION: A 53-year-old female with MMD presented with an intraventricular hematoma. The patient had already undergone bilateral, combined direct/indirect cerebral revascularization surgery 3 years prior. Digital subtraction angiography revealed an aneurysm along the abnormal collateral choroidal artery near the posterior horn of the left lateral ventricle. A neuroendoscopic technique was applied to approach and treat the aneurysm; this was performed successfully by trapping using aneurysm clips without intraoperative or postoperative complications. CONCLUSIONS: Neuroendoscopic aneurysm trapping using aneurysm clips is a treatment option for an intraventricular aneurysm that causes an intraventricular hematoma in patients with MMD. This technique is minimally invasive and offers good visibility of the surgical field.

Combined structural and diffusion tensor imaging detection of ischemic injury in moyamoya disease: relation to disease advancement and cerebral hypoperfusion.

OBJECTIVE: The microstructural integrity of gray and white matter is decreased in adult moyamoya disease, suggesting covert ischemic injury as a mechanism of cognitive dysfunction. Establishing a microstructural brain imaging marker is critical for monitoring cognitive outcomes following surgical interventions. The authors of the present study determined the pathophysiological basis of altered microstructural brain injury in relation to advanced arterial occlusion, cerebral hypoperfusion, and cognitive function. METHODS: The authors examined 58 patients without apparent brain lesions and 30 healthy controls by using structural MRI, as well as diffusion tensor imaging (DTI). Arterial occlusion in each hemisphere was classified as early or advanced stage based on MRA and posterior cerebral artery (PCA) involvement. Regional cerebral blood flow (rCBF) was measured with N-isopropyl-p-[123I]-iodoamphetamine SPECT. Furthermore, cognitive performance was examined using the Wechsler Adult Intelligence Scale, Third Edition and the Trail Making Test (TMT). Both voxel- and region of interest-based analyses were performed for groupwise comparisons, as well as correlation analysis, using parameters such as cognitive test scores; gray matter volume; fractional anisotropy (FA) of association fiber tracts, including the inferior frontooccipital fasciculus (IFOF) and superior longitudinal fasciculus (SLF); PCA involvement; and rCBF. RESULTS: Compared to the early stages, advanced stages of arterial occlusion in the left hemisphere were associated with a lower Performance IQ (p = 0.031), decreased anterior cingulate volumes (p = 0.0001, uncorrected), and lower FA in the IFOF, cingulum, and forceps major (all p < 0.01, all uncorrected). There was no significant difference in rCBF between the early and the advanced stage. In patients with an advanced stage, PCA involvement was correlated with a significantly lower Full Scale IQ (p = 0.036), cingulate volume (p < 0.01, uncorrected), and FA of the left SLF (p = 0.0002, uncorrected) compared to those with an intact PCA. The rCBF was positively correlated with FA of the SLF, IFOF, and forceps major (r > 0.34, p < 0.05). Global gray matter volumes were moderately correlated with TMT part A (r = 0.40, p = 0.003). FA values in the left SLF were moderately associated with processing speed (r = 0.40, p = 0.002). CONCLUSIONS: Although hemodynamic compensation may mask cerebral ischemia in advanced stages of adult moyamoya disease, the disease progression is detrimental to gray and white matter microstructure as well as cognition. In particular, additional PCA involvement in advanced disease stages may impair key neural substrates such as the cingulum and SLF. Thus, combined structural MRI and DTI are potentially useful for tracking the neural integrity of key neural substrates associated with cognitive function and detecting subtle anatomical changes associated with persistent ischemia, as well as disease progression.

Reversible Cerebral Angiopathy after Viral Infection in a Pediatric Patient with Genetic Variant of RNF213.

Ring finger protein (RNF) 213 is known as a susceptibility gene for moyamoya disease (MMD), which is characterized by bilateral carotid folk stenosis. Cerebral angiopathy after viral infection has been known to present angiographical appearance resembling MMD, however its pathogenesis and genetic background are not well known. We report a case of reversible cerebral angiopathy after viral infection in a pediatric patient with genetic variant of RNF213 mutation. The patient had developed a severe headache after hand, foot, and mouth disease. Magnetic resonance imaging and magnetic resonance angiography (MRA) performed 2-3 weeks after disease onset revealed bilateral carotid folk stenosis and an old cerebral infarction in the left putamen. The patient's headache spontaneously resolved and the follow-up MRA showed a complete spontaneous resolution of the arterial stenosis after 9 months. We were able to determine genetic predisposition to angiopathy by identifying the RNF213 c.14576G>A (rs112735431, p.R4859K) mutation. Based on the present case, we hypothesize that an RNF213 variant might play an important role for the onset of postviral cerebral angiopathy.

Association of cognitive function with cerebral blood flow in children with moyamoya disease.

OBJECTIVE: The cognitive effects of main cerebral artery occlusive lesions are unclear in children with moyamoya disease (MMD). The authors aimed to investigate cognitive function in the presurgical phase of pediatric patients with MMD with no apparent brain lesions. METHODS: In this prospective, observational, single-center study, 21 children (mean age 10 ± 3.0 years, range 5-14 years) diagnosed with MMD at Hokkaido University Hospital between 2012 and 2018 were enrolled. A cross-sectional evaluation of intellectual ability was performed using the Wechsler Intelligence Scale for Children-Fourth Edition at the initial diagnosis. rCBF was measured using [123I] N-isopropyl p-iodoamphetamine/SPECT. The associations among clinical factors, disease severity, regional cerebral blood flow (rCBF), and intelligence test scores were also examined. RESULTS: The mean full-scale intelligence quotient (FIQ) was 101.8 ± 12.5 (range 76-125) in children with no apparent brain lesions. A significant difference in the intelligence scale index score was observed, most frequently (42.9%) between working memory index (WMI) and verbal comprehension index (VCI; VCI - WMI > 11 points). Regional CBF was significantly reduced both in the left and right medial frontal cortices (left: 61.3 ± 5.3 ml/100 g/min, right 65.3 ± 5.3 ml/100 g/min; p < 0.001) compared to the cerebellum (77.8 ± 6.8 ml/100 g/min). There was a significant association of rCBF in the left dorsolateral prefrontal cortex (DLPFC) with FIQ (r = 0.46, p = 0.034), perceptual reasoning index (PRI; r = 0.44, p = 0.045), and processing speed index (PSI; r = 0.44, p = 0.045). There was an association between rCBF of the left medial frontal cortex and PSI (r = 0.49, p = 0.026). Age of onset, family history, ischemic symptoms, and angiographic severity were not associated with poor cognitive performance. CONCLUSIONS: Although average intellectual ability was not reduced in children with MMD, the association of reduced rCBF in the left DLPFC and medial frontal cortex with FIQ, PRI, and PSI suggests mild cognitive dysfunction due to cerebral hypoperfusion.

Brain Structure, Connectivity, and Cognitive Changes Following Revascularization Surgery in Adult Moyamoya Disease.

BACKGROUND: The effect of the combined direct/indirect revascularization surgery in Moyamoya disease has not been evaluated sufficiently with regard to cognitive function, brain microstructure, and connectivity. OBJECTIVE: To investigate structural and functional changes following revascularization surgery in patients with moyamoya disease (MMD) through a combined analysis of brain morphology, microstructure, connectivity, and neurobehavioral data. METHODS: Neurobehavioral and neuroimaging examinations were performed in 25 adults with MMD prior to and >12 mo after revascularization surgery. Cognitive function was investigated using the Wechsler Adult Intelligence Scale-III, Trail-Making Test, Wisconsin Card Sorting Test, Continuous Performance Test, Stroop test, and Wechsler Memory Scale. We assessed white matter integrity using diffusion tensor imaging, brain morphometry using magnetization-prepared rapid gradient-echo sequences, and brain connectivity using resting-state functional magnetic resonance imaging (MRI). RESULTS: Cognitive examinations revealed significant changes in the full-scale intelligence quotient (IQ), performance IQ (PIQ), perceptual organization (PO), processing speed, and Stroop test scores after surgery (P < .05). Enlargement of the lateral ventricle, volume reductions in the corpus callosum and subcortical nuclei, and cortical thinning in the prefrontal cortex were also observed (P < .05). Fractional anisotropy in the white matter tracts, including the superior longitudinal fasciculus, increased 2 to 4 yr after surgery, relative to that observed in the presurgical state (P < .05). Resting-state brain connectivity was increased predominantly in the fronto-cerebellar circuit and was positively correlated with improvements in PIQ and PO (P < .05). CONCLUSION: Revascularization surgery may improve processing speed and attention in adult patients with MMD. Further, multimodal MRI may be useful for detecting subtle postsurgical brain structural changes, reorganization of white matter tracts, and brain connectivity alterations.