Predictive value of the hemispheric magnetic resonance angiography score on the development of indirect pial synangiosis after combined revascularization surgery for adult moyamoya disease.

PURPOSE: It is difficult to precisely predict indirect bypass development in the context of combined bypass procedures in moyamoya disease (MMD). We aimed to investigate the predictive value of magnetic resonance angiography (MRA) signal intensity in the peripheral portion of the major cerebral arteries for indirect bypass development in adult patients with MMD. METHODS: We studied 93 hemispheres from 62 adult patients who underwent combined direct and indirect revascularization between 2005 and 2019 and genetic analysis for RNF213 p.R4810K. The signal intensity of the peripheral portion of the major intracranial arteries during preoperative MRA was graded as a hemispheric MRA score (0-3 in the middle cerebral artery and 0-2 in the anterior cerebral and posterior cerebral arteries, with a high score representing low visibility) according to each vessel's visibility. Postoperative bypass development was qualitatively evaluated using MRA, and we evaluated the correlation between preoperative factors, including the hemispheric MRA score and bypass development, using univariate and multivariate analyses. RESULTS: A good indirect bypass was observed in 70% of the hemispheres. Hemispheric MRA scores were significantly higher in hemispheres with good indirect bypass development than in those with poor indirect bypass development (median: 3 vs. 1; p < 0.0001). Multiple logistic regression analysis revealed hemispheric MRA score as an independent predictor of good indirect bypass development (odds ratio, 2.1; 95% confidence interval, 1.3-3.6; p < 0.01). The low hemispheric MRA score (< 2) and wild-type RNF213 predicted poor indirect bypass development with a specificity of 0.92. CONCLUSION: Hemispheric MRA score was a predictive factor for indirect bypass development in adult patients who underwent a combined bypass procedure for MMD. Predicting poor indirect bypass development may lead to future tailored bypass surgeries for MMD.

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.

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.

Rescue Extracranial-Intracranial Bypass for Ischemic Stroke Secondary to Progressive Human Immunodeficiency Virus-Associated Vasculopathy.

BACKGROUND: Human immunodeficiency virus (HIV) associated vasculopathy can cause ischemic cerebral stroke; however, there is limited evidence on optimal management. Herein, we report a case of acute ischemic stroke due to progressive internal carotid artery (ICA) stenosis in an HIV-positive patient. Superficial temporal artery to middle cerebral artery (STA-MCA) bypass, in addition to the best medical treatments, prevented stroke progression. CLINICAL DESCRIPTION: A 39-year-old man with HIV infection presented with a sudden onset of aphasia and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left basal ganglia and concentric thickening of the vessel wall in the terminal portion of the bilateral ICAs. Despite maximal medical treatments for HIV-associated vasculopathy and possible opportunistic infections, bilateral ICA stenoses progressed, leading to a second hemodynamic stroke event. Because tissue plasminogen activator treatment failed, we performed STA-MCA bypass. A significant improvement in neurologic symptoms and cerebral blood flow was observed after surgery. No further stroke events occurred during the continuation of medical treatments. CONCLUSION: This is the first case of STA-MCA bypass performed in a patient with recurrent ischemic stroke caused by HIV-associated vasculopathy. Although further evidence is needed, such treatment options can shed new light on the management of progressive HIV-associated vasculopathy, which is refractory to maximal medical treatment.

Intraoperative Early Venous Filling Phenomenon as an Intrinsic Sign of the Local Hemodynamic Change after Revascularization Surgery in a Patient with Adult Moyamoya Disease: Implications of a Potential Arteriovenous Shunt.

After revascularization surgery for patients with moyamoya disease (MMD), local and global hemodynamic changes occur intraoperatively and in the early postoperative period. Local cerebral hyperperfusion and watershed shift ischemia are well-known perioperative pathologies after revascularization for MMD, but early venous filling phenomenon is markedly rare. We report the case of a 19-year-old woman with hemorrhagic-onset MMD who presented with grand mal seizure and subarachnoid hemorrhage. She underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis on the affected hemisphere. Intraoperatively, notable early arterial blood filling in the fine cortical vein was observed around the site of anastomosis right after the STA-MCA anastomosis under the surgical microscope and fluorescence indocyanine green video angiography. Recovery of consciousness after general anesthesia was normal, although she exhibited a focal seizure 1 hour later. Postoperative magnetic resonance imaging was not remarkable, and cerebral hemodynamics significantly improved in the acute stage after surgical revascularization. Considering the intrinsic vulnerability of the microvascular anatomy of MMD, the present case is notable because early venous filling was observed intraoperatively. This phenomenon suggests the existence of a potential arteriovenous shunt as an underlying pathology of MMD, but its implications in the early postoperative course should be further verified in a larger number of MMD patients undergoing surgical revascularization.

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.

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.

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.

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.

A Pilot Study on Measuring Tissue Motion During Carotid Surgery Using Video-Based Analyses for the Objective Assessment of Surgical Performance.

BACKGROUND: The 'gentle' handling of tissue (i.e., 'respect for tissue') is a fundamental aspect of surgical performance and learning. To date, there have been no methodological assessments that quantitatively measure 'gentleness.' Therefore, the aims of this study were (1) to propose a novel metric for gentle surgical maneuvers, (2) to validate the feasibility of this methodology, and (3) to explore safer surgical techniques through this methodology. METHODS: Using surgical video-based motion software, the motion of the carotid artery around plaque was analyzed and quantified during a carotid endarterectomy. Kinematic parameters (minimum and maximum acceleration, and maximum and mean velocity) were compared among the surgical tasks and techniques, as well as between novice and expert surgeons. RESULTS: The surgical tasks of dissecting the common carotid artery, passing the proximal vessel loops, and ligating vessels showed the highest absolute values of kinematic parameters. Dissections perpendicular to the line of the internal carotid artery tended to show higher kinematic parameters than those in the parallel direction, with blunt dissections typically higher than sharp dissections. The kinematic parameters of novice surgeons were significantly higher than those of experts, and receiver operating curve analysis showed a strong discriminative power. CONCLUSION: This study shows that tissue motion parameters could be a novel and feasible surrogate marker for the objective assessment on the 'gentleness' of surgical performance. Future studies should be performed to further elucidate the relationship on the direct correlation between tissue kinematic data and clinical outcomes or surgical adverse events.

Efficacy of 'drive and retrieve' as a cooperative method for prompt endovascular treatment for acute ischemic stroke.

BACKGROUND: Outcomes of endovascular treatment for acute ischemic stroke depend on the time interval from onset to reperfusion. Although the centralized 'mothership' method is considered preferable, the required transportation time increases the risk that a patient with a stroke may not receive intravenous or endovascular therapy. In contrast, 'drive and retrieve' describes a system wherein doctors from comprehensive stroke centers travel to primary stroke centers and provide endovascular treatment for acute ischemic stroke. OBJECTIVE: To describe the drive and retrieve system and verify the effects of this new collaboration on outcomes in patients with acute ischemic stroke among facilities. METHODS: This non-randomized, single-arm study retrospectively analyzed patients who met the inclusion criteria for endovascular treatment provided through a drive and retrieve system. Among the 122 patients treated by this system, we analyzed the time of onset to recanalization as the primary outcome. We also analyzed the efficacy of the drive and retrieve system using geographic information system analysis. RESULTS: The median time from onset to recanalization was 229 min (IQR 170-307 min, 95% CI 201 to 252 min). The upper limit of the 95% CI for the time from onset to recanalization was shorter than the median times reported in two previous trials. Geographic information system analysis revealed an upward trend in the population coverage rate in each secondary medical area after the drive and retrieve method was introduced. CONCLUSION: The drive and retrieve method may be an effective form of cooperation between facilities located within 1 hour of a comprehensive stroke center.

Postoperative Intracerebral Hemorrhage After Combined Revascularization Surgery in Moyamoya Disease: Profiles and Clinical Associations.

OBJECTIVE: In combined revascularization surgery for patients with moyamoya disease, intracerebral hemorrhage (ICH) during the postoperative acute phase is a rarely observed but severe complication. Its clinical features remain unclear because of its low incidence rate. The aim of this study was to clarify the clinical characteristics of immediate postoperative ICH. METHODS: The frequency, onset timing, and hematoma location of patients who demonstrated immediate postoperative ICH were investigated in 201 consecutive surgeries performed in 134 patients. Associations between immediate postoperative ICH and demographics, clinical presentation type, perioperative blood pressure (BP), and neuroimaging data were analyzed. RESULTS: Postoperative ICH was observed in 6 cases (2.99%; mean age, 46.0 ± 7.6 years). The onset timing of ICH was within 24 hours after surgery in most patients (83.3%). Hematomas were located at the subcortical lesion beneath the anastomosed cortex (n = 5) and caudate head (n = 1). Three cases (50.0%) required hematoma evacuation. A higher age at surgery was associated with postoperative ICH (P = 0.046). In adult cases (132 surgeries, 65.7%), hemorrhagic presentation at onset (P = 0.0027) and an increase in BP from pre- to postoperative stage (systolic BP increase: P = 0.0058, diastolic BP increase: P = 0.0274) were significantly associated with postoperative ICH. CONCLUSIONS: The results suggest that older patients, with hemorrhagic presentation and greater postoperative BP increase, should be carefully managed to avoid postoperative ICH. Immediate hematoma evacuation may be effective in preventing devastating outcomes after postoperative ICH.

Cerebral Hyperperfusion Syndrome After Revascularization Surgery in Moyamoya Disease: Region-Symptom Mapping and Estimating a Critical Threshold.

BACKGROUND: Cerebral hyperperfusion complicates the postoperative course of patients with moyamoya disease after direct revascularization surgery. There is no clear distinction between cerebral hyperperfusion syndrome and benign postoperative increase in regional cerebral blood flow (rCBF). OBJECTIVE: The present study aimed to determine clinically relevant changes in rCBF, anatomical correlations, and factors associated with transient neurologic symptoms after revascularization surgery in moyamoya disease. METHODS: Whole-brain voxel-based perfusion mapping was used to identify regions involved in cerebral hyperperfusion and quantify the changes in 105 hemispheric surgeries with the use of single-photon computed tomography acquired on postoperative day 7. The changes in rCBF were quantitatively analyzed, and associations with cerebral hyperperfusion syndrome were determined. RESULTS: Transient neurologic symptoms appeared with rCBF increase in 37.9% of adults. Speech impairments were associated with an increase in rCBF in the operculo-insula region. Cheiro-oral syndrome was associated with the posterior insula as well as the prefrontal region. A receiver operating curve analysis yielded transient neurologic symptoms with maximum accuracy at >15.5% increase from baseline. Age and preoperative rCBF were independently associated with transient neurologic symptoms (P < 0.001). CONCLUSIONS: Areas showing rCBF increase during the experience of transient neurologic symptoms were spatially compatible with the known functional anatomy of the brain. An increase of approximately 15% from baseline was found to be critical, which is a far lower threshold than what has been reported previously. Increasing age was significantly associated with the occurrence of symptomatic hyperperfusion. Furthermore, patients with preserved rCBF also showed symptomatic hyperperfusion.

The frequency of postoperative stroke in moyamoya disease following combined revascularization: a single-university series and systematic review.

OBJECT: Although combined direct and indirect anastomosis in patients with moyamoya disease immediately increases cerebral blood flow, the surgical procedure is more complex. Data pertinent to the postoperative complications associated with combined bypass are relatively scarce compared with those associated with indirect bypass. This study investigated the incidence and characteristics of postoperative stroke in combined bypass and compared them with those determined from a literature review to obtain data from a large population. METHODS: A total of 358 revascularization procedures in 236 patients were retrospectively assessed by reviewing clinical charts and radiological data. PubMed was searched for published studies on surgical treatment to determine the incidence of postoperative complications in a larger population. RESULTS: Seventeen instances of postoperative stroke were observed in 16 patients (4.7% per surgery, 95% CI 2.8%-7.5%). Postoperative stroke was more frequent (7.9% per surgery) in adults than in pediatric patients (1.7% per surgery, OR 4.07, 95% CI 1.12-14.7; p < 0.05). Acute progression of stenoocclusive changes were identified in the major cerebral arteries (anterior cerebral artery, n = 3; middle cerebral artery, n = 1; posterior cerebral artery, n = 2). The postoperative stroke rate was comparable with that (5.4%) determined from a literature search that included studies reporting more than 2000 direct/combined procedures. No differences in the stroke rates between the direct/combined and indirect procedures were found. In the literature review, direct/combined bypass was more often associated with excellent revascularization (angiographic opacification greater than two-thirds) than indirect bypass (p < 0.05). CONCLUSIONS: This experience of 358 consecutive procedures is one of the largest series for which the postoperative stoke rate for direct/combined bypass performed with a unified strategy has been reported. A systematic review confirmed that the postoperative stroke rate for the direct/combined procedure was comparable to that for the indirect procedure.