Precision medicine in Moyamoya vasculopathy.

Cerebrovascular Reactivity Measured with ASL Perfusion MRI, Ivy Sign, and Regional Tissue Vascularization in Moyamoya

Moyamoya Vessel Pathology Imaged by Ultra–High-Field Magnetic Resonance Imaging at 7.0 T

Moyamoya is a progressive intracranial vasculopathy, primarily affecting distal segments of the internal carotid and middle cerebral arteries. Treatment may comprise angiogenesis-inducing surgical revascularization; however, lack of randomized trials often results in subjective treatment decisions. Compensatory presurgical posterior vertebrobasilar artery (VBA) flow-territory reactivity, including greater cerebrovascular reactivity (CVR) and reduced vascular delay time, portends greater neoangiogenic response verified on digital subtraction angiography (DSA) at 1-year follow-up. Prospective intervention cohort. Thirty-one patients with moyamoya (26 females; age=45± 13 years; 41 revascularized hemispheres). Anatomical MRI, hypercapnic CVR MRI, and DSA acquired presurgically in adult moyamoya participants scheduled for clinically indicated surgical revascularization. One-year postsurgery, DSA was repeated to evaluate collateralization. 3 T. Hypercapnic -weighted gradient-echo blood-oxygenation-level-dependent, T2 -weighted turbo-spin-echo fluid-attenuated-inversion-recovery, T1 -weighted magnetization-prepared-rapid-gradient-echo, and T2 -weighted diffusion-weighted-imaging. Presurgical maximum CVR and response times were evaluated in VBA flow-territories. Revascularization success was determined using an ordinal scoring system of neoangiogenic collateralization from postsurgical DSA by two cerebrovascular neurosurgeons (R.V.C. with 8 years of experience; M.R.F. with 9 years of experience) and one neuroradiologist (L.T.D. with 8 years of experience). Stroke risk factors (age, sex, race, vasculopathy, and diabetes) were recorded. Fisher's exact and Wilcoxon rank-sum tests were applied to compare presurgical variables between cohorts with angiographically confirmed good (>1/3 middle cerebral artery [MCA] territory revascularized) vs. poor (<1/3 MCA territory revascularized) outcomes. two-sided P< 0.05. Normalized odds ratios (ORs) were calculated. Criteria for good collateralization were met in 25 of the 41 revascularized hemispheres. Presurgical normalized VBA flow-territory CVR was significantly higher in those with good (1.12 ± 0.13 unitless) vs. poor (1.04 ± 0.05 unitless) outcomes. Younger (OR=-0.60 ± 0.67) and White (OR=-1.81 ± 1.40) participants had highest revascularization success (good outcomes: age=42 ± 14 years, race=84% White; poor outcomes: age=49 ± 11 years, race=44% White). Presurgical MRI-measures of VBA flow-territory CVR are highest in moyamoya participants with better angiographic responses to surgical revascularization. 1 TECHNICAL EFFICACY STAGE: 4.

Patients with moyamoya vasculopathy often experience cognitive impairments. In this prospective single-center study, the authors investigated the profile of neurocognitive impairment and its relation with the severity of ischemic brain lesions and hemodynamic compromise. Patients treated in a Dutch tertiary referral center were prospectively included. All patients underwent standardized neuropsychological evaluation, MRI, digital subtraction angiography, and [15O]H2O-PET (to measure cerebrovascular reactivity [CVR]). The authors determined z-scores for 7 cognitive domains and the proportion of patients with cognitive impairment (z-score < -1.5 SD in at least one domain). The authors explored associations between patient characteristics, imaging and CVR findings, and cognitive scores per domain by using multivariable linear regression and Bayesian regression analysis. A total of 40 patients (22 children; 75% females) were included. The median age for children was 9 years (range 1-16 years); for adults it was 39 years (range 19-53 years). Thirty patients (75%) had an infarction, and 31 patients (78%) had impaired CVR (steal phenomenon). Six of 7 cognitive domains scored below the population norm. Twenty-nine patients (73%) had cognitive impairment. Adults performed better than children in the cognitive domain visuospatial functioning (p = 0.033, Bayes factor = 4.0), and children performed better in processing speed (p = 0.041, Bayes factor = 3.5). The authors did not find an association between infarction, white matter disease, or CVR and cognitive domains. In this Western cohort, cognitive functioning in patients with moyamoya vasculopathy was below the population norm, and 73% had cognitive impairment in at least one domain. The cognitive profile differed between adults and children. The authors could not find an association with imaging findings.

Can CT angiography rule out aneurysmal subarachnoid haemorrhage in CT scan-negative subarachnoid haemorrhage patients?

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Intravascular ultrasound (IVUS) allows intraluminal imaging of blood vessels rather than the one-dimensional luminal outline depicted by digital subtraction angiography (DSA). Despite extensive literature in multiple adult vascular diseases, IVUS has not been directly compared to DSA in pediatric and adolescent vascular pathologies. The purpose of this manuscript is to compare absolute luminal diameter measurements obtained via IVUS and DSA during a variety of pediatric endovascular procedures. We conducted a retrospective review of all pediatric and adolescent endovascular procedures from October 2014 to March 2016 in which IVUS and DSA were used. We compared the vessel diameter measurements and analyzed them using SAS software with a paired t-test. There were 102 total measurements (DSA = 56; IVUS = 56; 22 procedures; 20 patients). On average, IVUS measured 0.6 ± 2.1mm larger than DSA (95% confidence interval [CI] -0.01 to 1.12; P = 0.06; r = 0.90). When venous compression syndrome (May-Thurner, Nutcracker, superior vena cava syndrome) measurements were excluded, IVUS measured 0.7 ± 1.6mm larger than DSA (95% CI 0.14 to 1.18; P = 0.01; r = 0.93). When venous compression syndrome measurements were evaluated separately, IVUS measured 0.3 ± 3.0mm larger than DSA (95% CI -1.16 to 1.82; P = 0.65; r = 0.45). Overall, IVUS measurements were slightly larger than DSA measurements in all data subsets. Absolute vessel diameter measurements obtained with IVUS in the pediatric and adolescent population are statistically significantly larger than those obtained using DSA when excluding venous compression syndromes. In venous compression syndromes, IVUS might provide a more accurate representation of vessel compression and diameter than DSA.

The aim of this study is to systematically review the literature on surgical revascularization techniques for flow-augmentation of the frontal areas and/or anterior cerebral artery (ACA) territory in children with Moyamoya vasculopathy (MMV), to elucidate the current surgical practice and describe the outcome associated to the different techniques. The systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. MEDLINE, Web of Science and EMBASE were searched up to April 2020. Published techniques were systematically analyzed according to level of evidence, revascularization technique, opening of the interhemispheric fissure (IF), uni- or bilateral revascularization, clinical, neurocognitive, angiographic, perfusion and hemodynamic outcome. Twenty-five studies were enrolled, including 829 patients: among these, 13 patients underwent direct revascularization of ACA territories, 570 indirect revascularization and 246 patients combined revascularization. One study reached a level of evidence II (grade of recommendation B), 8 studies were level III (grade B) and 16 studies were level IV (grade C). The surgical techniques proposed in the enrolled papers were systematically described. Combined techniques (grade of recommendation B) and indirect techniques (grade of recommendation C) are considered effective for revascularizing the frontal areas and/or anterior cerebral artery (ACA) territory in children with MMV. While performing the revascularization, surgical risks can be reduced by avoiding the exposure of the superior sagittal sinus and opening of IF (recommendation grade C). There is not sufficient evidence to define which type of surgical technique should be preferred. Future studies are needed for a longitudinal assessment of comparable outcomes and to determine which revascularization technique for the frontal areas and/or ACA territory is optimal for this highly specific pediatric population.

Digital subtraction angiography (DSA) is the gold standard for diagnosis and treatment of many intracranial cerebrovascular pathologies. With a growing recognition of pediatric cerebrovascular disorders and advances in endovascular treatments, there has been an increasing number of DSAs performed in children. Although the safety profile of DSA has been well studied in adults, emerging data on the safety of DSA in children shows a relatively strong safety profile. DSA in children poses unique challenges for neurointerventionalists, including the small size and fragility of pediatric vessels, limited application of devices designed for adults to the pediatric population, reduced radiation and contrast dosage, and specific anesthetic considerations. Further, children have unique cerebrovascular pathologies with specific vulnerabilities that may make errors more consequential. Here we discuss the indications, alternatives, and potential complications of DSA in children. We provide suggestions on how to tailor anesthesia, contrast, radiation exposure, femoral access, catheterization, and closures during DSA for the pediatric population.

IntroductionMoyamoya disease is the idiopathic bilateral progressive stenosis of the anterior circulation arteries at the skull base, followed by the compensatory formation and proliferation of collateral small vessel arteries typically in the lenticulostriate region. The clinical diagnosis is made by neurovascular imaging with digital subtraction angiography being the gold standard of diagnosis. The term moyamoya syndrome is used when the formation of collateral arteries occur after unilateral vasculopathy or if the progressive stenosis occurs in the setting of known associated conditions such as sickle cell disease or prior cranial radiation treatment. For patients who have undiagnosed moyamoya syndrome, stroke symptoms may be the first presentation of the underlying disease.MethodsWe present a case series of 15 patients who arrived to our tertiary care hospital from December 2014 to July 2022.ResultsThe majority of the patients were women with the average age of 43 years old. Patients were admitted with NIHSS ranging from 0 to 14, and two patients presented with signs suggestive of MCA syndrome. Including major ischemic stroke risk factors, five patients also had differentials of antiphospholipid antibody syndrome, connective tissue disorder, vasculitis, and congenital rubella as possible underlying conditions promoting the vasculopathy. Morbidity was high for moyamoya patients, with an average modified Rankin scale of 2 at discharge. Eleven patients had unknown moyamoya history at time of arrival and were identified based on hyperacute diagnostic CT angiography during stroke evaluation. Five patients were initially diagnosed as large vessel occlusion on CT angiography. Given the speed at which IV thrombolysis and mechanical thrombectomy decisions are made, patients with moyamoya vasculopathy require rapid and accurate interpretation of CT findings that distinguish them from standard large vessel occlusion patients and prevent the potentially catastrophic consequences of inappropriate treatment.ConclusionsThe pathophysiology leading to moyamoya disease is not well understood, but the stenosis process of major arteries is thought to be secondary to irregular hyperplasia of the tunica media, followed by compensatory growth of small collateral vessels. This collateralization leads to micro‐aneurysm formation in the small perforator branches. Moyamoya patients are at an increased risk of hemorrhage, representing a contraindication to IV thrombolysis, and, if mechanical thrombectomy is attempted, risk of possible large vessel rupture. In our case series, the 15 patients did not receive IV thrombolysis or mechanical thrombectomy based on appropriate diagnosis of moyamoya vasculopathy at time of emergency CT angiography, subsequently confirmed by elective, catheter cerebral angiography.

The aim of this study was to describe the clinical and radiological findings of patients with moyamoya syndrome and Graves' disease. Possible mechanisms predisposing these individuals to ischemic stroke are discussed. We retrospectively analyzed 12 consecutive patients with both moyamoya syndrome and Graves' disease. Moyamoya vasculopathy was diagnosed by digital subtract angiography or magnetic resonance angiography (MRA). The clinical characteristics, laboratory data, vascular radiological characteristics and outcome were reported. All patients were female and mean age was 33.33±12.65 years. Stenosis or occlusion of bilateral terminal internal carotid artery and/or proximal anterior/middle cerebral arteries was found in nine patients. Among them, three patients displayed asymmetrical stenosis. In addition, there were three patients with probable unilateral moamoya syndrome. Eleven patients presented with ischemic stroke and/or transient ischemic attack (TIA) and one with dizziness. Thyroid function tests demonstrated elevated thyroid hormone levels and suppressed thyroid stimulating hormone levels in all the patients with ischemic events. All patients received anti-thyroid therapy and two had recurrent ischemic attack after drug withdrawal. Moyamoya syndrome associated Graves' disease often presented with asymmetric stenosis or occlusion. We hypothesize cerebrovascular hemodynamic changes due to thyrotoxicosis contribute to the ischemic events.

Background and purpose Moyamoya disease is a cerebrovascular disorder characterized by bilateral progressive stenosis and occlusion of terminal portions of internal carotid artery (ICA) accompanying by typical net-like collateral vessels. Patients with both the characteristic moyamoya vasculopathy and the associated conditions are categorized as moyamoya syndrome. These conditions include sickle cell disease, neurofibromatosis type 1, Down’s disease, cranial therapeutic irradiation and other rare diseases. Moyamoya syndrome associated with Graves’ disease has been rarely reported and the underlying coexisting mechanism remains unclear. The aim of this study is to identify the clinical and radiological findings of the patients with simultaneous diagnosis of moyamoya syndrome and Graves’ disease. Possible mechanisms predisposing these individuals to ischemic accidents are discussed. Methods We retrospectively identified 12 patients in Peking Union Medical College Hospital and 4 patients in 307 hospital of PLA between May 2000 and December 2010. All patients were female and mean age (range) was 35.13±12.34 years (11-57 years). The patients were diagnosed with Graves’ disease in endocrinology clinic which meet the full diagnostic criteria and no atherosclerotic factor was found in them. Moyamoya vasculopathy was definitely or probably diagnosed by digital subtract angiography or magnetic resonance angiography. The clinical characteristics and prognosis, laboratory data, vascular radiological characteristics were all collected. Results Stenosis or occlusion of bilateral distal ICA and/or proximal anterior /middle cerebral arteries was found in 13 patients. Three patients had unilateral distal ICA stenosis and abnormal collateral vessels. PCA stenosis was found in 2 patients. Fifteen patients presented with infarction or transient ischemic attack and one with dizziness. Interestingly, thyroid function tests demonstrated predominantly elevated thyroxine and suppressed thyroid stimulating hormone level in 15 patients when cerebrovascular accidents occurred. All patients received antithyroid therapy and two had recurrent ischemic attack after several months of drug withdrawal. Four patients underwent revascularization procedures after normalization of their hormonal conditions in 307 Hospital of PLA and their neurologic status has remained stable during follow-up. Conclusions: Compared with classical moyamoya disease, moyamoya syndrome associated Graves’ disease more commonly presented asymmetric stenosis or occlusion and PCA lesions. Cerebrovascular hemodynamic changes attributable to thyrotoxicosis might be responsible for ischemic attack and further studies are required to verify this hypothesis.

Moyamoya disease (MMD) is a rare condition that affects the blood vessels of the central nervous system. This cerebrovascular disease is characterized by progressive narrowing and blockage of the internal carotid, middle cerebral, and anterior cerebral arteries, which results in the formation of a compensatory fragile vascular network. Currently, digital subtraction angiography (DSA) is considered the gold standard in diagnosing MMD. However, this diagnostic technique is invasive and may not be suitable for all patients. Hence, non-invasive imaging methods such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are often used. However, these methods may have less reliable diagnostic results. Therefore, High-Resolution Magnetic Resonance Vessel Wall Imaging (HR-VWI) has emerged as the most accurate method for observing and analyzing arterial wall structure. It enhances the resolution of arterial walls and enables quantitative and qualitative analysis of plaque, facilitating the identification of atherosclerotic lesions, vascular entrapment, myofibrillar dysplasia, moyamoya vasculopathy, and other related conditions. Consequently, HR-VWI provides a new and more reliable evaluation criterion for diagnosing vascular lesions in patients with Moyamoya disease.

Although intracranial hemorrhage in moyamoya disease can occur repeatedly, predicting the disease is difficult. Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors, evaluating the weight of different factors, and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease. To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes, we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling, including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes. Another 500 hemispheres with normal vessel appearance were selected as negative samples. We used deep residual neural network (ResNet-152) algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery, then trained and validated the model. The accuracy, sensitivity, and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64 ± 0.87%, 96.55 ± 3.44%, and 98.29 ± 0.98%, respectively. The area under the receiver operating characteristic curve was 0.990. We used a combined multi-view conventional neural network algorithm to integrate age, sex, and hemorrhagic factors with features of the digital subtraction angiography. The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69 ± 1.58% and the sensitivity and specificity were 94.12 ± 2.75% and 89.86 ± 3.64%, respectively. The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage. This study was approved by the Institutional Review Board of Huashan Hospital, Fudan University, China (approved No. 2014-278) on January 12, 2015.

Meningeal carcinoma has a variety of clinical manifestations and a high mortality and disability rate. Among them, cranial hypertension is one of the important causes of death, which is easy to be missed or misdiagnosed. The purpose of this case report is to describe the clinical features of diffuse leptomeningeal glioneuronal tumor (DNGNT) with the first symptom of headache accompanied by decreased vision misdiagnosed as venous sinus thrombosis. The patient initially suffered from headache and decreased vision, and rapidly developed blindness. According to the clinical manifestations and cerebrospinal fluid (CSF) examination results, the patient was initially misdiagnosed as venous sinus thrombosis, the intracranial pressure was relieved by Ommaya capsule, and the cerebrovascular condition was observed by magnetic resonance venogram (MRV) and digital subtraction angiography (DSA). The degree of meningeal enhancement was observed by enhanced magnetic resonance imaging (MRI), and meningeal cancer cells were found by CSF cytology. The patient was excluded from viral meningitis, tuberculous meningitis, cryptococcal meningitis, optic neuromyelitis, and central nervous system Behcet’s disease by routine examination. Ommaya capsule implantation relieved the intracranial hypertension, and vision was restored after treatment. No venous sinus thrombosis was found in MRV and DSA; brain-enhanced MRI revealed extensive linear enhancement of the meninges, and CSF cytology revealed grotesque, actively dividing tumor cells; she was diagnosed as DLGNT. Meningeal carcinoma cannot be excluded in adolescents without tumor history. When patient has unexplained intracranial hypertension, it is necessary to consider DLGNT; early brain-enhanced MRI and CSF cytology are helpful for early diagnosis. For cranial hypertension, timely placement of Ommaya capsule can improve patient quality of life and save vision in time; molecular targeted therapy as early as possible can prolong survival. J Neurol Res. 2019;9(3):41-47 doi: https://doi.org/10.14740/jnr539