Non-sinus type of transverse sinus dural arteriovenous fistulas on the arachnoid granulation of the dural sinus wall.

Background: The etiology of a non-sinus-type dural arteriovenous fistulas (DAVFs) with shunt points located on the sinus wall, previously described as on-the-wall-type DAVFs, is unknown. Case Description: Two cases of non-sinus-type transverse sinus DAVF with a shunt point limited to the dural sinus wall, causing cortical venous reflux, were successfully treated with endovascular transarterial Onyx embolization. The Onyx cast showed multiple feeders from the occipital and middle meningeal arteries aggregated in the arachnoid granulation (AG), which dilated the draining vein. Conclusion: Non-sinus-type DAVFs with shunt points located on the AG may be one of the presentations of an on-the-wall-type DAVF.

Assessment of Disease Activity, Structural Damage, and Function in Rheumatoid Arthritis.

The primary goal in the treatment of rheumatoid arthritis (RA) is to control disease activity, prevent structural damage in joints, and normalize function. Therefore, reliable tools are needed to disease activity, physical function, and radiographic progression in RA. We herein describe methods recently used to assess RA.

Design an Intervention Study.

Randomized controlled trials are commonly designed to compare the effectiveness of treatments in rheumatoid arthritis (RA). In a clinical trial (intervention study), researchers apply interventions or preventive services to patients and examine outcomes. Clinical trial design consists of the following categories: choice of intervention and control, selection of patients, informed consent, baseline measurement, bank specimens, randomized allocation and blinding, and outcome measurements. Here, we discuss the design of clinical trials for RA.

Establishing clinical remission criteria for giant cell arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis.

OBJECTIVE: To develop a proposal for giant cell arteritis remission criteria in order to implement a treat-to-target algorithm. METHODS: A task force consisting of 10 rheumatologists, 3 cardiologists, 1 nephrologist, and 1 cardiac surgeon was established in the Large-vessel Vasculitis Group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis to conduct a Delphi survey of remission criteria for giant cell arteritis. The survey was circulated among the members over four reiterations with four face-to-face meetings. Items with a mean score of ≥4 were extracted as items for defining remission criteria. RESULTS: An initial literature review yielded a total of 117 candidate items for disease activity domains and treatment/comorbidity domains of remission criteria, of which 35 were extracted as disease activity domains (systematic symptoms, signs and symptoms of cranial and large-vessel area, inflammatory markers, and imaging findings). For the treatment/comorbidity domain, ≤5 mg/day of prednisolone 1 year after starting glucocorticoids was extracted. The definition of achievement of remission was the disappearance of active disease in the disease activity domain, normalization of inflammatory markers, and ≤5 mg/day of prednisolone. CONCLUSION: We developed proposals for remission criteria to guide the implementation of a treat-to-target algorithm for giant cell arteritis.

Posterior cerebral artery involvement in unilateral moyamoya disease is exclusively ipsilateral and influenced by RNF213 mutation gene dose: The SUPRA Japan study: PCA involvement in unilateral moyamoya.

OBJECTIVES: The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. POPULATION AND METHODS: We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. RESULTS: Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. CONCLUSIONS: Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD.

Usefulness of Y-shaped PulseRider-assisted coil embolization for basilar artery tip aneurysm with a misaligned axis: A case report.

Background: Endovascular treatment of wide-necked bifurcation aneurysms remains challenging. Although the advent of PulseRider and Web has expanded treatment options, aneurysms with a large deviation from the parent artery axis remains difficult to treat. We present the case of a wide-necked bifurcation aneurysm that was misaligned with the angle between the long axis of the parent artery and the aneurysm and was successfully treated with Y-shaped PulseRider-assisted coil embolization. Case Description: A 64-year-old woman presented with an unruptured basilar tip aneurysm. Cerebral angiography showed a wide-necked aneurysm measuring 8.1 mm × 6.1 mm, neck 5.7 mm. The aneurysm was strongly tilted to the right and posterior relative to the basilar artery, and the bilateral posterior cerebral artery (PCA) and superior cerebellar artery (SCA) diverged from the aneurysm body. PulseRider-assisted coil embolization was performed. A Y-shaped PulseRider was selected to be placed in a hybrid fashion with the right arch in the aneurysm and the left arch in the branch. Adequate coil embolization with preservation of the bilateral PCA and SCA was possible, and cerebral angiography immediately after the treatment showed slight dome filling. Cerebral angiography 6 months after the procedure showed that the embolic status had improved to complete occlusion. Conclusion: For wide-neck bifurcation aneurysms with a misaligned axis, a Y-shaped PulseRider used in a hybrid fashion, in which the leaflet on the side with the tilted axis is placed in the aneurysm, allows the PulseRider to be deployed more closely to the aneurysm, thereby enabling good coil embolization.

Investigation of Mechanical Thrombectomy in Elderly Patients over 85 Years Old: A Multicenter Study.

In Japan, which has a super-aging society, there are increasing opportunities to perform mechanical thrombectomy for the elderly; however, there is no recorded evidence of thrombectomy for the elderly. This study examined the usefulness of thrombectomy in the elderly. We retrospectively analyzed patient data using a multicenter acute ischemic stroke registry (NGT-FAST). We examined outcomes in patients 75 years and older who underwent thrombectomies between January 1, 2021, and December 31, 2021. The patients were divided into two groups: the 75-84-year-old group and the 85+-year-old group. There was no difference in the pretreatment National Institutes of Health Stroke Scale score or Alberta Stroke Program Early Computed Tomography Score between the two groups, but the 85+-year-old group had a significantly lower rate of pre-stroke modified Rankin Scale (mRS) score of 0-2. There were no differences in time from onset to treatment or effective recanalization rate, but complications tended to be more common in the 85+-year-old group. The number of patients with a good outcome at discharge (an mRS score of 0-3) was significantly lower in the 85+-year-old group than in the 75-84-year-old group. In addition, 90.9% of patients in the 85+-year-old group with a pre-stroke mRS score of 3 deteriorated after treatment. The pre-stroke mRS score is very important in determining the indication for thrombectomy in the elderly because their preoperative condition is more likely to influence the outcome than that of younger patients.

Usefulness of silent magnetic resonance angiography for intracranial aneurysms treated with a flow re-direction endoluminal device.

PURPOSE: Flow re-direction endoluminal device (FRED) is a novel dual-layer flow-diverting stent to treat cerebral aneurysms with high obliteration rates, however, it induces inevitable metal-related artifacts. We compared silent magnetic resonance angiography (MRA), a new MRA method using ultra-short time of echo and arterial spin-labeling, with conventional time-of-flight (TOF)-MRA for imaging aneurysms treated using FRED. METHODS: Between May 2020 and September 2022, 16 patients with unruptured internal carotid aneurysms treated using FRED simultaneously underwent silent MRA and TOF-MRA after treatment, with 36 follow-up sessions in total. Two observers independently graded the quality of intra-aneurysmal flow and stented parent arteries under both types of MRA from 1 (not visible) to 4 (nearly equal to digital subtraction angiography [DSA]), with reference to DSA images as a standard criterion. RESULTS: The mean scores for intra-aneurysmal flow and stented parent arteries were significantly better for silent MRA (3.93 ± 0.21 and 3.82 ± 0.32, respectively) than for TOF-MRA (2.08 ± 0.99 and 1.92 ± 0.79, respectively) (P < 0.01). Intermodality agreements for intra-aneurysmal flow and stented parent arteries were 0.87 and 0.90, respectively. CONCLUSION: Silent MRA is superior to TOF-MRA for assessing patients treated with FRED, with potential as an alternative imaging modality to DSA.

Superior Visualization of Neovascularization with Silent Magnetic Resonance Angiography Compared to Time-of-Flight Magnetic Resonance Angiography After Bypass Surgery in Moyamoya Disease.

OBJECTIVE: The evaluation of postsurgical neoangiogenesis in patients with moyamoya disease (MMD) is crucial for appropriate patient management. This study aimed to assess the visualization of neovascularization after bypass surgery using noncontrast-enhanced silent magnetic resonance angiography (MRA) with ultrashort echo time and arterial spin labeling. METHODS: After bypass surgery, 13 patients with MMD were followed up for >6 months between September 2019 and November 2022. They underwent silent MRA in the same session as time-of-flight magnetic resonance angiography (TOF-MRA) and digital subtraction angiography (DSA). Two observers independently rated the visualization of neovascularization in both types of MRA from 1 (not visible) to 4 (nearly equal to DSA), with reference to DSA images as the standard. RESULTS: The mean scores were significantly higher for silent MRA compared with TOF-MRA (3.81 ± 0.48 and 1.92 ± 0.70, respectively) (P < 0.01). The intermodality agreements were 0.83 and 0.71 for silent MRA and TOF-MRA, respectively. TOF-MRA depicted the donor artery and recipient cortical artery after direct bypass surgery, although fine neovascularization developed after indirect bypass surgery was poorly visualized. Silent MRA could reveal the developed bypass flow signal and perfused middle cerebral artery territory, which was almost equal to the DSA images. CONCLUSIONS: Silent MRA achieves better visualization of postsurgical revascularization in patients with MMD than TOF-MRA. Moreover, it may have the potential to provide visualization of the developed bypass flow equivalent to DSA.

[Arteriovenous Malformations:Endovascular Techniques and Devices].

Endovascular embolization using liquid materials is a safe and effective treatment option for cerebral arteriovenous malformations(AVM). Onyx and n-butyl cyanoacrylate, currently available in Japan, have specific features. Appropriate embolic agents should be selected based on their characteristics. Transarterial embolization(TAE)is the standard endovascular treatment approach. However, there have been some recent reports regarding the efficacy of transvenous embolization(TVE). TVE is potentially curative for small AVM with hemorrhagic onset, inaccessible arterial feeders, deep location, and/or a single draining vein. In specific cases, TVE may provide a higher chance of complete obliteration of the AVM than TAE. Some unsolved problems need further clarification, such as the relative positions of liquid embolization against direct surgery, dealing with unruptured AVM, and effective treatment for high-grade AVM.

A Case of Paradoxical Cerebral Embolism Due to Pulmonary Arteriovenous Fistula Mimicking Vertebral Artery Dissection With Wallenberg Syndrome.

Pulmonary arteriovenous fistula (PAVF) leads to paradoxical cerebral embolism, which can be fatal if left untreated. We report a rare case of brainstem infarction with acute severe headache and Wallenberg syndrome caused by a PAVF mimicking vertebral artery (VA) dissection. A 40-year-old man presented with a sudden occipital headache accompanied by right hemisensory disturbance. Magnetic resonance imaging revealed left lateral medullary infarction and poor depiction of the left VA. However, it was clearly recanalized on day six, and there were no findings of VA dissection. Whole-body contrast-enhanced computed tomography (CT) revealed a PAVF in the right lung and a thrombus in the feeding artery. The patient was diagnosed with hereditary hemorrhagic telangiectasia due to recurrent epistaxis and peripheral vasodilation of the tongue. An anticoagulant was administered for preventing further ischemic stroke, and a follow-up CT confirmed the disappearance of the thrombus in three months. Thoracoscopic partial lung resection was performed five months after the onset, and no recurrence of ischemic stroke was observed.

Improving performance and self-efficacy of novice nurses using hybrid simulation-based mastery learning.

AIM: Acute chest pain is a commonly encountered symptom in hospital medical/surgical units; however, almost half of nurses in their second year of clinical experience in our facility have reported struggling to care for acute chest pain patients. We developed, implemented, and examined the effectiveness of a simulation-based, mastery learning clinical nursing educational program to improve self-efficacy and performance in caring for patients with acute chest pain. METHODS: The study adopted a single-site, single-cohort design using simulation-based performance assessment and self-efficacy surveys on a convenience sample of 37 second-year clinical nurse participants in multi-stage hybrid mastery learning educational intervention using asynchronous e-learning, and hands-on simulation training and assessment with feedback on caring for chest pain patients. Performance assessments and self-efficacy surveys were administered pre-, post-, and 5 months post-intervention. RESULTS: Clinical performance on the post- and 5 months follow-up assessments were significantly higher than those for the pre-test (P < .0001). The self-efficacy scores for the post- and the 5 months follow-up assessments were significantly higher than the pre-course scores (P < .0001). Participants' self-efficacy perceptions were positively correlated with their performances at 5 months post-intervention. CONCLUSION: Performance and self-efficacy of novice nurses in caring for acute chest pain patients improved significantly with the multi-stage hybrid mastery learning educational intervention, with improvements retained 5 months post-intervention. The results suggest the applicability of simulation-based mastery learning in a clinical setting for novice nurses to attain specific skills, and raise their self-perception of competence to care for patients in acute settings.

Low disease activity of microscopic polyangiitis in patients with anti-myosin light chain 6 antibody that disrupts actin rearrangement necessary for neutrophil extracellular trap formation.

BACKGROUND: Neutrophil extracellular traps (NETs) are critically involved in microscopic polyangiitis (MPA) pathogenesis, and some patients with MPA possess anti-NET antibody (ANETA). Anti-myosin light chain 6 (MYL6) antibody is an ANETA that affects NETs. This study aimed to determine the significance of anti-MYL6 antibody in MPA. METHODS: The influence of anti-MYL6 antibody on NET formation and actin rearrangement necessary for NET formation was assessed by fluorescent staining. An enzyme-linked immunosorbent assay was established to detect serum anti-MYL6 antibody, and the prevalence of this antibody in MPA was determined. Furthermore, the disease activity and response to remission-induction therapy of MPA were compared between anti-MYL6 antibody-positive and anti-MYL6 antibody-negative MPA patients. RESULTS: Anti-MYL6 antibody disrupted G-actin polymerization into F-actin, suppressing phorbol 12-myristate 13-acetate-induced NET formation. Serum anti-MYL6 antibody was detected in 7 of 59 patients with MPA. The Birmingham vasculitis activity score (BVAS) of anti-MYL6 antibody-positive MPA patients was significantly lower than anti-MYL6 antibody-negative MPA patients. Among the nine BVAS evaluation items, the cutaneous, cardiovascular, and nervous system scores of anti-MYL6 antibody-positive MPA patients were significantly lower than anti-MYL6 antibody-negative MPA patients, although other items, including the renal and chest scores, were equivalent between the two groups. The proportion of patients with remission 6 months after initiation of remission-induction therapy in anti-MYL6 antibody-positive MPA patients was significantly higher than in anti-MYL6 antibody-negative MPA patients. CONCLUSIONS: Collective findings suggested that anti-MYL6 antibody disrupted actin rearrangement necessary for NET formation and could reduce the disease activity of MPA.

Decadal-centennial-scale solar-linked climate variations and millennial-scale internal oscillations during the Early Cretaceous.

Understanding climate variability and stability under extremely warm 'greenhouse' conditions in the past is essential for future climate predictions. However, information on millennial-scale (and shorter) climate variability during such periods is scarce, owing to a lack of suitable high-resolution, deep-time archives. Here we present a continuous record of decadal- to orbital-scale continental climate variability from annually laminated lacustrine deposits formed during the late Early Cretaceous (123-120 Ma: late Barremian-early Aptian) in southeastern Mongolia. Inter-annual changes in lake algal productivity for a 1091-year interval reveal a pronounced solar influence on decadal- to centennial-scale climatic variations (including the ~ 11-year Schwabe cycle). Decadally-resolved Ca/Ti ratios (proxy for evaporation/precipitation changes) for a ~ 355-kyr long interval further indicate millennial-scale (~ 1000-2000-yr) extreme drought events in inner-continental areas of mid-latitude palaeo-Asia during the Cretaceous. Millennial-scale oscillations in Ca/Ti ratio show distinct amplitude modulation (AM) induced by the precession, obliquity and short eccentricity cycles. Similar millennial-scale AM by Milankovitch cycle band was also previously observed in the abrupt climatic oscillations (known as Dansgaard-Oeschger events) in the 'intermediate glacial' state of the late Pleistocene, and in their potential analogues in the Jurassic 'greenhouse'. Our findings indicate that external solar activity forcing was effective on decadal-centennial timescales, whilst the millennial-scale variations were likely amplified by internal process such as changes in deep-water formation strength, even during the Cretaceous 'greenhouse' period.

Psoriatic arthritis successfully treated with second-line anti-interleukin-6 treatment: a case report and review of the literature.

BACKGROUND: Psoriatic arthritis treatment with antitumor necrosis factor has been shown to reduce disease activity. Nonetheless, more than 30% of patients do not achieve a sufficient response to tumor necrosis factor blockers. Currently, treatment with interleukin-6 inhibitors is expected to be effective and suppress the joint destruction in patients with psoriatic arthritis; however, evidence regarding their efficacy is limited to a few reports. CASE PRESENTATION: A 78-year-old Japanese woman with psoriatic arthritis associated with rapid joint destruction was successfully treated with a second-line anti-interleukin-6 receptor agent. In this case, a tumor necrosis factor inhibitor induced an inadequate response, and the right knee and left hip joints required artificial joint replacement surgery. However, second line treatment with anti-interleukin-6 treatment was effective, and the right elbow joint function was preserved. CONCLUSIONS: We experienced a case of psoriatic arthritis, in which anti-interleukin-6 treatment repaired a bone cyst in the lateral epicondyle of the humerus and enthesitis of the distal interphalangeal joints. The patient is currently in clinical remission with no restrictions in daily life activities. Anti-interleukin-6 treatment may address the unmet needs of patients with psoriatic arthritis who are resistant or intolerant to antitumor necrosis factor treatment, with rapidly destructive large joints but with well-managed skin manifestations.

Opposite L-configuration double stenting for rupture of an extremely wide-necked anterior communicating artery aneurysm at the acute stage: illustrative case.

BACKGROUND: Wide-necked aneurysms can be treated by double stenting in an X- or Y-configuration or by a double waffle-cone technique. However, some aneurysms remain untreatable. OBSERVATIONS: The rupture of a complex wide-necked anterior communicating artery (AcomA) aneurysm that caused acute subarachnoid hemorrhage (SAH) was treated successfully using double stents with an opposite L-configuration as an alternative to the X-stent technique. The aneurysm involved both A1-A2 junctions in the aneurysm neck with acutely oriented A2 segments of the anterior cerebral artery bilaterally. It was densely packed and completely obliterated angiographically with preserved blood flow by implanting each stent in the ipsilateral A1-A2 bilaterally. Blood flow from the left A1 to the right A2 was confirmed through the AcomA on injection of the left internal carotid artery immediately after the procedure without critical infarction in the subthalamic area. Although the AcomA was not demonstrated by injection of the left internal carotid artery on angiography at 3 months or 1 year later, no cerebral infarction was seen on magnetic resonance images at the final hospital visit. LESSONS: Opposite L-configuration double stenting was used successfully as rescue stent-assisted coiling for a rupture of a complex wide-necked AcomA aneurysm in a patient with acute SAH.

Non-contrast-enhanced silent magnetic resonance angiography for assessing cerebral aneurysms after PulseRider treatment.

PURPOSE: Conventional time-of-flight (TOF) magnetic resonance angiography (MRA) failed to depict clear visualization of coiled cerebral aneurysms with PulseRider due to metal-induced susceptibility artifacts. Our aim was to overcome the metal artifact using a novel imaging technique of non-contrast-enhanced ultrashort echo-time magnetic resonance angiography (UTE-MRA). MATERIALS AND METHODS: Five unruptured intracranial aneurysms were treated using PulseRider and the patients underwent silent MRA (UTE-MRA). The images were compared with TOF-MRA and digital subtraction angiography (DSA). RESULTS: Silent MRA can visualize the residual cavity of the coiled aneurysms, which was not well visualized and rather defective when using TOF-MRA. While a segment of the proximal marker composed of stainless steel was poorly visualized, the other parts of the parent artery and the arteries of bifurcation, including the aneurysmal neck, were clearly visualized, equivalent to that of DSA. CONCLUSIONS: UTE-MRA achieves better visualization of cerebral aneurysms after PulseRider treatment than TOF-MRA.

Long-Term Characteristics of De Novo Bleb Formation at the Aneurysm Neck After Coil Embolization in Unruptured Cerebral Aneurysms.

OBJECTIVE: De novo bleb formation at the aneurysm neck after coil embolization of unruptured intracranial aneurysms is a rarely observed type of recurrence. The aim of this study was to elucidate the clinical characteristics of recurrent aneurysms in the long-term period. METHODS: Between January 2002 and December 2015, 290 unruptured intracranial aneurysms were treated with coil embolization at our institution. Patients who underwent retreatment due to aneurysm recurrence were divided into 2 patterns of recanalization: de novo bleb formation at the neck of a coiled sac (type DNV) and an enlarged residual cavity without de novo bleb formation (type non-DNV). RESULTS: Twenty-seven patients with aneurysms (9.3%) underwent retreatment (type DNV, 7; type non-DNV, 20). The initial aneurysm size of type DNV aneurysms was significantly smaller than that of type non-DNV (6.1 ± 2.2 mm vs. 10.1 ± 3.6 mm; P < 0.01), and time to retreatment in type DNV was significantly longer than that in type non-DNV (9.4 ± 5.3 years vs. 2.0 ± 2.0 years; P < 0.01). Two type DNV basilar artery (BA) aneurysms ruptured after a few years; however, the other type DNV aneurysms, including 4 anterior circulation aneurysms (including the internal carotid artery), were observed to grow gradually without rupture for >10 years until retreatment. CONCLUSIONS: De novo bleb formation at the neck of a coiled sac emerges with insidious growth during long-term follow-up. Constant caution should be exercised, even in cases of small- and medium-sized anterior circulation aneurysms. A risk of rupture risk may be anticipated, especially in BA lesions.

A case of clinically amyopathic dermatomyositis that was refractory to intensive immunosuppressive therapy including tofacitinib, but successfully treated with plasma exchange therapy.

Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: (1) cytokines that were not suppressed by TOF played an important role in RP-ILD; (2) TOF was administered later than previously reported; and (3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.

Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group.

OBJECTIVE: Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS: The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS: Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 67 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS: These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.