Effective Smartphone Application Use for Postoperative Management of Moyamoya Disease.

Continuous and careful management is necessary after revascularization surgery for moyamoya disease (MMD). The postoperative information has been shared in person or by telephone and emails among doctors; however, this is not always efficient. We aimed to describe the feasibility of remote diagnosis and text chats using a smartphone application on postoperative MMD management. Twenty consecutive patients who underwent combined direct and indirect revascularization for MMD were prospectively investigated in this study. In ten patients, the operator viewed postoperative images uploaded on a smartphone screen using the Join application (Allm Inc., Tokyo, Japan). The doctors shared the radiological findings and treatment plans using the group text chat function and performed postoperative management. We evaluated the intermodality agreements of radiological findings between the smartphone screen and conventional viewer. Postoperative courses were compared between the two patient groups that used or did not use the application. All postoperative images were uploaded to the cloud server and the operator viewed them remotely on the smartphone screen without restriction of location. Detected abnormal findings were cerebral hyperperfusion (CHP), CHP-related watershed shift phenomenon, fluid-attenuated inversion recovery cortical hyperintensity, high signal intensity on diffusion-weighted imaging, CHP-related crossed cerebellar diaschisis, and hypoperfusion. Radiological agreement between the modalities was good in all cases, and additional findings were not obtained on the conventional viewer. The postoperative courses of the Join group were as good as those of the control group. Remote radiological diagnosis and text chat using a smartphone application were feasible and useful for efficient and safe postoperative MMD management.

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.

Moyamoya Syndrome Associated with Late-onset Idiopathic Aqueduct Stenosis Successfully Treated with Endoscopic Third Ventriculostomy.

Moyamoya disease (MMD) is a rare idiopathic cerebrovascular disorder that causes transient ischemic attack (TIA) and ischemic stroke in the pediatric population. Herein, we report an extremely rare case of Moyamoya syndrome (MMS) and late-onset idiopathic aqueduct stenosis, a unique form of non-communicating hydrocephalus. A 17-year-old female presented with an intractable headache and occasional faintness. Pertinent medical history included a fourth ventricle epidermoid cyst without any evidence of aqueduct stenosis, which was surgically removed when she was two years of age. The patient subsequently experienced a TIA and was diagnosed with MMD at 14 years of age. Under the definitive diagnosis of MMS associated with a brain tumor, the patient underwent surgical revascularization of the symptomatic right hemisphere without complications. Although the ischemic symptoms resolved postoperatively, a medically intractable headache with occasional faintness persisted. Serial magnetic resonance imaging ultimately revealed newly developed non-communicating hydrocephalus due to acquired aqueduct stenosis at the age of 17. After careful exclusion of the development of either or both a periventricular anastomosis and vault moyamoya vessels along the surgical route using cerebral angiography, we performed an endoscopic third ventriculostomy (ETV) via the right anterior horn without complications. A complete resolution of her chronic headache with the shrinkage of the third ventriculomegaly was observed postoperatively. In cases of MMS associated with symptomatic aqueduct stenosis, transdural collaterals on the cranial vault and periventricular collaterals should be meticulously evaluated preoperatively using cerebral angiography to safely perform an ETV.

Long-term Outcomes of Combined Revascularization Surgery for Moyamoya Disease in the Elderly: A Single Institute Experience.

The opportunity to treat older patients with Moyamoya disease (MMD) is increasing. However, the surgical outcomes after combined direct and indirect revascularization for elderly patients with MMD are not fully understood, especially for those ≥60 years old. This retrospective study examined 232 consecutive hemispheres of 165 adults with MMD who underwent combined revascularization. Clinical features and surgical outcomes were compared between the elderly (≥60 years) and nonelderly group (<60 years). Thirteen (5.6%, 64.4 ± 4.0 years old) and 219 hemispheres (94.4%, 40.2 ± 10.8 years old) were included in the elderly and nonelderly group, respectively. The proportion of clinical presentations before surgery did not differ. However, the prevalence of hypertension and hyperlipidemia was significantly higher in the elderly group than in the nonelderly group. Meanwhile, hyperthyroidism was observed only in the nonelderly group. No significant intergroup differences were observed in the incidence of perioperative complications occurring within four weeks postsurgery. Notably, the elderly group was more prone to develop perioperative intracerebral hemorrhage (odds ratio (OR) 3.14, 95% confidence interval (CI) 0.45-13.5) than the nonelderly group. During a median follow-up period of 7.8 years, the incidence of stroke recurrence occurring later than four weeks postsurgery was not significantly different between the groups (hazard ratio, 1.19; 95% CI 0.133-10.6). The prevalence of independent outcomes (76.9% vs. 90.4%, P = 0.14) and mortality (7.7% vs. 1.4%, P = 0.21) did not differ significantly between the elderly and nonelderly groups, respectively. Perioperative intracerebral hemorrhage may be common in the elderly and should be considered to achieve a favorable surgical outcome.

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.

Chronological Volume Changes of the Temporal Muscle Pedicle Used for Encephalo-myo-synangiosis in Combined Revascularization for Moyamoya Disease: A Prospective Observational Study.

Although postoperative neurological events due to brain compression by the swollen temporal muscle are a rare complication, the chronological volume changes of the temporal muscle pedicle and their clinical impact have not yet been documented. This prospective observational study aimed to investigate the chronological volume changes in the temporal muscle pedicle in Moyamoya disease (MMD). Eighteen consecutive combined revascularization procedures using the temporal muscle were performed for symptomatic MMD in 2021. The postoperative pedicle volume was quantified using repeated computed tomography images on postoperative days (PODs) 0, 1, 7, 14, and 30. Postoperative neurological events with radiological evaluations and collateral development evaluated using magnetic resonance angiography obtained 6 months after surgery were studied. On average, the postoperative temporal muscle pedicle volume was most significantly increased by as much as 112% ± 9.6% on POD 7 (P < 0.001) and decreased by as little as 52% ± 21% on POD 30 (P < 0.0001) relative to POD 0. One exceptional patient (overall incidence, 5.6%) demonstrated postoperative transient neurological events due to brain compression by the swollen temporal muscle with decreased focal cerebral blood flow in the adjacent cortical area. The postoperative collateral development via direct and indirect revascularizations was confirmed in 16 (89%) and 12 (67%) hemispheres, respectively. All patients, except for one rebleeding case, showed independent outcomes at the mean latest follow-up period on 290 ± 96 days after surgery. Our observations confirmed the temporal profile of muscle pedicle volume changes after combined revascularization. Through routine attempts to avoid the unfavorable effects of temporal muscle swelling, combined revascularization can provide favorable outcomes in symptomatic 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.

Ameliorative Effects of Combined Revascularization Surgery on Abnormal Collateral Channels in Moyamoya Disease.

OBJECT: Abnormal collateral channels, so-called moyamoya vessels, play a critical role to compensate cerebral ischemia, but carry the risk for hemorrhagic stroke in moyamoya disease (MMD). The present study was aimed to clarify if superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-myo-duro-arterio-pericranial synangiosis (EDMAPS) can efficiently regress the abnormal collateral channels in MMD patients. METHODS: This study included 92 hemispheres of 61 MMD patients who underwent STA-MCA anastomosis combined with EDMAPS between 2013 and 2019. There were 17 children and 44 adults. We retrospectively analyzed the findings on cerebral angiography before and 3 to 6 months after surgery, including Suzuki's angiographical stage, the development of surgical collaterals, and the extent of abnormal collateral channels such as lenticulostriate, thalamic, and choroidal channels. RESULTS: Following surgery, no pediatric and adult patients experienced any stroke during follow-up periods (40.2±25.5 and 54.9±19.7 months, respectively). Suzuki's stage significantly advanced in both adult and pediatric patients after surgery (P=0.042 and P<0.001). In adult patients, all of the lenticulostriate, thalamic, and choroidal channels significantly regressed after surgery (P<0.001, P=0.012, and P=0.004, respectively). In pediatric patients, however, lenticulostriate and choroidal channels significantly regressed (P=0.005 and P=0.034, respectively). Correlation analysis revealed that the development of surgical collaterals determined the postoperative regression of choroidal channels (P<0.001). CONCLUSION: STA-MCA anastomosis and EDMAPS may be one of the most effective procedures to widely provide surgical collaterals to the operated hemispheres and prevent not only ischemic but also hemorrhagic stroke by regressing the hemorrhage-prone abnormal collateral channels in MMD.

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.

Specific clinical features and one-stage revascularization surgery for moyamoya disease with severe cerebral ischemia in the territory of posterior cerebral artery.

BACKGROUND: There are no reports describing the surgical procedure for moyamoya disease (MMD) patients with severe cerebral ischemia in the territory of the posterior cerebral artery (PCA) at initial presentation. In this study, therefore, we describe their clinical and radiological features and clinical results of one-stage revascularization surgery for both anterior and posterior circulation. METHODS: This study included 6 MMD patients who had severe cerebral ischemia in the PCA territory and underwent one-stage revascularization surgery for both anterior and posterior circulation. Of these, one patient underwent it on both sides. Their clinical and radiological data were precisely analyzed. Compared with usual procedure, craniotomy was extended towards the temporo-parietal area more widely. The parietal branch of superficial temporal artery (STA) was anastomosed to the angular or posterior temporal artery, while the frontal branch was anastomosed to the frontal branch of MCA. Ultimate indirect bypass was added. Their clinical and radiological outcomes were evaluated. RESULTS: Their neurological symptoms included visual and speech disturbance as well as numbness of the extremities. Cerebral infarct was distributed in the posterior temporal, parietal, and/or occipital lobe. Cerebral hemodynamics and metabolism were also impaired in the same regions. These findings were completely different from those in MMD patients without PCA lesion. Postoperative course was uneventful, and none of them recurred stroke during a mean follow-up period of 10.5 years. Surgical collaterals widely provided blood flow to the entire hemispheres, including the occipital lobe. Cerebral hemodynamics and metabolism markedly improved after surgery. CONCLUSION: One-stage revascularization surgery for both anterior and posterior circulation is feasible and effective to prevent future stroke in MMD patients with severe cerebral ischemia in the PCA territory at initial presentation.

Late (5-20 years) outcomes after STA-MCA anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis in patients with moyamoya disease.

OBJECTIVE: Surgical revascularization is known to reduce the incidence of further ischemic and hemorrhagic events in patients with moyamoya disease, but the majority of previous studies report only short-term (< 5 years) outcomes. Therefore, in this study the authors aimed to evaluate late (5-20 years) outcomes of moyamoya patients after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect bypass (encephalo-duro-myo-arterio-pericranial synangiosis [EDMAPS]). METHODS: Cumulative incidences of late morbidity/mortality and disease progression were evaluated among 93 patients who underwent STA-MCA anastomosis and EDMAPS. All of the patients were prospectively followed up for longer than 5 years postsurgery (10.5 ± 4.4 years). There were 35 pediatric and 58 adult patients. Initial presentation included transient ischemic attack/ischemic stroke in 80 patients and hemorrhagic stroke in 10 patients, and 3 patients were asymptomatic. Surgery was performed in a total of 141 hemispheres. Follow-up MRI/MRA was performed within a 6- or 12-month interval during the follow-up periods. RESULTS: During the follow-up periods, 92/93 patients were free from any stroke or death, but 1 patient had a recurrence of hemorrhagic stroke (0.10% per patient-year). Disease progression occurred in the territory of the contralateral carotid or posterior cerebral artery (PCA) in 19 hemispheres of 15 patients (1.5% per patient-year). The interval between initial surgery and disease progression varied widely, from 0.5 to 15 years. Repeat bypass surgery for the anterior and posterior circulation resolved ischemic attacks in all 10 patients. CONCLUSIONS: The study results indicate that STA-MCA anastomosis and EDMAPS would be the best choice to prevent further ischemic and hemorrhagic stroke for longer than 10 years on the basis of the demonstrated widespread improvement in cerebral hemodynamics in both the MCA and ACA territories in the study patients. However, after 10 years postsurgery regular follow-up is essential to detect disease progression in the territory of the contralateral carotid artery and PCA and prevent late cerebrovascular events.

Using postoperative remodeling of donor arteries on MR angiography to predict the development of surgical collaterals in moyamoya disease.

OBJECTIVE: The calibers of donor arteries can change dynamically after bypass surgery in patients with moyamoya disease (MMD). The present study aimed to evaluate the cutoffs of caliber changes in donor arteries associated with good surgical revascularization and to assess the impact of clinical factors potentially related to bypass development. METHODS: The authors studied 71 hemispheres of 30 adults and 16 children with MMD who underwent combined direct and indirect revascularization. They quantitatively measured the calibers of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) with MR angiography (MRA) source images and calculated the postoperative caliber change ratios (CCRs) to assess direct and indirect bypass development. These values were compared with the findings of digital subtraction angiography, in which revascularization areas were categorized into 3 groups (poor, good, and excellent). RESULTS: In both adult and pediatric hemispheres, the median STA and DTA CCRs were higher in better-revascularization groups (p < 0.05), while MMA CCRs were not significantly different among the groups. Receiver operating characteristic analysis revealed that the cutoff STA CCRs of > 1.1 and > 1.3 were associated with good direct revascularization in adult and pediatric hemispheres, respectively. Cutoff DTA CCRs of > 1.6 and > 1.2 were associated with good indirect revascularization in adult and pediatric hemispheres, respectively. Considering these cutoff values, STA and DTA CCRs showed high median values, irrespective of age, severity of cerebrovascular reserve, disease stage, and disease-onset type. CONCLUSIONS: Caliber changes in STAs and DTAs can be easily measured using MRA, and they could be indicators of direct and indirect bypass development. The dual development of a direct and indirect bypass was most frequently observed in the context of a combined bypass procedure in both adults and children with MMD.

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.

Strategy and effect of repeat bypass surgery for anterior/posterior circulation in refractory moyamoya disease.

OBJECTIVE: In this study the authors aimed to describe clinical features, surgical techniques, and long-term outcomes of repeat bypass surgery required for a certain subset of patients with moyamoya disease. METHODS: The authors retrospectively reviewed a total of 22 repeat bypass surgeries for 20 patients (age range 1-69 years) performed during the last 20 years at their institutions. The patients were classified into 2 groups. Group A included 10 patients who underwent repeat bypass surgery for anterior circulation due to insufficient revascularization on the ipsilateral side. Group B included 10 patients who underwent repeat bypass surgery for posterior circulation due to the involvement of the posterior cerebral artery (PCA) after successful initial surgery for anterior circulation. RESULTS: Preoperative symptoms included headache in 3 patients, transient ischemic attack in 10, cerebral infarction in 3, and intracranial hemorrhage in 4 patients. Intervals between the initial bypass surgery and repeat bypass surgery were 0.3-30 years (median 3 years). In group A, superficial temporal artery to middle cerebral artery (MCA) anastomosis and indirect bypass were performed on 7 hemispheres. Only indirect bypass was performed on 3 hemispheres because of the lack of suitable donor or recipient arteries. In group B, occipital artery (OA) to PCA anastomosis and indirect bypass were conducted on 4 hemispheres, and OA-MCA anastomosis and indirect bypass on 1 hemisphere. Only indirect bypass was conducted on 7 hemispheres because of the lack of suitable recipient arteries. All 22 repeat bypass surgeries were successfully conducted. During follow-up periods (median 4 years), none of the patients suffered repeat stroke except 1 patient who died of recurrent intracerebral hemorrhage 3 years after repeat bypass surgery for anterior circulation. CONCLUSIONS: Repeat bypass surgery was feasible and effective to reduce further incidence of headache attack, transient ischemic attack, and ischemic/hemorrhagic stroke in moyamoya disease patients. Through precise radiological analysis, surgical procedures should be planned to yield maximal therapeutic effects.

Persistent Primitive Olfactory Artery as Novel Collateral Channel to the Anterior Cerebral Artery in Moyamoya Disease.

BACKGROUND: There are a variety of collateral routes to compensate persistent cerebral ischemia in moyamoya disease. However, there is no report presenting the persistent primitive olfactory artery (POA) as a spontaneous collateral route to the anterior cerebral artery (ACA) in moyamoya disease. METHODS: We precisely examined cerebral angiography in 84 patients with moyamoya disease to identify the collateral channel through the persistent POA. Its anatomy was evaluated on pre- and postoperative angiography. RESULTS: Of 84 patients, four (4.8%) had spontaneous collateral channel through the persistent POA. All of these four hemispheres were categorized into Stage 5. In all four patients, the collateral blood flow arose from the ophthalmic artery and run to the persistent POA through the ethmoidal moyamoya. The persistent POA provided collateral blood flow from the ophthalmic artery to the ACA in all four patients. Superficial temporal artery to middle cerebral artery anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis was performed in three of four patients. After surgery, the collateral channel through the persistent POA completely disappeared or markedly regressed, suggesting a significant improvement of cerebral hemodynamics in the territory of not only the MCA but also the ACA. CONCLUSION: The persistent POA can potentially provide collateral blood flow to the ACA in about 5% of patients with moyamoya disease, and should be recognized as a novel collateral channel in moyamoya disease. The persistent POA may be useful to evaluate therapeutic effects of surgical revascularization on the ACA territory.

Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis.

OBJECTIVE: The relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed. METHODS: This study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)-, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels. RESULTS: Plaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2-, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α-positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α-positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous). CONCLUSIONS: The present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.

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.

Factors influencing cerebral aneurysm obliteration and reliability of indocyanine green video-angiography.

BACKGROUND: Indocyanine green video-angiography (ICG-V) is commonly used for intraoperative confirmation of aneurysm obliteration following clipping. However, direct puncture of the aneurysm wall occasionally results in blood leakage in patients for whom ICG-V has indicated complete closure. Therefore, the present study aimed to determine the reliability of ICG-V for confirming complete aneurysm closure, and to elucidate the factors underlying aneurysm obliteration and the occurrence of false-negative ICG-V findings. METHODS: Between June 2012 and June 2016, 89 patients (107 aneurysms total) undergoing aneurysm clipping were examined using ICG-V to confirm aneurysm closure. In ICG-V-negative cases, further confirmation of complete aneurysm closure was obtained via direct puncture of the aneurysm wall, except in cases where this procedure was deemed unsafe. To elucidate the possible causes of ICG-V inaccuracies, positive, negative, and false-negative ICG-V findings were compared in terms of aneurysm location (maximum height and length), neck width (parallel and orthogonal directions to the branching vessels), wall thickness around the neck, bifurcation angle, and direction of the clipping closure line. Statistical analyses were performed using the Welsh's t test and Chi-square test. RESULTS: Intraoperative ICG-V detected seven cases of incomplete aneurysm closure (6.5%), defined as positive ICG-V findings. Following direct aneurysm wall puncture, nine patients (8.4%) exhibited false-negative ICG-V findings. A Chi-square test revealed that false-negative ICG-V findings were significantly influenced by the presence of heterogeneous arteriosclerosis, and wall thickening at the clipping site, which were subjectively defined by the surgeon and confirmed by an independent observer, depending on the wall color and hardness, respectively. CONCLUSIONS: Although ICG-V is useful for intraoperative confirmation of aneurysm obliteration, our findings further highlight the risk of false-negative ICG-V findings. Acknowledgement of risk factors is crucial for efficient detection of false-negative ICG-V findings.

Novel insights into symptomatology of moyamoya disease in pediatric patients: survey of symptoms suggestive of orthostatic intolerance.

OBJECTIVE A specific population of young patients with moyamoya disease (MMD) persistently experience physical symptoms not attributable to focal ischemia. These symptoms, highly suggestive of orthostatic intolerance (also termed "orthostatic dysregulation"), were investigated and reported as potential determinants of quality of life in young MMD patients. METHODS Forty-six patients (6-30 years of age) were selected from a group of 122 patients who were diagnosed with MMD before 18 years of age. The authors administered a structured questionnaire consisting of 11 items based on screening checklists published in the Japanese clinical guidelines for juvenile orthostatic dysregulation in young patients. The results were tabulated, and correlations with clinical data were explored. RESULTS Thirty-seven (80%) patients (mean age 15.9 years) responded to the questionnaire. Frequent headache, vertigo/dizziness on standing, fatigue, difficulty with getting out of bed, and motion sickness were the top 5 symptoms, resulting in 57% of patients being unable to attend school. Forty-three percent of the patients demonstrated multiple symptoms suggestive of orthostatic intolerance, even as long as 5 years after revascularization surgery. The number of symptoms was inversely associated with the number of years after surgery (p = 0.028). The number of symptoms was not associated with a history of surgery, clinical presentations, vascular involvement, cerebral perfusion, brain lesions, or history of transient ischemic attacks. CONCLUSIONS The present study provided novel insight into the symptomatology of young patients with MMD. Failure to notice nonfocal physical symptoms can significantly impair quality of life in young patients with MMD even years after successful revascularization surgery. These symptoms may serve as independent clinical markers used to assess disease outcome, although the underlying mechanisms of this disease are, as of yet, unclear.