Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.

Effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis on the cerebrospinal fluid gas tensions and pH in hemodynamically compromised patients.

PURPOSE: This study was aimed to directly measure cerebrospinal fluid (CSF) gas tensions and pH before and after STA-MCA anastomosis for occlusive carotid artery diseases to investigate its direct effects on the ischemic brain. METHODS: This study included 9 patients who underwent STA-MCA anastomosis on the basis of CBF studies. About 1 mL of CSF was collected before and after bypass procedures, and CSF pH, CSF PO2, and CSF PCO2 were measured with a blood gas analyzer. As the controls, the CSF was collected from 6 patients during surgery for unruptured cerebral aneurysm. CSF PO2 and CSF PCO2 were expressed as the ratio to PaO2 and PaCO2, respectively. RESULTS: Before bypass procedure, CSF PO2/PaO2 was 0.88 ± 0.16, being lower than the controls (1.10 ± 0.09; P = 0.005). CSF PCO2/PaCO2 was 0.93 ± 0.13, being higher than the controls (0.84 ± 0.06; P = 0.039). Ipsilateral-to-contralateral CBF ratio had a positive correlation with CSF PO2/PaO2 (P = 0.0028) but a negative correlation with the CSF PCO2/PaCO2 (P = 0.0045). STA-MCA anastomosis increased CSF pH from 7.402 ± 0.133 to 7.504 ± 0.126 (P = 0.0011) and CSF PO2/PaO2 from 0.88 ± 0.16 to 1.05 ± 0.26 (P = 0.018) but decreased CSF PCO2/PaCO2 from 0.93 ± 0.13 to 0.70 ± 0.17 (P = 0.0006). CONCLUSION: The severity of cerebral ischemia before surgery is intensely reflected in the gas tensions and pH of the CSF. STA-MCA anastomosis carries dramatic effects on CSF gas tensions and pH in hemodynamically compromised patients. CSF would be a valuable surrogate biomarker to monitor the severity of cerebral ischemia.

Differentiation of Fibroblasts Into Myofibroblasts in the Arachnoid Membrane of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a very specific disorder in terms of spontaneous development of extracranial-to-intracranial collateral circulation through the dura mater, but the underlying mechanisms are unclear. This study aimed to investigate the role of the arachnoid membrane in this unique angiogenesis in MMD. METHODS: A piece of arachnoid membrane and 1- to 2-mL cerebrospinal fluid were simultaneously harvested during surgery from 26 patients with MMD. The specimens were also collected during surgery as the controls from 6 patients with atherosclerotic carotid artery diseases. The arachnoid membrane was subjected to immunohistochemistry and the cerebrospinal fluid was used to measure the concentration of cytokines using ELISA. RESULTS: The number of cells positive for PDGFR (platelet-derived growth factor receptor) α was significantly higher in MMD than in the controls (5.4±3.1 versus 2.3±2.1 cells/field; P=0.02). The results were same in PDGFRß-positive cells (10.1±4.6 versus 4.8±2.8; P=0.01) and α-SMA (alpha-smooth muscle actin)-positive cells (8.8±3.1 versus 2.0±2.5; P<0.01). On multicolor immunofluorescence, 80.5±15.6% of cells positive for PDGFRα in MMD also expressed α-SMA, being significantly higher than 14.6±7.2% in the controls (P<0.01). The density of collagen in the arachnoid membrane was significantly higher in MMD than in the controls (60.3±15.0% versus 40.1±15.3%; P<0.01). In MMD, advanced disease stage was significantly associated with a larger number of α-SMA-positive cells in the arachnoid membrane (P=0.04). On ELISA, the cerebrospinal fluid concentrations of bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), and TGF (transforming growth factor)-ß1 were significantly higher in MMD than in the controls. CONCLUSIONS: Based on these findings, MMD may elevate the concentrations of angiogenic factors in the cerebrospinal fluid and then promote the proliferation of fibroblasts in the arachnoid membrane and their differentiation into myofibroblasts, which may, in turn, enhance the production of collagen essential for spontaneous collateral formation across the arachnoid membrane.

A case of intestinal perforation with a residual shunt tube placed during childhood: should we remove the non-functioning tube?

We report a 22-year-old man who had abdominal shunt tube migration into colon. He was diagnosed with pilocytic astrocytoma at optic-chiasm to hypothalamus at age of 7, and treated by resection, chemotherapy, and irradiation. He developed hydrocephalus and had multiple ventriculo-peritoneal shunt surgery. At age of 19, he fell in coma due to the subarachnoid and intra-ventricular hemorrhage due to the aneurysm rupture. The ventricle tube was removed, leaving the shunt valve and abdominal tube. The new shunt system was reconstructed at the contralateral side. He was at bed rest after this episode. At age of 20, he had high fever unable to control with antibiotics. The abdominal computed tomogram showed the shunt tube migration in the descending colon. The tube was removed under laparoscopy, and the inflammation was cured. The abandoned peritoneal shunt tube should be removed in patients with high tube migration risks.

Thin calcification (< 2 mm) can highly predict intraplaque hemorrhage in carotid plaque: the clinical significance of calcification types.

PURPOSE: Calcification pathogenesis and the relationship between calcification and plaque composition remain unclear. This study explored the calcification characteristics of vulnerable plaques, especially focusing on calcification thickness, using computed tomography angiography and magnetic resonance plaque imaging. METHODS: Demographic, computed tomography angiography, and magnetic resonance plaque imaging data were acquired from 178 patients with 229 lesions diagnosed with carotid stenosis. The calcification types were categorized by calcification thickness. We evaluated their features, including the anatomical location and the plaque composition compared with MR plaque imaging, and clarify the clinical characteristics. Furthermore, an immunohistochemical subgroup analysis was performed on 84 lesions treated with carotid endarterectomy. RESULTS: The result of the ROC analysis suggested the threshold between symptomatic and asymptomatic calcification was 2.04 mm (AUC;0.841, 95%CI; 0.771-0.894). Calcification with ≥ 2 mm thickness was classified as thick calcification and < 2 mm thickness as thin calcification. Multivariate analysis suggested the prevalence of symptomatic patients in the thin calcification group was significantly higher than others (P = 0.01; odds ratio, 4.1; 95% confidence interval 2.8-7.2). Plaques with thin calcification were associated with plaque with intraplaque hemorrhage (P < 0.01). The interobserver reliability (κ) of calcification type was 0.962 (95% confidence interval, 0.941-0.988). Immunohistochemical analysis demonstrated that the numbers of CD68-positive cells and CD31-positive microvessels in shoulder lesions were significantly higher in the thin calcification group than in the non-thin group (both P < 0.01). CONCLUSIONS: Thin calcification was associated with plaques with intraplaque hemorrhage and had different clinical implications than thick calcification.

Impact of Low Ambient Temperature on the Occurrence of Spontaneous Intracerebral Hemorrhage-Analysis of Population-Based Stroke Registry in Toyama, Japan.

OBJECTIVE: Although several studies have reported that some meteorological factors such as ambient temperature and atmospheric pressure, affect the incidence of spontaneous intracerebral hemorrhage (ICH), the correlation remains unclear. This retrospective time-series analysis was aimed to clarify the effects of meteorological parameters on the incidence of ICH. MATERIALS AND METHODS: Data of patients with ICH were obtained from a population-based survey of acute stroke patients between April 2016 and March 2019. All days during the study period were categorized into "no ICH day" when no ICHs occurred, "single ICH day" when only one ICH occurred, and "cluster day" when two or more ICHs occurred. Meteorological data were compared for among the three categories. RESULTS: 1,691 ICH patients from 19 hospitals were registered. In a total of 1,095 days, 250 were categorized as no ICH days, 361 as single ICH days, and 484 as cluster days. Daily ambient temperature declined in parallel with the daily number of ICHs, and it was a significant predictor for single ICH days and cluster days. Furthermore, the incidence of ICH in patients aged 65 years or above, men, those who emerged at home, those with modified Rankin Scale 3-5; and those with hypertension; and ICHs in the basal ganglia, brain stem, and cerebellum were more likely to be affected by low ambient temperature. CONCLUSION: Daily ambient temperature was significantly associated with ICH incidence. Patients' activity, history of hypertension, and location of hemorrhage were also related to the impact of low ambient temperature on the incidence of ICH.

Cerebrospinal fluid may flow out from the brain through the frontal skull base and choroid plexus: a gold colloid and cadaverine injection study in mouse fetus.

PURPOSE: It has been commonly accepted for a long time that the cerebrospinal fluid (CSF) drains into arachnoid granulations from the subarachnoid space to the dural venous sinus unidirectionally. However, recently, periventricular capillaries and lymphatic concepts have been introduced. The CSF moves along the perivascular space and drains into the capillary vessels or meningeal lymphatic tissues. CSF is involved in removing brain waste out of the brain. In this study, we investigated the outflow mechanism of substances in the CSF from the brain. METHODS: We investigated the movement of CSF by injection of gold colloid conjugates (2, 40, and 200 nm) into the lateral ventricles of mouse fetuses and evaluated the deposition by silver stain with tissue transparency and electron microcopy. Cadaverine was also injected into the lateral ventricle to determine its movement tract. RESULTS: The gold particle deposition was mainly observed in the frontal skull base. Electron microscopic study showed that the gold particle deposition was observed on the choroid plexus and ependyma in the lateral ventricle and also red blood cells in the heart and liver. Two-nanometer particles were exclusively observed in the liver. Cadaverine injection study demonstrated that cadaverine was observed at the extracranial frontal skull base, choroid plexus, ependymal surface, and perivascular area in the brain white matter. CONCLUSION: The particles in the CSF were shown to move from the brain to the frontal skull base and also into the blood stream through the choroid plexus in the fetus. The outflow of particles in the CSF may be regulated by molecular size. This new information will contribute to the prevention of brain degeneration due to brain waste deposition.

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.

Dilated microvessel with endothelial cell proliferation involves intraplaque hemorrhage in unstable carotid plaque.

BACKGROUND: The purpose of the present study was to clarify the characteristics of endothelial cell (EC) proliferation in intraplaque microvessels in vulnerable plaques and impact on clinical results. METHODS: The present study included 76 patients who underwent carotid endarterectomy. Patients were classified into three groups based on their symptoms: asymptomatic, symptomatic without recurrent ischemic event, and symptomatic with recurrent ischemic event. MR plaque imaging was performed and surgical specimens underwent immunohistochemical analysis. The number of CD31+ microvessels, and Ki67+ and CD105+ ECs in the carotid plaques was quantified, as measurements of maximum CD31+ microvessel diameter. RESULTS: MR plaque imaging yielded 41 subjects (54.0%) diagnosed with plaque with intraplaque hemorrhage (IPH), 14 subjects (18.4%) diagnosed with fibrous plaques, and 21 (27.6%) subjects diagnosed with lipid-rich plaques. The average largest diameter of microvessel in fibrous plaques, lipid-rich plaques, and plaque with IPH was 12.7 ± 4.1 µm, 31.3 ± 9.3 µm, and 56.4 ± 10.0 µm, respectively (p < 0.01). Dilated microvessels (>40 µm) were observed in 9.6% of plaques with IPH but only in 2.8% of lipid-rich plaques and 0% of fibrous plaques (p < 0.01). Ki67+/CD31+ ECs were identified in 2.8 ± 1.2% of fibrous plaques, 9.6 ± 6.9% of lipid-rich plaques, and in 19.5 ± 5.9% of plaques with IPH (p < 0.01). The average largest diameter of microvessels in the asymptomatic group was 17.1 ± 8.7 µm, 32.3 ± 10.8 µm in the symptomatic without recurrence group, and 55.2 ± 13.2 µm in the symptomatic with recurrence group (p < 0.01). CONCLUSION: Dilated microvessels with proliferative ECs may play a key role in IPH pathogenesis. Furthermore, dilated microvessels are likely related to clinical onset and the recurrence of ischemic events. The purpose of the present study was to clarify the characteristics of EC proliferation in intraplaque microvessels in vulnerable plaques and their impact on clinical results, focusing on dilated intraplaque microvessels.

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.

Impact of Perihematomal Edema on Infectious Complications after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hematoma involves two mechanisms leading to brain injury: the mechanical disruption of adjacent brain tissue by the hematoma and delayed neurological injury. Delayed neurological injury involves perihematomal edema (PHE) formation. Infectious complications following intracerebral hemorrhage (ICH) are a significant contributor to post-ICH recovery. We sought to identify a correlation between PHE volumes and infectious complications following ICH. We also sought to explore the clinical impact of this association. MATERIALS AND METHODS: This retrospective study included 143 patients with spontaneous ICH. CT scans were performed on admission, and 3 h, 24 h, and 72 h following admission. Hematoma and PHE volumes were calculated using a semi-automatic method. The absolute PHE volume at each time point and changes in PHE volume (ΔPHE) were calculated. Neutrophil to lymphocyte ratio (NLR) and serum C-reactive protein (CRP) levels were measured from the obtained blood samples. Neurological deterioration (ND) was assessed in all patients. RESULTS: Infectious complications were associated with ΔPHE72-24 (P < 0.01), whereas there was no association between infectious complications and ΔPHE24-3 (P = 0.09) or ΔPHE3-ad (P = 0.81). There was a positive correlation between ΔPHE72-24 and NLR (r = 0.85, 95% CI: 0.79-0.90, P < 0.01) and between ΔPHE72-24 and CRP levels (r = 0.89, 95% CI: 0.84-0.92, P < 0.01). The ND rate in the group of patients with infectious complications comorbid with high ΔPHE72-24 was higher than the other patient groups (P < 0.01). CONCLUSIONS: This study revealed a correlation between ΔPHE72-24 and infectious complications after spontaneous ICH, which was associated with markers of systemic inflammation. This phenotype linkage is a negative cascade that drives ND.

High-intensity vessel sign on fluid-attenuated inversion recovery imaging: a novel imaging marker of high-risk carotid stenosis-a MRI and SPECT study.

BACKGROUND: Measurement of luminal stenosis and determination of plaque instability using MR plaque imaging are effective strategies for evaluating high-risk carotid stenosis. Nevertheless, new methods are required to identify patients with carotid stenosis at risk of future stroke. We aimed to clarify the mechanisms and clinical implications of the hyperintense vessel sign (HVS) as a marker of high-risk carotid stenosis. METHODS: We included 148 patients who underwent carotid stent (CAS) or carotid endarterectomy (CEA). MRI FLAIR was performed to detect HVS prior to and within 7 days after CAS/CEA. MR plaque imaging and 123I-iodoamphetamine SPECT was performed prior to CEA/CAS. Detailed characteristics of HVS were categorized in terms of symptomatic status, hemodynamic state, plaque composition, and HVS on time series. RESULTS: Forty-six of 80 symptomatic hemispheres (57.5%) and 5 of 68 asymptomatic hemispheres (7.4%) presented HVS (P < 0.01). Of the 46 symptomatic hemispheres with HVS, 19 (41.3%) presented with hemodynamic impairment and 27 (58.7%) presented without hemodynamic impairment. Of 19 hemispheres with hemodynamic impairment, 12 subjects (63.2%) showed high intensity and 7 (36.8%) showed iso-intensity plaques on T1WI. All 27 hemispheres without hemodynamic impairment showed high-intensity plaques. Of the five asymptomatic and HVS-positive hemispheres, one showed hemodynamic impairment; MR plaque imaging revealed T1 iso-intensity. The other four hemispheres that did not show hemodynamic impairment showed T1WI high-intensity plaques. CONCLUSION: There are two possible mechanisms of HVS, hemodynamic impairment due to severe carotid stenosis and micro-embolism from unstable plaques. HVS could be a radiological marker for high-risk carotid stenosis.

Unstable Carotid Plaque as a Phenotype of Chronic Systemic Inflammation Enhances Renal Insufficiency.

PURPOSE: Chronic systemic inflammation is prevalent in patients with chronic kidney disease (CKD) and is linked to the development of cerebrovascular disease. In this study, we explored the association between the unstable plaques and preoperative CKD in patients who underwent carotid endarterectomy (CEA)/carotid artery stenting (CAS). Furthermore, this study also aimed to explore whether there is a difference in the aggravation of renal function with the presence of stable or unstable plaques. PATIENTS AND METHODS: The study included 90 patients who underwent CEA/CAS for carotid artery stenosis. Multivariate analysis was performed to determine the risk factors for CKD. Kaplan-Meier estimation was employed to evaluate the aggravation of renal function following CEA/CAS. RESULTS: Multivariate analysis revealed that contralateral carotid occlusive disease (odds ratio [OR], 4.45; 95% confidence interval [CI], 1.36-14.6), and T1 high-intensity carotid plaque (OR, 3.26; 95% CI, 1.2-8.86) were independent factors of CKD. Kaplan-Meier estimation demonstrated a higher aggravation of renal function in the T1 high-intensity group compared to those in the iso-intensity (P =.03). Following CEA/CAS, the time until aggravation of renal insufficiency was 12.0 ± 9.4 months in the T1 high-intensity group and 24.5 ± 9.6 months in the iso-intensity group (P =.03). CONCLUSIONS: This study demonstrated that contralateral carotid artery stenosis and T1 high-intensity plaques are more frequently observed in patients with CKD. T1 high-intensity carotid plaque is well linked to CKD development in future.

Development of Hemorrhage-prone Anastomoses in Asymptomatic Moyamoya Disease-A Comparative Study with Japan Adult Moyamoya Trial.

OBJECTIVE: Present study was aimed to precisely evaluate the angio-architectures in patients with asymptomatic moyamoya disease (MMD) by comparing with those with hemorrhagic stroke. METHODS: This study used the data set of cerebral angiography in Asymptomatic Moyamoya Registry (AMORE) Study and Japan Adult Moyamoya (JAM) Trial at enrollment. The development of 3 subtypes of collateral vessels, including lenticulostriate, thalamic, and choroidal anastomosis, was evaluated on cerebral angiography. Suzuki's angiographical stage and posterior cerebral artery (PCA) involvement were also assessed. These findings were compared between asymptomatic (AMORE) and hemorrhagic (JAM) groups. RESULTS: This study included 55 hemispheres of 35 patients in asymptomatic group and 75 hemispheres of 75 patients in hemorrhagic group. In asymptomatic group, thalamic anastomosis was less developed than in hemorrhagic group (P = .011), but there were no significant differences in the development of lenticulostriate and choroidal anastomosis between the 2 groups (P = .077 and P = .26, respectively). Suzuki's stage was more progressed and the prevalence of PCA involvement was significantly higher in hemorrhagic group than in asymptomatic group (P = .0033 and P = .016, respectively). CONCLUSIONS: This study reveals no significant differences in the development of choroidal anastomoses between asymptomatic and hemorrhagic-onset MMD. On the other hand, disease stage and PCA involvement were less advanced in asymptomatic MMD than in hemorrhagic-onset MMD. These findings strongly suggest a certain subgroup of asymptomatic patients with MMD is at potential risk for hemorrhagic stroke.

Impact of Plaque Composition on Risk of Coronary Artery Diseases in Patients with Carotid Artery Stenosis.

OBJECT: Recent clinical studies have recently demonstrated a strong association between carotid artery stenosis and coronary artery disease (CAD). However, the clinical impact of carotid plaque composition on CAD remains unclear. This study was aimed to determine the relationship between carotid plaque composition and CAD in patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: This prospective cohort study included a total of 97 patients who were admitted to our institution between January 2012 and April 2016. Magnetic resonance (MR) imaging was performed to semi-quantitatively analyze the components of carotid plaques by calculating the ratio of plaque intensity to muscle intensity on T1-weighted image. Diagnosis of CAD was based on patient history and clinical examinations during preoperative, postoperative and follow-up periods. Multivariate logistic analysis was performed to determine the risk factors for CAD. The relationship between contralateral plaque composition and CAD was also investigated. RESULTS: Of 97 patients, 33 were diagnosed as having 44 episodes of CAD. Multivariate logistic analysis revealed that ASO (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-18.9), contralateral carotid occlusive disease (OR, 6.5; 95%CI, 1.7-22.9), and plaque/muscle ratio (OR, 3.0; 95%CI, 1.4-10.1) were independent factors for predicting CAD. The patients diagnosed as having CAD during the follow-up period had significantly higher plaque/muscle ratio than those with CAD on preoperative evaluations (2.29 ± .21vs. 1.97 ± .33, P < .01). CONCLUSIONS: This study clearly demonstrates that ASO, contralateral carotid artery stenosis, and high-intensity carotid plaque on T1-weighted MRI independently predict CAD. Contralateral carotid plaque composition was also associated with concomitant CAD. Moreover, high-intensity carotid plaque may predict the future development of CAD. Therefore, unstable carotid plaque should be considered as the clinical phenotype of systemic inflammation and a novel, robust marker for future CAD.

Inflammation Coupling Between Unstable Carotid Plaque and Spleen-A 18F-Fluorodeoxyglucos Positron Emission Tomography Study.

BACKGROUND AND PURPOSE: This study was aimed to assess the hypothesis that unstable plaque formation in the carotid artery is one of phenotypes of chronic and systemic inflammation. METHODS: This study included 8 symptomatic patients with internal carotid stenosis (ICS) and 7 healthy controls. All subjects underwent 18F-fluorodeoxyglucos positron emission tomography (18F-FDG PET) of whole body. Plaque vulnerability was evaluated on magnetic resonance imaging (MRI). On 18F-FDG PET, the maximum standardized uptake (SUVmax) value was measured in the carotid plaque, aorta, spleen, liver, and bone marrow. The SUVmax ratio of the spleen or bone marrow to the liver was also calculated. These values were compared between 2 groups. All 8 patients in ICS group underwent carotid endarterectomy, and surgical specimens were subjected to immunohistochemistry. RESULTS: All 8 patients in ICS group had unstable plaque on MRI. The mean SUVmax of carotid plaque was 2.5 ± .2 in ICS group. The SUVmax of spleen was significantly higher in ICS group than in the controls (3.20 ±  .25 and 2.51 ±  .40, respectively; P = .003). The SUVmax ratio (spleen/liver) was also significantly higher in ICS group than in the controls (1.12 ±  .06 and .85 ±  .12, respectively; P = .001). The SUVmax of aorta was also significantly higher in ICS group than in the controls (2.16 ±  .27 and 1.48 ±  .15, respectively; P = .001). However, there were no significant differences in the SUVmax in the bone marrow and SUVmax ratio (bone marrow/liver) between the 2 groups (P = .811 and P = .731, respectively). Histological examination showed that the plaque strongly expressed endothelial progenitor cells, microvessels, and M1 macrophages. CONCLUSIONS: These data strongly suggest the inflammation coupling between the spleen and unstable carotid plaque, and may be useful to develop novel therapeutic strategies against systemic inflammation in patients with ICS.

Indocyanine green visualization of middle meningeal artery before craniotomy during surgical revascularization for moyamoya disease.

BACKGROUND: The middle meningeal artery (MMA) is well known to function as an important collateral channel to the territory of the anterior cerebral artery in moyamoya disease. This study was aimed to evaluate whether indocyanine green (ICG) videoangiography could visualize the anterior branch of the MMA before craniotomy during surgical revascularization for moyamoya disease. METHODS: This study included 19 patients who developed TIA, ischemic stroke or hemorrhagic stroke due to moyamoya disease. Plain CT scan and three-dimensional time-of-flight MR angiography were performed in all patients before surgery. All of them underwent superficial temporal artery to middle temporal artery anastomosis and indirect bypass on 27 sides in total. RESULTS: ICG videoangiography could clearly visualize the anterior branch of the MMA in 10 (37%) of 27 sides. The patients with a "visible" MMA are significantly younger than those without. Radiological analysis revealed that ICG videoangiography could visualize it through the cranium when the diameter of the MMA is >1.3 mm and the sphenoid bone thickness over the MMA is <3.0 mm. The MMA could be preserved during craniotomy in all "visible" MMAs, but not in 4 (23.5%) of 17 "invisible" MMAs. The results strongly suggest that ICG videoangiography can visualize the anterior branch of the MMA before craniotomy in about one-third of patients with a large-diameter MMA (>1.3 mm) and thin sphenoid bone (<3.0 mm). CONCLUSION: ICG videoangiography is a safe and valuable technique to preserve the anterior branch of the MMA during craniotomy for moyamoya disease.

Surgical and Endovascular Treatments of Extracranial Carotid Artery Aneurysms-Report of Six Cases.

BACKGROUND: Although the natural course of extracranial carotid artery aneurysms (ECAAs) is still unknown, they may cause stroke or cranial nerve dysfunction unless they are treated. In this report, we reviewed the clinical results of 6 patients who underwent endovascular and surgical treatments for ECAAs. METHODS: A total of 6 patients underwent endovascular and surgical treatments for ECAAs for 9 years. The primary causes of ECAAs included Marfan syndrome (1 patient), infection (1 patient), trauma (2 patients), and unknown (2 patients). All 6 ECAAs were symptomatic. RESULTS: One patient underwent surgical resection of the ECAA followed by end-to-end anastomosis of the internal carotid artery (ICA). Another patient underwent proximal ICA ligation combined with high-flow external carotid artery-to-middle cerebral artery bypass using a radial artery graft, because the patient also had a giant thrombosed aneurysm in the cavernous portion of the ipsilateral ICA. Endovascular treatment was selected in the other 4 patients using a covered stent or a bare metal stent combined with coil embolization. Of these patients, one required proximal ICA ligation followed by superficial temporal artery-to-middle cerebral artery anastomosis due to an anatomical problem for stent placement. There was no neurological deterioration at the discharge in all but 1 patient who suffered ischemic stroke during surgery. CONCLUSION: Surgical or endovascular treatment yielded a relatively satisfactory outcome in patients with ECAAs.

Is Quasi-moyamoya Disease a Uniform Disease Entity? A Three-Dimensional Constructive Interference in Steady State Imaging Study.

BACKGROUND: Quasi-moyamoya disease (MMD) or moyamoya syndrome is based on various underlying diseases and radiologically simulates MMD, but its disease entity is still unclear. Recent studies have proven specific shrinkage of the involved arteries in MMD. Using 3-dimensional constructive interference in steady state (3D-CISS), therefore, this study aimed to analyze the outer diameter of the involved arteries in quasi-MMD. METHODS: This study included 9 patients with quasi-MMD (unilateral type, n = 2; bilateral type, n = 7). Using 3D-CISS, the outer diameter was quantified in the internal carotid artery distal to the posterior communicating artery (C1), the horizontal portion of the middle and anterior cerebral arteries (M1 and A1, respectively), and the basilar artery. Control values were obtained from 17 healthy subjects. RESULTS: In 7 of 9 patients, the outer diameters of C1, M1, and A1 were significantly smaller than those of the controls. On the other hand, the values were normal in other 2 patients. There was no significant difference in the underlying disorders between the 2 groups. All 3 pediatric patients are categorized into the arterial shrinkage group, but 2 of 6 adult patients were not. CONCLUSIONS: These findings strongly suggest that quasi-MMD is not a uniform disease entity and includes at least 2 pathophysiologically different groups: the arterial shrinkage group and the nonarterial shrinkage group. A certain subgroup of MMD patients may be misdiagnosed as quasi-MMD because of the patients' comorbid disorders and mixed up with the patients who present angiographic findings similar to MMD in spite of the lack of arterial shrinkage.

[A Case of Suprasellar Germinoma that Spontaneously Regressed before Endoscopic Biopsy].

We present a very rare case of suprasellar germinoma that spontaneously regressed before endoscopic biopsy. An 8-year-old boy was admitted to our hospital due to headache, polydipsia, and polyuria. Neurological examination performed on admission revealed bitemporal hemianopia. Enhanced MRI demonstrated a homogeneously enhanced tumor mass in the suprasellar region obstructing the foramen of Monro. Tests for all serum tumor markers were negative. Plain X-ray and CT scan were performed once and twice, respectively, for seven days between admission and endoscopic biopsy. The total dose of diagnostic radiation exposure before surgery was 110 mGy. Endoscopic observation during surgery revealed that the tumor had markedly decreased in size and the foramen of Monro had reopened. A very small piece of the tumor was harvested during surgery. Plain CT scan just after surgery showed a marked decrease in the tumor size, compared with the preoperative CT scan. The pathological diagnosis of the tumor was pure germinoma. The patient then underwent chemotherapy(four courses of CARE regimen)followed by radiation therapy with a dose of 24 Gy/15 fr. The tumor completely disappeared after treatment, and no recurrence was observed in the past four years.