Introduction: The focal cerebral hyperperfusion (CHP) is a potential complication after Superficial temporal artery-middle cerebral artery (STA-MCA) bypass for Moyamoya disease (MMD) that can result in delayed intracerebral hemorrhage and/or neurological deterioration. The focal CHP could accompany hemodynamic ischemia due to the “watershed shift (WS) phenomenon”. Preoperative prediction of the focal CHP and WS phenomenon remains challenging. Here, we aimed to assess the diagnostic value of the “to and fro” conflict sign, conflicting blood flow around the vascular territory of the recipient arteries on an indocyanine green video angiography (ICG-VA) for predicting the focal CHP and WS phenomenon.Methods: Ninety-seven consecutive adult patients with MMD, undergoing 106 surgeries, were enrolled. Serial quantitative analysis of cerebral blood flow (CBF) was routinely conducted using N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography preoperatively and postoperative day 1 and 7 after STA-MCA bypass. The association between the “to and fro” conflict sign on ICG-VA and the focal CHP/WS phenomenon incidence was then analyzed.Results: The incidence of the fokal CHP and WS phenomenon was 29.2% (31/106) and 10.4% (11/106), respectively. The “to and fro” conflict sign was evident in 35.5% (11/31) and 54.5% (6/11) of MMD patients with the focal CHP and WS phenomenon, respectively. The “to and fro” conflict sign was significantly associated with both the focal CHP and WS phenomenon.Conclusion: The “to and fro” conflict sign on ICG-VA may serve as an intraoperative warning sign of the focal CHP and WS phenomenon after STA-MCA bypass in adult patients with MMD, providing neurosurgeons with a valuable tool for early detection.

Background We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)–affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses. Methods We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed. Results We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro, exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition. Conclusions Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.

INTRODUCTION: Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive steno-occlusive lesions in the terminal portion of the internal carotid artery. Despite its unknown etiology, immune dysregulation is regarded as a critical trigger for delineating the pathophysiology of MMD. The gut microbiota produces short-chain fatty (SCFA) and organic acids, influencing immune regulation and vascular remodeling. We aimed to characterize the gut microbiota in patients with MMD. METHODS: Sixteen patients with MMD and sixteen healthy controls were included in this study. We performed 16S rRNA sequencing of fecal samples and analyzed microbiome diversity and composition, and quantified SCFA and organic acid levels using liquid chromatography. RESULTS: There were no significant differences in α- and b-diversities among feces from the MMD patients and controls. However, 16S rRNA sequencing identified defective Lactococcus lactis (0 ± 0 in the MMD patients vs. 0.026 ± 0.084 in healthy controls, p = 0.0181) and abundant Gordinobacter pamelaeae (0.030±0.039 in the patients vs. 0.001±0.005 in healthy controls, p = 0.003) are strongly linked to MMD. Propionic acid levels were significantly lower in feces of the MMD patients compared to healthy controls (0.83 ± 0.34 mg/g in the MMD patients vs. 1.20 ± 0.55 mg/g in healthy controls, p = 0.028). CONCLUSION: Decreased Lactococcus lactis can result in reduced lactic acid and propionic acid levels in the feces of the patients. This imbalance in the gut microbiome and SCFA/organic acid levels could contribute to immune dysregulation underlying the vascular remodeling seen in MMD.

Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.

Background: Postoperative hyperperfusion syndrome (PHS) is a well-known complication following superficial temporal artery (STA)-middle cerebral artery (MCA) bypass for moyamoya disease (MMD). The early detection of postoperative radiological hyperperfusion (PRH), characterized by a transient increase in local cerebral blood flow (CBF), is crucial for the early diagnosis of PHS. This study aimed to investigate the effectiveness of waveform analysis for early PRH detection.Methods: We reviewed 52 consecutive patients who underwent STA-MCA bypass for MMD. Patients were divided into PRH and non-PRH groups based on the postoperative/preoperative CBF ratio. We collected the intraoperative bypass graft waveform and bypass flow data using a flowmeter. The pulsatile index (PI), an indicator of peripheral vascular resistance (PVR), was calculated from bypass flow data. Next, the newly proposed index of PVR, the ratio of the time from peak to 50% decay and to 100% decay (RT50), was calculated through waveform analysis. The values were then compared between the PRH and non-PRH groups.Results: Twenty-seven of the 52 patients met the inclusion criteria. Fourteen of these 27 patients showed PRH. The RT50, but not the PI, was significantly higher in the PRH group. Linear regression analysis revealed a significant correlation between the RT50 and PI. In the receiver operating characteristic for predicting PRH, the area under the curve of RT50 was 0.750, with a cutoff value of 0.255, a sensitivity of 0.928, and a specificity of 0.500.Conclusions: The RT50 obtained from waveform analysis is associated with PVR and can be useful for the early detection of PRH in patients with MMD.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

BACKGROUND: Moyamoya disease (MMD) is linked to the formation of intracranial aneurysms. The authors recently observed an effective use of magnetic resonance vessel wall imaging (MR-VWI) to detect de novo unruptured MMD-associated microaneurysms. OBSERVATIONS: The authors describe a 57-year-old female who was diagnosed with MMD 6 years ago after suffering a left putaminal hemorrhage. MR-VWI revealed point-like enhancement in the right posterior paraventricular region during the annual follow-up. On the T2-weighted image, this lesion was surrounded by high intensity. Angiography revealed a microaneurysm in the periventricular anastomosis. Right combined revascularization surgery was performed to prevent future hemorrhagic events. Another de novo circumferential enhanced lesion on MR-VWI appeared in the left posterior periventricular region 3 months after surgery. Angiography revealed that the enhanced lesion was a de novo microaneurysm on the periventricular anastomosis. The left combined revascularization surgery went well. The bilateral microaneurysms vanished on follow-up angiography. LESSONS: Unruptured MMD-associated microaneurysms on the periventricular anastomosis can be detected using MR-VWI. Revascularization surgery can eliminate microaneurysms by reducing hemodynamic stress on the periventricular anastomosis.

Utilizing chemically synthesized an isotopically labeled internal standard, isodesmosine-13C3,15N1, an isotope-dilution LC-MS/MS method was established. Concentrations of desmosine and isodesmosine in plasma of acute cerebral stroke patients and healthy controls were determined. The concentration of desmosines was markedly higher in plasma from acute stroke patients compared with healthy controls. Desmosines are thus novel biomarkers for evaluating the extent of vascular injury after acute cerebral stroke.

INTRODUCTION: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. METHODS: This study included 16 consecutive pediatric MMD patients (age, 6-16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110-130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. RESULTS: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as "immediate redistribution pattern." In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as "transient hypoperfusion pattern." Although 8 patients, including 4 with "transient hypoperfusion pattern" (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. DISCUSSION/CONCLUSIONS: This study revealed that the "transient hypoperfusion pattern" after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.

BACKGROUND: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. METHODS: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. RESULTS: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. CONCLUSIONS: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.

Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is the standard surgical treatment for moyamoya disease (MMD). Local cerebral hyperperfusion (CHP) is one of the potential complications, which could enhance intrinsic inflammation and oxidative stress in MMD patients and accompany concomitant watershed shift (WS) phenomenon, defined as the paradoxical decrease in the cerebral blood flow (CBF) near the site of CHP. However, CHP and simultaneous remote reversible lesion at the splenium have never been reported. A 22-year-old man with ischemic-onset MMD underwent left STA-MCA bypass. Although asymptomatic, local CHP and a paradoxical CBF decrease at the splenium were evident on N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 day after surgery. The patient was maintained under strict blood pressure control, but he subsequently developed transient delirium 4 days after surgery. MRI revealed a high-signal-intensity lesion with a low apparent diffusion coefficient at the splenium. After continued intensive management, the splenial lesion disappeared 14 days after surgery. The patient was discharged without neurological deficits. Catheter angiography 2 months later confirmed marked regression of posterior-to-anterior collaterals via the posterior pericallosal artery, suggesting dynamic watershed shift between blood flow supplies from the posterior and anterior circulation. Mild encephalitis/encephalopathy with a reversible splenial lesion could explain the pathophysiology of the postoperative splenial lesion in this case, which is associated with generation of oxidative stress, enhanced inflammation, and metabolic abnormalities. Rapid postoperative hemodynamic changes, including local CHP and concomitant WS phenomenon, might participate in the formation of the splenial lesion.

Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard treatment for adult moyamoya disease (MMD) patients. Cerebral hyperperfusion (CHP) syndrome is one of the most serious complications of this procedure that can result in deleterious outcomes, but predicting CHP before revascularization surgery remains challenging. Furthermore, the hematological/serological factors associated with CHP syndrome are unknown. To investigate the correlation between pre-operative hematological/serological factors and the development of CHP syndrome after STA-MCA anastomosis with encephalo-duro-myo-synangiosis (EDMS) for MMD., a pre-operative peripheral blood test was performed within 5 days before surgery. Local cerebral blood flow (CBF) at the site of anastomosis was quantified by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, and the pre-operative CBF value at the corresponding area was measured. We defined CHP syndrome as a local CBF increase over 150% compared with the pre-operative value, which was responsible for delayed intracranial hemorrhage, transient focal neurological deterioration, and/or seizure. Then, we retrospectively investigated the correlation between peripheral blood test results and the development of CHP syndrome. CHP syndrome 1 day after STA-MCA anastomosis with EDMS was observed in nine patients (9/114 hemispheres; 7.9%). Multivariate analysis with multiple imputation revealed that higher hematocrit value and lower total protein level were significantly associated with the development of CHP syndrome (p value: 0.028 and 0.043, respectively). Higher pre-operative hematocrit levels and lower pre-operative total protein levels are novel risk factors for CHP syndrome after direct revascularization surgery in adult MMD patients.

We report an adult moyamoya disease (MMD) patient who developed persistent local vasogenic edema with dynamic change in the regional cerebral blood flow after left superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. A 49-year-old woman with ischemic-onset MMD underwent left STA-MCA anastomosis. Magnetic resonance (MR) imaging of fluid-attenuated inversion recovery 1 day after surgery revealed an asymptomatic local high-signal-intensity lesion at the site of anastomosis, and MR angiography demonstrated apparently patent STA-MCA bypass. Due to the increased apparent diffusion coefficient value, we diagnosed the lesion as vasogenic edema. A significant increase in focal cerebral blood flow (CBF) at the site of the anastomosis was observed on N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123I-IMP-SPECT) (139.8%; compared with the preoperative value). Under strict blood pressure control (systolic blood pressure under 130 mmHg), the patient remained asymptomatic during the entire peri-operative period, but the 123I-IMP-SPECT 7 days after surgery suggested paradoxical CBF decrease (72.9%). Based on this finding, we allow the patient to be maintained under normotensive condition (∼160 mmHg), which recovered the CBF (115.0%) 14 days after surgery. Vasogenic edema remained during the entire peri-operative period, but completely disappeared 83 days after surgery. Local vasogenic edema formation due to cerebral hyperperfusion is not uncommon after STA-MCA anastomosis for adult MMD, but dynamic CBF change at the site of persistent local vasogenic edema after STA-MCA anastomosis is extremely rare. We recommend serial CBF measurement in the acute stage after revascularization surgery for MMD, especially when MR imaging demonstrates local signal intensity change.

INTRODUCTION: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is an effective surgical procedure for adult patients with moyamoya disease (MMD) and is known to have the potential to prevent cerebral ischemia and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is one of the serious complications of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the prediction of CHP before revascularization surgery remains challenging. The present study evaluated the diagnostic value of preoperative three-dimensional (3D)-time-of-flight (TOF) magnetic resonance angiography (MRA) for predicting CHP after STA-MCA anastomosis for MMD. MATERIALS AND METHODS: The signal intensity of the peripheral portion of the intracranial major arteries, such as the anterior cerebral artery (ACA), MCA, and posterior cerebral artery (PCA) ipsilateral to STA-MCA anastomosis, on preoperative MRA was graded (0-2 in each vessel) according to the ability to visualize each vessel on 97 affected hemispheres in 83 adult MMD patients. Local cerebral blood flow (CBF) at the site of anastomosis was quantitatively measured by N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. Then, we investigated the correlation between the preoperative MRA score and the development of CHP. RESULTS: The CHP phenomenon 1 day after STA-MCA anastomosis (local CBF increase over 150% compared with the preoperative value) was evident in 27 patients (27/97 hemispheres; 28%). Among them, 8 (8 hemispheres) developed CHP syndrome. Multivariate analysis revealed that the hemispheric MRA score (0-6), the summed ACA, MCA, and PCA scores for the affected hemisphere, was significantly associated with the development of CHP syndrome (p = 0.011). The hemispheric MRA score was also significantly correlated with the CHP phenomenon, either symptomatic or asymptomatic (p < 0.001). CONCLUSION: The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.

Background: Intracranial vertebral artery dissection (VAD) and moyamoya disease (MMD) are rare cerebrovascular diseases, both of which have an ethnic predominance in the East Asian population. Disruption of the internal elastic lamina and subsequent rupture of the medial layer result in intracranial VAD. MMD is a chronic occlusive cerebrovascular disease of unknown etiology, in which the medial layer and internal elastic lamina of the intracranial arteries are significantly compromised. Recent genetic studies found ring finger protein 213 (RNF213) to be an important susceptibility gene for MMD in East Asian patients, but the association between VAD and RNF213 has not been investigated. . Methods: We investigated polymorphism of the RNF213 gene (c.14576G>A) in genomic DNA of 24 patients with intracranial VAD in comparison with 58 patients with definitive MMD and 48 healthy controls. Results: Although RNF213 gene polymorphism (c.14576G>A) was evident in 69% of the MMD patients (40/58), none of the patients with intracranial VAD had this characteristic polymorphism (0/24, p < 0.001). The incidence of RNF213 c.14576G>A polymorphism was 4.2% in healthy controls (2/48). After adjustment by age and sex, the incidence of RNF213 c.14576G>A was significantly lower in intracranial VAD patients (p = 0.021) than that in MMD patients. Conclusions: In contrast to MMD patients, the prevalence of RNF213 c.14576G>A polymorphism was significantly lower in patients with intracranial VAD. The RNF213 gene polymorphism may preferentially affect the cerebrovascular lesion in the anterior circulation, which is originated from the primitive internal carotid arteries. The genetic background underlying intracranial VAD should be elucidated in future studies. Abbreviations: VAD: vertebral artery dissection; MMD: moyamoya disease; RNF213: ring finger protein 213; CAD: carotid artery dissection.

OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for adult moyamoya disease (MMD) patients, but local cerebral hyperperfusion (CHP) and cerebral ischemia are potential complications of this procedure. Recent hemodynamic analysis of the acute stage after revascularization surgery for MMD revealed a more complex and unique pathophysiological condition, the so-called "watershed shift (WS) phenomenon," which is defined as a paradoxical decrease in the cerebral blood flow (CBF) at the adjacent cortex near the site of local CHP. The objective of this study was to clarify the exact incidence, clinical presentation, and risk factors of the WS phenomenon after direct revascularization surgery for adult MMD. PATIENTS AND METHODS: Among 74 patients with MMD undergoing STA-MCA anastomosis for 78 affected hemispheres, 60 adult patients comprising 64 hemispheres underwent serial quantitative CBF analysis by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography after revascularization surgery. The local CBF was quantitatively measured at the site of anastomosis and the adjacent cortex before surgery, as well as on 1 and 7 days after surgery. Then, we investigated the incidence, clinical presentation, and risk factors of the WS phenomenon. RESULTS: The WS phenomenon was evident in 7 patients (7/64 hemispheres; 10.9%) after STA-MCA anastomosis for adult MMD. None of the patients developed neurological deterioration due to the WS phenomenon, but 1 patient developed reversible ischemic change on diffusion-weighted imaging at the site of the WS phenomenon. Multivariate analysis revealed that a lower preoperative CBF value was significantly associated with the occurrence of the WS phenomenon (20.3 ± 7.70 mL/100 g/min in WS-positive group vs. 31.7 ± 8.81 mL/100 g/min in WS-negative group, p= 1.1 × 10-2). CONCLUSIONS: The incidence of the WS phenomenon was as high as 10.9% after STA-MCA anastomosis for adult MMD. The clinical outcome of the WS phenomenon is generally favorable, but there is a potential risk for perioperative cerebral infarction. Thus, we recommend routine CBF measurement in the acute stage after revascularization surgery for adult MMD to avoid surgical complications, such as local CHP and cerebral ischemia, caused by the WS phenomenon. Concomitant detection of the WS phenomenon with local CHP is clinically important because blood pressure reduction to counteract local CHP may have to be avoided in the presence of the WS phenomenon.

BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology. Growing evidence suggest its involvement of autoimmune and genetic mechanisms in the pathogenesis of MMD. This study aims to clarify the association between HLA allele and MMD. METHODS: Case-control study: the DNA of 136 MMD patients in Japan was extracted and the genotype of human leukocyte antigen (HLA) from this DNA was determined by super-high-resolution single-molecule sequence-based typing using next-generation sequencing. Next, the frequency of each HLA allele (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1) was compared with those in the Japanese control database. In addition, haplotype estimation was performed using the expectation maximization algorithm. RESULTS: The frequencies of the HLA-DRB1*04:10 allele (4.77% vs. 1.47% in the control group; P = 1.7 × 10-3; odds ratio [OR] = 3.35) and of the HLA-DRB1*04:10-HLA-DQB1*04:02 haplotype (haplotype frequency 4.41% vs. 1.35% in the control group; P = 2.0 × 10-3; OR = 3.37) significantly increased. The frequency of thyroid diseases, such as Graves' disease and Hashimoto thyroiditis, increased in HLA-DRB1*04:10-positive MMD patients compared with that in HLA-DRB1*04:10-negative MMD patients. CONCLUSIONS: HLA-DRB1*04:10 is a risk allele and HLA-DRB1*04:10-HLA-DQB1*04:02 a risk haplotype for MMD. In addition, HLA-DRB1*04:10 is associated with thyroid disease in MMD patients.

OBJECTIVE: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard surgical procedure for adult patients with moyamoya disease (MMD) and plays a role in preventing ischemic and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is a potential complication of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the exact threshold of the pathological increase in postoperative cerebral blood flow (CBF) is unclear. Thus, we analyzed local CBF in the acute stage after revascularization surgery for adult MMD to predict CHP syndrome under modern perioperative management. MATERIALS AND METHODS: Fifty-nine consecutive adult MMD patients, aged 17-66 years old (mean 43.1), underwent STA-MCA anastomosis with indirect pial synangiosis for 65 affected hemispheres. All patients were perioperatively managed by strict blood pressure control (systolic pressure of 110-130 mm Hg) to prevent CHP syndrome. Local CBF at the site of anastomosis was quantitatively measured using the autoradiographic method by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. We defined CHP phenomenon as a local CBF increase over 150% compared to the preoperative value. Then, we investigated the correlation between local hemodynamic change and the development of CHP syndrome. RESULTS: After 65 surgeries, 5 patients developed CHP syndrome, including 2 patients with delayed intracerebral hemorrhage (3.0%), 1 with symptomatic subarachnoid hemorrhage (1.5%), and 2 with focal neurological deterioration without hemorrhage. The CBF increase ratio was significantly higher in patients with CHP syndrome (270.7%) than in patients without CHP syndrome (135.2%, p = 0.003). Based on receiver operating characteristic analysis, the cutoff value for the pathological postoperative CBF increase ratio was 184.5% for CHP syndrome (sensitivity = 83.3%, specificity =  94.2%, area under the curve [AUC] value  =  0.825) and 241.3% for hemorrhagic CHP syndrome (sensitivity =  75.0%, specificity =  97.2%, AUC value  =  0.742). CONCLUSION: Quantitative measurement of the local CBF value in the early postoperative period provides essential information to predict CHP syndrome after STA-MCA anastomosis in patients with adult MMD. The pathological threshold of hemorrhagic CHP syndrome was as high as 241.3% by the local CBF increase ratio, but 2 patients (3.0%) developed delayed intracerebral hemorrhage in this series that were managed following the intensive perioperative management protocol. Thus, we recommend routine CBF measurement in the acute stage after direct revascularization surgery for adult MMD and satisfactory blood pressure control to avoid the deleterious effects of CHP.

BACKGROUND: Cerebral hyperperfusion (CHP) syndrome is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), but its biphasic and delayed development is extremely rare. CASE REPORT: A 47-year-old woman with autosomal dominant kidney disease (ADPKD) presented with transient ischemic attacks due to MMD, and underwent left STA-MCA anastomosis. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123IMP-SPECT) 1 day after surgery revealed asymptomatic CHP at the site of anastomosis. Strict blood pressure control and minocycline hydrochloride relieved CHP at postoperative day 7. However, 2 days later, the patient complained of sensory aphasia, and 123IMP-SPECT demonstrated significant focal CHP at the site of anastomosis accompanying high-intensity signal on magnetic resonance (MR) imaging of fluid attenuated inversion recovery (FLAIR) in her left temporal lobe near the site of anastomosis. We continued strict blood pressure control and additionally administered free radical scavenger (Edaravone) and antiepileptic agents, which gradually improved sensory aphasia. MR imaging and 123IMP-SPECT also confirmed the amelioration of the FLAIR-high lesion and focal CHP in her left temporal lobe. Two months later, the patient underwent right STA-MCA anastomosis without complications. CONCLUSIONS: Although the underlying mechanism is unknown, biphasic development of focal CHP after revascularization surgery in an MMD patient with ADPKD is unique. Due to the potential vulnerability of the systemic vessels in ADPKD, it is conceivable that intrinsic vascular wall fragility in MMD could be enhanced by ADPKD and have partly led to this rare complication.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard treatment for Moyamoya disease (MMD). Cerebral hyperperfusion syndrome is a potential complication of this procedure and can cause local vasogenic edema and/or delayed intracerebral hemorrhage. Cerebral hypoperfusion is a contradictory postoperative pathophysiological condition implicated in MMD, but its association with symptomatic local vasogenic edema has not been reported. CASE REPORT: A 31-year-old woman with MMD underwent left STA-MCA anastomosis 3 months after a minor completed stroke in bilateral hemispheres. Eight hours after the operation, the patient developed neurological deterioration of dysarthria and mono-paresis in her right hand. Magnetic resonance (MR) angiography showed apparently patent STA-MCA bypass, whereas MR imaging of fluid-attenuated inversion recovery demonstrated a local high-signal-intensity lesion at the vascular territory supplied by the bypass. The apparent diffusion coefficient value was significantly increased in this lesion, suggesting local vasogenic edema formation. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography revealed global hypoperfusion in the left hemisphere. The administration of a free-radical scavenger and antiepileptic agent gradually relieved her symptoms, and MR imaging 1 month after surgery confirmed the complete disappearance of local vasogenic edema. CONCLUSIONS: Vasogenic edema may be associated not only with cerebral hyperperfusion but also with hypoperfusion after STA-MCA anastomosis for MMD. Although the exact mechanism of this rare association is unknown, the intrinsic vulnerability of intracranial vascular wall structures and the increased vascular permeability in MMD may partly explain the paradoxical association of hypoperfusion and local vasogenic edema.

<p> 妊娠後期に水頭症で発症した小脳血管芽腫症例を経験した. 症例は29歳女性. 妊娠36週に頭痛と嘔気を訴え徐々に傾眠となった. MRIでは左小脳半球に主座をおき強く造影される境界鮮明な腫瘤性病変を認め広範な浮腫により脳幹および第四脳室は圧排され水頭症を呈していた. 緊急帝王切開術にて児娩出後に腫瘍を摘出した. 術後4週間のリハビリテーションを経て自宅退院した. 小脳血管芽腫においては妊娠中の循環血漿量増大およびエストロゲン上昇, 胎盤由来の血管新生因子により腫瘍容積増大や脳浮腫増悪を生じ頭蓋内圧亢進や水頭症をきたすと報告されている. 母体優先の大原則のもと, 治療に際しては妊娠週数や母体の状態に応じて個々の症例ごとに治療戦略を構築する必要がある.</p>

Reactivation of the hepatitis B virus (HBV) is a risk in the 350 million HBV carriers worldwide. HBV reactivation may cause hepatocellular carcinoma, cirrhosis, and fulminant hepatitis, and HBV reactivation accompanied with malignant tumor and/or chemotherapy is a critical problem for patients with chronic HBV infection. Multiple risk factors causing an immunosuppressive state can also induce HBV reactivation.We present a case of HBV reactivation during an immunosuppressive state caused by Cushing disease and physical and psychological stress after a disaster. A 47-year-old Japanese woman was an inactive HBV carrier until the Great East Japan Earthquake occurred and follow-up was discontinued. One year after the earthquake she had intractable hypertension, and her visual acuity gradually worsened. Head magnetic resonance imaging showed a sellar tumor compressing the optic chiasm, and hepatic dysfunction with HBV reactivation was identified. Endocrinologic examination established the diagnosis as Cushing disease. After normalization of hepatic dysfunction with antiviral therapy, transsphenoidal tumor removal was performed that resulted in subtotal removal except the right cavernous portion. Steroid hormone supplementation was discontinued after 3 days of administration, and gamma knife therapy was performed for the residual tumor. Eighteen months after the operation, adrenocorticotropic hormone and cortisol values returned to normal. The patient has been free from tumor regrowth and HBV reactivation throughout the postoperative course.Accomplishment of normalization with intrinsic steroid value with minimization of steroid supplementation should be established. Precise operative procedures and careful treatment planning are essential to avoid HBV reactivation in patients with this threatening condition.

BACKGROUND: The de novo development of moyamoya disease (MMD) in adults is extremely rare, with only 2 cases being previously reported. Furthermore, the mechanisms underlying the progression of adult MMD have not been elucidated yet. CASE REPORT: A transient ischemic attack occurred in a 46-year-old woman, owing to progressive MMD. Magnetic resonance (MR) angiography performed 7 years before the diagnosis of MMD did not detect any steno-occlusive changes in the major intracranial vessels, including the internal carotid artery (ICA) and the middle cerebral artery (MCA). However, during the last 2 years, serial MR angiography revealed the gradual progression of left MCA stenosis and ultimately showed apparent stenosis of the bilateral terminal ICA to proximal MCA. Catheter angiography confirmed the definitive diagnosis of MMD. A genetic analysis of RING-finger protein (RNF)-213, an MMD susceptibility gene, revealed that not only the patient, but also her sister, brother, and daughter had the heterozygous variant of the RNF-213 gene. Because of hemodynamic compromise with ischemic symptoms, the patient underwent revascularization surgery on the affected hemisphere, without complications. She had no cerebrovascular event in the postoperative follow-up period of 8 months, and there was no evidence of the further progression of MMD. CONCLUSION: We herein present the entire clinical course of the de novo development of MMD in a female adult. Newly developed MMD in an adult patient with a characteristic variant of the RNF-213 gene appears to be unique.

A 42-year-old man was referred to our hospital due to chest pain, diabetes mellitus, and sensorineural hearing loss. Transthoracic echocardiography revealed diffuse left ventricular hypokinesis. He was diagnosed with mitochondrial disease and a c.A3243G mutation was identified in his mitochondrial DNA. This case of mitochondrial cardiomyopathy demonstrated a low uptake of 123I-BMIPP, while the uptake of 99mTc-MIBI was preserved. In contrast, previous reports have noted the increased uptake of123I-BMIPP and the decreased uptake of 99mTc-MIBI. This is the first study to show this unique 99mTc-MIBI/123I-BMIPP mismatch pattern. We also discuss the relationships among the cardiac scintigraphy, cardiac magnetic resonance imaging, and histopathology findings.

BACKGROUND: An unfused or twiglike middle cerebral artery (MCA) is a congenital anomaly related to the abnormal development of the MCA. An unfused or twiglike MCA can cause both ischemic and hemorrhagic strokes. Previous reports have shown that an unfused or twiglike MCA with coexisting aneurysms can cause subarachnoid hemorrhage (SAH). CASES: Two patients presented with nonaneurysmal SAH due to an unfused or twiglike MCA. Both patients had stenosis of the proximal M1 segment of the left MCA and abnormal vascular nets distal to the stenotic lesion. Vasculature distal to the abnormal vascular nets remained grossly normal. These findings were not evident in computed tomography or magnetic resonance angiography. CONCLUSION: An unfused or twiglike MCA can cause nonaneurysmal SAH. Digital subtraction angiography is necessary for accurate diagnosis.

【背景】妊婦脳梗塞例に対し，血管内治療による急性期再開通療法施行例は報告されていない．【症例】33 歳女性，妊娠37 週，特記すべき既往歴なし．突然の意識障害，左上下肢麻痺で発症．レンズ核，島，放線冠に拡散強調像高信号域を認め，magnetic resonance angiography で右M1 閉塞を認めた．他院よりtPA 投与開始の後，血管内治療目的に当院へ搬送となる．血栓回収療法により，thrombolysis in cerebral infarction 2b の再開通が得られた．治療2 日後に帝王切開にて児を出産した．2カ月後にはmodified Rankin scale 0 に回復した．【結語】本症例はdrip，ship，retrieve，childbirth が成功した初めての症例報告である．

Malignant lymphoma of the cranial vault is a rare entity and the tumor growth patterns are not well understood. Here we report two cases of malignant lymphoma involving the scalp and epidural space with slight changes in the intervening skull. A 63-year-old woman presented with a scalp mass in her right frontal area. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated mass lesions in the scalp and epidural space with slight osteolytic changes in the intervening skull. She underwent resection of the lesions. A 53-year-old man presented with a mass in his right frontal area. CT and MR imaging showed mass lesions in the scalp and epidural space without changes in the skull. He underwent resection of the lesions. The histopathological diagnosis was diffuse large B cell lymphoma in both cases. Microscopic examination of the intervening skull found that the bone marrow was diffusely replaced by lymphoma cells, and lymphoma cells extended to the extra- or intra-cranial space along the emissary veins without destruction of the cortical or trabecular bone. These histopathological findings explain the radiological findings and provide the clues to elucidate the mechanism of extension of cranial vault lymphoma.