The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

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.

Transplantation of astrocytic mitochondria modulates neuronal antioxidant defense and neuroplasticity and promotes functional recovery after intracerebral hemorrhage.

Astrocytes release functional mitochondria (Mt) that play regulatory and pro-survival functions upon entering adjacent cells. We recently demonstrated that these released Mt could enter microglia to promote their reparative/pro-phagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, a relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt that upon entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH. Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt upon entering neurons prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels, while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. Furthermore, we found that Mt genome-encoded small peptide humanin (HN) that is normally abundant in Mt, could simulate Mt-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under ICH-like injury. This study demonstrates that adoptive astrocytic Mt transfer enhances neuronal Mn-SOD-mediated anti-oxidative defense and neuroplasticity in the brain, which potentiate functional recovery following ICH.SIGNIFICANCE STATEMENTMitochondrial dysfunction and antioxidant defense play essential role in brain damage after intracerebral hemorrhage (ICH). Astrocytes release functional mitochondria (Mt) that enter adjacent cells to help brain homeostatic function. Here, we show that systemic transplantation of astrocytic Mt restores ICH-impaired neuronal anti-oxidative defense, enhances neurite outgrowth, and improves stroke recovery after ICH. Our study suggests that systemic transplantation of astrocytic Mt could be considered as a novel and potentially promising strategy for ICH treatment.

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement.

Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving young Mt, but not aged Mt improved cognitive function and hippocampal integrity. Using a CCL11-induced aging-like model in vitro, we found that astrocytic Mt protect hippocampal neurons and enhance a regenerative environment through upregulating synaptogenesis-related gene expression and anti-oxidants that were suppressed by CCL11. Moreover, the inhibition of CCL11-specific receptor C-C chemokine receptor 3 (CCR3) boosted the expression of synaptogenesis-related genes in the cultured hippocampal neurons and restored the neurite outgrowth. This study suggests that young astrocytic Mt can preserve cognitive function in the CCL11-mediated aging brain by promoting neuronal survival and neuroplasticity in the hippocampus.

Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study.

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.

Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.

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.

Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation.

Growing evidence suggest the association between Moyamoya disease (MMD) and immune systems, such as antigen presenting cells in particular. Rnf213 gene, a susceptibility gene for MMD, is highly expressed in immune tissues, however, its function remains unclear. In addition, the physiological role of RNF213 gene polymorphism c.14576G > A (rs112735431), susceptibility variant for MMD, is also poorly understood. By studying Rnf213-knockout (Rnf213-KO) mice with deletion of largest exon32 and Rnf213-knockin (Rnf213-KI) mice with insertion of single-nucleotide polymorphism corresponding to c.14576G > A mutation in MMD patients, we aimed to investigate the role of RNF213 in dendritic cell development, and antigen processing and presentation. First, we found a high level of Rnf213 gene expression in conventional DCs and monocytes. Second, flow cytometric and confocal microscopic analysis revealed ovalbumin protein-pulsed Rnf213-KO and Rnf213-KI DCs showed impaired antigen uptake, proteolysis and reduced numbers of endosomes and lysosomes, and thereby failed to activate and proliferate antigen-specific T cells efficiently. In addition, Rnf213-KI DCs showed a similar phenotype to that of Rnf213-KO BMDCs. In conclusion, our findings suggest the critical role of RNF213 in antigen uptake, processing and presentation.

Pre-operative higher hematocrit and lower total protein levels are independent risk factors for cerebral hyperperfusion syndrome after superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in adult moyamoya disease patients-case-control study.

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.

Prediction of Cerebral Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis by Three-Dimensional-Time-of-Flight Magnetic Resonance Angiography in Adult Patients with Moyamoya Disease.

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.

Persistent Local Vasogenic Edema with Dynamic Change in the Regional Cerebral Blood Flow after STA-MCA Bypass for Adult Moyamoya Disease.

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.

Incidence and Risk Factors of the Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis for Adult Moyamoya Disease.

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.

Significance of Quantitative Cerebral Blood Flow Measurement in the Acute Stage after Revascularization Surgery for Adult Moyamoya Disease: Implication for the Pathological Threshold of Local Cerebral Hyperperfusion.

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.

[Anticoagulation Therapy for Prevention of Acute Pulmonary Thromboembolism in Patients with Intracerebral Hemorrhage in Acute Phase].

Pulmonary thromboembolism(PTE)can be a lethal complication in patients with intracerebral hemorrhage(ICH), and the early detection of deep venous thrombosis(DVT)is important for prevention of PTE. Anticoagulation therapy is effective for prevention of PTE; however, in ICH patients, the safety of anticoagulants is not established because of concern about ICH expansion. We investigated the clinical data of patients who developed ICH and assessed risk factors for DVT and the safety of anticoagulation therapy. Our study included 250 patients between 2014 and 2016. We performed weekly screening of D-dimer and ultrasonography of lower limb veins was performed when levels gradually increased or reached 10 µg/mL. In patients with DVT, we started anticoagulation therapy after systolic blood pressures were controlled at ≤140 mmHg. DVT was detected in 35(14.0%)patients, and 29(11.6%)underwent anticoagulation therapy. A hemorrhagic complication was observed in 1 case as gastrointestinal bleeding. Expansion of ICH was not detected in any cases. Symptomatic PTE occurred in 1 case with DVT, just before initiation of anticoagulants. Univariate logistic regression analysis revealed hemorrhage volume ≥30 mL and modified Rankin Scale score ≥5 at discharge were associated with increased risk of DVT, with odds ratios of 2.69 and 2.51, respectively. Our study suggests that DVT tends to occur in patients with severe ICH and that periodic measurement of D-dimer is useful for early detection of DVT. Anticoagulation therapy can be safely started in ICH patients under strict control of blood pressure.

Paradoxical Association of Symptomatic Local Vasogenic Edema with Global Cerebral Hypoperfusion after Direct Revascularization Surgery for Adult Moyamoya Disease.

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.

Biphasic Development of Focal Cerebral Hyperperfusion After Revascularization Surgery for Adult Moyamoya Disease Associated With Autosomal Dominant Polycystic Kidney Disease.

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.

[Coil Embolization of Vertebral Artery Aneurysm Using Direct Percutaneous Puncture of Vertebral Artery:A Technical Report].

Although direct puncture of the cervical vertebral artery(VA)is not commonly performed in neuroendovascular therapy, it is sometimes inevitable for procedural or technical reasons. We report a case of a ruptured VA aneurysm that required direct cervical VA puncture for treatment. A 79-year-old man was transferred to our hospital with the diagnosis of subarachnoid hemorrhage. Cerebral angiography revealed a right VA-posterior inferior cerebellar artery aneurysm. The aneurysm showed downward projection due to retrograde flow of the right VA caused by chronic occlusion of the right subclavian artery. For endovascular treatment, the approach through the VA union via the left VA was thought to be most appropriate;however, the left VA was very tortuous and the microcatheter could not cross the VA union. We performed percutaneous direct puncture of the left cervical VA. An 18-G intravenous catheter needle(Surflo®)was advanced and set into the C5/6 segment of the VA under biplane fluoroscopic road-mapping guidance. The microcatheter reached the aneurysm and coil embolization was successfully performed. The patient was kept intubated under general anesthesia overnight, to monitor for cervical subcutaneous hematoma. Several procedures for direct VA puncture have been reported. The major problem is the difficulty with hemostasis and maintenance of the airway is important. Although the indication is limited due to the difficulty of adjunctive techniques and postoperative antithrombotic therapy, direct VA puncture under biplane fluoroscopic guidance was useful in this case.

[A Case of Ventriculoperitoneal Shunt Dysfunction in an Adult Secondary to Constipation].

INTRODUCTION: Ventriculoperitoneal(VP)shunts function because of the pressure differential between the intracranial space and the peritoneal cavity. Although chronic constipation is often a cause of VP shunt dysfunction in children, it is not well recognized in adults. We present a case of shunt dysfunction that not only resolved after resolution of constipation but also resulted in overdrainage. CASE REPORT: A 28-year-old woman who had a VP shunt placed 11 years prior for hydrocephalus was referred to our department because of an enlarged ventricle diagnosed with computed tomography(CT). She had a previous history of pineal germinoma and a VP shunt was placed to treat the associated hydrocephalus. At presentation, she complained of headache and somnolence. Shunt dysfunction was suspected, but no problem was detected in the shunt system, including pressure settings. As constipation was detected, we treated this condition. Soon after, her symptoms resolved and ventricle size normalized. She was discharged without any deficit, but overdrainage was detected with CT obtained 1 month later. CONCLUSION: Although constipation is not a common cause of shunt dysfunction in adult patients, it is important to consider to avoid unnecessary shunt revision. In the present case, resolution of chronic constipation resulted in resolution of shunt dysfunction. This suggests the importance of resolution of constipation in case of shunt adjustment, even in adult cases.

De Novo Development of Moyamoya Disease in an Adult Female with a Genetic Variant of the RNF-213 Gene: Case Report.

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.

Nonaneurysmal Subarachnoid Hemorrhage Due to Unfused or Twiglike Middle Cerebral Artery Rupture: Two Case Reports.

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.

Waveform Analysis of STA-MCA Bypass graft in Revascularization Surgery for Moyamoya Disease.

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.

The use of vessel wall imaging to detect a de novo microaneurysm on the periventricular anastomoses in moyamoya disease: illustrative case.

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.