Human embryonic stem cell-derived cerebral organoids for treatment of mild traumatic brain injury in a mouse model.

OBJECTIVE: There are no effective treatments for relieving neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated therapeutic efficacy of human embryonic stem cell-derived cerebral organoids (hCOs) in a mild TBI model, in terms of repair of damaged cortical regions, neurogenesis, and improved cognitive function. METHODS: Male C57BL/6 J mice were randomly divided into sham-operated, mild TBI, and mild TBI with hCO groups. hCOs cultured at 8 weeks were used for transplantation. Mice were sacrificed at 7 and 14 days after transplantation followed by immunofluorescence staining, cytokine profile microarray, and novel object recognition test. RESULTS: 8W-hCOs transplantation significantly reduced neuronal cell death, recovered microvessel density, and promoted neurogenesis in the ipsilateral subventricular zone and dentate gyrus of hippocampus after mild TBI. In addition, increased angiogenesis into the engrafted hCOs was observed. Microarray results of hCOs revealed neuronal differentiation potential and higher expression of early brain development proteins associated with neurogenesis, angiogenesis and extracellular matrix remodeling. Ultimately, 8W-hCO transplantation resulted in reconstruction of damaged cortex and improvement in cognitive function after mild TBI. CONCLUSION: hCO transplantation may be feasible for treating mild TBI-related neuronal dysfunction via reconstruction of damaged cortex and neurogenesis in the hippocampus.

Influence of renal impairment on neurologic outcomes following mechanical thrombectomy in acute vertebrobasilar stroke.

PURPOSE: Renal impairment (RI) has been regarded as a risk factor for unfavorable neurologic outcomes after mechanical thrombectomy (MT) in acute ischemic stroke. However, most of the previous studies were conducted on patients with anterior circulation stroke. Accordingly, the influence of RI on MT outcomes has not been well elucidated in detail in acute vertebrobasilar stroke. METHODS: Consecutive stroke patients with MT due to acute vertebrobasilar artery occlusion between March 2015 and December 2020 at four institutions were included. Multivariable logistic regression analysis was conducted to assess the associations between RI and outcomes and mortality at 3 months, and the development of intracerebral hemorrhage (ICH) after the procedure. Additionally, the multivariable Cox proportional hazards model was performed to determine the influence of RI on survival probability after patient discharge. RESULTS: A total of 110 patients were included in the final analysis. The presence of RI (OR = 0.268, 95% CI: 0.077-0.935), National Institute of Health Stroke Scale scores (OR = 0.849, 95% CI: 0.791-0.910), and puncture-to-recanalization time (OR = 0.981, 95% CI: 0.966-0.997) were related to outcomes. There was no significant association between RI and 3-month mortality or ICH. The cumulative survival probability after adjusting for relevant risk factors demonstrated that RI remained significantly associated with poorer survival after MT compared to patients without RI (HR = 2.111, 95% CI: 0.919-4.847). CONCLUSION: RI was an independent risk factor for poor 3-month neurologic outcomes and survival probability after MT in patients with acute vertebrobasilar stroke.

Factors associated with the development and outcome of hydrocephalus after decompressive craniectomy for traumatic brain injury.

Posttraumatic hydrocephalus (PTH) is common in patients undergoing decompressive craniectomy (DC) for traumatic brain injury (TBI), but the incidence, mechanisms, and risk factors have not been fully elucidated. This study aimed to determine the incidence of and the factors associated with PTH. We retrospectively reviewed patients who underwent DC for TBI at our institute between January 2014 and December 2018. We identified and compared the demographic, clinical, and radiological data, and 12-month functional outcome (as assessed by the Glasgow Outcome Scale [GOS]) between patients who developed PTH and those who did not. Logistic regression analyses were performed to identify risk factors for PTH. Additionally, the influence of PTH on unfavorable functional outcome was analyzed. PTH developed in 18 (18.95%) of the 95 patients who survived at 1 month after DC. A multivariate analysis indicated that postoperative intraventricular hemorrhage (odds ratio [OR] 4.493, P = 0.020), postoperative subdural hygroma (OR 4.074, P = 0.021), and postoperative hypothermia treatment (OR 9.705, P = 0.010) were significantly associated with PTH. The 12-month functional outcome significantly differed between the patients who developed PTH and those who did not (P = 0.049). Patients who developed PTH had significantly poorer 12-month functional outcomes than those who did not (P = 0.049). Another multivariate analysis indicated that subdural hemorrhage (OR 6.814, P = 0.031) and the presence of at least one dilated pupil before DC (OR 8.202, P = 0.000) were significantly associated with unfavorable functional outcomes (GOS grades 1-3). Although the influence of PTH (OR 5.122, P = 0.056) was not statistically significant in the multivariate analysis, it had a great impact on unfavorable functional outcomes. PTH considerably affects functional outcomes at 12 months after DC for TBI. Furthermore, postoperative imaging findings such as intraventricular hemorrhage and subdural hygroma can predict the development of PTH; therefore, careful observation is required during the follow-up period.

Is nontraumatic intracerebral hemorrhage different between young and elderly patients?

Only a few studies have reported nontraumatic intracerebral hemorrhage in young patients notwithstanding its fatal and devastating characteristics. This study investigated the clinical characteristics and outcome of nontraumatic intracerebral hemorrhage in young patients in comparison to those of the elderly. A retrospective review of consecutive patients admitted at the department of neurosurgery of two tertiary care medical centers presenting with first-ever nontraumatic intracerebral hemorrhage was performed. We identified and compared the demographics, etiologies, risk factors, and laboratory, radiological, and clinical findings between elderly and young patients. Additionally, logistic regression analyses of independent prognostic factors associated with 1-month mortality and favorable functional outcome were performed. Altogether, 247 patients including 69 young patients and 178 elderly patients were enrolled. On multivariate analysis, young patients exhibited significantly more often an infratentorial hematoma location, excessive alcohol consumption, and high body mass index (BMI), but less frequent systemic hypertension. There was no statistical difference between the two groups in 1-month mortality (17.46% and 18.01% for young and elderly patients, respectively), but the favorable functional outcome based on modified Rankin scale score of 0 or 1 was significantly different between the two groups (favorable outcome in 51.79% and 29.93% of patients, respectively). Predictors of 1-month mortality was the presence of herniation in the young group, and lower Glasgow Coma Scale score, renal or heart disease, and leukocytosis (WBC > 10,000) in the elderly group. Lower National Institutes Health Stroke Scale score was associated with favorable functional outcome in both groups. Nontraumatic intracerebral hemorrhage in younger patients appears to be associated with excessive alcohol consumption and high BMI. Younger patients had similar short-term mortality but more favorable functional outcome than the elderly.

K-line tilt as a novel radiographic parameter in cervical sagittal alignment.

OBJECTIVE: To investigate the relationship between the K-line tilt and classical cervical parameters such as the C2-C7 sagittal vertical axis (SVA), cervical lordosis, and the T1 slope in cervical sagittal alignment. We assessed whether the K-line tilt can be used as an excellent cervical parameter. METHODS: We reviewed 50 patients aged 60-89 years who visited the spine center outpatient clinic from May 2017 to September 2017 through cervical spine lateral radiography and checked the cervical spine parameters. All targeted patients were randomized without any prejudice. Radiographic measurements included the K-line tilt, C2-C7 lordosis, the C2-C7 SVA, the T1 slope, and T1 slope minus C2-C7 lordosis (T1S-CL). Pearson correlation coefficients were calculated between the K-line tilt and each cervical parameter. RESULTS: Of the 50 patients, 33 were men. The mean age of the patients was 70.84 ± 7.52 years. The mean K-line tilt was 11.28 ± 8.31°. The K-line tilt was correlated with the C2-C7 SVA (r = 0.813, P = 0.000) and T1S-CL (r = 0.315, P = 0.026). CONCLUSION: This study showed that the K-line tilt is also a useful parameter like the C2-C7 SVA and T1S-CL in cervical sagittal alignment. These slides can be retrieved under Electronic Supplementary Material.

A risk factor analysis of prospective symptomatic haemorrhage in adult patients with cerebral cavernous malformation.

OBJECTIVE: The purpose of this study was to assess the risk factors of prospective symptomatic haemorrhage in a large series of adult patients with cerebral cavernous malformation (CM). METHODS: Three hundred twenty-six patients >18 years of age with 410 CMs were evaluated retrospectively. Symptomatic haemorrhage was defined as new clinical symptoms with radiographic features of haemorrhage. Clinical data and the characteristics of CM were analysed. MR appearance was divided into three groups according to Zabramski's classification. RESULTS: The overall haemorrhage rate of CM was 4.46% per lesion-year. The overall annual haemorrhage rate according to MR appearance was as follows: type I, 9.47%; type II, 4.74%; and type III, 1.43%. A multivariate analysis revealed that prior symptomatic haemorrhage (p<0.001) and MR appearance (p<0.001) were statistically significant. After multiple comparisons, type I (p<0.001) and type II (p=0.016) showed higher haemorrhage risk than type III. However, no significant difference in haemorrhage rate was observed between type I and type II (p=0.105). Other variables including female gender, age, location, multiplicity, hypertension, size and associated venous angioma were not significant. The haemorrhage rates based on risk factors were estimated at 3 years as follows: 33.77% in patients with prior haemorrhage versus 7.54% in patients without prior haemorrhage (p<0.001); type I, 27.62% vs type II, 15.44% vs type III, 5.38% (p<0.001). CONCLUSIONS: Prior symptomatic haemorrhage and MR appearance could be related to prospective symptomatic CM haemorrhage in adults. A prospective multicentre observational study is necessary to confirm our results.

A retrospective analysis on the natural history of incidental small paraclinoid unruptured aneurysm.

OBJECTIVE: The optimal consensus concerning treatment of incidental small paraclinoid unruptured intracranial aneurysms (UIAs) remains controversial. The aim of this retrospective study was to reveal the natural history of small paraclinoid UIAs with the goal of informing the treatment plan. METHODS: 524 patients harbouring 568 paraclinoid UIAs (≤5 mm) were retrospectively evaluated during the mean follow-up of 35.4 months. The aneurysms were divided into two groups with respect to arterial branch: related (ophthalmic and superior hypophyseal artery), and non-related. Medical records were reviewed concerning multiple variables, such as sex, age, hypertension (HTN), diabetes mellitus, smoking and aneurysmal factors (size, arterial relationship, multiplicity and the occurrence of rupture and growth). The cumulative risk and the risk factors of aneurysmal rupture and growth were analysed. RESULTS: Two aneurysmal (0.35%) ruptures and 17 growths (3.0%) were observed during the follow-up of 1675.5 aneurysm-years with an annual rupture of 0.12% and an annual growth of 1.01%. The cumulative survival without aneurysmal growth reached a significant difference in aneurysms ≥4 mm (p=0.001), HTN (p=0.002), and arterial branch-related location (p=0.001). Multivariate analysis disclosed that aneurysm ≥4 mm (HR, 4.41; p=0.003), HTN (HR, 5.74; p=0.003), arterial branch-related location (HR, 6.04; p=0.002), and multiplicity (HR, 0.27; p=0.042) were significant predictive factors for aneurysm growth. CONCLUSIONS: Although incidental small paraclinoid UIAs have a relatively lower rupture and growth risk, patients with high-risk factors, including aneurysm ≥4 mm, HTN, arterial branch-related aneurysms, and multiple aneurysms must be monitored closely. The limitation of the retrospective nature of this study should be taken into consideration.

Expression of cellular retinoic acid-binding protein-I (CRABP-I) in the cerebrospinal fluid of adult onset moyamoya disease and its association with clinical presentation and postoperative haemodynamic change.

OBJECTIVE: The elevation of cellular retinoic acid-binding protein-I (CRABP-I) has been suggested as a candidate in the pathogenesis of paediatric moyamoya disease (MMD). However, few studies have addressed CRABP-I in adult onset MMD. The aim of this study was to examine the expression of CRABP-I in the cerebrospinal fluid (CSF) of adult onset MMD, and to evaluate its association with clinical presentation and postoperative haemodynamic change. METHODS: This study examined the CSF from 103 patients: bilateral MMD, n=58 (56.3%); unilateral MMD, n=19 (18.4%); atherosclerotic cerebrovascular disease (ACVD), n=21 (20.4%); and control group, n=5 (4.9%). The intensity of CRABP-I was confirmed by western blotting and expressed as the median (25th-75th percentile). The differences in CRABP-I expression according to disease entity (unilateral MMD vs bilateral MMD vs ACVD), initial presenting symptoms (haemorrhage vs ischaemia) and postoperative haemodynamic change (vascular reserve in single photon emission CT and basal collateral vessels in digital subtraction angiography) were analysed. RESULTS: CRABP-I intensities in bilateral MMD (1.45(0.86-2.52)) were significantly higher than in unilateral MMD (0.91(0.78-1.20)) (p=0.044) or ACVD (0.85(0.66-1.11)) (p=0.004). No significant differences were noted based on the initial presenting symptoms (p=0.687). CRABP-I was not associated with improvement in vascular reserve (p=0.327), but with decrease in basal collateral vessels (p=0.023) postoperatively. CONCLUSIONS: Higher CRABP-I in the CSF can be associated with typical bilateral MMD pathogenesis in adults. Additionally, postoperative basal collateral change may be related to the degree of CRABP-I expression.

Microguidewire protection of wide-necked aneurysms incorporating orifices of tortuous acute-angled vessels: a novel approach.

INTRODUCTION: Protective/remodeling techniques for treating wide-necked intracranial aneurysms are constantly sought. However, their utility may be limited in lesions that incorporate the orifice of acute-angled efferent branch vessels. Furthermore, passage of a protective microcatheter may be challenging if a small branch is extremely tortuous. This study was conducted to explore a novel method of treating wide-necked aneurysms, utilizing microguidewire protection. METHODS: A microcatheter is first passed into parent artery (proximal to aneurysm) to position a microguidewire proximally in the involved branch. A second microcatheter is then inserted into aneurysmal sac. Advancement of the first microcatheter forces the microguidewire to shift, thus covering aneurysmal neck. A framing coil may then be placed within aneurysmal sac, under microguidewire protection. After completing initial coil insertion, easing of tension on the microcatheter allows separation of protective microguidewire and frame coil, confirming stability of the initial coil. RESULTS: This technique was applied to 11 intracranial saccular aneurysms of M1 segment (n=6), middle cerebral artery bifurcation (n=4), and anterior communicating artery (n=1) with success, combining stent protection in two patients. Coil embolization was thus facilitated, resulting in excellent outcomes for all patients. No morbidity or mortality was directly related to microguidewire protection. CONCLUSION: Our small study suggests that microguidewire protection may be a safe alternative, if traditional remodeling or protective options are infeasible due to intrinsic vascular properties. This technique is particularly suited for treatment of wide-necked aneurysms where passage of protective microcatheters into involved branches is not achievable.

Endovascular treatment for superior cerebellar artery aneurysms: morphological features, technique, and outcome.

INTRODUCTION: Superior cerebellar artery (SCA) aneurysms have distinctive morphologic configurations and vascular origins. Herein, we have analyzed the angioarchitectural characteristics of SCA aneurysms and outcomes achieved through endovascular treatment. METHODS: Data accruing prospectively from January, 2002 to September, 2013 yielded 53 SCA aneurysms in 53 patients. Each lesion was classified as either basilar artery (BA), BA-SCA, or SCA type, according to the nature of incorporated vasculature. Clinical and morphologic outcomes were assessed, with emphasis on technical aspects of treatment. RESULTS: Angles formed by SCA and posterior cerebral artery were obtuse (124.8 ± 29.1°) on sides ipsilateral to aneurysms, differing significantly from contralateral counterparts (44.8 ± 22.0°) (p<0.001). The most common type of aneurysm was BA-SCA (54.7 %), followed by SCA (28.3 %) and BA (17.0 %), and BA type aneurysms were the largest in size. Steam-shaped S-configured microcatheters (n=19, 67.9 %) facilitated aneurysm selection for approach via contralateral vertebral artery (n=28), whereas pre-shaped 45/90/J microcatheters (n=21, 84.0 %) primarily were used for ipsilateral vertebral artery approach (n=25). Single-microcatheter technique (52.8 %) was most often applied, followed by double-microcatheter (34.0 %), stent-assisted (9.4 %), and microcatheter-protection techniques (3.8 %). Aneurysmal occlusion was satisfactorily achieved in 45 lesions (82.1 %), with no procedure-related morbidity and mortality. In follow-up monitoring of 46 patients for a mean period of 25.8 ± 24.4 months, only a single instance of major recanalization (2.2 %) occurred. CONCLUSION: Coil embolization of SCA aneurysms is a safe and effective treatment modality, enabling individualized procedural strategies to accommodate distinctive angio-anatomic configurations.

Coil embolization in precommunicating (A1) segment aneurysms of anterior cerebral artery.

INTRODUCTION: Precommunicating (A1) segment aneurysms of the anterior cerebral artery are rare and often pose technical challenges for coil embolization due to their distinctive configurations. Clinical and radiologic outcomes of treating such aneurysms through endovascular coil embolization are presented herein. METHODS: Data accruing prospectively from May 2002 to August 2013 yielded 48 patients harboring 50 A1 segment aneurysms, each classified as proximal, middle, or distal by location. Clinical outcome of the patients and morphological outcome of the aneurysms were assessed, with emphasis on technical aspects of treatment. RESULTS: The aneurysms studied occupied either proximal (n = 39), middle (n = 6), or distal (n = 5). Proximal aneurysms were largely directed posteriorly (80 %), and most (97 %) were devoid of branches. Middle and distal aneurysms were associated with the medial lenticulostriate artery, cortical branches, or fenestrations. The preshaped "S" and steam-shaped "S" microcatheters facilitated aneurysm selection in 60 % of lesions. Single-microcatheter technique was most commonly applied for coil embolization (62 %), followed by balloon protection (16 %). Successful aneurysmal occlusion could be achieved in 76 % of the patients, with no procedure-related morbidity and mortality. At final follow-up (mean interval, 29.9 months), stable aneurysmal occlusion was sustained in 93 % of the patients (40/43). CONCLUSION: A1 segment aneurysms are amenable to safe and efficacious endovascular coil embolization by adjusting procedural strategy to accommodate distinctive anatomic configurations.

Contralateral progression and its risk factor in surgically treated unilateral adult moyamoya disease with a review of pertinent literature.

BACKGROUND: The fate of the contralateral unaffected side of the surgically treated unilateral moyamoya disease (MMD) in adults has not been well described due to the limited number of cases and the heterogeneous ages and treatment methods. The aim of this study was to evaluate the contralateral angiographic progression rate and its risk factors in homogeneous adult MMD patients who underwent surgical revascularization, with a review of pertinent literature. METHODS: Forty-one surgically treated unilateral MMD patients were retrospectively evaluated. We reviewed medical and radiological records including data on gender, age, hypertension (HTN), smoking, familial MMD, presenting symptom, surgical method, Suzuki stage, and contralateral progression. Then, we conducted univariate and multivariate analyses to determine risk factors. RESULTS: Six of the 41 cases (14.6%) exhibited contralateral progression during the mean follow-up of 34 months. Four of those six patients (66.7%) were asymptomatic. Additional revascularization surgery was performed in the two symptomatic patients. The presence of a contralateral angiographic abnormality on initial angiography was a statistically significant risk factor for progression (OR, 49.00; p = 0.04). Younger age at diagnosis (32.7 ± 7.8 years in progression group vs. 42.5 ± 10.3 years in non-progression group, p = 0.046) was statistically significant in the univariate analysis, but age was not a significant factor in the multivariate analysis (p = 0.82). Other variables, such as gender (p = 0.13), HTN (p = 0.24), smoking (p = 0.47), and familial MMD (p = 0.20), did not show statistical significance. CONCLUSIONS: The presence of a contralateral angiographic abnormality on initial angiography was a significant risk factor for progression in surgically treated unilateral adult MMD. Consequently, patients with contralateral abnormalities should be monitored closely.

Atypical case of bow hunter's syndrome linked to aberrantly coursing vertebral artery: A case report.

BACKGROUND: In bow hunter's syndrome (BHS), also known as rotational vertebral artery (VA) syndrome, there is dynamic/rotational compression of the VA producing vertebrobasilar insufficiency. Most occurrences involve atlantoaxial rather than mid-cervical VA compromise, the latter being rarely reported. Herein, we detail successful VA decompression at mid-cervical spine, given a departure from its usual course. CASE SUMMARY: The patient, a 45-year-old man, presented to our hospital with occipital headache and vertigo. Computed tomography angiography showed anomalous C4 entry of right VA, with compression upon head rotation to that side. Thyroid cartilage and anterior tubercle of C5 transverse process were visibly at fault. We opted for surgery, using an anterior cervical approach to remove the anterior tubercle. Patient recovery was uneventful and brought resolution of all preoperative symptoms. CONCLUSION: BHS is an important consideration where aberrant coursing of VA and neurologic symptoms coexist.

Updated Trans-Ethnic Meta-Analysis of Associations between Inflammation-Related Genes and Intracranial Aneurysm.

OBJECTIVE: We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. METHODS: We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. RESULTS: Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56-0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80-1.47; p=0.5929). Three other variants, rs16944 (IL-1ß), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01

Development of Cloud-Based Telemedicine Platform for Acute Intracerebral Hemorrhage in Gangwon-do : Concept and Protocol.

We aimed to develop a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local hospitals in rural and underserved areas in Gangwon-do using artificial intelligence and non-face-to-face collaboration treatment technology. This is a prospective and multi-center development project in which neurosurgeons from four university hospitals in Gangwondo will participate. Information technology experts will verify and improve the performance of the cloud-based telemedicine collaboration platform while treating ICH patients in the actual medical field. Problems identified will be resolved, and the function, performance, security, and safety of the telemedicine platform will be checked through an accredited certification authority. The project will be carried out over 4 years and consists of two phases. The first phase will be from April 2022 to December 2023, and the second phase will be from April 2024 to December 2025. The platform will be developed by dividing the work of the neurosurgeons and information technology experts by setting the order of items through mutual feedback. This article provides information on a project to develop a cloud-based telemedicine platform for acute ICH patients in Gangwon-do.

Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State: Recommendations for Doctors with Less Expertise at Local Emergency Rooms.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

Hemorrhagic moyamoya disease in children: clinical features and surgical outcome.

OBJECTIVE: The clinical presentation of moyamoya disease (MMD) typically includes cerebral ischemia in children and intracranial hemorrhage in adults. Because of its rarity, the benefit of surgery in the hemorrhagic type of pediatric MMD has not been clearly established. The purpose of this study was to delineate the clinical features and surgical outcome of hemorrhagic MMD in children. METHODS: Thirteen patients (six boys and seven girls with a combined mean age of 11.1 years and a range of 4-18 years) were retrospectively confirmed as having MMD with intracranial hemorrhage between 1988 and 2009. All of the patients underwent indirect bypass surgery that followed a relatively uniform scheme at a single institution. We retrospectively reviewed their clinical features and surgical outcome. The mean time of follow-up was 50.3 months (with a range of 3-99 months). RESULTS: Six of the patients presented with intracerebral hemorrhage (ICH), and six others presented with intraventricular hemorrhage (IVH); the remaining patient presented with both ICH and IVH. Preoperative angiography demonstrated that the patients were in various stages of the disease, but the majority of the patients (i.e., 16 of the 26 hemispheres) were in stage 3 with abundant moyamoya vessels (MMV). Three of four patients who presented with a history of prior hemorrhage or infarct exhibited a poor clinical outcome. Five patients with good revascularization had a decreased degree of MMV in their follow-up angiogram and showed good clinical outcome. Recurrent bleeding occurred after surgery in one patient. CONCLUSIONS: Revascularization surgery may have a role for prevention of rebleeding and cerebral infarction in pediatric MMD patients who present with intracranial hemorrhage.

Transvenous coil embolization of hypoglossal canal dural arteriovenous fistula using detachable coils: A case report.

The hypoglossal canal (HC) is an unusual location of the posterior fossa dural arteriovenous fistula (AVF), which usually occurs in the transverse or sigmoid sinus. Herein, we report a case of HC dural AVF successfully treated with transvenous coil embolization using detachable coils in a 68-year-old woman who presented with headache and left pulsatile tinnitus for 2 months. Brain magnetic resonance imaging (MRI) and cerebral angiography revealed left HC dural AVF. The pulsatile bruit disappeared immediately after the procedure. Follow-up MRI showed complete disappearance of the fistula. Precise localization of the fistula through careful consideration of the anatomy and transvenous coil embolization using a detachable coil can facilitate the treatment for HC dural AVF.

Association of Haptoglobin Phenotypes with Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECT: We aimed to investigate the association of Haptoglobin (Hp) phenotypes with perihematomal edema (PHE) and neurological outcomes after intracerebral hemorrhage (ICH). METHODS: This prospective multicenter study enrolled patients that suffered ICH from March 2017 to February 2020. Hp phenotypes were determined using Western blotting; relative α1 intensity was calculated in patients with Hp2-1. A multivariable logistic regression analysis was then conducted to identify risk factors for increased relative PHE at 96 h and 3-month poor outcomes. RESULTS: In total, 120 patients were ultimately enrolled: Hp1-1 (n = 15, 12.5%); Hp2-1 (n = 51, 42.5%); and Hp2-2 (n = 54, 45.0%). Hp phenotype was significantly associated with PHE (p = 0.028). With Hp1-1 as a reference value, Hp2-2 significantly increased the likelihood of increased rPHE (OR = 6.294, 95% CI: 1.283-30.881), while Hp2-1 did not (OR = 2.843, 95% CI: 0.566-14.284). Poor outcomes were found to be closely associated with hematoma volume at admission (OR = 1.057, 95% CI: 1.015-1.101) and surgical treatment (OR = 5.340, 95% CI: 1.665-17.122) but not Hp phenotypes (p = 0.190). Further, a high level of relative α1 intensity was identified to be significantly associated with decreased rPHE (OR = 0.020, 95% CI: 0.001-0.358). However, the relative α1 intensity was not associated with poor outcomes (OR = 0.057, 95% CI: 0.001-11.790). CONCLUSIONS: ICH patients with Hp2-2 exhibited a higher likelihood of increased rPHE than those with Hp1-1. Higher relative α1 intensities were identified to be closely associated with rPHE in patients with Hp2-1.

Genome-wide polygenic risk impact on intracranial aneurysms and acute ischemic stroke.

Polygenic risk scores (PRSs) have an important relevance to approaches for clinical usage in intracranial aneurysm (IA) patients. Hence, we aimed to develop IA-predicting PRS models including the genetic basis shared with acute ischemic stroke (AIS) in Korean populations. We applied a weighted PRS (wPRS) model based on a previous genome-wide association study (GWAS) of 250 IA patients in a hospital-based multicenter cohort, 222 AIS patients in a validation study, and 296 shared controls. Risk predictability was analyzed by the area under the receiver operating characteristic curve (AUROC). The best-fitting risk models based on wPRSs were stratified into tertiles representing the lowest, middle, and highest risk groups. The weighted PRS, which included 29 GWASs (p < 5×10-8) and two reported genetic variants (p < 0.01), showed a high predictability in IA patients (AUROC = 0.949, 95% CI: 0.933-0.966). This wPRS was significantly validated in AIS patients (AUROC = 0.842, 95% CI: 0.808-0.876; p < 0.001). Two-stage risk models stratified into tertiles showed an increased risk for IA (OR = 691.25, 95% CI: 241.77-1976.35; p = 3.1×10-34; sensitivity/specificity = 0.728/0.963), which was replicated in AIS development (OR = 39.76, 95% CI: 16.91-93.49; p = 3.1×10-17; sensitivity/specificity = 0.284/0.963). A higher wPRS for IA may be associated with an increased risk of AIS in the Korean population. These findings suggest that IA and AIS may have a shared genetic architecture and should be studied further to generate a precision medicine model for use in personalized diagnosis and treatment.