Subdural Empyema from Streptococcus suis Infection, South Korea.

In Jeju Island, South Korea, a patient who consumed raw pig products had subdural empyema, which led to meningitis, sepsis, and status epilepticus. We identified Streptococcus suis from blood and the subdural empyema. This case illustrates the importance of considering dietary habits in similar clinical assessments to prevent misdiagnosis.

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.

Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway.

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons (100 µM, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner (1-50 µM) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of Ca2+ and ROS, mitochondrial membrane potential (ΔΨm) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.

Extended monitoring of coiled aneurysms completely occluded at 6-month follow-up: late recanalization rate and related risk factors.

OBJECTIVES: To estimate long-term durability in coiled aneurysms completely occluded at 6-month follow-up imaging, focusing on late recanalization rate and the risk factors involved. METHODS: A cohort of 620 patients harbouring 698 completely occluded coiled aneurysms at 6-month follow-up was subjected to extended monitoring (mean, 24.5 ± 7.9 months). Cumulative recanalization rate and related risk factors were analysed using Cox proportional hazards regression and Kaplan-Meier product-limit estimator. RESULTS: Forty-three aneurysms (6.2 %) occluded completely at 6-months displayed recanalization (3.02 % per aneurysm-year) during continued surveillance (1425.5 aneurysm-years), with 26 (60.5 %) surfacing in another 6 months, 15 (34.9 %) within 18 months and 2 (4.6 %) within 30 months. Cumulative survival rates without recanalization were significantly lower in subjects with aneurysms >7 mm (p = 0.014), with bifurcation aneurysms (p = 0.009) and with subarachnoid haemorrhage (SAH) at presentation (p < 0.001). Multivariate analysis indicated that aneurysms >7 mm (HR = 2.37, p = 0.02) and bifurcation aneurysms (HR = 2.70, p = 0.03) were significant factors in late recanalization, whereas a link with SAH at presentation was marginal (HR = 1.92, p = 0.06) and stent placement fell short of statistical significance (HR = 0.47; p = 0.12). CONCLUSION: Most (93.8 %) coiled aneurysms showing complete occlusion at 6 months post-procedure were stable in long-term monitoring. However, aneurysms >7 mm and bifurcation aneurysms were predisposed to late recanalization. KEY POINTS: • Most coiled aneurysms showing complete occlusion at 6 months were stable. • Forty-three aneurysms (6.2 %) occluded completely at 6-month follow-up displayed late recanalization. • Late recanalization rate was 3.02 % per aneurysm-year during follow-up of 1425.5 aneurysm-years. • Aneurysms over 7 mm and bifurcation aneurysms were predisposed to late recanalization.

Modified coil protection for proper coil frame configuration in wide-necked aneurysms.

INTRODUCTION: Although various protective techniques for treating wide-necked intracranial aneurysms currently exist and continue to evolve, their utility may be limited in some lesions with complex configurations, small-caliber channels, or inherently tortuous vascular patterns. Described herein is a modified coil protection technique as a novel adjunct for proper coil frame configuration. METHODS: Initially, a microcatheter is passed into aneurysmal sac, and the first coil is inserted to build a frame. Inevitably, some coils may abut opposite poles of aneurysms and protrude into parent arteries. Should this happen, a second microcatheter may be placed at the site of coil protrusion, so that a separate and smaller coil may be partially deployed for protection. A framing coil may then be configured within aneurysmal sac, under protection of the secondary coil. Once the first coil is entirely in place, the remainder of second coil is carefully inserted, and additional coil may be inserted as needed via dual microcatheters. RESULTS: This technique was successfully applied to 23 saccular intracranial aneurysms of internal carotid (n = 8), middle cerebral (n = 6), anterior cerebral (n = 6), and superior cerebellar artery (n = 3), combining stent protection in two patients and balloon remodeling in one. Selective endovascular treatment was effective as a result. Excellent outcomes were achieved in all patients, with no morbidity or mortality directly related to the modified procedure. CONCLUSION: As suggested by outcomes of this small study, our modified coil protection method may be a safe option if traditional coiling strategies are not feasible, enabling stable coil frame configuration in wide-necked aneurysms.

Progressive thrombosis of small saccular aneurysms filled with contrast immediately after coil embolization: analysis of related factors and long-term follow-up.

INTRODUCTION: Although it is well-known that incomplete occlusion of aneurysms after coil embolization predisposes to later recanalization, not all aneurysms will be fully occluded by coiling. In follow-up, we evaluated outcomes of small aneurysms (<10 mm) that showed filling of the sac with contrast immediately after coil embolization and assessed factors implicated in subsequent progressive thrombosis. METHODS: Between January 2008 and December 2010, a total of 1035 aneurysms in 898 patients were treated by endovascular coiling. Of these, 210 small aneurysms displayed filling of the sac by contrast immediately after coil embolization. Time-of-flight magnetic resonance angiography (TOF-MRA; at 6, 12, 24, and 36 months) and digital subtraction angiography (as needed) were used for postoperative monitoring. Complete occlusion of these aneurysms at the 6-month follow-up point was attributed to progressive thrombosis. RESULTS: In 186 (88.5 %) of the 210 aneurysms that showed filling of the sac with contrast, complete occlusion was observed on follow-up imaging studies at 6 months. Multiple logistic regression analysis indicated that progressive thrombosis was linked to aneurysmal neck diameter ≤4 mm (p < 0.001) and packing density >30 % (p = 0.016). Aneurysms originating from non-branching vessels were of marginal statistical significance (p = 0.056). In 179 progressively thrombosed aneurysms with follow-up evaluations of ≥12 months (mean, 31.9 ± 7.6 months), 168 aneurysms (93.9 %) exhibited stable occlusion, whereas minor recanalization was observed in 6 (3.3 %) instances, and major recanalization occurred in 5 (2.8 %). CONCLUSIONS: In aneurysms where filling of the sac with contrast was demonstrable after coil embolization, aneurysms with small neck diameters or high coil packing density, and non-branching aneurysms seem predisposed to progressive intra-aneurysmal thrombosis over the course of time.

A Case of Severe Delayed Vasospasm after Clipping Surgery for an Unruptured Intracranial Aneurysm.

Delayed ischemic stroke associated with intractable vasospasm after clipping of unruptured intracranial aneurysms (UIAs) has been rarely reported. We report a patient with delayed ischemic stroke associated with intractable vasospasm following UIA clipping. A middle-aged female underwent surgery for unruptured middle cerebral artery bifurcation aneurysms. The patient tolerated the neurosurgical procedure well. Seven days postoperatively, the headache was unbearable; a postcraniotomy headache persisted and abruptly presented with global aphasia and right-sided hemiplegia after a nap. Emergency digital subtraction angiography showed severe luminal narrowing with segmental vasoconstriction, consistent with severe vasospasm. The patient's neurological deficit improved after chemical angioplasty. Neurosurgeons should pay close attention to this treatable/preventive entity after neurological deterioration following UIA clipping, even in patients without subarachnoid hemorrhage.

Delayed Unilateral Facet Interlocking After a Stable Superior Articular Process Fracture of the Cervical Spine: A Case Report.

A 42-year-old man presented with neck pain after a fall from a tree. Spine computed tomography (CT) illustrated the right C5 superior articular process fracture without displacement. Magnetic resonance imaging (MRI) confirmed the fracture and injury of the posterior ligament complex. Initially he was managed conservatively with a neck brace as there were no signs of instability or vertebral body misalignment. However, three days after discharge, right shoulder weakness and numbness of the right upper arm became prominent. X-rays and CT showed anterior slippage of the C4 vertebral body and locked C4/5 facet ??a fractured bony fragment of the C5 superior articular process was pushed forward by the locked inferior articular process of C4 and invaded the neural foramen. Anterior cervical discectomy and fusion (ACDF) was performed using allograft and plate/screws fixation. Although initial imaging showed no evidence of subluxation, surgeons should be aware of occult instability and the possibility of delayed dislocation associated with the unilateral cervical facet fracture.

WITHDRAWN: Effect of Therapeutic Hypothermia on Cognitive Impairment in a Mouse Model of Ischemia-Reperfusion Injury.

Ahead of Print article withdrawn by publisher.

Ruptured Fusiform Anterior Cerebral Artery Aneurysm in an Infant : Case Report and a Literature Review.

Ruptured intracranial aneurysms in infants are rare and infantile fusiform anterior cerebral artery (ACA) aneurysms are much rarer. In this report, we described the case of a 7-month-old infant with a ruptured fusiform ACA aneurysm who presented with seizure and underwent endovascular treatment. The patient was initially in a coma and the neurologic condition did not improve after treatment. The clinical characteristics of the case and literature review were discussed.

Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm.

OBJECTIVE: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. METHODS: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. RESULTS: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. CONCLUSION: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

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.

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

Safety of discontinuing antiplatelet therapy 12-24 months after stent-assisted coil embolization: a multicenter retrospective study.

OBJECTIVE: Antiplatelet medication is required after stent-assisted coil embolization (SACE) to avoid thromboembolic complications. Currently, there is no consensus on how long the antiplatelet agent should be maintained. The authors investigated clinical outcomes in patients who discontinued their antiplatelet agent 12-24 months after SACE. METHODS: Data were retrieved from a prospective database for 373 consecutive patients with SACE at 6 institutions who discontinued antiplatelet therapy 12-24 months after SACE. Thromboembolic complications associated with discontinuation were defined as neurological or radiographic ischemia that occurred within 6 months after discontinuation of the antiplatelet agent; the lesion had to be correlated with the territory of the stented artery. RESULTS: The mean time until discontinuation of the antiplatelet medication was 15.8 ± 4.7 months after SACE (12-18 months, n = 271; 19-24 months, n = 102). The most common location of treated aneurysms was the internal carotid artery (n = 223, 59.8%). A laser-cut open-cell stent was most commonly applied (n = 236/388, 60.8%), followed by laser-cut closed-cell stents (n = 119, 30.7%) and braided closed-cell (n = 33, 8.5%); double stenting was applied in 15 aneurysms. There were no patients who experienced cerebral ischemia related to discontinuation of antiplatelet medications, except for 1 patient at high risk of ischemia (0.27%, 95% CI 0.01%-1.48%). CONCLUSIONS: These results suggest that it may be safe to discontinue antiplatelet medication after SACE in patients at low risk for ischemia, and that it appears safe to discontinue the agent at approximately 15 months after the procedure. Large cohort-based prospective studies or randomized clinical trials are warranted to confirm these results.

Intrawound Vancomycin Powder Application for Preventing Surgical Site Infection Following Cranioplasty.

OBJECTIVE: Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics. METHODS: This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated. RESULTS: Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4-333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006-0.762; adjusted OR, 0.068; 95% CI, 0.006-0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up. CONCLUSION: Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.

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.

Early and Prolonged Mild Hypothermia in Patients with Poor-Grade Subarachnoid Hemorrhage: A Pilot Study.

We assessed the feasibility of therapeutic early and prolonged mild hypothermia (MH) in patients with poor-grade subarachnoid hemorrhage (SAH). A retrospective pilot study was conducted for poor-grade SAH patients at two university hospitals from March 2015 to December 2018 who had received MH immediately after coil embolization and maintained a target temperature of 34-35°C for 5 days. A matched controlled design at a 1:2 ratio was used to compare MH therapy outcomes. The primary goal was to assess the two groups' severe functional outcomes at discharge defined as a modified Rankin Scale score of 4-6. The secondary aim was to assess mortality and severe vasospasm depending upon MH. A binary logistic regression analysis was performed to identify relevant risk factors for the outcomes. A total of 54 patients (18 with MH treatment and 36 without MH treatment) were included. Severe functional outcome was significantly decreased in poor-grade SAH patients with MH (n = 7, 38.9%) than those without MH (n = 25, 69.4%; p = 0.031). In patients treated with MH, mortality and severe vasospasm tended to be less common, although the difference was not statistically significant. A binary logistic regression analysis revealed that early and prolonged MH (odds ratio [OR] = 0.156, 95% confidence intervals [CI]: 0.037-0.644) and severe vasospasm (OR = 5.593, 95% CI: 1.372-22.812) were risk factors for severe functional outcomes. This study shows potential therapeutic effect of early and prolonged MH treatment in poor-grade SAH patients. A randomized controlled study with a large number of patients is warranted in the future.

Recent Stem Cell Research on Hemorrhagic Stroke : An Update.

Although technological advances and clinical studies on stem cells have been increasingly reported in stroke, research targeting hemorrhagic stroke is still lacking compared to that targeting ischemic stroke. Studies on hemorrhagic stroke are also being conducted, mainly in the USA and China. However, little research has been conducted in Korea. In reality, stem cell research or treatment is unfamiliar to many domestic neurosurgeons. Nevertheless, given the increased interest in regenerative medicine and the increase of life expectancy, attention should be paid to this topic. In this paper, we summarized pre-clinical rodent studies and clinical trials using stem cells for hemorrhagic stroke. In addition, we discussed results of domestic investigations and future perspectives on stem cell research for a better understanding.

Treatment of ruptured aneurysms of the choroidal collateral system in moyamoya disease: a systematic review and data analysis.

OBJECTIVE: Moyamoya disease (MMD) is a chronic, progressive steno-occlusive condition of the distal internal carotid arteries of unknown etiology. Collateral arterial networks typically develop in MMD, bypassing the steno-occlusion. Aneurysms arising on the collateral networks are a known source of hemorrhage. The choroidal collateral system is the most common location for collateral pathway aneurysms in MMD and associated hemorrhage. The authors performed data collection and analysis to further elucidate the best treatment approaches for ruptured aneurysms of the choroidal collateral system in MMD, which as yet remain unclear. METHODS: A comprehensive data collection and analysis of case reports and case series with ruptured choroidal collateral artery aneurysms (CCAAs) was performed. PRISMA guidelines for systematic reviews were followed and the Medline, Embase, and Scopus databases were searched for relevant studies. A database was created including patients with ruptured CCAA in MMD. Original data from case series were included whenever possible. A previously unreported case of a ruptured choroidal artery aneurysm in MMD treated by the authors was also included. RESULTS: The database comprised 72 patients with ruptured CCAA in MMD. The most common clinical symptoms were headache, nausea, and vomiting (39%). Initially, a conservative treatment approach was chosen in 29% of cases but led to rehemorrhage in 40% of cases; 63% of these rehemorrhages occurred during the first 35 days. Endovascular treatment seemed a safe option for aneurysm exclusion, mainly through parent vessel sacrifice, but had a treatment failure rate of 21%, due to inadequate access. Aneurysm treatment with revascularization as the initial treatment strategy led to aneurysm regression in 82% with no reported rehemorrhage. Aneurysm exclusion through open surgery was effective but was associated with a relatively high complication rate (25%). Outcome after rupture of CCAA was poor, with 41% of patients deceased or permanently disabled. Overall, patient outcomes were better in the endovascular and revascularization treatment group than in the conservative treatment group. CONCLUSIONS: Rupture of CCAA in MMD is associated with high morbidity and rerupture rate requiring urgent treatment.