Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

"Recycling" A Failed Superficial Temporal Artery Indirect Bypass into a Double Barrel Direct Bypass in Moyamoya Disease.

OBJECTIVES: Moyamoya disease is an idiopathic cerebrovascular disorder in which patients experience recurrent transient ischemic attacks, ischemic or hemorrhagic strokes, headaches, and seizures from progressive stenosis of the vessels of the anterior circulation. The mainstay of treatment in symptomatic patients is surgical revascularization. Here, we present the case of a moyamoya patient in which a failed encephaloduroarteriosynangiosis, after new strokes, is recycled and converted into a combined "double barrel" direct superficial temporal artery to middle cerebral artery bypass with included video. CASE REPORT/RESULTS: We describe a 37-year-old woman with a history of hypertension, obstructive sleep apnea, celiac disease, and moyamoya disease complicated by multiple ischemic strokes who presented with progressive dysarthria, dysphagia, and new left-sided ischemic infarcts. The patient had previously undergone right-sided direct bypass and left-sided encephaloduroarteriosynangiosis in the setting of multiple ischemic strokes. After more strokes, the patient underwent a left-sided frontotemporoparietal craniotomy for conversion of the failed indirect bypass into a "double barrel" direct bypass. CONCLUSIONS: The literature is divided over which revascularization procedure should be preferred. Irrespectively, most failed bypass grafts are repaired via direct bypasses, to good effect. We highlight a case in which a failed indirect bypass is directly incorporated into a combined direct bypass with resulting restoration of blood flow. In the case of a failed indirect bypass in an adult patient with moyamoya disease, this method provides the operator with an additional option for restoration of perfusion, especially in patients without other viable vessels available for anastomosis.

Posterior Cerebral Artery Aneurysm Re-Rupture Following Revascularization for Moyamoya Disease.

OBJECTIVES: Aneurysms associated with hemorrhagic moyamoya disease (MMD) are reported to stabilize or recede following revascularization. CASE REPORT/RESULTS: A 29 year-old male with no past medical history presented obtunded with diffuse intraventricular hemorrhage and vascular imaging demonstrating bilateral MMD without any associated aneurysms. He underwent a delayed right-sided STA-MCA bypass and pial synangiosis, and was subsequently discharged on hospital day 24 with a modified Rankin Scale score (mRS) of 2. He returned eleven days later from a rehabilitation facility with recurrent IVH. A saccular 5 mm right P4 segment posterior cerebral artery aneurysm was seen on a diagnostic angiogram and embolized with Onyx glue. CONCLUSIONS: Distal posterior circulation artery aneurysmal rupture is a rare cause of hemorrhagic MMD. This case demonstrates the capacity of these aneurysms to re-rupture following revascularization and underscores the importance of treating the aneurysms directly.

Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor.

The function of melatonin as a protective agent against newborn hypoxic-ischemic (H-I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H-I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H-I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H-I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H-I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.

Vision outcomes in patients with paraclinoid aneurysms treated with clipping, coiling, or flow diversion: a systematic review and meta-analysis.

OBJECTIVE Patients with paraclinoid aneurysms commonly present with visual impairment. They have traditionally been treated with clipping or coiling, but flow diversion (FD) has recently been introduced as an alternative treatment modality. Although there is still initial aneurysm thrombosis, FD is hypothesized to reduce mass effect, which may decompress the optic nerve when treating patients with visually symptomatic paraclinoid aneurysms. The authors performed a meta-analysis to compare vision outcomes following clipping, coiling, or FD of paraclinoid aneurysms in patients who presented with visual impairment. METHODS A systematic literature review was performed using the PubMed and Web of Science databases. Studies published in English between 1980 and 2016 were included if they reported preoperative and postoperative visual function in at least 5 patients with visually symptomatic paraclinoid aneurysms (cavernous segment through ophthalmic segment) treated with clipping, coiling, or FD. Neuroophthalmological assessment was used when reported, but subjective patient reports or objective visual examination findings were also acceptable. RESULTS Thirty-nine studies that included a total of 2458 patients (520 of whom presented with visual symptoms) met the inclusion criteria, including 307 visually symptomatic cases treated with clipping (mean follow-up 26 months), 149 treated with coiling (mean follow-up 17 months), and 64 treated with FD (mean follow-up 11 months). Postoperative vision in these patients was classified as improved, unchanged, or worsened compared with preoperative vision. A pooled analysis showed preoperative visual symptoms in 38% (95% CI 28%-50%) of patients with paraclinoid aneurysms. The authors found that vision improved in 58% (95% CI 48%-68%) of patients after clipping, 49% (95% CI 38%-59%) after coiling, and 71% (95% CI 55%-84%) after FD. Vision worsened in 11% (95% CI 7%-17%) of patients after clipping, 9% (95% CI 2%-18%) after coiling, and 5% (95% CI 0%-20%) after FD. New visual deficits were found in patients with intact baseline vision at a rate of 1% (95% CI 0%-3%) for clipping, 0% (95% CI 0%-2%) for coiling, and 0% (95% CI 0%-2%) for FD. CONCLUSIONS To the authors' knowledge, this is the first meta-analysis to assess vision outcomes after treatment for paraclinoid aneurysms. The authors found that 38% of patients with these aneurysms presented with visual impairment. These data also demonstrated a high rate of visual improvement after FD without a significant difference in the rate of worsened vision or iatrogenic visual impairment compared with clipping and coiling. These findings suggest that FD is an effective option for treatment of visually symptomatic paraclinoid aneurysms.

ICA aneurysm surgically treated utilizing a choroidal to PCOM bypass and vein bypass.

This video shows the surgical repair of a 2.3 cm ICA aneurysm found in a 58-year-old woman, who presented for right eye vision changes. The patient underwent a right modified orbitozygomatic craniotomy and saphenous vein bypass from the common carotid to the temporal M2. The aneurysm was then opened and repaired. However, since the anterior choroidal artery was not filling, a salvage bypass between the anterior choroidal and the PCOM was done. Both bypasses were patent and the patient has done well with a mRS of 1 for vision symptoms. The video can be found here: http://youtu.be/ciMyzfXgo8l.

Double-duct sign in the era of endoscopic ultrasound: the prevalence of occult pancreaticobiliary malignancy.

BACKGROUND AND AIM: Simultaneous dilatation of the common bile duct and pancreatic duct, "double-duct sign" (DDS), is an ominous finding concerning for pancreaticobiliary malignancy. Little evidence exists to guide the initial evaluation and subsequent follow-up for patients with DDS in the absence of jaundice or focal mass noted on computed tomography (CT)/ magnetic resonance imaging (MRI). Endoscopic ultrasound (EUS) is often recommended in the evaluation of such patients, however, the prevalence of malignancy remains unclear. We sought to determine the prevalence of pancreaticobiliary neoplasm in this patient group on initial EUS evaluation and on subsequent clinical follow-up. METHODS: We performed a retrospective analysis of a prospective database at a tertiary-care academic medical center between 2010 and 2012. Eighty-two patients were identified who underwent EUS evaluation for DDS without evidence of a mass on CT/MRI and without jaundice. RESULTS: Sixty-eight of 82 patients had confirmed DDS on EUS with biductal dilation. Six (9 %) of 68 patients were found to have a mass lesion on EUS. In these patients, final diagnoses were pancreatic carcinoma (n = 4), ampullary carcinoma (n = 1) and ampullary adenoma (n = 1). In the 62 patients without evidence of a focal mass on initial EUS, the most common diagnoses were benign ductal dilation (n = 42), chronic pancreatitis (n = 9) and choledocholithiasis (n = 8). Fifty-eight (94 %) of 62 patients had documented median follow-up of 13 months, and none developed subsequent evidence of previously unrecognized malignancy. CONCLUSIONS: The presence of double-duct sign on EUS in patients without jaundice or mass lesion on CT/MRI is most frequently associated with benign conditions. When a mass is not detected on EUS, subsequent evidence of malignancy is unlikely.

Combination endovascular and microsurgical treatment of partially thrombosed ruptured ICA terminus aneurysm, with common carotid artery to MCA bypass via saphenous vein graft and parent vessel sacrifice after coil embolization.

A 63-year-old woman presented with ruptured giant ICA terminus aneurysm, temporized with coil embolization and definitively treated with parent vessel sacrifice and high-flow bypass.

Craniocervical dural arteriovenous fistula: Microsurgical clipping and technical nuances with ICG.

A 48-year-old male with progressive congestive myelopathy had a craniocvervical DAVF treated with surgical clipping using ICG to confirm solitary inflow.

Brain AVM surgery without endovascular embolization in a low to middle income country.

We treated a 20-year-old woman in Paraguay with a ruptured intraventricular Spetzler-Martin Grade 3 AVM, and illustrate microsurgical resection without embolization in this video.

Randomized Clinical Trials in Cerebrovascular Neurosurgery From 2018 to 2022.

There has been an exponential increase in randomized controlled trials (RCTs) on cerebrovascular disease within neurosurgery. The goal of this study was to review, outline the scope, and summarize all phase 2b and phase 3 RCTs impacting cerebrovascular neurosurgery practice since 2018. We searched PubMed, MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for relevant RCTs published between January 1, 2018, and July 1, 2022. We searched for studies related to eight major cerebrovascular disorders relevant to neurosurgery, including acute ischemic stroke, cerebral aneurysms and subarachnoid hemorrhage, intracerebral hemorrhage, subdural hematomas, cerebral venous thrombosis, arteriovenous malformations, Moyamoya disease and extracranial-intracranial bypass, and carotid and intracranial atherosclerosis. We limited our search to phase 2b or 3 RCTs related to cerebrovascular disorders published during the study period. The titles and abstracts of all relevant studies meeting our search criteria were included. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded.  From an initial total of 2,797 records retrieved from the database searches, 1,641 records were screened after duplicates and studies outside of our time period were removed. After screening, 511 available reports within our time period of interest were assessed for eligibility. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded. We found 80 unique phase 2b or 3 RCTs that fit our criteria, with 165 topic-relevant articles published within the study period.  Numerous RCTs in cerebrovascular neurosurgery have been published since 2018. Ischemic stroke, including mechanical thrombectomy and thrombolysis, accounted for a majority of publications, but there were large trials in intracerebral hemorrhage, subdural hemorrhage, aneurysms, subarachnoid hemorrhage, and cerebral venous thrombosis, among others. This review helps define the scope of the large RCTs published in the last four years to guide future research and clinical care.

Changes in inpatient brain arteriovenous malformation management in the United States following the ARUBA trial: analysis of an interrupted time series design.

The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates METHODS: This study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009-2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. RESULTS: Elective and asymptomatic patient admissions declined 2009-2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. CONCLUSIONS: The publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA's conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA's findings in managing unruptured brain AVMs.

Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era.

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

A Novel Approach for Free, Affordable, and Sustainable Microsurgery Laboratory Training for Low- and Middle-Income Countries: University of Wisconsin-Madison Microneurosurgery Laboratory Experience.

BACKGROUND AND OBJECTIVES: In low- and middle-income countries (LMICs), approximately 5 million essential neurosurgical operations per year remain unaddressed. When compared with high-income countries, one of the reasons for this disparity is the lack of microsurgery training laboratories and neurosurgeons trained in microsurgical techniques. In 2020, we founded the Madison Microneurosurgery Initiative to provide no-cost, accessible, and sustainable microsurgery training opportunities to health care professionals from LMICs in their respective countries. METHODS: We initially focused on enhancing our expertise in microsurgery laboratory training requirements. Subsequently, we procured a wide range of stereo microscopes, light sources, and surgical instrument sets, aiming to develop affordable, high-quality, and long-lasting microsurgery training kits. We then donated those kits to neurosurgeons across LMICs. After successfully delivering the kits to designated locations in LMICs, we have planned to initiate microsurgery laboratory training in these centers by providing a combination of live-streamed, offline, and in-person training assistance in their institutions. RESULTS: We established basic microsurgery laboratory training centers in 28 institutions across 18 LMICs. This was made possible through donations of 57 microsurgery training kits, including 57 stereo microscopes, 2 surgical microscopes, and several advanced surgical instrument sets. Thereafter, we organized 10 live-streamed microanastomosis training sessions in 4 countries: Lebanon, Paraguay, Türkiye, and Bangladesh. Along with distributing the recordings from our live-streamed training sessions with these centers, we also granted them access to our microsurgery training resource library. We thus equipped these institutions with the necessary resources to enable continued learning and hands-on training. Moreover, we organized 7 in-person no-cost hands-on microanastomosis courses in different institutions across Türkiye, Georgia, Azerbaijan, and Paraguay. A total of 113 surgical specialists successfully completed these courses. CONCLUSION: Our novel approach of providing microsurgery training kits in combination with live-streamed, offline, and in-person training assistance enables sustainable microsurgery laboratory training in LMICs.

A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Long-Term Follow-Up of Cerebral Aneurysms Completely Occluded at 6 Months After Intervention with the Woven EndoBridge (WEB) Device: a Retrospective Multicenter Observational Study.

The Woven EndoBridge (WEB) device has been widely used to treat intracranial wide neck bifurcation aneurysms. Initial studies have demonstrated that approximately 90% of patients have same or improved long-term aneurysm occlusion after the initial 6-month follow up. The aim of this study is to assess the long-term follow-up in aneurysms that have achieved complete occlusion at 6 months. We also compared the predictive value of different imaging modalities used. This is an analysis of a prospectively maintained database across 13 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB device who achieved complete occlusion at first follow-up and had available long-term follow-up. A total of 95 patients with a mean age of 61.6 ± 11.9 years were studied. The mean neck diameter and height were 3.9 ± 1.3 mm and 6.0 ± 1.8 mm, respectively. The mean time to first and last follow-up was 5.4 ± 1.8 and 14.1 ± 12.9 months, respectively. Out of all the aneurysms that were completely occluded at 6 months, 84 (90.3%) showed complete occlusion at the final follow-up, and 11(11.5%) patients did not achieve complete occlusion. The positive predictive value (PPV) of complete occlusion at first follow was 88.4%. Importantly, this did not differ between digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA). This study underlines the importance of repeat imaging in patients treated with the WEB device even if complete occlusion is achieved short term. Follow-up can be performed using DSA, MRA or CTA with no difference in positive predictive value.

Delayed Rupture of an Anterior Communicating Artery Aneurysm After Elective Woven Endobridge Embolization, Re-Treated With Microsurgical Clipping: Operative Technique and Systematic Review.

BACKGROUND: The Woven EndoBridge (WEB) device is designed for intrasaccular flow disruption for embolization of intracranial aneurysms. In limited experience so far, the rate of rupture after adequate occlusion by embolization has been low. METHODS: A 58-year-old man initially had an incidental, unruptured 10.4-mm anterior communicating artery aneurysm treated with WEB embolization. Although his 6 months follow-up angiogram showed adequate occlusion of the aneurysm, he presented to our facility with aneurysmal recurrence caused by WEB compaction and rupture. This condition was treated with surgical clipping of the aneurysm. The literature was systematically reviewed for cases of delayed rupture after WEB embolization. Statistical analyses included studies with at least 20 patients and follow-up of 3 months. RESULTS: We identified 36 studies, which were primarily retrospective observational studies. The rate of complete occlusion ranged from 33% to 89%, and the rate of re-treatment ranged from 1.5% to 27%. Across 4 studies, the rate of recanalization ranged from 8.7% to 13%. Two cases of delayed rupture were reported; an additional 4 cases were found in case reports and case series. In only 1 previous case, the aneurysm was reported as previously untreated. CONCLUSIONS: Early retrospective data have begun to define the history of WEB-treated aneurysms. Rupture of a previously unruptured, WEB-treated aneurysm with adequate initial occlusion is rare. We describe such a case with techniques for management, showing that aneurysm recurrence and delayed rupture are possible despite good interim angiographic results. This report raises questions about follow-up for WEB-treated aneurysms.

Safety Profile and Factors Associated With Good Outcome for Endovascularly Treated Infectious Intracranial Aneurysms.

BACKGROUND: Infectious intracranial aneurysms (IIAs), or mycotic aneurysms, are infectious inflammatory lesions that can cause devastating neurological damage or death. Recent systemic reviews have suggested endovascular treatment to be efficacious for IIA management. OBJECTIVE: To compare the safety profile of different endovascular methods for treating ruptured and unruptured IIAs and factors associated with good clinical and radiographic outcomes. METHODS: We conducted a retrospective single study of endovascularly treated ruptured and unruptured IIAs between 2003 and 2019. Univariate and multivariate analyses were used to study patient presentation, endovascular treatments used, and clinical and radiographic outcomes. RESULTS: Thirty-eight patients with ruptured (n = 20) and unruptured (n = 18) IIAs treated with endovascular methods were included. One patient required retreatment after aneurysm recanalization, and 2 patients demonstrated new infarcts after embolization. There was no postprocedural radiographic hemorrhage or infarct and no difference in clinical and radiographic outcomes comparing treatment modality. Hypertension was associated with ruptured IIA status and worse clinical outcome at 6 mo (odds ratio: 0.03 [95% confidence interval: 0.002-0.52]). CONCLUSION: In this study, the largest single-center series to date, we showed that endovascular intervention is a safe and effective strategy for both ruptured and unruptured IIAs. Hypertension was associated with ruptured status and worse clinical outcome. Procedures are generally well-tolerated and safe, with good outcomes for patients.