Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:The Silk Vista Baby (SVB) flow diverter (FD) stent (Balt SAS) is the first device designed for treating distally located brain aneurysms. It can be delivered through a 0.017-inch ID microcatheter, enabling access to small, distal vessels. The aim of this study was to evaluate the effectiveness, safety, technical success, occlusion rate, and clinical outcomes of the SVB device. METHODS:This retrospective, multicenter study included data from 18 centers from November 2023 to September 2024. Procedures were performed by experienced neurointerventionalists following institutional standards of care. Outcomes analyzed included effectiveness, safety, and aneurysm occlusion rates. Descriptive analyses and Pearson χ2 or Independent t-Test were used for statistical evaluation. RESULTS:A total of 95 patients, mean age 55.4 years, were included. A total of 31% of aneurysms were ruptured at admission. Most (58.3%) were located in the anterior circulation, and 45% had previous treatment, mainly coiling (69.4%). Complication rates were higher for ruptured aneurysms (24.1%) compared with unruptured ones (9.2%). Two deaths occurred, 1 (1.1%) related to the procedure. At discharge, 87% of patients had modified Rankin Scale ≤2. The latest follow-up showed overall complete/near-complete occlusion rates of 76.1%, with 81.14% for ruptured and 73.43% for unruptured aneurysms. Technical success was higher in unruptured cases (100% vs 93.1%). CONCLUSION/CONCLUSIONS:Our case series demonstrated the efficacy of the SVB with a high rate of technical success. The occlusion rates for ruptured cases are comparable with those of other FDs. However, the rates are lower for unruptured cases. This discrepancy is likely due to the characteristics of the aneurysms, particularly in the presence of side branches in bifurcation lesions. The SVB safety profile is similar to other FDs in unruptured cases, while the ruptured group presented more complications.

This article looks at the current state of aneurysm risk modeling, exploring the limitations of linear measurement. It reviews articles using Food and Drug Administration (FDA)-approved artificial intelligence-driven volumetric measurement tools both for evaluating potential aneurysm growth in patients being managed conservatively as well as in assessing morphologic change prerupture and postrupture. The challenges of defining the aneurysm boundary are explored, and a novel definition of aneurysm/parent artery interface is proposed.

BACKGROUND:Recent studies have suggested that favorable venous outflow (VO) may be a promising imaging biomarker to predict clinical outcomes following reperfusion therapy in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). METHODS:A comprehensive literature search was conducted in PubMed, Scopus, WOS, and Cochrane to identify studies that evaluated VO profiles, assessed using the Cortical Vein Opacification Score (COVES). The risk ratio (RR) and 95% confidence interval (CI) for the outcomes, including functional independence, assessed by modified rankin scale at 90 days (mRS 0-2), hemorrhagic infarction, parenchymal hematoma, 90-day mortality, intracranial hemorrhage (ICH), and symptomatic ICH (sICH), were calculated and analyzed using the 'meta' package in R version 4.4.1. RESULTS:A total of six studies encompassing 2249 patients were included. Patients with favorable VO had a higher likelihood of achieving functional independence at 90 days (RR = 2.15; 95% CI: 1.35, 3.42; p = 0.01) and a lower incidence of 90-day mortality (RR = 0.39; 95% CI: 0.30, 0.51; p < 0.01), parenchymal hematoma (RR = 0.36; 95% CI: 0.27, 0.47; p < 0.01). Furthermore, sICH was less frequent in patients with favorable VO (RR = 0.39; 95% CI: 0.17, 0.89; p = 0.03). However, hemorrhagic infarction and any ICH did not differ significantly between the two groups (p-values: 0.06 and 0.32, respectively). CONCLUSION/CONCLUSIONS:VO is a promising imaging biomarker for predicting outcomes in patients with AIS-LVO following reperfusion therapy. Prospective clinical trials are warranted to investigate the predictive value of VO, assessed on multiphasic computed tomography angiography (CTA), as a prognostic marker in this patient population.

Imaging follow-up is an established component of intracranial aneurysm management that allows ongoing assessment of rupture risk and timely intervention to maintain protection from bleeding. Yet the frequency, duration, and imaging modality for follow-up vary widely. This review outlines contemporary imaging techniques and practice for follow-up of treated and untreated aneurysms, highlighting existing knowledge gaps and technical limitations that limit standardization. Updated evidence on the expected evolution and long-term outcome of common treatment strategies is presented to guide accurate reporting of radiological outcome after treatment and considerations regarding follow-up regimen.

Although the concept of treating cerebral aneurysms by filling the sac from the inside (endosaccular) started many years ago first with detachable balloons and then coils, the use of a single metallic resheathable device acting as a flow disruptor is a much more recent innovation. The most studied device among these is certainly the WEB, which became part of standard clinical practice for treatment of wide-neck bifurcation aneurysms. This study reviews the most important features of the WEB device with a short summary of the most important literature. A small section at the end reviews also other endosaccular devices.

Decreased brain levels of coenzyme Q₁₀ (CoQ₁₀), an endogenously synthesized lipophilic antioxidant^1,2, underpin encephalopathy in primary CoQ₁₀ deficiencies^3,4 and are associated with common neurodegenerative diseases and the ageing process^5,6. CoQ₁₀ supplementation does not increase CoQ₁₀ pools in the brain or in other tissues. The recent discovery of the mammalian CoQ₁₀ headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ₁₀ headgroup precursor 4-hydroxybenzoate (4-HB)⁷, offers an opportunity to pharmacologically restore CoQ₁₀ synthesis and mechanistically treat CoQ₁₀ deficiencies. To test whether 4-HMA or 4-HB supplementation promotes CoQ₁₀ headgroup synthesis in vivo, here we administered 4-HMA and 4-HB to Hpdl^-/- mice, which model an ultra-rare, lethal mitochondrial encephalopathy in humans. Both 4-HMA and 4-HB were incorporated into CoQ₉ and CoQ₁₀ in the brains of Hpdl^-/- mice. Oral treatment of Hpdl^-/- pups with 4-HMA or 4-HB enabled 90-100% of Hpdl^-/- mice to live to adulthood. Furthermore, 4-HB treatment stabilized and improved the neurological symptoms of a patient with progressive spasticity due to biallelic HPDL variants. Our work shows that 4-HMA and 4-HB can modify the course of mitochondrial encephalopathy driven by HPDL variants and demonstrates that CoQ₁₀ headgroup intermediates can restore CoQ₁₀ synthesis in vivo.

OBJECTIVE/UNASSIGNED:To examine the effects of Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) on ADHD symptoms throughout the day in adults with DSM-5 ADHD. METHOD/UNASSIGNED:This was a 6-week pilot study that included 3 weeks of open label treatment with SDX/d-MPH (39.2/7.8 mg/day to 52.3/10.4 mg/day in clinical titration) after completion of a one-week screening period and a two-week observation period in seventeen adults with ADHD. Two subjects were discontinued from the trial, one for being placebo-responder and another for exhibiting blood pressure lability during the observation period. Of the remaining 15 subjects, one dropped out after one week on 39.2/7.8 mg/day, while all others completed the trial. All fifteen participants were included in the data analyses. RESULTS/UNASSIGNED:There were substantial effects of SDX/d-MPH on all clinical measures, including investigator symptom scores (AISRS); self-report (ASRS) scores, time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A) and measures of medication smoothness (AMSES). SDX/d-MPH was generally well tolerated. CONCLUSIONS/UNASSIGNED:This pilot study is the first systematic treatment effect trial data for SDX/d-MPH in adults with DSM-5 ADHD. The data preliminarily supports the clinical efficacy of DSM/d-MPH in adult ADHD and its ability to ameliorate symptoms throughout the day.

Sharp wave-ripples (SPW-Rs) are critical to hippocampal function, and the same is true of gonadal steroids, but the interactions are unclear. We find that surgical removal of the gonads greatly reduces SPW rates in both sexes. Ripples are greatly reduced also. Testosterone treatment rescues SPW and ripple rates in males, and 17β-estradiol restores SPW rates in females. We also find that male SPW rates are higher than females but have less power. Furthermore, in intact females, SPW rates fluctuate with the stage of the ovarian cycle. These data demonstrate that hippocampal SPWs are significantly affected by gonadal removal, testosterone, and 17β-estradiol. In addition, there are sex differences. The data are consistent with past demonstrations that testosterone and 17β-estradiol play central roles in hippocampus and significantly expand the views of hormone action and SPW-Rs.

Definitive endoluminal reconstruction, widely known as flow diversion, revolutionized treatment of brain aneurysms. A range of targets, by location, size, etiology, and acuity, can be cured with an excellent risk/benefit profile. Requirement for effective antiplatelet state is balanced with superior treatment durability. Implant and delivery system technology continue to evolve. Some aneurysm types/locations remain undertreated. Maximizing efficacy while minimizing risks requires deep understanding of flow diversion principles, pathologic anatomy, endoluminal implants, delivery systems, and clinical management.

PURPOSE/UNASSIGNED:To investigate the fairness of existing deep models for diabetic retinopathy (DR) detection and introduce an equitable model to reduce group performance disparities. METHODS/UNASSIGNED:We evaluated the performance and fairness of various deep learning models for DR detection using fundus images and optical coherence tomography (OCT) B-scans. A Fair Adaptive Scaling (FAS) module was developed to reduce group disparities. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), and equity across various groups was assessed by equity-scaled AUC, which accommodated both overall AUC and AUCs of individual groups. RESULTS/UNASSIGNED:Using color fundus images, the integration of FAS with EfficientNet improved the overall AUC and equity-scaled AUC from 0.88 and 0.83 to 0.90 and 0.84 (P < 0.05) by race. AUCs for Asians and Whites increased by 0.05 and 0.03, respectively (P < 0.01). For gender, both metrics improved by 0.01 (P < 0.05). Using DenseNet121 on OCT B-Scans by race, FAS improved the overall AUC and equity-scaled AUC from 0.875 and 0.81 to 0.884 and 0.82, with gains of 0.03 and 0.02 for Asians and Blacks (P < 0.01). For gender, DenseNet121's metrics rose by 0.04 and 0.03, with gains of 0.05 and 0.04 for females and males (P < 0.01). CONCLUSIONS/UNASSIGNED:Deep learning models demonstrate varying accuracies across different groups in DR detection. FAS improves equity and accuracy of deep learning models. TRANSLATIONAL RELEVANCE/UNASSIGNED:The proposed deep learning model has a potential to improve both model performance and equity of DR detection.