Complex Morphologic Analysis of Cerebral Aneurysms Through the Novel Use of Fractal Dimension as a Predictor of Rupture Status: A Proof of Concept Study.

BACKGROUND: Aneurysm morphology has been correlated with rupture. Previous reports identified several morphologic indices that predict rupture status, but they measure only specific qualities of the morphology of an aneurysm in a semiquantitative fashion. Fractal analysis is a geometric technique whereby the overall complexity of a shape is quantified through the calculation of a fractal dimension (FD). By progressively altering the scale of measurement of a shape and determining the number of segments required to incorporate the entire shape, a noninteger value for the dimension of the shape is derived. We present a proof-of-concept study to calculate the FD of an aneurysm for a small cohort of patients with aneurysms in 2 specific locations to determine whether FD is associated with aneurysm rupture status. METHODS: Twenty-nine aneurysms of the posterior communicating and middle cerebral arteries were segmented from computed tomography angiograms in 29 patients. FD was calculated using a standard box-counting algorithm extended for use with three-dimensional shapes. Nonsphericity index and undulation index (UI) were used to validate the data against previously reported parameters associated with rupture status. RESULTS: Nineteen ruptured and 10 unruptured aneurysms were analyzed. Through logistic regression analysis, lower FD was found to be significantly associated with rupture status (P = 0.035; odds ratio, 0.64; 95% confidence interval, 0.42-0.97 per FD increment of 0.05). CONCLUSIONS: In this proof-of-concept study, we present a novel approach to quantify the geometric complexity of intracranial aneurysms through FD. These data suggest an association between FD and patient-specific aneurysm rupture status.

Percutaneous transluminal angioplasty and/or stenting for the treatment of basilar artery stenosis: a systematic review and meta-analysis.

PURPOSE: Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes after endovascular treatments. We systematically reviewed the literature on percutaneous transluminal angioplasty and/or stenting (PTAS) for BAS. METHODS: PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include prospective/retrospective cohort studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses. RESULTS: We included 25 retrospective cohort studies comprising 1016 patients. All patients were symptomatic, presenting with transient ischemic attack or ischemic stroke. BAS frequently involved the middle basilar artery (51.4%), mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in severe (≥ 50-70%), symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) and/or stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53-99%), while median post-intervention BAS was 13% (0-75%). Actuarial rates of successful intervention and "good" final outcome were 100% (95% CI: 100-100%) and 89% (95% CI: 85-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI: 4-7%), differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI: 0-0%), 1% (95% CI: 0-1%), and 0% (95% CI: 0-2%). CONCLUSION: Elective PTAS appears to be safe and effective in selected patients with medically refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions. Future randomized controlled trials are required to corroborate these findings.

Association between underlying autoimmune disease and small aneurysm size at rupture.

OBJECTIVE: Although the role of inflammation in the development of aneurysms is established, less is known about the development of intracranial aneurysms in the setting of underlying autoimmune disease. The underlying systemic inflammatory characteristics of disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome may influence the development of intracranial aneurysms through common inflammatory pathways. The authors hypothesized that there is an association between underlying autoimmune disease and aneurysm growth and rupture. METHODS: Medical records of patients who underwent cerebral angiography between August 2018 and August 2021 were manually reviewed. Autoimmune diseases as defined for this study are those known to have systemic inflammatory effects on the central nervous system or multiple other organ systems. Statistical analysis, including construction of multivariable linear and logistic regression models, was performed using R version 4.1.0. RESULTS: Chart review identified 190 patients with 469 ruptured and unruptured saccular intracranial aneurysms. There were 31 patients with 44 aneurysms identified as having an autoimmune disease. The mean size of a ruptured aneurysm was significantly smaller among patients with autoimmune disease compared with patients without autoimmune disease (4.14 mm vs 5.34 mm, p = 0.03). The multivariate logistic regression model did not identify any significant association between rupture and autoimmune disease when controlling for other variables (p = 0.49). In the multivariate linear regression model, autoimmune disease was still significantly associated with a smaller size at rupture (p = 0.04), and smoking was associated with a larger size at rupture (p = 0.03) when controlling for other variables. A second multivariate logistic regression model found autoimmune disease to be independently associated with rupture at a size smaller than 7 mm (p = 0.02), while smoking was independently associated with rupture at a size larger than 7 mm (p = 0.01). CONCLUSIONS: Autoimmune disease is associated with a smaller aneurysm size at rupture, although it is not associated with rupture itself. This association may be due to inflammatory pathways that are common to autoimmune diseases as well as aneurysm wall development. Although the authors were unable to identify any association between rupture status and the presence of autoimmune disease, the association between smaller size at rupture and autoimmune disease warrants further studies, as autoimmune disease may influence the trajectory of aneurysm development and the decision to treat.

Exclusively endoscopic management of complicated pineal cysts in young children: Definitive treatment through single burr-hole technique.

Background: The management of complicated symptomatic pineal cysts in the pediatric population is challenging and variable. Surgical management may include treatment of hydrocephalus alone, or direct treatment of the cyst with or without direct hydrocephalus management. This is typically done through craniotomy-based microsurgical approaches to the pineal region or an endoscopic transventricular approach. Methods: We present a stepwise minimally invasive technique to treat complicated pineal cysts in young children associated with an obstructive hydrocephalus in a single procedure through third ventriculostomy combined with an intraventricular marsupialization of the pineal cyst through a single burr-hole using stereotactic navigation. Results: Two young patients with over 2 years of follow-up have done well without complication using this technique. Other literature reports for complex pineal cysts in pediatric patients are reviewed and this technique is not previously described for this population. Conclusion: Endoscopic third ventriculostomy and cyst marsupialization using a single burr-hole and stereotactic navigation for symptomatic or enlarging pineal cysts in children allow for minimally invasive management, a rapid recovery, short hospital stay, and durable outcome owed to redundant CSF flow pathways.

Super-Pedicle Osteotomy for Correction of Focal Thoracolumbar Kyphosis.

BACKGROUND: Focal thoracolumbar kyphotic deformities require operative correction through osteotomies to restore normal spinal balance. Traditional osteotomies, such as the pedicle subtraction osteotomy, that are often used in the lumbar spine are less useful in the thoracolumbar region. The super-pedicle osteotomy is a pedicle-sparing wedge osteotomy that can be used for correction of kyphosis in patients with thoracolumbar deformities. METHODS: A retrospective review was conducted of 9 consecutive cases using the super-pedicle technique. Clinical data regarding patient age at presentation, etiology of deformity, symptoms, neurological status at presentation, American Society of Anesthesiologists class, type of surgery performed, estimated blood loss during surgery, and complications up to last follow-up were recorded. The primary parameter of interest was the angle at the planned osteotomy site before and after correction. RESULTS: Nine patients with an average age of 64 years were included. All 9 patients had focal thoracic kyphosis either at T11-T12 or T12-L1. All patients underwent thoracolumbar operations with super-pedicle osteotomies at their main level of kyphosis. Estimated blood loss was 600 mL. Average correction at the osteotomy site as measured on preoperative and postoperative radiographs was 31°. At an average follow-up of 338 days, no patients experienced rod fracture, but 1 patient required extension of fusion for proximal junctional kyphosis. CONCLUSIONS: In this small series of patients with thoracolumbar kyphosis, the super-pedicle osteotomy technique was clinically useful. More robust examination is required to determine the safety, utility, and durability of this osteotomy technique.

Differential Induction of Cytoplasmic Vacuolization and Methuosis by Novel 2-Indolyl-Substituted Pyridinylpropenones.

Because many cancers harbor mutations that confer resistance to apoptosis, there is a need for therapeutic agents that can trigger alternative forms of cell death. Methuosis is a novel form of non-apoptotic cell death characterized by accumulation of vacuoles derived from macropinosomes and endosomes. Previous studies identified an indole-based chalcone, 3-(5-methoxy-2-methylindol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), that induces methuosis in human cancer cells. Herein, we describe the synthesis of related 2-indolyl substituted pyridinylpropenones and their effects on U251 glioblastoma cells. Increasing the size of the 2-indolyl substituent substantially reduces growth inhibitory activity and cytotoxicity, but does not prevent cell vacuolization. Computational models suggest that the results are not due to steric-driven conformational effects. The unexpected uncoupling of vacuolization and cell death implies that the relationship between endosomal perturbations and methuotic cell death is more complex than previously realized. The new series of compounds will be useful in further defining the molecular and cellular mechanisms underlying methuosis.

Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death.

Methuosis is a novel caspase-independent form of cell death in which massive accumulation of vacuoles derived from macropinosomes ultimately causes cells to detach from the substratum and rupture. We recently described a chalcone-like compound, 3-(2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MIPP), which can induce methuosis in glioblastoma and other types of cancer cells. Herein, we describe the synthesis and structure-activity relationships of a directed library of related compounds, providing insights into the contributions of the two aryl ring systems and highlighting a potent derivative, 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MOMIPP) that can induce methuosis at low micromolar concentrations. We have also generated biologically active azide derivatives that may be useful for future studies aimed at identifying the protein targets of MOMIPP by photoaffinity labeling techniques. The potential significance of these studies is underscored by the finding that MOMIPP effectively reduces the growth and viability of Temozolomide-resistant glioblastoma and doxorubicin-resistant breast cancer cells. Thus, it may serve as a prototype for drugs that could be used to trigger death by methuosis in cancers that are resistant to conventional forms of cell death (e.g., apoptosis).