Connor A. Sierra

Chiari I malformation (CM-I) is conventionally defined by cerebellar tonsil position, yet tonsil position is an indirect surrogate for the anatomic obstruction that impairs cerebrospinal fluid (CSF) flow across the craniocervical junction (CCJ). We hypothesized that CCJ crowding, quantified as subarachnoid space narrowing at the foramen magnum and C1, would explain CSF flow impairment more directly than tonsil position. Using non-invasive low b-value diffusion-weighted MRI (low-b dMRI), we quantified effective CSF motility, indexed by mean pseudo-diffusivity (MΨ), across the upper cervical spine, CCJ, and posterior fossa. Voxel-wise CCJ CSF pseudo-diffusion spatial statistics were integrated with CSF Waterways atlas-based regional analyses. We applied this approach in 81 pediatric and adult participants with CM-I to determine how CCJ structural features shape regional CSF dynamics and clinical outcomes. Voxel-wise analyses revealed that crowding at the foramen magnum was the dominant structural determinant of reduced intracranial CSF effective motility across the CCJ, basilar cisterns, and fourth ventricular outflow pathways (family-wise error corrected p < 0.05). While lower tonsil position and C1 level crowding were also associated with reduced CSF effective motility across the CCJ and fourth ventricular outflow pathways, but their associations within the basilar cisterns were spatially restricted to regions adjacent to the Liliequist membrane. Atlas-based region-of-interest analyses confirmed that greater foramen magnum crowding was associated with lower MΨ across multiple basilar cisterns, but with higher MΨ in the ventral spinal CSF compartment. Mediation analyses indicated that CCJ crowding at the foramen magnum and C1 accounted for the majority of the relationship between tonsil position and reduced CSF motility in the basilar cisterns. Multivariate MΨ profiles across the CSF regions identified data-driven foramen magnum crowding thresholds of 69.5% and 77.5%, stratifying patients into mild, moderate, and severe physiological crowding groups. Exploratory analyses linked lower pre-operative CSF MΨ to greater pain-related functional impairment, reduced cognitive function, and a higher likelihood of subsequent decompression surgery. Together, these findings demonstrate that CCJ crowding, particularly at the foramen magnum, exerts a quantifiable, region-specific impact on CSF effective motility in CM-I, and that low-b dMRI provides a sensitive, complementary marker of CSF flow impairment. This integrative CCJ structural and CSF flow imaging framework establishes a mechanistic link between CCJ anatomy, CSF dynamics, and symptom burden, offering a scalable tool for phenotyping CM-I and informing clinical decision-making.

Background: Osteosarcoma is the most common malignant bone tumor in childhood and adolescence. Involvement of the skull is rare, and metastatic spread to the temporal bone has been scarcely described in the literature. In this case report, we present a patient with metastatic osteosarcoma to the squamous temporal bone who underwent successful tumor resection. Case Description: A 19-year-old male with a history of the left tibial osteosarcoma and multiple prior metastases treated with surgery and chemotherapy was admitted for nausea, somnolence, and headache. Imaging demonstrated a large osseous mass of the left squamous temporal bone with intracranial extension causing significant mass effect. He successfully underwent left radical mastoidectomy and left frontotemporal craniotomy for mass resection and cranioplasty. Histopathology confirmed the diagnosis of metastatic osteosarcoma. Conclusion: Osteosarcoma of the skull, particularly arising from metastatic spread, is rare. This case report demonstrates the efficacy of surgery as a means of local control, even in the setting of intracranial extension, and the benefit of multidisciplinary involvement in surgical planning and execution.

Background: The transradial approach (TRA) has recently gained significant interest in the neuro-interventional community. A 6 French (6Fr) guide sheath system is the gold standard for most neuro-interventions. Most 6Fr devices available in the market are developed for transfemoral access and thus lack the torqueability necessary for TRAs. This study aimed to evaluate the safety and feasibility of the 6Fr Terumo R2P Destination Slender Guiding Sheath (TDGS) for neuro-interventional procedures. Methods: A retrospective review of consecutive patients who underwent TRA neuro-interventions using a 6Fr Terumo R2P Destination Slender Guiding Sheath between June 2021 and November 2023 was conducted. Clinical, radiographic, procedural data, complications, and immediate outcomes were reviewed. Results: Ninety-seven patients were identified. The 6Fr TDGS was able to navigate into the carotid system for the interventional procedure via TRA in 90 cases (92.78%). Two cases were initiated via TRA but were aborted due to vessel tortuosity (2.06%), and five cases were pre-operatively converted to a transfemoral approach due to operator preference (5.15%). Pre-procedure radial artery diameter ranged from 1.6 to 4.1 mm. The immediate post-procedure radial artery occlusion rate was 0%. No immediate or delayed access site complications were identified. Conclusion: The 6Fr TDGS is safe and efficacious for TRA neuro-intervention procedures. It provided adequate support, torqueability, and kink resistance for the majority of cases. These results may change clinical practice and demonstrate the need for larger studies regarding the safety and efficacy of the 6Fr TDGS.

The development of periprosthetic soft tissue reactions is a well-documented complication in patients who have previously undergone metal-on-metal (MoM) total hip arthroplasty (THA). Adverse reactions resulting from the shedding of intraarticular metal ions have been broadly classified into several modes of failure, including pseudotumor development and aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). We present a case report of a 76-year-old female with a history of MoM THA who presented with left thigh pain and swelling. Radiographic and histologic analysis were consistent with ALVAL and pseudotumor, despite normal serum metal ion levels. The patient underwent revision total hip arthroplasty with pseudotumor debridement of 3300 mL cystic fluid, and at nearly five years postoperatively, is functioning well with no recurrence of pain or swelling. Review of the literature demonstrates an average pseudotumor area of 73 cm2. Further literature review reveals that serum metal ion levels may not reliably exclude clinically significant pseudotumor formation. As such, this case report challenges the assumption of elevated serum metal ions as an indicator for MoM failure by demonstrating a massive pseudotumor in the context of normal serum levels. Clinicians should maintain a high index of suspicion for adverse local tissue reactions in patients with MoM THA, regardless of serum metal ion levels. Advanced imaging and clinical correlation remain essential for diagnosis and management.

Understanding the timing of fetal brain vulnerability to inflammatory changes in pregnancy complications is crucial for predicting neurodevelopmental risks. Beyond the placenta, the developing brain’s vascular system is believed to form a secondary defense, the blood–brain barrier (BBB), which restricts harmful substances that could disrupt neurodevelopment. However, the precise timing and mechanisms underlying BBB development are poorly understood. In this study, we examined the spatiotemporal expression of key BBB components and fetal brain vascularization in mice from gestational days (GD) 10 to 18. Fetal brain sections were immunostained to identify BBB components, including CD31, Factor VIII, NG2, and claudin-5. Our results showed that endothelial precursor cells form the primitive vascular network in a caudal-to-rostral gradient by GD10, with pericyte recruitment stabilizing vessels by GD12 in a lateral-to-medial gradient that aligns with neurogenesis, despite some regional exceptions. However, Factor VIII was not detected until GD15, and claudin-5 until GD18, suggesting a significant delay in endothelial maturation and tight junction formation. These findings highlight the critical timing of structural developments in the fetal brain vasculature and its vulnerability to placental diseases, laying the groundwork for future research on the impact of placental disorders on fetal brain development and potential therapeutic interventions.

Understanding the timing of fetal brain vulnerability to inflammatory changes in pregnancy complications is crucial for predicting neurodevelopmental risks. Beyond the placenta, the developing brain's vascular system is believed to form a secondary defense, the blood-brain barrier (BBB), which restricts harmful substances that could disrupt neurodevelopment. However, the precise timing and mechanisms underlying BBB development are poorly understood. In this study, we examined the spatiotemporal expression of key BBB components and fetal brain vascularization in mice from gestational days (GD) 10 to 18. Fetal brain sections were immunostained to identify BBB components, including CD31, Factor VIII, NG2, and claudin-5. Our results showed that endothelial precursor cells form the primitive vascular network in a caudal to rostral gradient by GD10, with pericyte recruitment stabilizing vessels by GD12 in a lateral-to-medial gradient that aligns with neurogenesis, despite some regional exceptions. However, Factor VIII was not detected until GD15, and claudin-5 until GD18, suggesting a significant delay in endothelial maturation and tight junction formation. These findings highlight the critical timing of structural developments in the fetal brain vasculature and its vulnerability to placental diseases, laying the groundwork for future research on the impact of placental disorders on fetal brain development and potential therapeutic interventions.

Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after excluding those known to derive from microbial symbionts), using a systematic approach based on chemical space, drug-likeness, predicted toxicity, and virtual screens. Previous drug-likeness measures: the rule-of-five, quantitative estimate of drug-likeness (QED), and relative drug likelihoods (RDL) are based on a relatively small number of molecular properties. We augmented this approach using reference drug and toxin data sets defined for 51 predicted molecular properties. Cnidaria natural products overlap with drugs and toxins in this chemical space, although a multivariate test suggests that there are some differences between the groups. In terms of the established drug-likeness measures, Cnidaria natural products have generally lower QED and RDL scores than drugs, with a higher prevalence of metabolites that exceed at least one rule-of-five threshold. An index of drug-likeness that includes predicted toxicity (ADMET-score), however, found that Cnidaria natural products were more favourable than drugs. A measure of the distance of individual Cnidaria natural products to the centre of the drug distribution in multivariate chemical space was related to RDL, ADMET-score, and the number of rule-of-five exceptions. This multivariate similarity measure was negatively correlated with the QED score for the same metabolite, suggesting that the different approaches capture different aspects of the drug-likeness of individual metabolites. The contrasting of different drug similarity measures can help summarise the range of drug potential in the Cnidaria natural product data set. The most favourable metabolites were around 210–265 Da, quite often sesquiterpenes, with a moderate degree of complexity. Virtual screening against cancer-relevant targets found wide evidence of affinities, with Glide scores <−7 in 19% of the Cnidaria natural products.