A review of technological innovations leading to modern endovascular brain aneurysm treatment

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment

Validating a Curvature‐Based Marker of Cervical Carotid Tortuosity for Risk Assessment in Heritable Aortopathies

Background Cervical arterial tortuosity is associated with adverse outcomes in Loeys‐Dietz syndrome and other heritable aortopathies. Methods and Results A method to assess tortuosity based on curvature of the vessel centerline in 3‐dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys‐Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow‐up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow‐up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298, P=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656, P=0.818). Baseline total absolute curvature correlated with aortic root diameter (r=0.456, P=0.004) and was independently associated with aortic events during the 4‐year follow‐up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02–6.85]). Baseline tortuosity index correlated with age (r=0.532, P<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79–4.51]). Finally, baseline total absolute curvature had good discrimination of 4‐year outcomes (area under the curve=0.724, P=0.014), which may be prognostic or predictive. Conclusions Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature‐based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys‐Dietz syndrome

Neuronal defects in a human cellular model of 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease