Hyperpigmented nodular rash in a 61-year-old African American female

A 61-year-old African American female presents to an outpatient family health center with a hyperpigmented nodular rash of 2 months’ duration. The rash first appeared on her abdomen before spreading across her upper arms, lower leg, back, face and scalp. She has a history of controlled type 2 diabetes mellitus, cerebral aneurysm rupture, Sjögren’s syndrome, asthma and a left below-the-knee amputation due to osteomyelitis. She smokes cigarettes but does not use alcohol or illicit substances. She has also noticed a dry cough with mild dyspnea on exertion over the past 6 months. On physical exam, hyperpigmented nodules are palpable in both the intradermal and subcutaneous layers of the skin. Nodules are firm, mobile and nontender. Alopecia is noted where scalp nodules are present. Her lungs exhibit diminished air movement throughout, with scattered, end-expiratory wheezing.

Unruptured Intradural Posterior Circulation Dissecting/Fusiform Aneurysms Natural History and Treatment Outcome

Background The natural history and outcome of unruptured posterior circulation dissecting fusiform aneurysms is not fully understood. These have a high risk of morbidity and mortality, not only due to natural history but also due to the challenging and controversial treatment approaches currently available compared to other types of intracranial aneurysms. Methods We performed a retrospective study of a prospectively collected aneurysm database at a quaternary neurovascular hospital. We included consecutive patients with unruptured intradural vertebrobasilar dissecting aneurysms between January 2000 and July 2016 who were followed to 2020. Description of baseline, procedural, and outcomes data was performed. Comparisons of patient who had aneurysm rupture on follow-up, increase in 2 or more points of mRS in follow-up and progression of the aneurysm was performed. Results Seventy patients with 78 fusiform posterior circulation aneurysms were identified. Thirty-nine (55.7%) patients were male with a mean age of 51.7 years (SD ± 17.6). When multiple, aneurysms were more likely to be fusiform (60%) than saccular (40.0%). Baseline diameter (measured on CTA/MRA/DSA), length as well as symptomatic presentation were significantly higher in aneurysms which grew over time. Coronary disease, diabetes and growth were associated an >2 increase in mRS. Diabetes as well as initial symptomatic presentation were associated with rupture. Conclusions Unruptured dissecting/fusiform aneurysm are associated with a considerable rate of rupture during follow-up. Growth is associated with morbidity even in the absence of rupture. Initial large size, coronary disease, diabetes, and to a lesser extent female gender may merit closer follow-up and/or prophylactic treatment.

ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients

Background Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. Results EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. Conclusions We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.

Underlying mechanism of hemodynamics and intracranial aneurysm

In modern society, subarachnoid hemorrhage, mostly caused by intracranial aneurysm rupture, is accompanied by high disability and mortality rate, which has become a major threat to human health. Till now, the etiology of intracranial aneurysm has not been entirely clarified. In recent years, more and more studies focus on the relationship between hemodynamics and intracranial aneurysm. Under the physiological condition, the mechanical force produced by the stable blood flow in the blood vessels keeps balance with the structure of the blood vessels. When the blood vessels are stimulated by the continuous abnormal blood flow, the functional structure of the blood vessels changes, which becomes the pathophysiological basis of the inflammation and atherosclerosis of the blood vessels and further promotes the occurrence and development of the intracranial aneurysm. This review will focus on the relationship between hemodynamics and intracranial aneurysms, will discuss the mechanism of occurrence and development of intracranial aneurysms, and will provide a new perspective for the research and treatment of intracranial aneurysms.