Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy.

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2's role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.

Endovascular therapy of a craniocervical pial AVF fed by the anterior spinal artery.

Though pial arteriovenous fistulae (PAVF) are an uncommon cerebrovascular disorder, their presentation with subarachnoid hemorrhage (SAH) is not rare. PAVF near the craniocervical junction are rare and may have a worse outcome. These fistulae are often fed from either the carotid and/or the vertebrobasilar systems, but are rarely fed by the anterior spinal artery. We report the case of a young man presenting with SAH. Cerebral angiography revealed 2 AVF, a symptomatic PAVF located at the craniocervical junction and fed from the anterior spinal artery and incidental dural AVF (DAVF) originate from the left occipital and middle meningeal arteries. These fistulae were treated with different endovascular techniques, including Onyx and platinum coil embolization into the feeding arteries of the DAVF and PAVF, respectively.

Age-associated vasospasm in aneurysmal subarachnoid hemorrhage.

The relationship between age and vasospasm caused by subarachnoid hemorrhage (SAH) is controversial. We evaluated this relationship in a contemporary sample from a single institution. In a retrospective study design, we included patients with SAH caused by ruptured intracranial aneurysms. All patients underwent an evaluation that included head imaging, cerebral angiography, and treatment for the underlying aneurysm. Vasospasm was classified as absent, any vasospasm, or symptomatic vasospasm. Age was classified into 2 categories with a cutoff of 50 years, and also was stratified by decade. All patients had received preventative and therapeutic measures for vasospasm. Logistic regression analysis was used to assess the association between age and the occurrence of vasospasm. A total of 108 patients were included in this analysis, 67 of whom were age ≥50 years. The older patients had a higher incidence of vascular risk factors, and the younger patients had a higher incidence of smoking and illicit substance abuse. The mean age of the patients with any vasospasm (n = 41) was 48.51 ± 11.23 years, compared with 59.67 ± 13.30 years in those without vasospasm (P < .0001). Adjusted analysis found a greater risk of vasospasm in the younger patients compared with the older patients (odds ratio, 5.83; 95% confidence interval, 2.41-14.12 for any vasospasm; odds ratio, 2.66; 95% confidence interval, 1.008-7.052 for symptomatic vasospasm). This risk of vasospasm decreased with advanced age (P < .0001). Our findings suggest that patients age <50 years are at 5-fold greater risk of any vasospasm compared with older patients, and that age-adjusted prevention protocols may need to be considered.

Yield of catheter angiography in patients with intracerebral hemorrhage with and without intraventricular extension.

BACKGROUND AND AIM: The role of imaging for the detection of vascular lesions in patients with intracerebral hemorrhage (ICH) is poorly defined. A study was undertaken to compare the yield of digital subtraction angiography (DSA) in patients with ICH with intraventricular hemorrhage (IVH) and those without IVH. METHODS: The DSA database at our institution was reviewed for patients who underwent DSA for acute spontaneous ICH over a period of 68 months. Patients with known vascular malformation or brain neoplasm, prior surgery, ischemic infarction, subarachnoid hemorrhage or isolated IVH were excluded. Patients were grouped into those with associated IVH (group A) and those without (group B). Baseline demographic and clinical data, non-contrast head CT (NCCT) probability for a vascular lesion and angiographic results were compared. RESULTS: 293 patients met the inclusion and exclusion criteria (141 women, 152 men, mean age 57, range 18-88), 139 in group A and 154 in group B. Age and sex distributions were similar (p>0.05). Group A patients were more likely to be hypertensive or coagulopathic (p=0.001). Group B had more patients with high probability NCCT scans (p<0.001). Underlying vascular lesions were found in 21 patients (15.1%) in group A and 34 (22.1%) in group B (p>0.05). CONCLUSION: The presence of IVH in patients with acute spontaneous ICH is not associated with an increased risk of an underlying vascular lesion and should not be used to select patients for neurovascular evaluation.

Hospital mortality and complications of electively clipped or coiled unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: To determine the hospital mortality rates associated with elective surgical clipping and endovascular coiling of unruptured intracranial aneurysms. METHODS: We identified a cohort of patients electively admitted to US hospitals with the diagnosis of unruptured intracranial aneurysm from the National Inpatient Sample database for the years 2000 through 2006. Patient demographics, hospital-associated complications, and in-hospital mortality were compared among the treatment groups. A multivariate logistic regression analysis was used to identify independent variables associated with hospital mortality. Cochrane-Armitage test was used to assess the trend of hospital use of these procedures. RESULTS: After data cleansing, 3738 (34.3%) patients had aneurysm clipping and 3498 (32.1%) had endovascular coiling. The basic demographics including age, race, and comorbidity indices were similar between the groups. The length of hospital stay was longer in the clipped population (median 4 versus 1 day; P<0.0001), incurring a higher hospital charge in the coiled population (median $42 070 versus $38 166; P<0.0001). Hospital mortality was higher in the clipped population: 60 (1.6%) versus 20 (0.57%; adjusted odds ratio 3.63; 95% CI, 1.57, 8.42). Perioperative intracerebral hemorrhage and acute ischemic stroke were higher in the clipped population. The rate of hospital use of the endovascular coiling has increased over the years included in this study (<0.0001). CONCLUSIONS: Elective coiling of unruptured intracranial aneurysms is associated with fewer deaths and perioperative complications compared with elective clipping. The trend of hospital use of the coiling procedures has increased during recent years.