Limited usefulness of routine head and neck CT angiogram in the imaging assessment of dizziness in the emergency department.

OBJECTIVE: To assess the usefulness of head and neck computed tomography angiogram for the investigation of isolated dizziness in the emergency department in detecting significant acute findings leading to a change in management in comparison to non-contrast computed tomography scan of the head. METHODS: Patients presenting with isolated dizziness in the emergency department investigated with non-contrast computed tomography and computed tomography angiogram over the span of 36 months were included. Findings on non-contrast computed tomography were classified as related to the emergency department presentation versus unrelated/no significant abnormality. Similarly, computed tomography angiogram scans were classified as positive or negative posterior circulation findings. RESULTS: One hundred and fifty-three patients were imaged as a result of emergency department presentation with isolated dizziness. Fourteen cases were diagnosed clinically as of central aetiology. Non-contrast computed tomography was positive in three patients, all with central causes with sensitivity 21.4%, specificity 100%, positive predictive value 100%, negative predictive value 92.6% and accuracy 92.8%. Computed tomography angiogram was positive for angiographic posterior circulation abnormalities in five cases, and only two of them had a central cause of dizziness, with sensitivity 14.3%, specificity 97.7%, positive predictive value 40%, negative predictive value 91.46% and accuracy 92.1%. CONCLUSION: Both non-contrast computed tomography and computed tomography angiogram of the head and neck have low diagnostic yield for the detection of central causes of dizziness, However, non-contrast computed tomography has higher sensitivity and positive predictive value than computed tomography angiogram, implying a lack of diagnostic advantage from the routine use of computed tomography angiogram in the emergency department for the investigation of isolated dizziness. Further studies are required to determine the role of computed tomography angiogram in the work-up of isolated dizziness in the emergency department.

Modulating alpha-actinin-4 dynamics in podocytes.

Podocytes are epithelial cells that line the outer aspect of renal blood vessels and provide a platform for the kidney's filtering apparatus, the slit diaphragm. Mutations in alpha-actinin-4, an actin bundling protein highly expressed in podocytes, result in increased affinity for actin and cause a familial form of focal segmental glomerulosclerosis. We hypothesized that such gain-of-affinity mutations would override alpha-actinin-4's sensitivity to regulatory factors such as calcium (acting via two EF-hand motifs), and phosphoinositides. We generated calcium- (mutEF) and phosphoinositide- (mutPI) insensitive variants of alpha-actinin-4, comparing their properties to a disease-associated mutant (K256E) and to the wildtype (wt) protein. alpha-Actinin-4(mutPI) displayed increased affinity for actin, while the affinity of alpha-actinin-4(mutEF) was unchanged. Addition of calcium to actin sedimentation assays caused a decrease in the association of alpha-actinin-4(wt) with filamentous actin, while phosphoinositides generally increased this association. Similar to alpha-actinin-4(K256E), alpha-actinin-4(mutPI) was mislocalized in cultured podocytes, being preferentially associated with filamentous actin and focal adhesions. Fluorescence recovery after photobleaching experiments revealed a rapid turnover of alpha-actinin-4(wt) and alpha-actinin-4(mutEF) along stress fibers and focal adhesions, while the turnover of alpha-actinin-4(K256E) and alpha-actinin-4(mutPI) was dramatically reduced at these subcellular locales. Equibiaxial mechanical stimulation of podocytes, a mimic of intraglomerular forces, reduced podocyte surface area by 50%; this decrease was more severe (70%) in the presence of high-affinity mutants of alpha-actinin-4. These data suggest that dynamic regulation of alpha-actinin-4/actin interactions may be necessary for maintaining podocyte structure in response to glomerular hydrostatic forces.