Detection of Early Endothelial Dysfunction by Optoacoustic Tomography.

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin αvß3 has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE-/- and LDLR-/-), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2-12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of αv-positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin αvß3 was detected within vascular structures.

Phenotypic spectrum of musician's dystonia: a task-specific disorder?

BACKGROUND: Musician's dystonia (MD) is traditionally considered a sporadic and task-specific movement disorder. METHODS: The phenotypic spectrum of the disorder was studied in 116 patients suffering from MD including videotaping. RESULTS: Based on the movement disorders observed, we categorized our patients into two different groups: (i) 65 patients with isolated MD, that is only present when playing the instrument and (ii) 51 patients with MD and one or more additional features of primary dystonia independent of MD (complex MD). Patients with a positive family history of movement disorders had an increased risk to develop complex MD [odds ratio = 4.80; 95% confidence interval: 1.94-11.92; P = 0.001]. DISCUSSION: In previous studies, we recently identified 22 relatives with different types of movement disorders in the families of 28 MD patients. Taken together, our results further support a genetic contribution to MD with a broad individual and familial phenotypic spectrum consisting of MD, other dystonias and even other, non-dystonic movement disorders.

Musician's dystonia and comorbid anxiety: two sides of one coin?

BACKGROUND: Psychological abnormalities, including anxiety, have been observed in patients with musician's dystonia (MD). It is unclear if these conditions develop prior to MD or if they are psychoreactive phenomena. METHODS: Psychological conditions were studied in 44 professional musicians with MD, 45 healthy musicians, and 44 healthy nonmusicians using the State-Trait Anxiety Inventory (STAI) and NEO Five-Factor Inventory (NEO-FFI). RESULTS: Musicians with MD had significantly higher STAI state and trait anxiety scores than healthy musicians (P = .009 and P = .012, respectively) and nonmusicians (P = .013 and P = .001, respectively) and significantly higher NEO-FFI neuroticism scores than healthy musicians (P = .018) and nonmusicians (P = .001). Duration of dystonia did not correlate with anxiety or neuroticism scores. CONCLUSIONS: Musicians with MD display increased levels of anxiety and neuroticism. The lack of correlation between anxiety and the duration of dystonia suggests that anxiety may not be a psychoreactive phenomenon and is consistent with the hypothesis that anxiety and MD share a common pathophysiological mechanism.