Multisite rTMS for the Treatment of Chronic Tinnitus: Stimulation of the Cortical Tinnitus Network—A Pilot Study

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the auditory cortex has been shown to significantly reduce tinnitus severity in some patients. There is growing evidence that a neural network of both auditory and non-auditory cortical areas is involved in the pathophysiology of chronic subjective tinnitus. Targeting several core regions of this network by rTMS might constitute a promising strategy to enhance treatment effects. This study intends to test the effects of a multisite rTMS protocol on tinnitus severity. 45 patients with chronic tinnitus were treated with multisite stimulation (left dorsolateral prefrontal, 2,000 stimuli, 20 Hz; left temporoparietal, 1,000 stimuli, 1 Hz; right temporoparietal, 1,000 stimuli, 1 Hz). Results were compared with a historical control group consisting of 29 patients who received left temporal stimulation (2,000 stimuli, 1 Hz). Both groups were treated on ten consecutive working days. Tinnitus severity was assessed at three time points: at baseline, after the last treatment session (day 12) and after a follow-up period of 90 days. A change of tinnitus severity over time was tested using repeated measures ANOVA with the between-subjects factor treatment group. Both groups improved similarly from baseline to day 12. However, there was a difference on day 90: the multisite stimulation group showed an overall improvement whereas patients receiving temporal stimulation returned to their baseline level of tinnitus severity. These pilot data suggest that multisite rTMS is superior to temporal rTMS and represents a promising strategy for enhancing treatment effects of rTMS in tinnitus. Future studies should explore this new protocol with respect to clinical and neurobiological effects in more detail.     

The effect of spironolactone on diastolic function in haemodialysis patients

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e’. Changes in the frequency of HFpEF were analysed using the comprehensive ‘HFA-PEFF score’. Complete echocardiographic assessment was available in 65 individuals (59.5?±?13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF?>?50%). At baseline, mean E/e’ was 15.2?±?7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e’ between the spironolactone group and the placebo group (+?0.93?±?5.39 vs.?+?1.52?±?5.94, p?=?0.68) or in mean change of left atrial volume index (LAVi) (1.9?±?12.3 ml/m² vs. 1.7?±?14.1 ml/m², p?=?0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+?0.8?±?14.2 g/m² vs.?+?2.7?±?15.9 g/m²; p?=?0.72) or NT-proBNP (p?=?0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p?=?0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.

The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012).

     

Cellular markers of inflammation in the airways of allergic sheep with and without allergen-induced late responses

Allergic sheep respond to inhaled Ascaris suum antigen either with an acute bronchoconstriction alone (acute responders, AR) or both an acute and late bronchoconstriction (dual responders, DR). In this study, we determined if: (1) inflammatory cell composition of bronchoalveolar lavage (BAL) obtained during the late response differs between DR and AR; (2) the difference in inflammatory cells is dependent on the prechallenge BAL cell composition; and (3) drugs that block late airway responses also modify this airway inflammation. Antigen challenge caused significant immediate mean increases in specific lung resistance (SRL) both in DR (n = 28) and in AR (n = 14), but only DR had a late increase in SRL. There were no differences between the two groups in total cell returns or in the percentage of neutrophils in BAL 7.5 to 8 h after challenge, but DR had a 3.5-fold increase (p less than 0.05) in the percentage of eosinophils. Methylprednisolone succinate (15 mg/kg intravenously) given to DR (n = 7) 3 h after antigen challenge blocked the late airway response and the eosinophil response. When BAL was performed both before and after (i.e., 7.5 to 8 h) antigen challenge, similar results were observed: AR (n = 7) and DR (n = 14) exhibited characteristic airway responses. No significant differences in prechallenge BAL cell composition were observed between AR and DR; after challenge both groups showed increases in neutrophils, but only the DR showed an increase (p less than 0.05) in eosinophils. Pretreatment of DR with the antiallergic agents (cromolyn sodium or nedocromil sodium aerosol, 20 mg) blocked the immediate and late responses and the late increase in BAL eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)     

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

AIMS: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function. Magnetic resonance imaging was performed to assess late-enhancement for the detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20 years of age had no hypertrophy, no late-enhancement, and normal radial and longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement, normal radial and longitudinal function in the septal wall, but reduced longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male patients without hypertrophy and no late-enhancement had normal radial function but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/-0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had reduced radial and longitudinal function. Twelve patients displaying hypertrophy and late-enhancement had severely reduced radial and longitudinal function (SR=-1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=-0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results illustrate the variation of morphological changes and its functional consequences in Fabry cardiomyopathy.     

Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins

In this paper, we demonstrate the possibility to reconstruct the actual blood flow velocity vector field in retinal microvessels from dual-beam bidirectional Doppler optical coherence tomography measurements. First, for a better understanding of measured phase patterns, several flow situations were simulated on the basis of the known dual beam measurement geometry. We were able to extract the vector field parameters that determine the measured phase pattern, allowing for the development of an algorithm to reconstruct the velocity vector field from measured phase data. In a next step, measurements were performed at a straight vessel section and at a venous convergence; the obtained phase data were evaluated by means of the new approach. For the straight vessel section, the reconstructed flow velocity vector field yielded a parabolic flow. For the venous convergence, however, the reconstructed vector field deviated from a parabolic profile, but was in very good accordance with the simulated vector field for the given vessel geometry. The proposed algorithm allows predictions of the velocity vector field. Moreover, the algorithm is also sensitive to directional changes of the flow velocity as small as <1°, thereby offering insight in the flow characteristics of the non-Newtonian fluid blood in microvessels.OCIS codes: (110.4500) Optical coherence tomography, (170.2655) Functional monitoring and imaging, (280.2490) Flow diagnostics