These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

We demonstrate that not only frameshift and nonsense mutations but also splice mutations result in SPG11. Mutations are distributed throughout the spatacsin gene and emerge as major cause for ARHSP with TCC associated with severe motor and cognitive impairment. The clinical phenotype and the ultrastructural analysis suggest a disturbed axonal transport of long projecting neurons.

Adoptive T cell therapy has been successfully used for treatment of viral and malignant diseases. However, little is known about the fate and trafficking of transferred Ag-specific T cells. Using the tetramer (TM) technology which allows for detection and quantification of Ag-specific CTL, we assessed the frequency of circulating Melan-A-specific CTL in advanced melanoma patients during adoptive T cell therapy. Melan-A-specific CTL were generated from HLA-A2.1+ patients by in vitro stimulation of CD8+ T cells with dendritic cells pulsed with a mutated HLA-A2-binding Melan-A (ELAGIGILTV) peptide. Eight patients received three infusions of 0.25–11 × 108 Melan-A-specific CTL i.v. at 2-wk intervals along with low-dose IL-2. The transferred T cell product contained a mean of 42.1% Melan-A-TM+ CTL. Before therapy, the frequencies of Melan-A-specific CTL in patients’ circulating CD8+ T cells ranged from 0.01 to 0.07%. Characterization of the TM frequencies before and at different time points after transfer revealed an increase of circulating Melan-A-specific CTL up to 2%, correlating well with the number of transferred CTL. An elevated frequency of TM+ T cells was demonstrated up to 14 days after transfer, suggesting long-term survival and/or proliferation of transferred CTL. Combining TM analysis with a flow cytometry-based cytokine secretion assay, unimpaired production of IFN-γ was demonstrated in vivo for at least 24 h after transfer. Indium-111 labeling of Melan-A-specific CTL demonstrated localization of transferred CTL to metastatic sites as early as 48 h after injection. Overall, the results suggest that in vitro-generated Melan-A-specific CTL survive intact in vivo for several weeks and localize preferentially to tumor.

PET data demonstrated an asymmetric activation of the central auditory system. Seventeen patients revealed increased activity of the primary auditory cortex on the left side, three on the right side. The extent of hypermetabolic activity prior to treatment correlated significantly with tinnitus reduction after rTMS, but not with clinical characteristics such as tinnitus severity, tinnitus laterality or tinnitus duration.

Progressive axonal degeneration occurs in the corticocortical projections, corticospinal tract, and peripheral nerves in HSP with thin CC linking to chromosome 15q13-15 in a German pedigree.

Background: Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positronemission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single-and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitusquestionnaire.

Large vessel vasculitis can be visualized by 18F-FDG positron emission tomography (PET). However, the diagnostic value of 18F-FDG PET is yet to be determined. We therefore performed a study to evaluate this technique for the diagnosis of giant cell arteritis (GCA) and Takayasu arteritis (TA). Patients with GCA or TA, who fulfilled the American College of Rheumatology (ACR) criteria and also had a pathologic PET scan in clinical routine, were selected. These PET scans, as well as PET scans obtained from age- and sex-matched control patients, were independently re-evaluated by two experienced nuclear medicine experts. PET scans of 20 patients (17 GCA, 3 TA) and 20 controls were evaluated. In 85% of the examinations, both observers agreed on the diagnosis or exclusion of vasculitis. Specificity was calculated with 80% and sensitivity with 65%, yielding an overall diagnostic accuracy of 72%. The mean maximum standardized uptake values (SUVmax) of the subclavian region was significantly higher in vasculitis than in control patients (2.77 ± 1.02 vs 2.09 ± 0.64; difference 0.69; CI(95%): 0.14-1.24, p = 0.0161). SUVmax of the iliacal regions did not differ significantly. Receiver- operating characteristics (ROC) analysis revealed the highest sensitivity of 90% (CI(95%): 68-99%) and specificity of 45% (CI(95%): 23-69%) for a SUVmax cut-off point of 1.78 (AUC 0.72, (CI(95%): 0.56-0.86). PET findings are reproducible and independent of the observer. The low sensitivity and specificity indicate that enhanced vascular uptake might be overrated if clinical details are suggestive for vasculitis. Therefore, the diagnosis of large vessel vasculitis should not be based on PET findings only.

High-volume centers >50 ESDs/year Middle-volume centers >20-50 ESDs/year Low-volume centers ≤20 ESDs/year