BACKGROUND Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P = 0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P = 0.08). CONCLUSIONS In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone.

SummaryBackground Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the eff ect of DBS on cognitive functions and its psychiatric side-eff ects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment.

In neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and prion diseases, deposits of aggregated disease-specific proteins are found. Oligomeric aggregates are presumed to be the key neurotoxic agent. Here we describe the novel oligomer modulator anle138b [3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole], an aggregation inhibitor we developed based on a systematic high-throughput screening campaign combined with medicinal chemistry optimization. In vitro, anle138b blocked the formation of pathological aggregates of prion protein (PrPSc) and of α-synuclein (α-syn), which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Notably, anle138b strongly inhibited all prion strains tested including BSE-derived and human prions. Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers in vitro and in vivo both for prion protein and α-synuclein. Both in mouse models of prion disease and in three different PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. Anle138b had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood–brain-barrier penetration. Our findings indicate that oligomer modulators provide a new approach for disease-modifying therapy in these diseases, for which only symptomatic treatment is available so far. Moreover, our findings suggest that pathological oligomers in neurodegenerative diseases share structural features, although the main protein component is disease-specific, indicating that compounds such as anle138b that modulate oligomer formation by targeting structure-dependent epitopes can have a broad spectrum of activity in the treatment of different protein aggregation diseases.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-013-1114-9) contains supplementary material, which is available to authorized users.

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IMPORTANCE Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.OBJECTIVE To investigate the potential of the novel tau radiotracer 18 F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, participants underwent dynamic 18 F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans.

In this work we propose a novel approach to perform segmentation by leveraging the abstraction capabilities of convolutional neural networks (CNNs). Our method is based on Hough voting, a strategy that allows for fully automatic localisation and segmentation of the anatomies of interest. This approach does not only use the CNN classification outcomes, but it also implements voting by exploiting the features produced by the deepest portion of the network. We show that this learning-based segmentation method is robust, multi-region, flexible and can be easily adapted to different modalities. In the attempt to show the capabilities and the behaviour of CNNs when they are applied to medical image analysis, we perform a systematic study of the performances of six different network architectures, conceived according to state-of-the-art criteria, in various situations. We evaluate the impact of both different amount of training data and different data dimensionality (2D, 2.5D and 3D) on the final results. We show results on both MRI and transcranial US volumes depicting respectively 26 regions of the basal ganglia and the midbrain. * Corresponding author URL: fausto.milletari@tum.de (Fausto Milletari) 1 Fausto Milletari and Seyed-Ahmad Ahmadi contributed equally to this work.

Several reports have described that a positive vertex peak of an evoked potential varied in amplitude and latency specifically when images of faces were the eliciting stimulus. The scalp topography and the possible underlying dipole sources of this peak are the subject of this report. We presented black-and-white photographs of human faces, flowers and leaves to 16 healthy subjects and recorded the evoked brain potentials from 31 scalp electrodes. We found the previously described higher amplitude of the positive vertex peak when faces were the crucial stimulus, but the latency of this peak was the same (180 ms) for all three categories of stimulus. At the posterior temporal electrodes, the face waveforms showed a negative peak at 175 ms, which was only rudimentary in the waveforms elicited by the other stimuli. Since in most previous reports a mastoid reference was used, it is most likely that the previously described latency shift of the positive vertex peak associated with face stimuli was due to the interaction with this posterior temporal peak. The dipole analysis of the possible generators of the recorded potentials suggested the sequential activation of occipital, lateral temporal and mesio-temporal brain structures during the perception of a human face.

Serious adverse events (SAEs) during the first 30 postoperative days after stereotactic surgery for Deep-Brain-Stimulation performed in 1,183 patients were retrospectively collected from five German stereotactic centers. The mortality rate was 0.4% and causes for death were pneumonia, pulmonary embolism, hepatopathy, and a case of complicated multiple sclerosis. The permanent surgical morbidity rate was 1%. The most frequently observed SAEs were intracranial hemorrhage (2.2%) and pneumonia (0.6%). Skin infection occurred in 5 of 1,183 patients (0.4%). Surgical complications caused secondary AEs (e.g. pneumonia) preferentially in older patients and in patients treated for Parkinson's disease (PD). Complication rates did not differ among the five centers.