Aggression Toward Others Misdiagnosed as Primary Tics

Background: Tics describe a wide range of sudden and repetitive behaviors. Their multifaceted clinical features may resemble other explosive behaviors, including repetitive episodes of aggression toward others (allo-aggression) reported by subjects without tics. Here, we document 3 exemplary cases that help disentangle allo-aggressive behaviors from tics. Cases: We report 3 cases who presented with an array of complex repetitive behaviors, most notably allo-aggression (eg, sudden kicking, hitting, slapping and biting others, or pushing someone off a bike), which were misdiagnosed as primary tics. In all cases, additional symptoms, such as blackouts, feeling of being controlled by different personalities, or being empowered by repetitive behaviors, and examination pointed toward different neuropsychiatric diagnoses. Conclusions: Repetitive allo-aggressive behaviors are not part of the range of motor manifestations of tics. This observation not only has important medico-legal implications but is also relevant for the overall perception of Tourette syndrome and other primary tic disorders

Supramolecular exo-functionalized palladium cages: fluorescent properties and biological activity

Metallosupramolecular systems are promising new tools for pharmaceutical applications. Thus, novel self-assembled Pd(II) coordination cages were synthesized which were exo-functionalized with naphthalene or anthracene groups with the aim to image their fate in cells. The cages were also investigated for their anticancer properties in human lung and ovarian cancer cell lines in vitro. While the observed cytotoxic effects hold promise and the cages resulted to be more effective than cisplatin in both cell lines, fluorescence emission properties were scarce. Therefore, using TD-DFT calculations, fluorescence quenching observed in the naphthalene-based system could be ascribed to a lower probability of a HOMO–LUMO excitation and an emission wavelength outside the visible region. Overall, the reported Pd2L4 cages provide new insights into the chemical–physical properties of this family of supramolecular coordination complexes whose understanding is necessary to achieve their applications in various fields

the influence of auditory feedback and deep brain stimulation

Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long- range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico-basal ganglia-thalamocortical circuits play a role in the modulation of the serial correlations of timing fluctuations exhibited in skilled musical performance

Effects of subthalamic nucleus deep brain stimulation on emotional working memory capacity and mood in patients with Parkinson's disease

Background: In Parkinson’s disease (PD), cognitive symptoms and mood changes may be even more distressing for the patient than motor symptoms. Objective: Our aim was to determine the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on working memory (WM) and mood. Methods: Sixteen patients with PD were assessed with STN-DBS switched on (DBS-ON) and with dopaminergic treatment (Med-ON) compared to switched off (DBS-OFF) and without dopaminergic treatment (Med-OFF). The primary outcome measures were a Visual Analog Mood Scale (VAMS) and an emotional 2-back WM task at 12 months after DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF. Results: Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016) and contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001, n=16), and a trend for reduction in sedation (P=0.060), which was related to stimulation as shown in a subgroup of seven patients. The N-back task revealed a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med- OFF (82.0% vs 76.0%, respectively) (P=0.044), regardless of stimulus valence. Conclusion: In line with previous studies, we found that patients rated themselves subjectively as more alert, content, and less sedated during short- term DBS-ON. Accuracy in the WM task increased with the combination of DBS and medication, possibly related to higher alertness of the patients. Our results add to the currently mixed results described for DBS on WM and suggest that there are no deleterious DBS effects on this specific cognitive domain

StimFit — A Data‐Driven Algorithm for Automated Deep Brain Stimulation Programming

Background: Finding the optimal deep brain stimulation (DBS) parameters from a multitude of possible combinations by trial and error is time consuming and requires highly trained medical personnel. Objective: We developed an automated algorithm to identify optimal stimulation settings in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) DBS based on imaging-derived metrics. Methods: Electrode locations and monopolar review data of 612 stimulation settings acquired from 31 PD patients were used to train a predictive model for therapeutic and adverse stimulation effects. Model performance was then evaluated within the training cohort using cross-validation and on an independent cohort of 19 patients. We inverted the model by applying a brute-force approach to determine the optimal stimulation sites in the target region. Finally, an optimization algorithm was established to identify optimal stimulation parameters. Suggested stimulation parameters were compared to the ones applied in clinical practice. Results: Predicted motor outcome correlated with observed outcome (R = 0.57, P < 10-10 ) across patients within the training cohort. In the test cohort, the model explained 28% of the variance in motor outcome differences between settings. The stimulation site for maximum motor improvement was located at the dorsolateral border of the STN. When compared to two empirical settings, model-based suggestions more closely matched the setting with superior motor improvement. Conclusion: We developed and validated a data-driven model that can suggest stimulation parameters leading to optimal motor improvement while minimizing the risk of stimulation-induced side effects. This approach might provide guidance for DBS programming in the future

Development of Antibodies against Anthrose Tetrasaccharide for Specific Detection of Bacillus anthracis Spores

Methods for the immunological detection of Bacillus anthracis in various environmental samples and the discrimination of B. anthracis from other members of the B. cereus group are not yet well established. To generate specific discriminating antibodies, we immunized rabbits, mice, and chickens with inactivated B. anthracis spores and, additionally, immunized rabbits and mice with the tetrasaccharide beta-Ant-(1-->3)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-L-Rhap. It is a constituent of the exosporium glycoprotein BclA and contains the newly discovered sugar anthrose 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-beta-D-glucose. The BclA protein is a major component of the exosporium of B. anthracis spores and is decorated by the tetrasaccharide indicated above. The anthrose-containing tetrasaccharide chain seems to be highly specific for B. anthracis, which makes it a key biomarker for the detection of these spores. The different immunizations led to anthrose-reactive polyclonal and monoclonal antibodies which were analyzed by various methods to characterize their ability to discriminate between B. anthracis and other Bacillus spp. Multiple applications, such as enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and electron microscopy, revealed the specificities of the polyclonal and monoclonal antibodies generated for B. anthracis spore detection. All polyclonal antibodies were able to correctly identify the B. anthracis strains tested and showed only minimal cross-reactivities with other Bacillus strains. Moreover, the antibodies generated proved functional in a new capture assay for B. anthracis spores and could therefore be useful for the detection of spores in complex samples

Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16 years

Objective: Observational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia. Background: Dystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an established treatment for severe isolated dystonia but long-term data are sparse. Methods: We considered 36 consecutive patients with isolated generalized (n = 14) and cervical/segmental (n = 22) dystonia operated at Charité-University Hospital between 2000 and 2007 in a retrospective analysis for long-term outcome of pallidal DBS. In 19 of these patients, we could analyze dystonic symptoms and disability rated by the Burke–Fahn–Marsden Dystonia Rating scale (BFMDRS) at baseline, short-term (ST-FU, range 3–36 months) and long-term follow-up (LT-FU, range 93–197 months). Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires. Results: Patients reached an improvement in motor symptoms of 63.8 ± 5.7% (mean ± SE) at ST-FU and 67.9 ± 6.1% at LT-FU. Moreover, a significant and stable reduction in disability was shown following DBS (54.2 ± 9.4% at ST-FU and 53.8 ± 9.2% at LT-FU). BDI and SF36 had improved by 40% and 23%, respectively, at LT-FU (n = 14). Stimulation-induced adverse events included swallowing difficulties, dysarthria, and bradykinesia. Pulse generator (n = 3) and electrodes (n = 5) were revised in seven patients due to infection. Conclusions: Pallidal DBS is a safe and efficacious long-term treatment for dystonia with sustained effects on motor impairment and disability, accompanied by a robust improvement in mood and quality of life

Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series

Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13 years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the “Abnormal Involuntary Movement Scale” (AIMS) as well as the motor part of the “Burke Fahn Marsden Dystonia Rating Scale” (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80–90%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13 years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term