Subthalamic deep brain stimulation for refractory Gilles de la Tourette’s syndrome: clinical outcome and functional connectivity

Background

Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette’s syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated.

Methods

Ten patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive–compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset.

Results

The overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices.

Conclusions

STN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.

     

Brain structural correlates of upward social mobility in ethnic minority individuals

Purpose

Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system.

Methods

To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging.

Results

Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group.

Conclusion

Our findings extend prior work by pointing to a biological signature of the “allostatic costs” of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.

     

Predictors of psychiatric comorbidity in cancer patients at the time of their discharge from the hospital

Purpose

A cancer diagnosis can have a substantial impact on one’s mental health. The present study investigated the prevalence and predictors of psychiatric comorbidities in cancer patients at the time of their discharge from the hospital.

Methods

Psychiatric comorbidities were assessed shortly before hospital discharge and half a year after hospitalization using a structured clinical interview (SCID), based on the diagnostic and statistical manual of mental disorders (DSM-IV). Frequencies at both time points were estimated using percentages and corresponding 95% confidence intervals. Predictors of mental disorders were identified using binary logistic regression models.

Results

At time of hospital discharge, 39 out of 334 patients (12%) were diagnosed with a psychiatric comorbidity, and 15 (7%) were diagnosed half a year later. Among the diagnoses, adjustment disorders (3%) were most frequent at the time of hospital release, while major depression (3%) was the most frequent 6 months later. Having a mental disorder was associated with unemployment (odds ratio (OR) 3.4, confidence interval (CI) 1.1–10.9, p = 0.04). There was no evidence that school education (OR 2.0, CI 0.4–9.0, p = 0.38), higher education (OR 0.7, CI 0.2–2.4, p = 0.60), income (OR 1.0, CI 1.0–1.0, p = 0.06), tumor stage (OR 1.1, CI 0.4–3.2, p = 0.85), type of disease (OR 0.6, CI 0.2–2.1, p = 0.47), pain (OR 1.0, CI 1.0–1.0, p = 0.15), fatigue (OR 1.0, CI 1.0–1.0, p = 0.77), or physical functioning (OR 1.0, CI 1.0–1.0, p = 0.54) were related to the presence of a psychiatric comorbidity.

Conclusions

Unemployment was associated with at least a threefold increased risk of mental disorder, which highlights the need for special attention to be given to this subgroup of cancer patients.

     

Cortical morphology and illness insight in patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked...     

Predicting alcohol dependence from multi-site brain structural measures

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.     

Fear conditioning and stimulus generalization in association with age in children and adolescents

The aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

     

Confluent abscesses in autochthonous back muscles after spinal injections

Wiener Medizinische Wochenschrift - Injection therapy is a frequently used method for the treatment of subacute and chronic low back pain (LBP) despite scant evidence for its...     

Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index (ET‐DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET‐DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18–25; 3: >25–35; 4: >35), and ET‐DRI. Mean ET‐DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET‐DRI. Accordingly, four ET‐DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET‐DRI categories with labMELD revealed significant differences in long‐term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET‐DRI > 2 and labMELDcategory 3 combined with ET‐DRI > 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs (ET‐DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET‐DRI > 2 should be avoided in patients with a labMELD of >25–35.     

Influence of antithymocyte globulin treatment of brain‐dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice

The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF‐1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6‐h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL‐2 and IL‐6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL‐2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL‐2 levels in the myocardium. We observed a reduction of IL‐6 deposition in media cells in ATG‐treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL‐2‐directed inflammatory response and possible reduction of IL‐6‐mediated vascular changes.