Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study

background: directional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing. objective: this study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD). materials and methods: In this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. neuroimaging reconstruction obtained through brainlab elements planning software detected contacts localized within the STN. clinical DBS programming contact scheme data were collected after one year from the implant. statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. we evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction. results: LFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. the combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts. conclusions: the combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. the use of predictors in contact selection could guide clinical programming and reduce time needed for it

Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

OBJECTIVE: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. METHODS: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

Extradural Motor Cortex Stimulation might improve episodic and working memory in patients with Parkinson\u2019s disease

Electric Extradural Motor Cortex Stimulation (EMCS) is a neurosurgical procedure suggested for treatment of patients with advanced Parkinson\u2019s disease (PD). We report two PD patients treated by EMCS, who experienced worsening of motor symptoms and cognition 5 years after surgery, when EMCS batteries became discharged. One month after EMCS restoration, they experienced a subjective improvement of motor symptoms and cognition. Neuropsychological assessments were carried out before replacement of batteries (off-EMCS condition) and 6 months afterward (on-EMCS condition). As compared to off-EMCS condition, in on-EMCS condition both patients showed an improvement on tasks of verbal episodic memory and backward spatial short-term/working memory task, and a decline on tasks of selective visual attention and forward spatial short-term memory. These findings suggest that in PD patients EMCS may induce slight beneficial effects on motor symptoms and cognitive processes involved in verbal episodic memory and in active manipulation of information stored in working memory

Ergonomics Characterization in Digital Manufacturing: A new Ergonomic Index Proposal

Ergonomics can be employed in refining manufacturing tasks, tools handiness and workplace assessment. An ergonomic study is able to increase worker safety (preventing and avoiding hazards within working environment) and eliminate awkward positions and useless actions. These reflect on worker productivity and motivation, reduction of absenteeism (for diseases), increase of attention on core tasks and finally improving of product quality. Therefore, the principal objective of an ergonomic study and procedure optimization is to reduce, or possibly avoid, those bad postures that cause stresses and/or physical disorders (which generally affect upper and lower limbs). Many observational, epidemiological and anthropometrical studies have been conducted to assess these disorders. On the other hand, these models often employ qualitative and too much subjective parameter. They focus on particular and very specific aspects regarding the posture. Hence, traditional models cannot be considered as standalone approach for a complete ergonomic analysis of working tasks. The present investigation has aimed at highlighting the limits of the traditional methods, the presence of overlaps and field of applicability. Furthermore, the analysis and joining of the advantages of the principal ergonomics indexes have driven to develop a new synthetic index (ViRWL) which surpasses the actual models limitations. The relative simplicity of such a model (which calculates the stresses on the limbs, the maximum allowable load with the absence of subjective and uncertain parameters contribute) has allowed the developing of a completely automatic routine which can be easily introduced in digital ergonomic environments

Imaging studies on dopamine transporter and depression: A review of literature and suggestions for future research

We review the conflicting results from imaging studies of dopamine transporter availability in depressed patients and also discuss the heterogeneity of the variables involved. Major depression includes diverse clinical manifestations and in recent years there has been an increasing interest in the identification of homogeneous phenotypes and different clinical subtypes of depression, e.g. anhedonic depression, retarded depression, etc. In addition, the use of different radioligands and imaging techniques, diverse rating scales, together with the lack of control of clinical variables (clinical course, recent or past use of substances of abuse, etc.) make it difficult to clearly identify neuronal regions or networks with consistently abnormal structures or functions in major depressive disorder. It is probably necessary to build a shared approach between clinicians and researchers in order to identify standardized procedures to better understand the role of the dopamine transporter in depression. We outline a list of major issues and also suggest some standardized procedures in collecting clinical and imaging data on major depressed patients. Our aim is to delineate a possible "modus operandi" that would be a proposal for neuroreceptor studies on major depression. (C) 2013 Elsevier Ltd. All rights reserved