Longitudinal Optogenetic Motor Mapping Revealed Structural and Functional Impairments and Enhanced Corticorubral Projection after Contusive Spinal Cord Injury in Mice

Current evaluation of impairment and repair after spinal cord injury (SCI) is largely dependent on behavioral assessment and histological analysis of injured tissue and pathways. Here, we evaluated whether transcranial optogenetic mapping of motor cortex could reflect longitudinal structural and functional damage and recovery after SCI. In Thy1-Channelrhodopsin2 transgenic mice, repeated motor mappings were made by recording optogenetically evoked electromyograms (EMGs) of a hindlimb at baseline and 1 day and 2, 4, and 6 weeks after mild, moderate, and severe spinal cord contusion. Injuries caused initial decreases in EMG amplitude, losses of motor map, and subsequent partial recoveries, all of which corresponded to injury severity. Reductions in map size were positively correlated with motor performance, as measured by Basso Mouse Scale, rota-rod, and grid walk tests, at different time points, as well as with lesion area at spinal cord epicenter at 6 weeks post-SCI. Retrograde tracing with Fluoro-Gold showed decreased numbers of cortico- and rubrospinal neurons, with the latter being negatively correlated with motor map size. Combined retro- and anterograde tracing and immunostaining revealed more neurons activated in red nucleus by cortical stimulation and enhanced corticorubral axons and synapses in red nucleus after SCI. Electrophysiological recordings showed lower threshold and higher amplitude of corticorubral synaptic response after SCI. We conclude that transcranial optogenetic motor mapping is sensitive and efficient for longitudinal evaluation of impairment and plasticity of SCI, and that spinal cord contusion induces stronger anatomical and functional corticorubral connection that may contribute to spontaneous recovery of motor function

A randomized, single-blind cross-over design evaluating the effectiveness of an individually defined, targeted physical therapy approach in treatment of children with cerebral palsy

Objective: A pilot study to compare the effectiveness of an individual therapy program with the effects of a general physical therapy program. Design: A randomized, single-blind cross-over design. Participants: Ten ambulant children with bilateral spastic cerebral palsy, age four to nine years. Intervention: Participants were randomly assigned into a ten-week individually defined, targeted or a general program, followed by a cross-over. Main outcome measures: Evaluation was performed using the Gross Motor Function Measure-88 and three-dimensional gait analysis. General outcome parameters were Gross Motor Function Measure-88 scores, time and distance parameters, gait profile score and movement analysis profiles. Individual goal achievement was evaluated using z-scores for gait parameters and Goal Attainment Scale for gross motor function. Results: No significant changes were observed regarding gross motor function. Only after individualized therapy, step-and stride-length increased significantly (p = 0.022; p = 0.017). Change in step-length was higher after the individualized program (p = 0.045). Within-group effects were found for the pelvis in transversal plane after the individualized program (p = 0.047) and in coronal plane after the general program (p = 0.047). Between-program differences were found for changes in the knee in sagittal plane, in the advantage of the individual program (p = 0.047). A median difference in z-score of 0.279 and 0.419 was measured after the general and individualized program, respectively. Functional goal attainment was higher after the individual therapy program compared with the general program (48 to 43.5). Conclusion: The results indicate slightly favorable effects towards the individualized program. To detect clinically significant changes, future studies require a minimal sample size of 72 to 90 participants

Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents : a cross-sectional study

Background: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. Methods: As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. Results: A two-fold increase of the sum of serum PBDE's was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE's on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. Conclusions: This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones

Motor function evaluation in merosin-deficient congenital muscular dystrophy children

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by early onset of hypotonia and weakness. Almost 50% of the cases are caused by primary deficiency of a protein named merosin (MD), and present a homogenous phenotype with a severe motor and respiratory involvement. Eleven children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15 years, were studied using the manual muscle testing (Medical Research Council), goniometric analysis, motor ability and day life activities (Barthel index) scales, with the objective to characterize the main motor function limitations. The muscular groups most affected were cervical flexors, paravertebral and proximal portions of limbs. The muscular groups of upper limbs were as affected as the lower limbs, and the extensors were more affected than the flexors groups. All children had severe muscular retractions on the hip, knee and elbow. Other frequent deformities were scoliosis and equinus-varum feet. No children presented the motor ability to walk, stand up and crawl; and all of them were classified as dependents or semi-dependents in the day life activities scale. Our findings confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients, producing serious motor limitations and deformities.A distrofia muscular congênita (DMC) compõe um grupo de miopatias caracterizadas por hipotonia e fraqueza muscular notadas até o primeiro ano de vida. Em torno de 40% a 50% dos casos são decorrentes de deficiência primária da proteína merosina (DM), os quais apresentam um fenótipo mais homogêneo, com grave comprometimento motor e respiratório. Foram avaliadas neste estudo onze crianças com diagnóstico clínico e histológico de DMC-DM, com idade de 3 a 15 anos, através de exame de força muscular (Medical Research Council), análise goniométrica, avaliação das habilidades motoras e das atividades de vida diária (AVDs) (indicador de Barthel), com o objetivo de caracterizar as principais limitações funcionais motoras. Os grupos musculares mais comprometidos foram os flexores cervicais, paravertebrais e proximais dos membros. Os grupos musculares dos membros superiores estavam tão comprometidos quanto os dos membros inferiores, enquanto que os extensores encontravam-se mais comprometidos que os flexores. Todas as crianças apresentavam importantes retrações musculares nos quadris, joelhos e cotovelos. Outras deformidades freqüentes foram escoliose e pés eqüino-varo. Nenhuma criança possuía a habilidade motora necessária para engatinhar, ficar de pé ou andar; e todas foram classificadas como dependentes ou semidependentes para a maioria das AVDs estudadas. Nossos achados confirmam o envolvimento difuso e intenso da musculatura esquelética na DMC-DM, acarretando graves limitações funcionais motoras e deformidades músculo-esqueléticas.Associação de Assistência à Criança Deficiente Clínica de Doenças NeuromuscularesUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Machine Learning in Falls Prediction; A cognition-based predictor of falls for the acute neurological in-patient population

Background Information: Falls are associated with high direct and indirect costs, and significant morbidity and mortality for patients. Pathological falls are usually a result of a compromised motor system, and/or cognition. Very little research has been conducted on predicting falls based on this premise. Aims: To demonstrate that cognitive and motor tests can be used to create a robust predictive tool for falls. Methods: Three tests of attention and executive function (Stroop, Trail Making, and Semantic Fluency), a measure of physical function (Walk-12), a series of questions (concerning recent falls, surgery and physical function) and demographic information were collected from a cohort of 323 patients at a tertiary neurological center. The principal outcome was a fall during the in-patient stay (n = 54). Data-driven, predictive modelling was employed to identify the statistical modelling strategies which are most accurate in predicting falls, and which yield the most parsimonious models of clinical relevance. Results: The Trail test was identified as the best predictor of falls. Moreover, addition of any others variables, to the results of the Trail test did not improve the prediction (Wilcoxon signed-rank p < .001). The best statistical strategy for predicting falls was the random forest (Wilcoxon signed-rank p < .001), based solely on results of the Trail test. Tuning of the model results in the following optimized values: 68% (+- 7.7) sensitivity, 90% (+- 2.3) specificity, with a positive predictive value of 60%, when the relevant data is available. Conclusion: Predictive modelling has identified a simple yet powerful machine learning prediction strategy based on a single clinical test, the Trail test. Predictive evaluation shows this strategy to be robust, suggesting predictive modelling and machine learning as the standard for future predictive tools

Learning Pose Grammar to Encode Human Body Configuration for 3D Pose Estimation

In this paper, we propose a pose grammar to tackle the problem of 3D human pose estimation. Our model directly takes 2D pose as input and learns a generalized 2D-3D mapping function. The proposed model consists of a base network which efficiently captures pose-aligned features and a hierarchy of Bi-directional RNNs (BRNN) on the top to explicitly incorporate a set of knowledge regarding human body configuration (i.e., kinematics, symmetry, motor coordination). The proposed model thus enforces high-level constraints over human poses. In learning, we develop a pose sample simulator to augment training samples in virtual camera views, which further improves our model generalizability. We validate our method on public 3D human pose benchmarks and propose a new evaluation protocol working on cross-view setting to verify the generalization capability of different methods. We empirically observe that most state-of-the-art methods encounter difficulty under such setting while our method can well handle such challenges.Comment: Accepted by AAAI 201

Cognitive-behaviour therapy and skilled motor performance in adults with chronic tic disorder

The first aim of the present study was to compare performance of people with tic disorders (TD) and controls on executive function and a range of skilled motor tests requiring complex performance, guided movements, hand co-ordination, and fine control of steadiness. The second aim was to investigate the effect of cognitive behaviour therapy (CBT) on motor performance. A total of 55 patients with TD were recruited at baseline from participants in a behavioural management programme. A comparison group of 55 patients suffering from a variety of habit disorders (HD) involving complex manual movements, were matched on age and level of education to 34 non-psychiatric controls. Participants were evaluated pre- and post-treatment and post-waitlist with a neuropsychological evaluation focusing on executive function (Wisconsin Card Sorting Test, WCST) and skilled motor performance (Purdue Pegboard, Hole Steadiness Test, and the Groove Test). Results revealed WCST scores in the normal range, while motor performance differed significantly on the Purdue Pegboard Tests in both TD and HD as compared to the control group. Cognitive-behavioural treatment selectively improved motor performance in both clinical groups compared to waitlist control, and this improvement related to clinical outcome measures

Patient-Reported Disability Measures Do Not Correlate with Electrodiagnostic Severity in Carpal Tunnel Syndrome.

BACKGROUND: Electrophysiologic studies including electromyography and nerve conduction studies play a role in the evaluation of carpal tunnel syndrome (CTS), despite evidence that these studies do not correlate with CTS-specific symptom scores. There is a lack of evidence comparing electrophysiologic data with general measures of function. METHODS: Fifty patients presenting for CTS treatment over an 8-month period were analyzed retrospectively. All patients completed surveys including the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Medical Outcomes Study 12-Item Short-Form Survey [(physical component summary 12, mental component summary (MCS-12)]. Electromyography and nerve conduction studies were performed on all patients and compared with outcome scores. RESULTS: Analysis demonstrated no relationship between DASH or MCS-12 and electrodiagnostic severity. No significant correlations were noted between DASH or MCS-12 and median motor or sensory latency. There was a moderate-weak correlation (rho = 0.34) between more severe electrophysiologic grade and better function based on physical component summary 12. CONCLUSIONS: Electrodiagnostic severity grades do not correlate with patient-reported disability, including the DASH and MCS-12 surveys. There is a counterintuitive correlation between more-severe electrodiagnostic findings and decreased physical disability. These findings indicate that disability may not correlate with electrodiagnostic severity of median neuropathy in CTS

Use of the NESS Handmaster to restore handfunction in tetraplegia: clinical experiences in ten patients

Objective: To explore possible functional effects of the Handmaster in tetraplegia and to determine suitable patients for the system. \ud \ud Patients: Patients with a cervical spinal cord injury between C4 and C6, motor group 0-3. Important selection criteria were a stable clinical situation and the absence of other medical problems and complications. \ud \ud Design: Ten patients were consecutively selected from the in- and outpatient department of a large rehabilitation hospital in The Netherlands. Each patient was fitted with a Handmaster by a qualified therapist and underwent muscle strength and functional training for at least 2 months. \ud \ud Methods: Functional evaluation comprised the performance of a defined set of tasks and at least one additional task as selected by patients themselves. Tasks were performed both with and without the Handmaster. Finally, patients were asked for their opinion on Handmaster use as well as their willingness to future use. \ud \ud Results: In six patients a stimulated grasp and release with either one or both grasp modes (key- and palmar pinch) of the Handmaster was possible. Four patients could perform the set of tasks using the Handmaster, while they were not able to do so without the Handmaster. Eventually, one patient continued using the Handmaster during ADL at home. \ud \ud Conclusion: The Handmaster has a functional benefit in a limited group of patients with a C5 SCI motor group 0 and 1. Suitable patients should have sufficient shoulder and biceps function combined with absent or weak wrist extensors. Though functional use was the main reason for using the Handmaster, this case series showed that therapeutic use can also be considered. \ud \u