Background

This study examines the correlation, and clinical meaningfulness, between reachable workspace outcome and reported activities of daily living (ADL) function of individuals with facioscapulohumeral dystrophy (FSHD).

Methods

Twenty-one FSHD subjects with various disease severity (clinical severity scores 1-4) underwent reachable workspace evaluation and completed the Quality of Life in Neurological Disorders (NeuroQoL) upper extremity questionnaire. Spearman and receiver operator curve analyses were performed.

Results

Moderate correlation was found between NeuroQoL scores and total (ρ = 0.7609; P < .01), and upper-quadrants relative surface areas (RSAs) (ρ = 0.6969; P < .01). Five specific items (ie, shirt on, shirt off, use spoon, pull on pants, pick-up clothes) demonstrated even higher correlations with total (ρ = 0.8397; P < .01) and above shoulder (ρ = 0.8082; P < .01) RSAs. A total RSA cuffoff value of 0.70 would achieve 100% sensitivity and 94% specificity (area under the curve = 0.975).

Conclusions

Reachable workspace values identify when individuals have difficulties performing ADLs at home. This information improves patient monitoring, and clinical decision making by enabling more timely recommendations for medications, assistive devices, or considerations for clinical trial enrollments.

Facioscapulohumeral Dystrophy (FSHD) results in slowly progressive strength impairment, especially the upper extremities. Recent discoveries regarding pathophysiology have led to exciting novel therapeutic strategies. To further facilitate drug development, improved FSHD outcome measures that are functionally-relevant and sensitive to longitudinal change will be critical. Recently, a motion sensor (Kinect)-based upper extremity outcome called 'reachable workspace' that provides a quantitative reconstruction of an individual's reachability was developed. In this study, changes in reachable workspace were tracked upwards for five-years in 18 FSHD subjects. Results show -1.63 %/year decline in total reachable workspace (p = 0.144); with most notable decline in the above-the-shoulder level quadrants (upper-lateral Q3: -9.5 %/year, p < 0.001 and upper-medial Q1: -6.8 %/ year, p = 0.063) with no significant changes in the lower quadrants (Q2, Q4). Reachable workspace declined more significantly if the subjects were challenged with 500 g wrist weights: total reachable workspace: -1.82 %/year, p = 0.039; Q1: -7.20 %/year, p = 0.041; Q3: -8.09 %/year, p = 0.001. Importantly, reachable workspace outcome was also able to distinguish subgroups in FSHD: mildly- and severely-affected with essentially unchanging reachability over years, and moderately-affected who demonstrate the most detectable changes longitudinally. The study demonstrates utility for measuring declines in upper quadrant reachability, and provides enrichment/stratification of FSHD populations most likely to show treatment effects in clinical trials.

Pain after stroke is commonly reported but often incompletely managed, which prevents optimal recovery. This situation occurs in part because of the esoteric nature of poststroke pain and its limited presence in current discussions of stroke management. The major specific afflictions that affect patients with stroke who experience pain include central poststroke pain, complex regional pain syndrome, and pain associated with spasticity and shoulder subluxation. Each disorder carries its own intricacies that require specific approaches to treatment and understanding. This review aims to present and clarify the major pain syndromes that affect patients who have experienced a stroke in order to aid in their diagnosis and treatment.

We reported previously the formation of ectopic colonies in widespread areas of the nervous system after transplantation of fetal neural stem cells (NSCs) into spinal cord transection sites. Here, we characterize the incidence, distribution, and cellular composition of the colonies. NSCs harvested from E14 spinal cords from rats that express GFP were treated with a growth factor cocktail and grafted into the site of a complete spinal cord transection. Two months after transplant, spinal cord and brain tissue were analyzed histologically. Ectopic colonies were found at long distances from the transplant in the central canal of the spinal cord, the surface of the brainstem and spinal cord, and in the fourth ventricle. Colonies were present in 50% of the rats, and most rats had multiple colonies. Axons extended from the colonies into the host CNS. Colonies were strongly positive for nestin, a marker for neural precursors, and contained NeuN-positive cells with processes resembling dendrites, GFAP-positive astrocytes, APC/CC1-positive oligodendrocytes, and Ki-67-positive cells, indicating ongoing proliferation. Stereological analyses revealed an estimated 21,818 cells in a colony in the fourth ventricle, of which 1005 (5%) were Ki-67 positive. Immunostaining for synaptic markers (synaptophysin and VGluT-1) revealed large numbers of synaptophysin-positive puncta within the colonies but fewer VGluT-1 puncta. Continuing expansion of NSC-derived cell masses in confined spaces in the spinal cord and brain could produce symptoms attributable to compression of nearby tissue. It remains to be determined whether other cell types with self-renewing potential can also form colonies.

The elderly population experiences a decline in upper extremity range of motion (ROM), impairing activities of daily living. The primary mode of quantification is by goniometer measurement. In this cross-sectional observation study, we investigate a sensor-acquired reachable workspace for assessing shoulder ROM decline in an elderly population in comparison to traditional measurements. Sixty-one healthy subjects aged ≥ 65 years were included and compared to a cohort of 39 younger subjects, aged 20 to 64. A sensor acquired reachable workspace using a Kinect motion capture camera measured the maximum reaching ability of both arms while in a seated position, measured in m2 and normalized to arm length to calculate a novel score defined as a relative surface area. This score approximates range of motion in the upper extremity. This measurement was compared to goniometer measurements, including active ROM in shoulder flexion and abduction. Total RSA shows moderate to strong correlation between goniometer in flexion and abduction in the dominant arm (R = 0.790 and R = 0.650, P < .001, respectively) and moderate correlations for the nondominant arm (R = 0.622 and R = 0.615, P < .001). Compared to the younger cohort, the elderly population demonstrated significantly reduced total RSA in the dominant arm (meanelderly = 0.774, SD = 0.09; meanyounger = 0.830, SD = 0.07, P < .001), with significant reductions in the upper lateral quadrant in both arms (dominant: meanelderly = 0.225, SD = 0.04; meanyounger = 0.241, SD = 0.01; P < .001; nondominant: meanelderly = 0.213, SD = 0.03; meanyounger = 0.228, SD = 0.01; P = .004). The test-retest reliability was strong for both dominant and nondominant total RSA (ICC > 0.762). The reachable workspace demonstrates promise as a simple and quick tool for clinicians to assess detailed and quantitative active shoulder ROM decline in the elderly population.

Valosin Containing Protein (VCP) disease is an autosomal dominant disorder caused by mutations in the VCP gene and is associated with progressive muscle weakness and atrophy. Affected individuals exhibit striking scapular winging due to shoulder girdle weakness. Currently, there are no treatments available and patients are dying early from cardiac and respiratory failure, typically in their 40’s and 50’s. The generation of disease-specific induced pluripotent stem cells (iPSC) offers a novel platform to investigate mechanisms of VCP disease and potential treatments similar to other disease models including Amyotrophic Lateral Sclerosis (ALS), Duchenne muscular dystrophy (DMD), Parkinson’s disease (PD), Alzheimer’s disease (AD), Best Disease (BD), and type I juvenile diabetes mellitus (T1DM). Herein, we report the generation and characterization of a human iPSC line to examine the cellular and molecular processes underlying VCP disease. The VCP iPSC line expressed specific pluripotency markers NANOG, SSEA4, OCT-4, TRA-1-81 and exhibited characteristic morphology. We differentiated the human iPSC cell line into a neuronal lineage confirmed by TUJ-1 staining, a neuronal class III β-tubulin marker. We detected higher protein expression levels of ubiquitin (Ub), TAR DNA-binding protein-43 (TDP-43), Light Chain 3-I/II (LC3), p62/SQSTM1, and optineurin (OPN) in the iPSC neural lineage compared to the control neural line. Collectively, our results demonstrate that patient-specific iPSC technology may provide useful disease modeling for understanding the complex mechanisms and for developing novel treatments of VCP and related disorders.

Introduction/aims

Neuralgic amyotrophy (NA) is a multifocal neuropathy involving the nerves of the upper extremity, limiting functional capability and reducing range of motion. The reachable workspace (RWS) is a computerized three-dimensinal analysis system that evaluates the relative surface area (RSA) of an individual's arm reachability and has shown utility in several neuromuscular disorders. The aims of this study were to examine the ability of the RWS to quantitatively detect limitations in upper extremity active range of motion in patients with NA, and correlate these with other upper extremity functional outcome measures.

Methods

Forty-seven patients with NA and 25 healthy age- and sex-matched controls were measured with the RWS. Study participants' RSAs were correlated with scores on the Shoulder Rating Questionnaire (SRQ), the Disabilities of Arm Shoulder and Hand (DASH) questionnaire, and upper extremity strength measurements using hand-held dynamometry.

Results

Patients with NA showed significantly lower values in the affected arm for all quadrants (except for the ipsilateral lower quadrant) and total RSA compared with controls (P < 0.001). We found moderate correlations between the reachable workspace, the DASH questionnaire result (r = -0.415), and serratus anterior muscle strength (r = 0.414).

Discussion

RWS is able to detect limitations in active range of motion of the affected arm in patients with NA, and is moderately correlated with upper extremity functional measures. RWS can demonstrate impairment of the affected upper extremity in NA and it has potential as a clinical outcome measure.