Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients

<div><p>Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials.</p></div

Repeatability.

<p>The first column shows the scatter plots of three features for the two assessments of controls within the same day (angles in degrees and velocity in m/s). The second column shows the Bland-Altman plots of the same two assessments. Values are colored by individual IDs of the controls. The third column displays between visit assessments for SMA patients and controls. Measurements from the same subject are connected by lines and are colored by groups.</p

Game scene.

<p>In the game scene, a visual skeleton figure represents the body of the subject. A flashing indicator and information below (pink) instruct the subject where to reach with which hand. On the upper left corner a counter and a timer are shown.</p

Feature—disease association.

<p>Distributions of three features are displayed by group and by visit. Elbow angle and lifting angle show no group differences as opposed to velocity.</p

Trace plot.

<p>Movement trajectories of all 9 tracked body points in x-y dimension for a patient with a tremor and a healthy control.</p

Pearson correlations for the three features from test-retest data within the same day for controls and from between visits for controls and patients.

<p>Pearson correlations for the three features from test-retest data within the same day for controls and from between visits for controls and patients.</p

Irradiation-induced ablation of neurogenesis.

<p>A, schematic diagram of experimental procedures. Female wistar rats received a high (12 gy) or low (6 gy) irradiation dose or were sham-treated at P10 (N = 10 per group). Mice were sacrificed 7 weeks after treatment. A subset of brains were processed for immunohistochemistry (12 gy: N = 2, 6 gy: N = 3, sham: N = 3). Residual brains were split into hemispheres and dissected for mRNA and protein analysis (N = 6/group). B, Representative images of Dcx-IR in the olfactory bulb of formalin-fixed paraffin embedded (FFPE) sections. Left-to-right: A high density of dendritic Dcx-IR is observed in the olfactory bulb granular layer sham-irradiated animals. Dendritic labeling is reduced with low-irradiation and virtually absent in animals after 12 gy-irradiation. Scale bar: 200 µm. C, bar graphs of Dcx-protein-levels in the olfactory bulb. A dose-dependent decrease in Dcx-protein levels is observed in irradiated animals vs sham-controls. D, bar graphs of Dcx-mRNA-levels in the olfactory bulb. A dose-dependent decrease in Dcx-mRNA levels is observed in irradiated animals vs sham-controls. E, Representative images Dcx-IR in the dentate gyrus of FFPE sections. Upper panel: overview of Dcx-IR in the dentate gyrus. Left-to-right: Dcx-IR is restricted to cells in the dentate gyrus SGZ with dendrites spanning into the granular and molecular layer. Lower panel: higher magnification of the SGZ. F, bar graphs of Dcx-protein-levels in the hippocampus. A slight dose-dependent decrease in DCX-protein levels is observed in irradiated animals. G, bar graphs of Dcx-mRNA-levels in the hippocampus. DCX-mRNA levels do not change significantly between sham and irradiated groups. H, bar graphs of Dcx-protein-levels in the cerebral cortex. I, bar graphs Dcx-mRNA-levels in cerebral cortex. DCX-mRNA levels do not change significantly between sham and irradiated groups. J, bar graphs of Dcx-protein-levels in the cerebellum. K, bar graphs of Dcx-mRNA-levels in cerebellum. Dcx-mRNA levels do not change significantly between sham and irradiated groups. Dunnett’s Multiple Comparisons Test.</p

Learning effect.

<p>Total time spent in finishing the test for all visits is plotted with lines connecting the records from the same subject. Thick lines display the linear fit per group, with 95% confidence intervals.</p

14-day voluntary running wheel experiment.

<p>In two separate experiments, adult mice with or without access to a running wheel were sacrificed after 2 weeks. The right hemisphere was dissected for either protein or mRNA-analysis while the left hemisphere was used to confirm exercise-induced increase in Dcx-IR via immunohistochemistry. A, Dcx-IR was quantified by calculating the total Dcx-IR area in µm² for four different sections within the dorsal hippocampus (left). Bar graph of hippocampal Dcx-protein-levels in DG and resHp (right). N = 12/group. B, Dcx-IR was quantified by calculating the total Dcx-IR area in µm² for four different sections within the dorsal hippocampus (left). Bar graph of hippocampal Dcx-mRNA-level in DG and resHp (right). N = 15/group. C, Bar graph mRNA-level in DG and resHp for Sox11 and Tbr2/EOMES. N = 15/group. Bonferroni’s Multiple Comparisons Test.</p

Dcx protein-levels in rat brain homogenates and CSF during development.

<p>Olfactory bulb, whole hippocampus, pieces of cerebral cortex and cerebellum, and CSF were analyzed from rats at different developmental stages (postnatal day 5 to 40). A, Dcx-protein levels in rat brain tissue homogenates during postnatal development. B, Dcx-protein levels in CSF during postnatal development (N = 4).</p