Objective
Voluntary upper limb movements are an ecologically important yet insufficiently explored digital‐motor outcome domain for trials in degenerative ataxia. We extended and validated the ...trial‐ready quantitative motor assessment battery “Q‐Motor” for upper limb movements with clinician‐reported, patient‐focused, and performance outcomes of ataxia.
Methods
Exploratory single‐center cross‐sectional assessment in 94 subjects (46 cross‐genotype ataxia patients; 48 matched controls), comprising five tasks measured by force transducer and/or position field: Finger Tapping, diadochokinesia, grip‐lift, and—as novel implementations—Spiral Drawing, and Target Reaching. Digital‐motor measures were selected if they discriminated from controls (AUC >0.7) and correlated—with at least one strong correlation (rho ≥0.6)—to the Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (FARS‐ADL), and the Nine‐Hole Peg Test (9HPT).
Results
Six movement features with 69 measures met selection criteria, including speed and variability in all tasks, stability in grip‐lift, and efficiency in Target Reaching. The novel drawing/reaching tasks best captured impairment in dexterity (|rho9HPT| ≤0.81) and FARS‐ADL upper limb items (|rhoADLul| ≤0.64), particularly by kinematic analysis of smoothness (SPARC). Target hit rate, a composite of speed and endpoint precision, almost perfectly discriminated ataxia and controls (AUC: 0.97). Selected measures in all tasks discriminated between mild, moderate, and severe impairment (SARA upper limb composite: 0–2/>2–4/>4–6) and correlated with severity in the trial‐relevant mild ataxia stage (SARA ≤10, n = 20).
Interpretation
Q‐Motor assessment captures multiple features of impaired upper limb movements in degenerative ataxia. Validation with key clinical outcome domains provides the basis for evaluation in longitudinal studies and clinical trial settings.
BackgroundQuantitative digital assessments in clinical trials may increase effect sizes while reducing population sizes, resulting in more accurate and cost effective trials and less burden for ...participants, compared to qualitative scales. In an internship program (University of Tübingen - TüREx), we explored the feasibility of dual-task assessments using the Q-Motor devices, to amplify differentiation between HD gene carriers and healthy controls.AimsTo assess feasibility of a dual-task design of Q-Motor finger tapping and target pointing task in a small cohort.Methods10 healthy controls (non-gene carriers or status unknown) and 5 manifest and pre-manifest HD gene carriers have been enrolled in this proof-of-concept project. Participants were asked to perform three Q-Motor tasks: 1) Speeded finger tapping (non-dominant hand); 2) 3D pointing with the position tracking Polhemus Stylus to defined targets on a x-y plane installed in front of the subject in a pre-defined sequence (dominant hand); 3) Interference task, performing both tasks simultaneously.ResultsWe found that while neither task single performed task could differentiate between the participant groups, the interference task showed good differentiation (p < 0.01) between the groups for defined parameters. Specifically, HD gene carriers tended to use higher tapping forces in finger tapping, when doing target pointing simultaneously.ConclusionsWe found assessment of the described dual-tasks using Q-Motor devices feasible and well tolerated. While we acknowledge the limitations of the small sample size and unmatched groups, the results are encouraging and support confirmation of these findings in a larger cohort longitudinal study.
BackgroundQ-Motor provided reliable quantitative endpoints in TRACK-HD and several clinical trials. Finger tapping was the most sensitive assessment of disease progression and to detect treatment ...effects. Recently a foot tapping test was introduced to expand Q-Motor to the lower extremity. However, subjects had difficulties to properly lift the foot from the force sensor.AimsTo assess the feasibility of using a novel foot tapping apparatus that requires subjects to lift their foot properly.MethodsTwo novel setups were constructed with the force sensor above the foot, one using a rigid (G1), one with a non-rigid bar (G2) to carry the sensor. Both setups were compared with the old setup carrying the sensor underneath the foot (G3). 6 healthy controls were asked to perform the foot tapping task on each setup on 4 consecutive days. They tapped with the foot on the force sensor as fast as possible for 10 seconds with 5 repetitions at each foot.ResultsThe ‘Tap-Speed-Inter-Onset-Interval-Mean-Foot’ is the main endpoint of foot tapping. It is the average time between the start of each successive tap. A density plot showed normally distributed data only for G2 and G3, thus G1 was not analyzed further. The data showed that the new inverted test setup (G2) provided less variability and better reproducibility over time.ConclusionsThe novel foot tapping task is feasible and provided more reliable data. The new setup with the non-rigid bar merits further exploration in upcoming studies and should be tested in a larger cohort of subjects over longer periods.
Background and ObjectiveWith its relevance for everyday function, upper-limb-coordination is an insufficiently explored domain for digital-motor-outcomes in ataxia. Leveraging the trial-ready ...quantitative-motor (Q-Motor) system, we developed and validated a comprehensive task battery to capture upper-limb-ataxia.MethodsCross-sectional single-center-study (46 patients with predominantly degenerative cross-genotype cerebellar-ataxias (mean-age: 50 years; mean-SARA: 12 points), and 48 age- and sex-matched controls. Q-Motor assessments with a force transducer and an electromagnetic position sensor comprised both existing bilateral-tasks particularly promising for ataxia (foot-tapping, finger-tapping, diadochokinesia, grip-lift) (47 parameters/side), and tasks newly designed to capture ataxia (multi-directional two-dimensional-target-pointing, spiral-drawing) with the dominant hand (450 parameters, including spatial, temporal, spatiotemporal, and texture measures).ResultsTarget hits per second (AUC: 0.97) and frequency of foot-tapping, finger-tapping or diadochokinesia (AUC: 0.91-0.94) were excellent discriminators between ataxia and controls. Target hits per second and finger-tapping-frequency correlated strongly with the SARA (Spearman rho: -0.87 and -0.81), and even specifically with the sum of its upper limb items (-0.85 and -0.72). For diadochokinesia, temporal variability showed the strongest correlation with SARA (0.71) and its upper-limb composite (0.67, all p<0.001). Parameters in upper-limb tasks had moderate to strong correlations with activities-of-daily-living-function (FARS ADL, |rho|: 0.5-0.6), and dexterity as assessed by the 9-hole peg-test (0.53-0.78, all p<0.001).Discussion and ConclusionSeverity of upper-limb ataxia can be captured by Q-Motor with physiologically interpretable and functionally relevant measures of a finger-tapping, diadochokinesia, and a novel two-dimensional target-pointing-task of interest also for HD. Longitudinal assessments are ongoing to explore their responsiveness to change in a clinical trial setting.
Background and ObjectiveUpper-limb function is insufficiently explored as digital-motor outcome in ataxia. The Archimedes spiral-drawing-task might serve as a meaningful outcome requiring fine-motor ...skills of everyday-living. We implemented Archimedes-spiral-drawing in the trial-ready quantitative-motor (Q-Motor) system and explored underlying movement kinematics as digital outcomes.MethodsCross-sectional single-center validation study in 46 patients with predominantly degenerative cross-genotype cerebellar-ataxias (mean-age: 50 years; mean-SARA: 12 points), and 48 age- and sex-matched controls. Subjects were instructed to draw – as accurate as possible at self-paced speed - two Archimedes spirals with their dominant hand on a paper template while traced by a Polhemus FASTRAK digitizer with a pencil lead attachment. Thirty-five parameters were validated against the Scale for the assessment and rating of ataxia (SARA), activities of daily living (FARS ADL), and the 9-hole peg-test (9HPT).ResultsParameters in the spatial domain, namely the summed 10th decile, standard deviation and maximum of the error distribution (distance from template), discriminated best between ataxia and controls (AUC: 0.83-0.89), and showed the strongest correlation with FARS-ADL (rho: 0.38-0.47). In contrast, parameters in the frequency (Fourier power, 1-4 Hz, Spearman rho: 0.75) and spatiotemporal domain (90th percentile of speed, rho: 0.72) correlated most with the total SARA (specifically a composite of upper-limb items), as well as the 9HPT (rho: 0.59-0.74).Discussion and ConclusionQuantitative analysis of Archimedes-spiral-drawing allows to capture fine-motor impairment, with differential correlations to clinical severity, function, and ADL across domains in ataxia – encouraging its exploration in HD. Longitudinal analyses are ongoing to investigate sensitivity to change.
BackgroundQ-Motor assessments have been used in a number of large multicenter clinical studies in Huntington’s disease and beyond. Q-Motor has proven to be a robust and sensitive tool to track and ...compare motor performance cross-sectionally or longitudinally, reducing placebo effects and rater bias compared to clinical scales.AimsThe current study investigated whether the application of Q-Motor assessments in a large population-based sample is feasible, and whether it provides the opportunity to generate normative data and to investigate the effects of demographic variables on Q-Motor measures.MethodsThe BiDirect study is an observational, prospective cohort study conducted at the University of Muenster in Germany. All participants, including the population-based control cohort, performed the Q-Motor speeded tapping (digitomotography) and grasping & lifting (manumotography and choreomotography) tasks. Normative data was gathered with regard to age and sex, thereby considering further mediating variables. Effects were estimated using univariate multiple linear regression analyses.ResultsThe use of Q-Motor assessments was feasible in the setting of this longitudinal cohort study. Normative data was generated for all tasks applied and measures proposed. The applied models showed significant effects of age and sex on some tapping speed measures and involuntary movements: participants showed decreasing performance with increasing age. Moreover, women tended to tap slower than men, and the non-dominant hand showed reduced performance compared to the dominant hand across tests.ConclusionsQ-Motor assessments are feasible for population-based cohort studies. The normative data generated here will enable comparative analysis in other studies and clinical trials, including more robust conclusions about clinical change.
BackgroundClinical rating scales in clinical trials for Huntington’s disease (HD) have shown limited sensitivity in the premanifest stage of HD and often suffer from inter- and intra-rater ...variability and bias. Thus, there is an unmet need for objective and reliable assessments to serve as outcome measures in clinical trials. The Q-Motor, a sensor-based assessment battery, was developed to provide accurate and precise quantification of motor performance. During the analysis of the TRACK-HD study, a couple of variables turned out to be particularly sensitive, but further approaches on testing alternative variables have not been conducted, yet.ObjectiveTo identify novel conceptual variables for the Q-Motor digitomotography (speeded tapping) assessment, that have the potential to be more sensitive and robust particularly in the premanifest stage. The applicability of these variables should be investigated for cross-sectional and longitudinal analyses, using the TRACK-HD data.MethodsQ-Motor raw-data from the TRACK-HD study was used to extract the novel variables. The data sample included 4 year follow up data from 288 participants (age: 48 ± 10 years, female: 124, number of unaffected controls: 94). Statistical analyses were conducted using R. Generalized linear mixed models and ANOVA was used for group comparisons cross-sectional and longitudinally. Correlation with clinical rating scales and imaging parameters was performed.ResultsMost novel identified variables allow discrimination between controls pre-HD and manifest HD groups. Some even show significance in the more subtle distinction between pre-HD subgroups. Most variables also show good correlations with the clinical Total Motor Score (TMS) and with several magnet resonance (MR) imaging variables.ConclusionThe sensitivity observed in the novel variables is comparable to that of previously used variables. However, the additional information may be useful for the creation of a combined measure, which will be explored in a next step.
