Upper limb sensorimotor recovery in Asian stroke survivors: a study protocol for the development and implementation of a Technology-Assisted dIgitaL biOmaRker (TAILOR) platform.

Background: Stroke is a leading cause of lifelong disability worldwide, partially driven by a reduced ability to use the upper limb in daily life causing increased dependence on caregivers. However, post-stroke functional impairments have only been investigated using limited clinical scores, during short-term longitudinal studies in relatively small patient cohorts. With the addition of technology-based assessments, we propose to complement clinical assessments with more sensitive and objective measures that could more holistically inform on upper limb impairment recovery after stroke, its impact on upper limb use in daily life, and on overall quality of life. This paper describes a pragmatic, longitudinal, observational study protocol aiming to gather a uniquely rich multimodal database to comprehensively describe the time course of upper limb recovery in a representative cohort of 400 Asian adults after stroke. Particularly, we will characterize the longitudinal relationship between upper limb recovery, common post-stroke impairments, functional independence and quality of life. Methods: Participants with stroke will be tested at up to eight time points, from within a month to 3 years post-stroke, to capture the influence of transitioning from hospital to community settings. We will perform a battery of established clinical assessments to describe the factors most likely to influence upper limb recovery. Further, we will gather digital health biomarkers from robotic or wearable sensing technology-assisted assessments to sensitively characterize motor and somatosensory impairments and upper limb use in daily life. We will also use both quantitative and qualitative measures to understand health-related quality of life. Lastly, we will describe neurophysiological motor status using transcranial magnetic stimulation. Statistics: Descriptive analyses will be first performed to understand post-stroke upper limb impairments and recovery at various time points. The relationships between digital biomarkers and various domains will be explored to inform key aspects of upper limb recovery and its dynamics using correlation matrices. Multiple statistical models will be constructed to characterize the time course of upper limb recovery post-stroke. Subgroups of stroke survivors exhibiting distinct recovery profiles will be identified. Conclusion: This is the first study complementing clinical assessments with technology-assisted digital biomarkers to investigate upper limb sensorimotor recovery in Asian stroke survivors. Overall, this study will yield a multimodal data set that longitudinally characterizes post-stroke upper limb recovery in functional impairments, daily-life upper limb use, and health-related quality of life in a large cohort of Asian stroke survivors. This data set generates valuable information on post-stroke upper limb recovery and potentially allows researchers to identify different recovery profiles of subgroups of Asian stroke survivors. This enables the comparisons between the characteristics and recovery profiles of stroke survivors in different regions. Thus, this study lays out the basis to identify early predictors for upper limb recovery, inform clinical decision-making in Asian stroke survivors and establish tailored therapy programs. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05322837.

The Evolution of Hand Proprioceptive and Motor Impairments in the Sub-Acute Phase After Stroke.

BACKGROUND: Hand proprioception is essential for fine movements and therefore many activities of daily living. Although frequently impaired after stroke, it is unclear how hand proprioception evolves in the sub-acute phase and whether it follows a similar pattern of changes as motor impairments. OBJECTIVE: This work investigates whether there is a corresponding pattern of changes over time in hand proprioception and motor function as comprehensively quantified by a combination of robotic, clinical, and neurophysiological assessments. METHODS: Finger proprioception (position sense) and motor function (force, velocity, range of motion) were evaluated using robotic assessments at baseline (<3 months after stroke) and up to 4 weeks later (discharge). Clinical assessments (among others, Box & Block Test [BBT]) as well as Somatosensory/Motor Evoked Potentials (SSEP/MEP) were additionally performed. RESULTS: Complete datasets from 45 participants post-stroke were obtained. For 42% of all study participants proprioception and motor function had a dissociated pattern of changes (only 1 function considerably improved). This dissociation was either due to the absence of a measurable impairment in 1 modality at baseline, or due to a severe lesion of central somatosensory or motor tracts (absent SSEP/MEP). Better baseline BBT correlated with proprioceptive gains, while proprioceptive impairment at baseline did not correlate with change in BBT. CONCLUSIONS: Proprioception and motor function frequently followed a dissociated pattern of changes in sub-acute stroke. This highlights the importance of monitoring both functions, which could help to further personalize therapies.

The locations of stroke lesions next to the posterior internal capsule may predict the recovery of the related proprioceptive deficits.

Background: Somatosensory deficits after stroke correlate with functional disabilities and impact everyday-life. In particular, the interaction of proprioception and motor dysfunctions affects the recovery. While corticospinal tract (CST) damage is linked to poor motor outcome, much less is known on proprioceptive recovery. Identifying a predictor for such a recovery could help to gain insights in the complex functional recovery processes thereby reshaping rehabilitation strategies. Methods: 50 patients with subacute stroke were tested before and after neurological rehabilitation. Proprioceptive and motor impairments were quantified with three clinical assessments and four hand movement and proprioception measures using a robotic device. Somatosensory evoked potentials (SSEP) to median nerve stimulation and structural imaging data (MRI) were also collected. Voxel-based lesion-symptom mapping (VLSM) along with a region of interest (ROI) analysis were performed for the corticospinal tract (CST) and for cortical areas. Results: Before rehabilitation, the VLSM revealed lesion correlates for all clinical and three robotic measures. The identified voxels were located in the white matter within or near the CST. These regions associated with proprioception were located posterior compared to those associated with motor performance. After rehabilitation the patients showed an improvement of all clinical and three robotic assessments. Improvement in the box and block test was associated with an area in anterior CST. Poor recovery of proprioception was correlated with a high lesion load in fibers towards primary sensorymotor cortex (S1 and M1 tract). Patients with loss of SSEP showed higher lesion loads in these tracts and somewhat poorer recovery of proprioception. The VSLM analysis for SSEP loss revealed a region within and dorsal of internal capsule next to the posterior part of CST, the posterior part of insula and the rolandic operculum. Conclusion: Lesions dorsal to internal capsule next to the posterior CST were associated with proprioceptive deficits and may have predictive value. Higher lesion load was correlated with poorer restoration of proprioceptive function. Furthermore, patients with SSEP loss trended towards poor recovery of proprioception, the corresponding lesions were also located in the same location. These findings suggest that structural imaging of the internal capsule and CST could serve as a recovery predictor of proprioceptive function.

Reliability, validity and clinical usability of a robotic assessment of finger proprioception in persons with multiple sclerosis.

BACKGROUND: Multiple sclerosis often leads to proprioceptive impairments of the hand. However, it is challenging to objectively assess such deficits using clinical methods, thereby also impeding accurate tracking of disease progression and hence the application of personalized rehabilitation approaches. OBJECTIVE: We aimed to evaluate test-retest reliability, validity, and clinical usability of a novel robotic assessment of hand proprioceptive impairments in persons with multiple sclerosis (pwMS). METHODS: The assessment was implemented in an existing one-degree of freedom end-effector robot (ETH MIKE) acting on the index finger metacarpophalangeal joint. It was performed by 45 pwMS and 59 neurologically intact controls. Additionally, clinical assessments of somatosensation, somatosensory evoked potentials and usability scores were collected in a subset of pwMS. RESULTS: The test-retest reliability of robotic task metrics in pwMS was good (ICC=0.69-0.87). The task could identify individuals with impaired proprioception, as indicated by the significant difference between pwMS and controls, as well as a high impairment classification agreement with a clinical measure of proprioception (85.00-86.67%). Proprioceptive impairments were not correlated with other modalities of somatosensation. The usability of the assessment system was satisfactory (System Usability Scale ≥73.10). CONCLUSION: The proposed assessment is a promising alternative to commonly used clinical methods and will likely contribute to a better understanding of proprioceptive impairments in pwMS.

Design and Preliminary Evaluation of a Robot-assisted Assessment-driven Finger Proprioception Therapy.

Neurological injuries such as stroke often lead to motor and somatosensory impairments of the hand. Deficits in somatosensation, especially proprioception, result in difficulties performing activities of daily living involving fine motor tasks. However, it is challenging to accurately detect those impairments due to the limitations of clinical assessments. Hence therapies rarely focus on proprioception specifically, while such training could promote functional benefits. In this work we propose and preliminarily evaluate a robot-assisted, assessment-driven therapy of finger proprioception. We designed and implemented two therapeutic exercises, one targeting passive and the other active position sense. The difficulty level of the therapy exercises was adapted to each patient's proprioceptive impairment. We evaluated the exercises and their usability with 7 stroke participants and 8 clinicians in a 45-minutes protocol. We found that the exercises were feasible for stroke participants, as 5 individuals progressed in difficulty levels over multiple exercise repetitions, indicating adequacy of the adaptation algorithm. Moreover, usability was rated mostly as satisfactory by the patients (System Usability Scale = 73), and they also found the exercises interesting. Clinicians rated the exercises as difficult but clinically meaningful. Overall, these promising preliminary results pave the way for further development and validation of the proposed therapy approach.

Reliable and Valid Robotic Assessments of Hand Active and Passive Position Sense in Children With Unilateral Cerebral Palsy.

Impaired hand proprioception can lead to difficulties in performing fine motor tasks, thereby affecting activities of daily living. The majority of children with unilateral cerebral palsy (uCP) experience proprioceptive deficits, but accurately quantifying these deficits is challenging due to the lack of sensitive measurement methods. Robot-assisted assessments provide a promising alternative, however, there is a need for solutions that specifically target children and their needs. We propose two novel robotics-based assessments to sensitively evaluate active and passive position sense of the index finger metacarpophalangeal joint in children. We then investigate test-retest reliability and discriminant validity of these assessments in uCP and typically developing children (TDC), and further use the robotic platform to gain first insights into fundamentals of hand proprioception. Both robotic assessments were performed in two sessions with 1-h break in between. In the passive position sense assessment, participant's finger is passively moved by the robot to a randomly selected position, and she/he needs to indicate the perceived finger position on a tablet screen located directly above the hand, so that the vision of the hand is blocked. Active position sense is assessed by asking participants to accurately move their finger to a target position shown on the tablet screen, without visual feedback of the finger position. Ten children with uCP and 10 age-matched TDC were recruited in this study. Test-retest reliability in both populations was good (intraclass correlation coefficients (ICC) >0.79). Proprioceptive error was larger for children with uCP than TDC (passive: 11.49° ± 5.57° vs. 7.46° ± 4.43°, p = 0.046; active: 10.17° ± 5.62° vs. 5.34° ± 2.03°, p < 0.001), indicating discriminant validity. The active position sense was more accurate than passive, and the scores were not correlated, underlining the need for targeted assessments to comprehensively evaluate proprioception. There was a significant effect of age on passive position sense in TDC but not uCP, possibly linked to disturbed development of proprioceptive acuity in uCP. Overall, the proposed robot-assisted assessments are reliable, valid and a promising alternative to commonly used clinical methods, which could help gain a better understanding of proprioceptive impairments in uCP, facilitating the design of novel therapies.