Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments

Bad research, invalid comparison between the groups with one group getting an extra 10 hours. 

Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments

Alma S. Merians¹, Gerard G. Fluet¹, Qinyin Qiu¹, Mathew Yarossi^2,3, Jigna Patel¹, Ashley J. Mont⁴, Soha Saleh^5,6, Karen J. Nolan^5,6, AM Barrett^6,7, Eugene Tunik^2,8,9 and Sergei V. Adamovich^1,4*

• ¹Department of Rehabilitation and Movement Sciences, School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ, United States
• ²Movement Neuroscience Laboratory, Department of Physical Therapy, Movement and Rehabilitation Science, Bouve College of Health Sciences, Northeastern University, Boston, MA, United States
• ³SPIRAL Group, Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States
• ⁴Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, United States
• ⁵Center for Mobility and Rehabilitation Engineering Research, Kessler Foundation, West Orange, NJ, United States
• ⁶Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, United States
• ⁷Center for Stroke Rehabilitation Research, Kessler Foundation, West Orange, NJ, United States
• ⁸Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA, United States
• ⁹Department of Electrical and Computer Engineering, College of Engineering, Northeastern University, Boston, MA, United States

Introduction: Innovative motor therapies have attempted to reduce upper extremity impairment after stroke but have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits affecting their self-care and participation in daily activities. Intervention studies have focused on the role of increased dosing, however recent studies have indicated that timing of rehabilitation interventions may be as important as dosing and importantly, that dosing and timing interact in mediating effectiveness. This study is designed to empirically test dosing and timing.

Methods and Analysis: In this single-blinded, interventional study, subjects will be stratified on two dimensions, impairment level (Fugl-Meyer Upper Extremity Assessment (FM) and presence or absence of Motor Evoked Potentials (MEPs) as follows; (1) Severe, FM score 10–19, MEP+, (2) Severe, FM score 10–19, MEP–, (3) Moderate, FM score 20–49, MEP+, (4) Moderate, FM score 20–49, MEP–. Subjects not eligible for TMS will be assigned to either group 2 (if severe) or group 3 (if moderate). Stratified block randomization will then be used to achieve a balanced assignment. Early Robotic/VR Therapy (EVR) experimental group will receive in-patient usual care therapy plus an extra 10 h of intensive upper extremity therapy focusing on the hand using robotically facilitated rehabilitation interventions presented in virtual environments and initiated 5–30 days post-stroke. Delayed Robotic/VR Therapy (DVR) experimental group will receive the same intervention but initiated 30–60 days post-stroke. Dose-matched usual care group (DMUC) will receive an extra 10 h of usual care initiated 5–30 days post-stroke. Usual Care Group (UC) will receive the usual amount of physical/occupational therapy.

Outcomes: There are clinical, neurophysiological, and kinematic/kinetic measures, plus measures of daily arm use and quality of life. Primary outcome is the Action Research Arm Test (ARAT) measured at 4 months post-stroke.

Discussion: Outcome measures will be assessed to determine whether there is an early time period in which rehabilitation will be most effective, and whether there is a difference in the recapture of premorbid patterns of movement vs. the development of an efficient, but compensatory movement strategy.

Ethical Considerations: The IRBs of New Jersey Institute of Technology, Rutgers University, Northeastern University, and Kessler Foundation reviewed and approved all study protocols. Study was registered in https://ClinicalTrials.gov (NCT03569059) prior to recruitment. Dissemination will include submission to peer-reviewed journals and professional presentations.

Introduction

Stroke is the leading cause of long-term adult disability (1). Independent upper extremity function is critically important to restore full independence and reduce the need for costly supportive care. Although innovative upper limb motor therapies, (2–5) have attempted to reduce upper extremity impairment after stroke, we have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits that affect their self-care and ability to participate in daily activities (6). This lack of progress might be explained in part by the complexity of coordination of the multiple degrees of freedom required for normal upper limb function. Clearly, there is a need to develop more effective rehabilitation programs for the arm and the hand of persons with stroke.

The focus of recent rehabilitation studies has been on increasing the dosing and intensity of the interventions. Findings in a group of randomized controlled trials (7–10) indicated that the critical ingredients needed for arm and hand movement recovery may be the amount of treatment provided and the value of progressively increasing the level of difficulty of a task. The importance of dosage was further supported in a meta-analysis (11) of physical therapy interventions utilizing high repetition activities. These findings led to the growing consensus on the importance of intensity (number of repetitions per time on task) or dosage (time on task) to achieve better outcomes post-stroke. However, a recent phase 3 study of over 350 patients showed no differences among an additional 30 h of upper extremity structured task-oriented therapy, an equivalent dose of customary occupational therapy, or even a lower dose of customary therapy when these interventions were initiated 45 days post-stroke (12). Therefore, a consensus on optimal dosing in the early period post-stroke remains elusive (13).

It is apparent that it is not just dosing that needs to be considered. Several authors suggest that the timing of rehabilitation interventions may be as important as the dosing and have proposed that the dosing and timing of an intervention are not independent factors (14–16). Although the optimal time period is not clear, it has been shown that the first month post-stroke is a crucial time for synaptic plasticity where the brain is most responsive to sensorimotor input and training (14). The post-stroke sensitivity to intervention decreases as time post-stroke increases (17, 18). Both animal and human studies of early intervention reported better functional recovery [1–2 weeks in animals; 4 weeks in humans; (14, 19–21)] when training was initiated during the first month of recovery during this proposed period of intensive plasticity (14, 21–23). Thus, increasing rehabilitation treatment dose during this initial recovery period might have particularly beneficial effects. Nevertheless, most of the research on novel therapies involved subjects in the chronic phase after stroke, with a rather limited number of intervention studies available during the early and late acute phases (24).

However, contrary to these positive findings, some animal studies have shown that lesion size increased after early excessive limb training (25–27). Some human studies have also shown similar negative findings. Although, a meta-analysis of training studies showed a favorable effect on ADL resulted when augmented therapy was begun very early post-stroke (28), two studies did not find benefits from early intervention. The AVERT study was an early mobilization (<24 h) walking study and may not be an equivalent comparison (29). The Vectors study showed no differences between 2 h of early Constraint Induced Movement Therapy (CIMT) training and the control group but found less improvement with 3 h/day of early CIMT (30).

Therefore, it is particularly important to understand the impact of early motor training after stroke. Although, it has been proposed that early rehabilitation be integrated into comprehensive stroke centers to enhance care quality (31), the current state of health care delivery systems, in many countries, provides for limited in-patient rehabilitation post stroke. During this restricted time period, the focus is on ambulation and compensatory upper extremity activities necessary for activities of daily living. There is inadequate attention paid to rehabilitation and restoration of upper extremity movements so necessary for future independence in self-care activities. The conflicting evidence regarding timing, dosage and even the method of delivery of the increased dosing, robotics, virtual reality (32), or traditionally presented repetitive practice, suggests the need to examine both high volume training and method of training during the first-months post-stroke. Clearly, we do not yet have a good understanding of these relationships and their potential impact on recovery of motor function and brain reorganization.