Jayme S. Knutson, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Project Summary: This proposal describes the first randomized controlled trial of a new therapy for stroke rehabilitation. Many stroke survivors never regain function of their hemiparetic upper extremity. Recent research has shown that rehabilitation techniques such as active repetitive goal-oriented motion of the paretic limb, neuromuscular electrical stimulation, bilateral arm exercise, and motor imagery improve motor recovery. However, many of these emerging therapies require some residual movement and therefore are not applicable to severely disabled stroke survivors. Moreover, these techniques often require significant amounts of therapist time and long intense therapy sessions. This pilot study investigates an innovative neuromuscular electrical stimulation (NMES) therapy that incorporates several rehabilitation techniques shown to improve recovery. Contralaterally Controlled Functional Electrical Stimulation (CCFES) activates paretic muscles to open and close the affected hand in direct proportion to the degree of opening and closing of the unimpaired contralateral hand, as detected by a sensor glove. The primary objective of the study is to collect pilot data estimating the effect of CCFES on upper extremity motor impairment and activity limitation. Thirty acute stroke survivors (< 3 mo) with severe hemiparesis will be randomized to CCFES, cyclic NMES, or bilateral symmetric volitional exercise without stimulation for six weeks and will be followed for 3 months. The six-week treatment consists of daily home exercises plus functional task practice sessions twice a week. Outcome measures will include assessments of upper extremity motor impairment and activity limitation. Relevance: There is a need for more effective rehabilitation techniques for individuals who are disabled by stroke. This study is an important step in the development of a new stroke therapy that is applicable to a wide range of stroke survivors, including those with severe degrees of motor disability. As more effective stroke therapies are developed, the prevalence of post-stroke disability may be decreased. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Stroke is the leading cause of severe, long-term disability among older adults in the United States. Nearly one third of stroke survivors have chronic hemiparesis. One of the most frequently persisting consequences of stroke is impaired hand function. The long-term objective of this research program is to develop an implanted neuromuscular electrical stimulation (NMES) neuroprosthesis that enables stroke survivors to use their paretic arm and hand again to perform activities of daily living. This exploratory study proposes to implement in two chronic stroke survivors (>6 months post-stroke) a neuroprosthesis that has previously been successfully implemented in tetraplegic spinal cord injury patients. The specific aims are to establish the feasibility of implementing the system in stroke survivors and to evaluate the effect of the neuroprosthesis on upper extremity motor impairment and activity limitation. The participants will undergo a surgical procedure in which the neuroprosthesis will be implanted. The implanted components include a multi- channel stimulator-telemeter, stimulation electrodes, and EMG-recording electrodes. The stimulating electrodes will be implanted on paralyzed upper extremity muscles. The EMG-recording electrodes will be implanted on upper extremity muscles of which the subject retains voluntary control. The individual will control their stimulated arm and hand movements by making particular muscle contractions. Special attention will be devoted to creating control strategies that are intuitive to the subjects and do not require unnatural movements or muscle contractions. The post-surgical course includes 3-4 weeks of immobilization, then 4-6 weeks of muscle strengthening with stimulation, followed by a two-week period of system customization and training. Feasibility of system implementation and effectiveness will be evaluated with assessments of technical performance and safety and clinical outcomes, which will be made at 3, 6, and 9 months after the training period. The clinical assessments will include measurements of upper extremity motor impairment and activity limitation with and without using the neuroprosthesis, which will be compared to baseline assessments. The neuroprosthesis is expected to enable the users to perform bimanual tasks that cannot be independently achieved otherwise. The successful completion of this study will: a) demonstrate the feasibility of an implanted upper extremity neuroprosthesis for hemiplegic stroke survivors, b) provide valuable information for improving the technology so that its applicability in stroke may be defined and expanded, c) provide an initial estimate of the effect of the neuroprosthesis on motor impairment and activity limitation, and d) generate pilot data to be used to design an R01 efficacy trial.

DESCRIPTION (provided by applicant): Hemiparesis of the upper limb is one of the most serious and most common impairments resulting from stroke. Approximately 75% of the over 750,000 strokes that occur annually in the United States cause some degree of upper extremity paralysis. Approximately 65% of stroke survivors still cannot use their affected hand to assist with activities of daily living 6 months after their stroke. The impact of upper extremity impairments on disability and health is great, yet there are relatively few rehabilitation interventions designed to restore function to the impaired upper limb. Therefore, our long-term objective is to develop upper extremity rehabilitation therapies that are effective at restoring arm and hand function, that are applicable across a wide range of impairment severity, and that are readily implemented in the present healthcare environment. The purpose of this study is to estimate the efficacy of Contralataterally Controlled Functional Electrical Stimulation (CCFES) in reducing upper extremity impairment and activity limitation in chronic upper extremity hemiplegia. CCFES is a rehabilitation intervention in which neuromuscular electrical stimulation (NMES) is applied to the finger and thumb extensor muscles of the paretic upper limb to open the hand. The stroke survivor controls the stimulation intensity, and consequent degree of hand opening, by modulating the degree of opening of the contralateral unimpaired hand, which is detected by an instrumented glove. Thus, volitional opening of the unaffected hand produces stimulated opening of the affected hand. The stimulation paradigm is used to assist the stroke survivor in practicing functional tasks with their affected hand. Pilot studies of CCFES in chronic hemiplegia were encouraging. This project will expand on the work already begun by: 1) determining if 12 weeks of CCFES is therapeutically effective in chronic stroke survivors, 2) determining if a plateau in treatment effect is achieved before 12 weeks is completed, 3) determining how initial level of motor impairment affects treatment efficacy, and 4) determining whether therapeutic gains persist over time. We will conduct a randomized controlled trial in which 102 chronic stroke survivors (>6 months post-stroke) will be randomly assigned to receive 12 weeks of CCFES or cyclic NMES, an intervention that provides electrical stimulation of the hand extensors, but with preprogrammed timing and intensity. Randomization will be stratified on two levels of baseline hand impairment defined by the degree of voluntary finger extension present. Assessments of upper extremity impairment and activity limitation will be made every 3 weeks during the treatment period and every 2 months during a 6-month follow-up period. This study is the first randomized controlled trial of CCFES in chronic upper extremity hemiplegia. Ultimately, the information learned in this study will serve to accelerate the development of treatments for reducing post-stroke disability. PUBLIC HEALTH RELEVANCE There is a need for effective rehabilitation interventions for individuals who have become disabled by stroke. This study is an important step toward the development of a new treatment that may be found to be more effective in facilitating lasting motor recovery, more widely applicable to a broader range of stroke survivors, and more readily implemented than existing stroke rehabilitation techniques. As more effective stroke rehabilitation therapies are developed, the prevalence of post-stroke disability may be decreased.

DESCRIPTION (provided by applicant): Hemiparesis of the lower limb is one of the most common impairments resulting from stroke. Approximately 80% of the over 780,000 strokes that occur annually in the United States result acutely in loss of ability to walk household distances independently. By 6 months after stroke, approximately 40% of all stroke survivors are still either unable to walk or require personal assistance to walk even short distances. The impact of lower limb impairment on disability and health is great;therefore, our long-term objective is to develop lower limb rehabilitation therapies that are effective at reducing impairment and improving ambulation, that are applicable across a wide range of impairment severity, and that are readily implemented in the present healthcare environment. A major contributor to impaired ambulation is the inability to dorsiflex the ankle during the swing phase of gait, which results in inefficient and unsafe ambulation or non-ambulation. This proposal investigates a new intervention that aims to reduce lower limb motor impairment and improve gait in stroke survivors with chronic lower extremity hemiplegia by improving voluntary ankle dorsiflexion. Contralaterally controlled neuromuscular electrical stimulation (CCNMES) incorporates several rehabilitation techniques shown to improve motor recovery. CCNMES activates the paretic ankle dorsiflexors through surface electrodes over the peroneal nerve and tibialis anterior. The stimulation intensity is directly proportional to the degree of volitional dorsiflexion of the unimpaired contralateral ankle, as detected by an instrumented sock. Thus, volitional dorsiflexion of the unaffected ankle produces stimulated dorsiflexion of the affected ankle, thereby enabling the patient to control their ankle movement. The system is not used for walking but for motor control therapy. The primary objective of the study is to collect pilot data estimating the effect of CCNMES therapy on lower extremity impairment and ambulation. Twenty-six chronic stroke survivors (>6 months post-CVA) with significant ankle dorsiflexor paresis will be randomized to CCNMES or cyclic NMES for six weeks and will be followed for 3 months. The six-week treatment consists of subject-administered stimulation-mediated ankle exercises at home 5 days a week plus therapist-supervised ankle motor control task practice in the laboratory twice a week. Outcome measures will include assessments of lower extremity impairment and ambulation. This study is the first randomized controlled trial of CCNMES for ankle dorsiflexor paresis. Ultimately, the information learned in this study will serve to accelerate the development of treatments for reducing post- stroke disability. PUBLIC HEALTH RELEVANCE: There is a need for more effective rehabilitation interventions for individuals who have become disabled by stroke. This study is an important step toward the development of a new treatment that may be found to be more effective in facilitating lasting motor recovery, more widely applicable to a broader range of stroke survivors, and more readily implemented than existing stroke rehabilitation techniques. As more effective stroke rehabilitation therapies are developed, the prevalence of post-stroke disability may be decreased.

DESCRIPTION (provided by applicant): Impaired arm and hand function is one of the most disabling and most common consequences of stroke. Approximately 75% of the over 795,000 strokes that occur annually in the Unites States cause some degree of upper limb paralysis acutely. By 6 months post-stroke an estimated 65% of patients still cannot incorporate the impaired arm and hand into their daily activities, and nearly one third have chronic loss of upper limb function, which is often characterized by inability to extend the arm and open the hand. While the impact of upper limb impairments on disability and health is great, there are relatively few rehabilitation interventions designed to restore function to the impaired upper limb. Therefore, our long-term objective is to develop rehabilitation therapies for the paretic upper limb that are optimized for effectiveness, applicability, and implementation. Contralaterally Controlled Functional Electrical Stimulation (CCFES) is an innovative neuromuscular electrical stimulation (NMES) treatment for improving the recovery of hand function after stroke. CCFES stimulates the paretic hand to open in proportion to the degree of volitional opening of the contralateral unimpaired hand. This enables the stroke survivor to perform active repetitive hand opening exercises, hand motor-control tasks, and functional tasks with the paretic hand. In this study, we add stimulation of elbow extensors controlled by the contralateral elbow in order to improve reach as well as hand opening. The purpose of this study is to optimize CCFES by adding stimulated elbow extension, increasing and evaluating the effect of treatment duration, and estimating the best time after stroke to begin treatment. The specific aims include: 1) estimating the effect of Arm+Hand CCFES on upper limb motor impairment and activity limitation, 2) estimating the effect of treatment duration, 3) defining the relationship between treatment effect and time elapsed between stroke onset and start of treatment. One hundred eight (108) stroke survivors with acute/subacute (? 6 months post-stroke) upper limb hemiplegia will be randomly assigned in equal proportions to receive either 6, 9, or 12 weeks of Arm+Hand CCFES or 12 weeks of cyclic NMES, which is an intervention that stimulates the elbow and hand to extend, but with pre-set timing and intensity. Upper limb impairment and activity limitation will be assessed at baseline, 6, 9, 12, 20, 28, and 36 weeks. By optimizing the CCFES treatment for acute stroke survivors, its therapeutic effect will be maximized and the optimum treatment duration and timeframe to start treatment will be estimated. This information is critical for the design of a large-scale efficacy trial of Arm+Hand CCFES, and will serve to accelerate the development and ultimately the dissemination of a new treatment for reducing post-stroke disability.

PROJECT SUMMARY/ABSTRACT Stroke rehabilitation technologies and treatments must progress through multiple phases of research and development before they reach clinical acceptance and are translated to clinical practice. Progressing from single-site to multi-site clinical trials is a critical step in the process. Multi-site studies prove whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. The study proposed here is the first multi-site clinical trial of a new intervention called contralaterally controlled functional electrical stimulation (CCFES). CCFES is an innovative technology and rehabilitation therapy for improving the recovery of hand function in patients with upper extremity hemiparesis. CCFES applies electrical stimulation to the paretic finger and thumb extensor muscles through surface electrodes, causing the weak hand to open, a function that is often lost in stroke survivors. The patient controls the intensity of stimulation to their paretic hand by wearing a glove with sensors on their unaffected contralateral hand. When the patient opens their unaffected hand, a proportional intensity of stimulation opens their paretic hand. CCFES puts the patient back in control of their paretic hand, and this may drive neuroplastic changes that lead to better recovery of hand function. CCFES therapy includes using the device to assist hand opening during functional task practice sessions with a therapist in the lab plus self-administering a CCFES- mediated repetitive hand opening exercise at home. Our previous single-site study showed that CCFES improves dexterity more than conventional cyclic NMES (cNMES) in chronic (> 6 months) stroke patients, and identified most likely responders to be stroke survivors who are less than 2 years post-stroke. The main purpose of this study is to confirm and demonstrate the generalizability of these preliminary results in a larger group of most likely responders across multiple sites. The study will enroll 171 stroke survivors who are 6 to 24 months post-stroke. They will be randomized to 12 weeks of CCFES, cNMES (which applies electrical stimulation to the hand extensors, but with pre-set timing and intensity), or task-oriented training without electrical stimulation. The study will be conducted by research teams at three sites, who will administer the treatments and blinded outcome assessments. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or task-oriented training, and explore the effects of CCFES therapy on the central nervous system. Retention of improvements will be evaluated through a 6- month post-treatment follow-up period. This Phase II multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination.