570325
research-article2015
NNRXXX10.1177/1545968315570325Neurorehabilitation and Neural RepairBethoux et al
Original Research Article
Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke
Neurorehabilitation and Neural Repair 1–12 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1545968315570325 nnr.sagepub.com
Francois Bethoux, MD1, Helen L. Rogers, PhD2, Karen J. Nolan, PhD3,4, Gary M. Abrams, MD5, Thiru Annaswamy, MD, MA6,7, Murray Brandstater, MD, PhD8, Barbara Browne, MD9, Judith M. Burnfield, PhD10, Wuwei Feng, MD, MS11, Mitchell J. Freed, MD12, Carolyn Geis, MD13, Jason Greenberg, MD14, Mark Gudesblatt, MD15, Farha Ikramuddin, MD16, Arun Jayaraman, PhD17, Steven A. Kautz, PhD11,18, Helmi L. Lutsep, MD19, Sangeetha Madhavan, PhD20, Jill Meilahn, DO21, William S. Pease, MD22, Noel Rao, MD23, Subramani Seetharama, MD24, Pramod Sethi, MD25, Margaret A. Turk, MD26, Roi Ann Wallis, MD27,28, and Conrad Kufta, MD2
Abstract Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. Objective. Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. Methods. Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). Results. A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints.
1
Cleveland Clinic, Cleveland, OH, USA Innovative Neurotronics, Austin, TX, USA 3 Kessler Foundation, West Orange, NJ, USA 4 Rutgers—New Jersey Medical School, Newark, NJ, USA 5 UCSF/San Francisco VA Medical Center, San Francisco, CA, USA 6 VA North Texas Health Care System, Dallas, TX, USA 7 UT Southwestern Medical Center, Dallas, TX, USA 8 Loma Linda University Medical Center, Loma Linda, CA, USA 9 Magee Rehabilitation Hospital, Philadelphia, PA, USA 10 Madonna Rehabilitation Hospital’s Institute for Rehabilitation Science and Engineering, Lincoln, NE, USA 11 Medical University of South Carolina, Charleston, SC, USA 12 Florida Hospital Neuroscience and Orthopedic Research Institute, Orlando, FL, USA 13 Halifax Health Center for Neurosciences, Daytona Beach, FL, USA 14 Helen Hayes Hospital, West Haverstraw, NY, USA 15 South Shore Neurologic Associates, Patchogue, NY, USA 16 University of Minnesota Fairview, Minneapolis, MN, USA 2
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Rehabilitation Institute of Chicago, Chicago, IL, USA Ralph H Johnson VA Medical Center, Charleston, SC, USA 19 Oregon Health and Science University, Portland, OR, USA 20 University of Illinois at Chicago, Chicago, IL, USA 21 Marshfield Clinic Research Foundation, Marshfield, WI, USA 22 The Ohio State University Wexner Medical Center, Columbus, OH, USA 23 Marianjoy Rehabilitation Hospital, Wheaton, IL, USA 24 Hartford Hospital, Hartford, CT, USA 25 Guilford Neurologic Associates, Greensboro, NC, USA 26 SUNY Upstate Medical University, Syracuse, NY, USA 27 West Los Angeles VA Healthcare Center, Los Angeles, CA, USA 28 David Geffen School of Medicine, UCLA, Los Angeles, CA, USA 18
Corresponding Author: Francois Bethoux, The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk U10, Cleveland, OH 44195, USA. Email: [email protected]
Downloaded from nnr.sagepub.com at UCSF LIBRARY & CKM on February 24, 2015
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Neurorehabilitation and Neural Repair
Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. Conclusions. At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings. Keywords functional electrical stimulation, ankle foot orthosis, stroke rehabilitation, gait speed, foot drop, quality of life
Introduction Every year 795 000 individuals in the United States and 15 million worldwide experience a new stroke.1,2 With a 75% overall survival rate1 and an estimated yearly cost of 3.6 billion dollars,3 stroke has a significant and serious impact on public health and health care costs. Seventy percent of stroke survivors regain the ability to walk, but residual impairments such as spasticity, muscle weakness, and poor balance may persist and limit functional ambulation.4 Foot drop, a significant gait impairment affecting approximately 20% of all stroke survivors, is a consequence of spastic hemiparesis from stroke.5 Foot drop, typically due to a combination of ankle dorsiflexor muscle weakness and plantarflexor muscle spasticity, results in a slower, less efficient gait and increases fall risk.6 Walking limitations have a continued and pervasive impact on functional mobility, community integration, and quality of life (QoL) for stroke survivors;4 many accomplish independent ambulation only by using an assistive device.4 Traditionally, the standard of care for foot drop is the ankle foot orthosis (AFO).7 An AFO, usually made of polypropylene or carbon fiber, is a lower leg brace worn to hold the foot and ankle in the neutral position. Published evidence demonstrates the effectiveness of AFOs for improving speed,8 gait stability,9,10 symmetry,9,11 and static balance12 in individuals with neurologic gait impairment. However, AFOs have the disadvantages of limiting ankle mobility13 and decreasing muscle activity,9,14 which may impair dynamic balance.12,13 Functional Electrical Stimulation (FES), the use of neuromuscular electrical stimulation to activate muscles during functional tasks, is an alternative to the AFO.15 FES applied to the peroneal nerve during the swing phase of ambulation provides active dorsiflexion and can reduce foot drop by facilitating voluntary muscle activity,16 and improving gait quality and symmetry.15,17 Disadvantages of FES are increased possibility of skin irritation,18,19 difficulty with electrode placement,18,20,21 and stimulus discomfort.19 Published literature also supports the efficacy of peroneal nerve FES. Several studies have demonstrated that FES utilization can increase gait speed,15,20,22-24 decrease
energy expenditure during walking,15,20,22-24 and improve gait symmetry.15,17,25 Previous evidence in support of both AFOs and FES originates from nonrandomized pre–post intervention studies, but 4 recently published randomized controlled trials (RCTs) comparing FES to AFOs have added higher quality evidence to the literature.7,26-28 Additionally, several studies have investigated the longterm effects of FES with follow-up periods ranging from 6 to 7 months7,27,29 to 1 year,16,20-22,25,28,30 with the longest describing a follow-up of 10 years.31 Only 3 of these longterm studies were RCTs that compared FES to AFOs.7,27,28 Sheffler et al7 compared use of FES to a control group (wearing AFO or no device) for only 12 weeks, but reassessed subjects at 12 and 24 weeks after device wear ended to determine the durability of changes in motor impairment, functional mobility, and QoL. Kluding et al27 followed subjects for 7.5 months of full-time device wear and Bethoux et al28 for 6 months; both studies assessed changes in gait speed and function, endurance, balance, and QoL. However, there is currently no published RCT comparing FES and AFOs in terms of safety and efficacy up to 1 year. This article reports the results of a 12-month follow-up to the RCT. Primary endpoint (6 months) analysis results were previously published by Bethoux et al.28 The main objective of this follow-up analysis was to assess if the noninferiority of the WalkAide (WA; Innovative Neurotronics, Austin, TX) compared to the AFO at 6 months, on gait speed and serious adverse event (SAE) rate, was still observed at 12 months. The secondary objective was to assess the magnitude of changes in efficacy measures at 12 months and to compare them to the changes observed at 6 months.
Methods Study Design This multicenter, unblinded, parallel-group RCT (ClinicalTrials.gov #NCT01087957) was approved by the Western Institutional Review Board and conducted in 30 rehabilitation research centers in the United States.28 Individuals with foot drop secondary to stroke meeting eligibility criteria (see Table 1) were enrolled and randomized into
Downloaded from nnr.sagepub.com at UCSF LIBRARY & CKM on February 24, 2015
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Bethoux et al Table 1. INSTRIDE Inclusion and Exclusion Criteria. Inclusion Criteria Included Subjects Demonstrating: •• Stroke onset ≥6 months before enrollment •• Positive response to peroneal nerve stimulation testing (able to safely clear toes in swing phase on the involved lower extremity, defined as >−5° plantar flexion, with the FES device (determined at fitting) •• Adequate mental function (MMSE score >17 and BDI 0.0 m/s and
research-article2015
NNRXXX10.1177/1545968315570325Neurorehabilitation and Neural RepairBethoux et al
Original Research Article
Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke
Neurorehabilitation and Neural Repair 1–12 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1545968315570325 nnr.sagepub.com
Francois Bethoux, MD1, Helen L. Rogers, PhD2, Karen J. Nolan, PhD3,4, Gary M. Abrams, MD5, Thiru Annaswamy, MD, MA6,7, Murray Brandstater, MD, PhD8, Barbara Browne, MD9, Judith M. Burnfield, PhD10, Wuwei Feng, MD, MS11, Mitchell J. Freed, MD12, Carolyn Geis, MD13, Jason Greenberg, MD14, Mark Gudesblatt, MD15, Farha Ikramuddin, MD16, Arun Jayaraman, PhD17, Steven A. Kautz, PhD11,18, Helmi L. Lutsep, MD19, Sangeetha Madhavan, PhD20, Jill Meilahn, DO21, William S. Pease, MD22, Noel Rao, MD23, Subramani Seetharama, MD24, Pramod Sethi, MD25, Margaret A. Turk, MD26, Roi Ann Wallis, MD27,28, and Conrad Kufta, MD2
Abstract Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. Objective. Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. Methods. Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). Results. A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints.
1
Cleveland Clinic, Cleveland, OH, USA Innovative Neurotronics, Austin, TX, USA 3 Kessler Foundation, West Orange, NJ, USA 4 Rutgers—New Jersey Medical School, Newark, NJ, USA 5 UCSF/San Francisco VA Medical Center, San Francisco, CA, USA 6 VA North Texas Health Care System, Dallas, TX, USA 7 UT Southwestern Medical Center, Dallas, TX, USA 8 Loma Linda University Medical Center, Loma Linda, CA, USA 9 Magee Rehabilitation Hospital, Philadelphia, PA, USA 10 Madonna Rehabilitation Hospital’s Institute for Rehabilitation Science and Engineering, Lincoln, NE, USA 11 Medical University of South Carolina, Charleston, SC, USA 12 Florida Hospital Neuroscience and Orthopedic Research Institute, Orlando, FL, USA 13 Halifax Health Center for Neurosciences, Daytona Beach, FL, USA 14 Helen Hayes Hospital, West Haverstraw, NY, USA 15 South Shore Neurologic Associates, Patchogue, NY, USA 16 University of Minnesota Fairview, Minneapolis, MN, USA 2
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Rehabilitation Institute of Chicago, Chicago, IL, USA Ralph H Johnson VA Medical Center, Charleston, SC, USA 19 Oregon Health and Science University, Portland, OR, USA 20 University of Illinois at Chicago, Chicago, IL, USA 21 Marshfield Clinic Research Foundation, Marshfield, WI, USA 22 The Ohio State University Wexner Medical Center, Columbus, OH, USA 23 Marianjoy Rehabilitation Hospital, Wheaton, IL, USA 24 Hartford Hospital, Hartford, CT, USA 25 Guilford Neurologic Associates, Greensboro, NC, USA 26 SUNY Upstate Medical University, Syracuse, NY, USA 27 West Los Angeles VA Healthcare Center, Los Angeles, CA, USA 28 David Geffen School of Medicine, UCLA, Los Angeles, CA, USA 18
Corresponding Author: Francois Bethoux, The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk U10, Cleveland, OH 44195, USA. Email: [email protected]
Downloaded from nnr.sagepub.com at UCSF LIBRARY & CKM on February 24, 2015
2
Neurorehabilitation and Neural Repair
Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. Conclusions. At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings. Keywords functional electrical stimulation, ankle foot orthosis, stroke rehabilitation, gait speed, foot drop, quality of life
Introduction Every year 795 000 individuals in the United States and 15 million worldwide experience a new stroke.1,2 With a 75% overall survival rate1 and an estimated yearly cost of 3.6 billion dollars,3 stroke has a significant and serious impact on public health and health care costs. Seventy percent of stroke survivors regain the ability to walk, but residual impairments such as spasticity, muscle weakness, and poor balance may persist and limit functional ambulation.4 Foot drop, a significant gait impairment affecting approximately 20% of all stroke survivors, is a consequence of spastic hemiparesis from stroke.5 Foot drop, typically due to a combination of ankle dorsiflexor muscle weakness and plantarflexor muscle spasticity, results in a slower, less efficient gait and increases fall risk.6 Walking limitations have a continued and pervasive impact on functional mobility, community integration, and quality of life (QoL) for stroke survivors;4 many accomplish independent ambulation only by using an assistive device.4 Traditionally, the standard of care for foot drop is the ankle foot orthosis (AFO).7 An AFO, usually made of polypropylene or carbon fiber, is a lower leg brace worn to hold the foot and ankle in the neutral position. Published evidence demonstrates the effectiveness of AFOs for improving speed,8 gait stability,9,10 symmetry,9,11 and static balance12 in individuals with neurologic gait impairment. However, AFOs have the disadvantages of limiting ankle mobility13 and decreasing muscle activity,9,14 which may impair dynamic balance.12,13 Functional Electrical Stimulation (FES), the use of neuromuscular electrical stimulation to activate muscles during functional tasks, is an alternative to the AFO.15 FES applied to the peroneal nerve during the swing phase of ambulation provides active dorsiflexion and can reduce foot drop by facilitating voluntary muscle activity,16 and improving gait quality and symmetry.15,17 Disadvantages of FES are increased possibility of skin irritation,18,19 difficulty with electrode placement,18,20,21 and stimulus discomfort.19 Published literature also supports the efficacy of peroneal nerve FES. Several studies have demonstrated that FES utilization can increase gait speed,15,20,22-24 decrease
energy expenditure during walking,15,20,22-24 and improve gait symmetry.15,17,25 Previous evidence in support of both AFOs and FES originates from nonrandomized pre–post intervention studies, but 4 recently published randomized controlled trials (RCTs) comparing FES to AFOs have added higher quality evidence to the literature.7,26-28 Additionally, several studies have investigated the longterm effects of FES with follow-up periods ranging from 6 to 7 months7,27,29 to 1 year,16,20-22,25,28,30 with the longest describing a follow-up of 10 years.31 Only 3 of these longterm studies were RCTs that compared FES to AFOs.7,27,28 Sheffler et al7 compared use of FES to a control group (wearing AFO or no device) for only 12 weeks, but reassessed subjects at 12 and 24 weeks after device wear ended to determine the durability of changes in motor impairment, functional mobility, and QoL. Kluding et al27 followed subjects for 7.5 months of full-time device wear and Bethoux et al28 for 6 months; both studies assessed changes in gait speed and function, endurance, balance, and QoL. However, there is currently no published RCT comparing FES and AFOs in terms of safety and efficacy up to 1 year. This article reports the results of a 12-month follow-up to the RCT. Primary endpoint (6 months) analysis results were previously published by Bethoux et al.28 The main objective of this follow-up analysis was to assess if the noninferiority of the WalkAide (WA; Innovative Neurotronics, Austin, TX) compared to the AFO at 6 months, on gait speed and serious adverse event (SAE) rate, was still observed at 12 months. The secondary objective was to assess the magnitude of changes in efficacy measures at 12 months and to compare them to the changes observed at 6 months.
Methods Study Design This multicenter, unblinded, parallel-group RCT (ClinicalTrials.gov #NCT01087957) was approved by the Western Institutional Review Board and conducted in 30 rehabilitation research centers in the United States.28 Individuals with foot drop secondary to stroke meeting eligibility criteria (see Table 1) were enrolled and randomized into
Downloaded from nnr.sagepub.com at UCSF LIBRARY & CKM on February 24, 2015
3
Bethoux et al Table 1. INSTRIDE Inclusion and Exclusion Criteria. Inclusion Criteria Included Subjects Demonstrating: •• Stroke onset ≥6 months before enrollment •• Positive response to peroneal nerve stimulation testing (able to safely clear toes in swing phase on the involved lower extremity, defined as >−5° plantar flexion, with the FES device (determined at fitting) •• Adequate mental function (MMSE score >17 and BDI 0.0 m/s and
