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C 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Copyright V
Artificial Walking Technologies to Improve Gait in Cerebral Palsy: Multichannel Neuromuscular Stimulation *†Jessica Rose, *†Katelyn Cahill-Rowley, and ‡§Erin E. Butler *Department of Orthopaedic Surgery, Stanford University, Stanford; †Motion & Gait Analysis Lab, Lucile Packard Children’s Hospital, Palo Alto, CA; ‡Thayer School of Engineering; and §Neukom Institute for Computational Sciences, Dartmouth College, Hanover, NH, USA
Abstract: Cerebral palsy (CP) is the most common childhood motor disability and often results in debilitating walking abnormalities, such as flexed-knee and stiff-knee gait. Current medical and surgical treatments are only partially effective in improving gait abnormalities and may cause significant muscle weakness. However, emerging artificial walking technologies, such as step-initiated, multichannel neuromuscular electrical stimulation (NMES), can substantially improve gait patterns and promote muscle strength in children with spastic CP. NMES may also be applied to specific lumbar-sacral sensory roots to reduce spasticity. Development of tablet computer-based multichannel NMES can leverage lightweight, wearable wireless stimulators, advanced control design, and surface electrodes to activate lower-limb muscles. Musculoskeletal models have been used to characterize muscle contributions to unimpaired gait and identify high muscle demands, which can help guide multichannel NMES-assisted gait protocols. In addition, patient-specific NMES-assisted gait protocols
based on 3D gait analysis can facilitate the appropriate activation of lower-limb muscles to achieve a more functional gait: stance-phase hip and knee extension and swingphase sequence of hip and knee flexion followed by rapid knee extension. NMES-assisted gait treatment can be conducted as either clinic-based or home-based programs. Rigorous testing of multichannel NMES-assisted gait training protocols will determine optimal treatment dosage for future clinical trials. Evidence-based outcome evaluation using 3D kinematics or temporal-spatial gait parameters will help determine immediate neuroprosthetic effects and longer term neurotherapeutic effects of step-initiated, multichannel NMES-assisted gait in children with spastic CP. Multichannel NMES is a promising assistive technology to help children with spastic CP achieve a more upright, functional gait. Key Words: Neuromuscular electrical stimulation—NMES-assisted gait—Functional electrical stimulation—Artificial walking technologies—Cerebral palsy—Neuroprosthetic effect.
Cerebral palsy (CP) is the most common childhood disability and results in limited mobility throughout life. The Center for Disease Control estimates approximately 3/1000 8-year-old children in the USA are diagnosed with CP (1), which is defined as “a group of disorders affecting the development of movement and posture, attributed to nonprogressive disturbances to the developing fetal or infant brain” (2). Although the initial brain injury is non-progressive, musculoskeletal impairments and
functional limitations associated with CP are indeed progressive (3). Spastic CP, the most common form of CP, is characterized by four interrelated neuromuscular deficits: muscle weakness, spasticity, short muscletendon length, and impaired selective motor control (4–6). One of the first descriptions of gait abnormalities in CP was reported in 1890 by EH Bradford (7) as, “the heel is not placed upon the ground, the knee is bent, and the knee is thrown to the inner side.” The muscles affected by spastic CP have substantially reduced neuromuscular activation and strength (4,8,9) and there is an inability to sufficiently recruit and drive motor-units at higher firing rates (4), resulting in the aforementioned neuromuscular deficits of weakness, a velocity-dependent
doi: 10.1111/aor.13058 Received June 2017; accepted September 2017. Address correspondence and reprint requests to Jessica Rose, PhD, Professor, Department of Orthopaedic Surgery, Stanford University, 770 Welch Road, Suite 400, Stanford, CA 94304, USA. E-mail:
[email protected]
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FIG. 1. Three-dimensional gait analysis of a child with spastic cerebral palsy who walks with flexed-knee gait as well as a stiff-knee gait; kinematics demonstrate increased knee flexion at initial contact and reduced peak knee flexion in swing phase (black lines), compared to unimpaired gait (gray bands).
sensitivity to stretch, reduced muscle growth relative to skeletal growth, and impaired selective motor control (6). These neuromuscular deficits contribute to two of the most common walking disorders in children with spastic CP, specifically, flexed-knee gait, which is characterized by increased hip and knee flexion in stance (Fig. 1), and stiff-knee gait, which is characterized by reduced peak knee flexion in swing (10) (Fig. 1). Flexed-knee gait in CP can arise from short and spastic hip and knee flexors, as well as from weak hip extensors and ankle plantar flexors. Stiffknee gait can arise from spastic knee extensors, as well as plantar flexor weakness, which impair preswing mechanics. Frequently, musculoskeletal manifestations continue to progress as skeletal growth out-paces muscle growth and musculoskeletal deformities develop. Flexed-knee gait in young children causes abnormal mechanical loads and muscle forces across the hip, knee, ankle and foot which can result in bone deformities and permanently flexed, rotated gait (3,11). Thus, flexed-knee gait and stiff-knee gait cause fatigue, limited mobility, and poor foot clearance. These gait disorders typically worsen over time, with many children losing independence in functional mobility as they transition to teenagers and adults (3,12–14). It has been demonstrated that children with physical disabilities are less active than typically developing children and thus, are more at risk for health problems, musculoskeletal impairment, and poor self-image (15–17). Indeed, reduced mobility and activity levels among children with spastic CP result in a progressive loss of function in all three components of the World Health Organization’s International Classification of Functioning, Disability and Health: body function and structure, activity, and participation. Orthopedic surgery is the most common treatment for flexed-knee and stiff-knee gait in children with Artif Organs, Vol. 41, No. 11, 2017
spastic CP, but studies suggest that postoperative outcome is uncertain, flexed-knee gait improved in only 48% of limbs (18). For example, hamstring lengthening, which is the most common intervention for flexed-knee gait, was only found to result in an average of 10.98 improvement in knee extension during the stance phase of gait (19). To date, surgical and pharmaceutical treatments for gait deficits offer only partial improvement, thus, more effective treatments are needed. Specifically, more effective treatments for gait deficits in children with CP are needed at an early age when there is optimal neuronal plasticity, rapid musculoskeletal growth, and a greater likelihood of preventing musculoskeletal deformities and gait deficits. Neuromuscular electrical stimulation (NMES)-assisted gait is a developing technology that shows promise as an effective and costefficient treatment for walking disorders in children with spastic CP. Here we present the current state of NMES technology and offer suggestions to advance the development of NMES-assisted gait in children with CP, based on a review of the literature, as well as preliminary studies conducted at our laboratory. MULTICHANNEL NMES NMES has the ability to generate purposeful movements through activation of weak or paralyzed muscles in adults and children with spinal cord injury, stroke, and spastic CP. Previous research suggests that NMES-assisted gait may normalize walking patterns and has the potential to improve muscle physiology and strength, and therefore, may improve muscle growth in children with CP (20). An early study of multichannel NMES-assisted gait in children with CP suggests that NMES-assisted gait in combination with more limited surgery may provide similar functional gains
NMES-ASSISTED GAIT FOR CEREBRAL PALSY with fewer ablative procedures than traditional orthopedic surgery (21). A systematic approach to NMES-assisted gait for children with flexed-knee and stiff-knee gait is essential prior to widespread clinical translation. This includes rigorous evaluation of the appropriate muscle activation patterns and training paradigms necessary to achieve a neuroprosthetic effect, as well as meaningful outcome measures to evaluate improvements in gait. Three-dimensional gait analysis and patient-specific musculoskeletal modeling can be utilized to determine the muscle activation patterns needed to promote hip and knee extension during the stance phase of gait or rapid hip and knee flexion in initial swing for individuals with flexed-knee or stiff-knee gait, respectively. Musculoskeletal models have identified muscle contributions to hip and knee extension in normal and flexed-knee gait (22,23), helping to guide timing of NMES activation sequences. Regarding training paradigms, NMES can utilize variable frequency stimulations for optimal muscle activation (24), and employ over-ground and treadmill training to promote longer-term effects (25). Step-initiated NMES, rather than time-based or pedal-dependent activation, provides an opportunity to promote functional ambulation and can be tested in multi-week trials that incorporate both self-selected, over-ground walking, and higher intensity treadmill walking to facilitate neuroprosthetic effects. In addition, alternating trials of on– off periods of NMES can be employed to promote neurotherapeutic effects by encouraging the individual to actively engage in the novel gait patterns. Primary outcome measures, such as the Gait Deviation Index (GDI), can quantitatively assess changes in gait for children with CP. The GDI is a comprehensive index of gait pathology based on 16 different kinematic measures; a clinically relevant improvement in GDI is considered an increase of 5.0 (normal gait 5 100 6 10) (26). The goal of NMES-assisted gait is to improve gait patterns and stimulate more normal musculoskeletal physiology and growth in children with spastic CP, ultimately reducing muscle contractures, growth-related deformities, and the need for orthopedic intervention. Prior studies of single and dual-channel NMESassisted gait in CP show improved gait kinematics and temporal-spatial parameters after 1-week (27–29) and 3-months (30). Single-channel NMES has been used to improve ankle dorsiflexion during the swing phase of gait in children with spastic CP. Evidence indicates that this single-channel NMESassisted gait improves both walking patterns and
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ankle dorsiflexor muscle size (20,30). Because a lack of ankle dorsiflexion in swing hinders foot clearance and contributes to tripping, it can be corrected with single-channel activation of tibialis anterior muscle. However, flexed-knee and stiffknee gaits are more involved and, thus, challenging to correct. Flexed-knee gait requires NMES activation of multiple muscles to promote hip and knee extension during the stance phase of gait, as well as to support the child’s body weight against gravity. Stiff-knee gait, in contrast, requires NMES activation of multiple muscles to provide hip and knee flexion in initial swing, followed quickly by knee extension and ankle dorsiflexion prior to initial contact. At least one multichannel NMES device, the Xcite RT50z multichannel NMES-assisted gait device, is FDA approved (FDA 510 K090750) and available for testing. The Xcite RT50z (Restorative Therapies, Inc., Baltimore, MD, USA) consists of a tablet computer and 6–8 small (2.500 3 1.500 ) wireless stimulators that can be placed over the muscles of the lower limbs (Fig. 2). The RT50z builds upon the multichannel prototype that was used in prior research (21), and while it features wireless, userfriendly tablet control, it is not yet step-initiated. Preliminary data for three children with spastic CP using the Xcite RT50z multichannel NMES-assisted gait device is shown in Fig. 3. The study was approved by the IRB and consent was obtained from all study participants. Gait kinematics were recorded before and toward the end of an initial session of NMES-assisted gait. Baseline knee kinematics demonstrates the inclusion criteria of 20–408 of knee flexion in stance. Results indicate clinically relevant improvement in the GDI, the primary outcome measure, for Participant 2, associated with improved hip and knee extension and reduced ankle dorsiflexion in stance phase. Minor improvement in GDI is noted for Participant 3, associated with improved knee extension in stance and ankle dorsiflexion in swing. Negligible improvement is noted for Participant 1, who used the lowest level NMES. All participants demonstrated minor to moderate improvement in knee extension in initial contact, but continued to demonstrate excessive knee flexion at initial contact. Velocity increased for Participant 2 but decreased for Participants 1 and 3, which may be expected, initially. Application of NMES to the quadriceps just prior to initial contact may help further improve knee extension at initial contact, and warrants investigation. Artif Organs, Vol. 41, No. 11, 2017
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FIG. 2. NMES-assisted gait training can be administered in the clinic using (a) a tablet computer to control and monitor the activation of (b) lightweight, wearable wireless surface electrodes (c) placed over lower-limb muscles. Patient-specific NMES patterns of activation are based on gait analysis and patient preference. No known side effects exist for use of NMES within a wide range of proper settings.
FIG. 3. Gait kinematics for three children with spastic CP recorded at baseline and at the end of an initial session of NMES-assisted gait training. The immediate neuroprosthetic effects on gait were assessed while using the multichannel Xcite RT50z NMES device. Parameters were set at a comfortable level of amplitude (mA), frequency (Hz), and pulse width (ms). All three children demonstrated increased knee extension at initial contact. Two children demonstrated improved hip and/or knee extension in mid-stance, and one child demonstrated an improved GDI while walking with the multichannel NMES device. Kinematics are shown for the more affected lower extremity during the gait cycle (0–100%, with vertical lines indicating opposite toe-off (TO), opposite initial contact (IC), and ipsilateral toe-off (TO). NMES-assisted gait is shown as black lines. Unimpaired gait curves are shown in gray. Artif Organs, Vol. 41, No. 11, 2017
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Although advances have been made in multichannel NMES assistive devices to improve walking, further development is required to deliver optimal patient-specific stimulation sequences with feedback control for step-initiated activation, rather than time-based or manual, pedal-dependent activation. Step-initiated control will improve NMES delivery and reduce the demands on clinicians and device users, thereby increasing ease of operation. NMES DESIGN ELEMENTS AND PROTOCOL There are two primary design elements that require further development and integration into existing multichannel NMES devices: step-initiated activation and Bluetooth capability. Automated step-initiated NMES would utilize detection of the gait events of initial contact and toe-off using inertial sensors embedded into the NMES stimulators. Preliminary data indicates that the anterior tibial electrode is best-suited to provide robust, reliable data for gait-event detection to trigger NMES patterns with each step (Fig. 4). Bluetooth capability on each stimulator would provide communication with a central tablet computer, allowing real-time monitoring and adjustment of stimulation patterns. Onboard event detection is also plausible, following a training period for an individual’s particular gait pattern. NMES is typically applied through direct activation of weak muscles. However, sensory-level NMES has also been found to improve ankle dorsiflexion during swing (31) among children with spastic CP and reduce muscle spasticity in individuals with spinal cord injury. Recently, indirect sensory nerve stimulation (sNS) and transcutaneous spinal cord stimulation (tSCS) have been applied to reduce spasticity and enhance volitional motor control. Novel lumbar-sacral tSCS can use surface electrode arrays to focus electric fields more precisely and provide sensory root stimulation to reduce spasticity (32,33). Lower-limb NMES can be augmented with tSCS lumbar-sacral electrode arrays in which the 3D tissue and electrode conductivity, including electrode shape and anatomical arrangement together with stimulus waveforms, are optimized using a computer model. NMES can also be utilized to reduce lower-limb spasticity with sNS applied over sensory dermatomes of affected muscles. Further research will clarify the most effective applications of tSCS and sNS for reduction of muscle spasticity during gait. Patient-specific protocols for NMES can be applied to correct specific gait deficits, including
FIG. 4. Preliminary recordings from (a) a 3-axis accelerometer and gyroscope, similar to sensors embedded in some NMES electrodes, in relation to (b) gold-standard, pressure-sensitive footswitch data of the stance and swing phases of gait*. We experimented with different filters and derivations of the accelerometer and gyroscope signals. The best results came from placement of the sensor over the anterior tibial region, using a third-order Butterworth low-pass filtered gyroscope signal with a 1 Hz cutoff frequency. This was the most reliable signal due to a distinct ‘inverse sine wave’ pattern for both unimpaired and flexed-knee gait. Also, the gyroscope signal maintained its pattern regardless of walking speed, whereas the accelerometer signal weakened during slow walking. Note: The medium-gray line of gyroscope data, representing the speed of tibia rotation in the sagittal plane, consistently demonstrates an upward excursion at toe-off. Data are unfiltered; with a low-pass filter, the signal is robust. TO, toe-off, IC, initial contact. *The footswitches recorded the measurable magnetic field (microTesla) generated by the change in voltage from a coil of wire running adjacent to the sensor, that is, in accordance with Farraday’s law.
flexed-knee and stiff-knee gait. For flexed-knee gait, application of NMES during the normal timing of gluteus maximus and medius, vastus lateralis and medialis, and gastrocnemius-soleus muscles can facilitate hip and knee extension in stance. Furthermore, as noted above, stimulation applied to vastus lateralis in terminal swing can promote knee extension at initial contact, and represents a more efficient preventive approach to correcting flexed-knee position in stance. Gastrocnemius-soleus activation in stance can stabilize the ankle, restrain forward tibial rotation over the foot, and thus promote knee Artif Organs, Vol. 41, No. 11, 2017
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extension during stance. Distal electrode placement over the soleus is recommended to avoid knee flexor influence of gastrocnemius. For stiff-knee gait, application of NMES to hip and knee flexors in initial swing can facilitate rapid hip and knee flexion in swing. Furthermore, sensory-level stimulation to rectus femoris may reduce spasticity and improve knee flexion in swing. A dosage goal of 30 one-hour sessions of NMESassisted gait training over a 10-week period has demonstrated a positive treatment effect for treadmill gait training in stroke (34) and for activitybased training in children with CP (35). An hourlong session can include five, 6-min trials of NMES-assisted gait training, allowing for 5-min rest periods between trials, including both treadmill and over-ground walking trials. Treadmill walking is conducted at speeds at least 25% faster than selfselected comfortable walking speed, to optimize physiological response and to maximize training effects. It will be essential to demonstrate accurate, reliable, and safe operation of the NMES device by clinicians, as well as participant tolerance of the NMES protocol, prior to widespread clinical translation of multichannel NMES-assisted gait in children with CP. CONCLUSIONS Multichannel NMES-assisted gait using intelligent control has the potential to leverage lightweight wireless surface stimulators applied over lower-limb muscles, using patient-specific NMES activation sequences to help children with cerebral palsy achieve a more upright, stable gait. Ideally, multichannel NMES with transcutaneous spinal cord stimulation or sensory nerve stimulation will shift current clinical practice paradigms away from ablative procedures and toward preventing musculoskeletal deformities, by improving musculoskeletal physiology and growth while improving gait deficits. Acknowledgments: We wish to dedicate this paper to the memory of Ron Crane for his valuable contributions to this work. We also wish to thank Professor Brian Andrews, and Tim Brochier for their valuable contributions to the field and to this work. This material is based upon work supported by the Koret Foundation, San Francisco, CA, USA and the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1147470. Artif Organs, Vol. 41, No. 11, 2017
Author Contributions: Jessica Rose: Concept/ design, literature analysis/interpretation, drafting article, critical revision of article, approval of article. Funding secured by Jessica Rose. Katelyn CahillRowley: Concept/design, literature analysis/interpretation, drafting article, critical revision of article, approval of article. Erin E Butler: Concept/design, literature analysis/interpretation, drafting article, critical revision of article, approval of article. REFERENCES 1. Christensen D, Van Naarden Braun K, Doernberg NS, et al. Prevalence of cerebral palsy, co-occurring autism spectrum disorders, and motor functioning. Dev Med Child Neurol 2014;56:59–65. 2. Bax M, Goldstein M, Rosenbaum P, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol 2005;47:571–6. 3. Bell KJ, Ounpuu S, DeLuca PA, Romness MJ. Natural progression of gait in children with cerebral palsy. J Pediatr Orthop 2002;22:677–82. 4. Rose J, McGill KC. Neuromuscular activation and motorunit firing characteristics in cerebral palsy. Dev Med Child Neurol 2005;47:329–36. 5. Rose J. Selective motor control in spastic cerebral palsy. Dev Med Child Neurol 2009;51:578–9. 6. Cahill-Rowley K, Rose J. Etiology of impaired selective motor control: emerging evidence and its implications for research and treatment in cerebral palsy. Dev Med Child Neurol 2014;56:522–8. 7. Bradford EH. The surgical treatment of spastic paralysis in children. J Bone Joint Surg 1890;1:548–83. 8. Stackhouse SK, Binder-Macleod SA, Lee SC. Voluntary muscle activation, contractile properties, and fatigability in children with and without cerebral palsy. Muscle Nerve 2005;31:594–601. 9. Damiano DL, Quinlivan J, Owen BF, Shaffrey M, Abel MF. Spasticity versus strength in cerebral palsy: relationships among involuntary resistance, voluntary torque, and motor function. Eur J Neurol 2001;8:40–9. 10. Wren TA, Rethlefsen S, Kay RM. Prevalence of specific gait abnormalities in children with cerebral palsy: influence of cerebral palsy subtype, age, and previous surgery. J Pediatr Orthop 2005;25:79–83. 11. Steele KM, Demers MS, Schwartz MH, Delp SL. Compressive tibiofemoral force during crouch gait. Gait Posture 2012;35:556–60. 12. Hanna SE, Rosenbaum PL, Bartlett DJ, et al. Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years. Dev Med Child Neurol 2009;51:295–302. 13. Rosenbaum PL, Walter SD, Hanna SE, et al. Prognosis for gross motor function in cerebral palsy: creation of motor development curves. JAMA 2002;288:1357–63. 14. Kerr C, McDowell BC, Parkes J, Stevenson M, Cosgrove AP. Age-related changes in energy efficiency of gait, activity, and participation in children with cerebral palsy. Dev Med Child Neurol 2011;53:61–7. 15. Durstine JL, Painter P, Franklin BA, Morgan D, Pitetti KH, Roberts SO. Physical activity for the chronically ill and disabled. Sports Med 2000;30:207–19. 16. Rimmer JH. Physical fitness levels of persons with cerebral palsy. Dev Med Child Neurol 2001;43:208–12. 17. Strong WB, Malina RM, Blimkie CJ, et al. Evidence based physical activity for school-age youth. J Pediatr 2005;146: 732–7.
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