SURVIVORS WITH SPINAL CORD injury (SCI) at the C5

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1 119 Persons With C5 or C6 Tetraplegia Achieve Selected Functional Gains Using a Neuroprosthesis Gad Alon, PhD, PT, Keith McBride, MPT ABSTRACT. Alon G, McBride K. Persons with C5 or C6 tetraplegia achieve selected functional gains using a neuroprosthesis. Arch Phys Med Rehabil 2003;84: Objective: To test the efficacy and safety of the NESS Handmaster neuroprosthesis with subjects with C5 or C6 tetraplegia. Design: Interventional, nonrandomized case series. Setting: Subjects residence and university research laboratory. Participants: Men, 3 to 17 years after C5 (n 5) and C6 (n 2) spinal cord injury (SCI). Intervention: Subjects practiced with the neuroprosthesis daily to regain grasp, hold, and release ability and to restore selected functions of 1 of the 2 paralyzed hands. Subjects were observed 2 to 3 times weekly for 3 weeks. Main Outcome Measures: Three activities of daily living (ADL) tasks: (1) pick up a telephone, (2) eat food with a fork, and (3) perform 1 individually selected ADL task and 2 grasp, hold, and release tasks (lift a videocassette, lift a 150-g weight). Secondary outcomes were grip strength, electrically induced finger motion, and Fugl-Meyer spherical grasp. Nonparametric data were analyzed with the Wilcoxon signed-rank test, and parametric data (grip strength and finger motion) were analyzed by analysis of variance. All tests were considered significant at P equal to.01. Results: At study completion, all 7 subjects were 100% successful at using the Handmaster in the studied ADL and grasp, hold, and release tasks. Significant improvements occurred in grip strength (from.57.98n at baseline to N), finger linear motion (from 0.0cm at baseline to cm), and Fugl-Meyer scores. No safety issues were encountered. Six of 7 subjects rated their overall performance as excellent. Conclusions: The Handmaster is a safe, noninvasive neuroprosthesis that improves hand function of selected subjects with C5 or C6 SCI. Key Words: Activity of daily living; Electrical stimulation; Prostheses and implants; Rehabilitation; Tetraplegia by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation From the Department of Physical Therapy, University of Maryland, School of Medicine, Baltimore, MD. Supported by NESS Ltd (grant no ). Presented in part at the First Congress of The International Society of Physical Medicine and Rehabilitation, July 7-13, 2001, Amsterdam, The Netherlands. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Gad Alon, PhD, PT, University of Maryland, Sch of Medicine, Dept of Physical Therapy, 100 Penn St, Rm 107, Baltimore, MD , galon@som.umaryland.edu /03/ $35.00/0 doi: /apmr SURVIVORS WITH SPINAL CORD injury (SCI) at the C5 level are expected to retain voluntary control of the shoulder abductors, flexors, and rotators and elbow flexors. Control of elbow extension occurs through the use of gravity and eccentric contraction of the elbow flexors. There is also variable control of forearm supination and pronation. Muscles generating motion at the wrist, fingers, and thumb, however, are no longer under voluntary control. Consequently, a seated subject with C5 SCI is able to control forearm/hand placement and movements against gravity but is unable to grasp, hold, and release, thereby limiting the functional use of the upper limbs. 1 Rehabilitation efforts to restore partial hand function have included surgical intervention, splinting with wrist/hand orthosis or cuffs, and various functional electric stimulation (FES) systems. Over the past several years, an approach of combined surgical reconstruction and implantation of an FES system (also known as a neuroprosthesis) has been shown to improve the grasp, hold, and release capabilities of selected individuals with C5 and C6 tetraplegia. 2-5 Some externally driven FES devices have also been reported to improve hand function in tetraplegia but require active wrist extension against gravity (C6 motor level, according to the American Spinal Injury Association [ASIA] Impairment Scale) to be beneficial. 6,7 An open-loop external system operated via a microcomputer has also shown the potential for obtaining functional grasp in C5 and C6 tetraplegia. 8 Because individuals with C5 tetraplegia generally have little or no volitional motor control below the level of the elbow, their surgical rehabilitation options to improve hand function are limited. 9 Restricting the degrees of freedom at the wrist by means of an orthosis theoretically should allow the muscles activated by the FES to transfer the generated force to the fingers and thumb and thus to simulate grasp and release in these persons. The Handmaster system, a an externally driven neuroprosthesis that combines wrist stabilization and FES, was developed to test this hypothesis. A recent study 10 using the device has shown efficacy for functional improvement in selected persons with tetraplegia. However, that study lacked appropriate subject screening methods and did not feature systematic, quantitative, statistical testing of impairment level and functional ability. The purpose of this investigation was to determine whether the Handmaster system could improve (1) grip strength, (2) ability to grasp, hold, and release, and (3) selected hand functions of persons with C5 and C6 tetraplegia. METHODS Participants Subjects were recruited through local rehabilitation centers, physicians, and support groups. All potential subjects gave written evidence of informed consent approved by the institutional review board of the University of Maryland, Baltimore. Inclusion criteria are listed in table 1. Criteria for participation were chosen to match both the design of the Handmaster and the scope of the study to a suitable patient population. To permit adequate stimulation force to be generated, screening

2 120 FUNCTIONAL GAINS USING A NEUROPROSTHESIS, Alon Table 1: Subject Inclusion Criteria 6mo postinjury with the following: C5 motor tetraplegia, per ASIA criteria C6 motor tetraplegia, per ASIA criteria, with absent tenodesis Completion of standard rehabilitation program Stable neurologic status Wheelchair mobility score of 5 or more on the FIM instrument Adequate passive motion of the fingers* Strength grade of 4 in the deltoid and elbow flexors Forearm and hand size compatible with the size of the neuroprosthesis Adequate vision to read the control box Ability to follow multiple-step directions Ability to induce contraction electrically in the muscles of the forearm and hand * Extension: middle finger opens at least 7cm measured from the tip of the finger to the midpalmar crease and 5cm from the tip of the thumb to the proximal interphalangeal joint of the index finger; flexion: fingertips reach the midpalmar crease with the thumb contacting the lateral side of the index finger. Grades 4 or 5 on the Medical Research Council Scale for finger and thumb flexors; grades 3 through 5 for finger and thumb extensors. for intact lower motoneurons to targeted muscles was of particular importance. Given that the study was of short duration, adequate range of motion of the fingers and thumb and a spasticity grade of less than 2 (Ashworth Scale) were considered prerequisites because potential improvement of these impairments was not expected within 3 weeks. Persons with C6 motor-level injuries were included only if they had nonexistent tenodesis, because persons with strong functional tenodesis would not likely benefit from a hand neuroprosthesis. These criteria alone accounted for exclusion of 12 of the 21 subjects screened. Subjects were excluded if they had structural instability in the upper limb, a pacemaker or other electronic implant, skin lesions at the site of proposed electrode placement, infection or malignancy in the upper limb, pregnancy, or spasticity of grade 2 on the Ashworth Scale or if they had participated in other clinical investigations within the last 6 months that could directly or indirectly affect the results of the study. Of 21 subjects screened, 7 met the inclusion criteria: 5 with C5 and 2 with C6 SCI (table 2). All subjects were classified as having a complete lesion by Frankel classification. The Device The Handmaster neuroprosthesis (fig 1) combines a wrist/ hand orthosis (to provide stabilization) with integrated surface electrodes to activate muscles of the paralyzed forearm and hand. The device s specifications have been previously detailed. 10 Briefly, the control unit, which is attached to the Subject Sex Age (y) Table 2: Subject Characteristics Fitted Hand Level of Injury Frankel Grade* Time Since Injury (y) 1 Male 37 Left C5 A Male 38 Right C5 A Male 35 Right C5 A Male 28 Right C5 A Male 25 Left C5 A Male 40 Left C6 A Male 46 Left C6 A 17.3 * Frankel grade A denotes a complete lesion. Fig 1. The Handmaster neuroprosthesis system: (A) components and (B) subject showing key grip when eating with a fork. orthosis by a cable, enables the user to select among 3 exercise and 3 functional modes. The exercise modes provide repetitive stimulation of the targeted finger and thumb extensor and flexor muscles to improve strength and conditioning. The functional modes are (1) key grip and release, (2) palmar grasp and release, and (3) static open hand posture. After patient-triggered activation, the key grip mode activates finger flexors and thumb extensors; for the palmar grasp, the finger and thumb extensors are stimulated. The adjustable preset duration for hand opening enables the user to position the hand and automatically sequences into stimulation of the appropriate flexors for maintenance of either the key grip or palmar grasp. The open-hand posture is maintained in the open mode. Release of the key grip or palmar grasp is accomplished by a second triggering that activates extensors. Triggering the system for exercise or functional mode can be done by pressing a push pad on the control unit or by activating a remote trigger that is incorporated into the orthosis. The subject can don the orthosis independently or with minimal assistance. The spiral design for wrist stabilization places the wrist in 10 to 20 of extension. This maintains the orthosis position on the forearm in a manner that provides consistent electrode alignment and directs the extensor activation to the fingers, thereby limiting tenodesis action. Fitting Each subject underwent an initial custom fitting of the Handmaster orthosis. During this procedure, optimal electrode po-

3 FUNCTIONAL GAINS USING A NEUROPROSTHESIS, Alon 121 sition (1 for each targeted muscle) and size were determined. The 5 electrodes were fixed to the subject s orthosis, ensuring consistent activation of the following targeted muscles: extensor digitorum communis, extensor pollicis brevis, flexor digitorum superficialis, flexor pollicis longus, and thenar muscles. Subjects or caregivers received instruction on operation of the control unit, donning and doffing of the orthosis, and electrode maintenance. The intensity of the stimulation was set to a level that provided consistent activation of the flexors and extensors of the fingers and thumb. A patient-controlled external button was available for the subject to adjust the intensity if needed. The exercise mode was set as the default mode when the unit was turned on at the preset intensity level. Subjects were given additional items such as rolls, balls, weights, utensils, and cups to assist in their conditioning and functional training. The clinician, if needed, made subsequent adjustments during follow-up. Training After their baseline evaluation, subjects were issued a home exercise program. The prescribed conditioning program started with a 10-minute session twice daily; after the first session, the stimulation time increased by 5 minutes every other day up to a 30-minute session twice daily with the device in exercise mode. The decision to limit session time to 30 minutes was based on the assumption that reaching the objectives of this study would not require much training. During the first week of training, a follow-up visit was done to ensure proper fit and to advance the conditioning protocol as indicated. Subjects were also instructed on the use of the functional modes to assist with grasp and release of objects. The use of this mode was integrated into the home exercise program as part of the daily conditioning. In weeks 2 and 3, subjects were observed 2 to 3 times weekly in their homes to progressively increase the gradual conditioning program and functional training. For conditioning, the visiting therapist set the stimulation intensity to the highest allowable level that would not produce visible fatigue for the entire exercise session. The subject was able to adjust stimulation intensity on the control unit (see fig 1)to match the strength of contraction to the requirement of a given activity of daily living (ADL). For example, most subjects needed less intensity to lift a videocassette than to lift a bottle and drink from it. Pulse frequency was fixed at 36Hz for exercise modes and at 18Hz for grasping in the functional modes. In week 2, the subject and the visiting therapist selected an additional ADL that the subject was unable to perform at baseline without the use of the neuroprosthesis. This selected ADL was practiced with the neuroprosthesis and assessed at the conclusion of the study. Training sessions in the third week focused on the functional use of the neuroprosthesis in tasks of daily living. Outcome Measures Subjects hand function was evaluated by a battery of upperlimb measures, including 3 ADL tasks, 1 of which was selected by the subject; 3 hand impairment measures; and 2 grasp and release tests. Baseline testing (test 1) was performed without stimulation, test 2 was performed with the Handmaster system after the subject completed 1 week of training, and the final testing (test 3) was performed both with and without the neuroprosthesis. For the first ADL task, all subjects attempted to pick up and lift a telephone handset, bring it to the ear, and return it to the cradle. The second ADL was to grasp a fork from a holder (mug) or from the table, take a piece of food, eat it, and return the utensil to the holder or table. During the second week of the study, each subject was asked to choose an additional upperextremity ADL that he was unable to perform without the neuroprosthesis. Scoring for each of the 3 ADL tasks was yes if the subject was able to perform it or no if he was unable to perform it. Subjects were given 3 attempts to perform the ADL tasks without the Handmaster system and 3 attempts while wearing it. The 3 hand tests were (1) grip strength, measured in newtons by using a handheld dynamometer; (2) distance of finger motion from the distal palmar crease to the fingertip of the most extended finger, measured in centimeters; and (3) Fugl-Meyer hand subset of spherical grasp (scored 0 cannot perform; 1 ball can be kept in the hand against slight tug; 2 ball is held against firm tug). Subjects performed each test 3 times, and the best score was used for outcome determination. For the grasp and release tests, each subject was given 3 attempts to grasp, hold, and lift a 150-g weight and to grasp, hold, and lift a videocassette. Use of the contralateral upper extremity was permitted to stabilize the objects for initial grasping, but not to assist in lifting. Scoring for the grasp and release tests was yes if the subject was able to perform the tests or no if the subject was unable to perform them. In addition to the upper-extremity function tests, subjects were asked at the conclusion of the study to answer a questionnaire regarding their performance with the Handmaster system and its utility for improving their hand function. Data Analyses Statistical analyses included analysis of variance or t test for the parametric variables (grip force, finger motion measurements) and Wilcoxon ranked-sum tests for the nonparametric variables (Fugl-Meyer subset, ADLs, grasp and release test). All tests were considered significant at P equal to.01 level. Statistical comparisons were analyzed with ProStat software. b RESULTS ADL Tasks and Grasp and Release Tests The combined results of the ADL and grasp and release scores are listed in table 3. Subjects were successful in 3 (21%) of 14 attempts without the neuroprosthesis at both baseline and final testing for the 2 required ADLs. Notably, subjects who had C6 motor function achieved 2 of the 3 success scores. Combining the ADL results, we found that, when using the Handmaster system, subjects succeeded at 13 (93%) of 14 attempts after the first week of training (test 2) and were 100% successful at the final assessment. All 7 subjects successfully performed their selected ADL (table 4) with the Handmaster system. Outcomes of the grasp and release tests are also summarized in table 3. When we combined the grasp and release tests, we found that none of the subjects was successful in the 42 attempts without the Handmaster system. All 7 subjects were able to perform the 2 tasks with the use of the neuroprosthesis. Moreover, when we combined the stimulated results for the weight and the videotape, we found that subjects were able to perform the task on the first attempt 92% of the time with stimulation. Hand Impairment Tests All 7 subjects improved their performance on the 3 hand tests when they used stimulation. Mean grip strength standard deviation significantly improved when the Handmaster system was being used during test 2 ( N) and during the final assessment ( N), as compared with baseline

4 122 FUNCTIONAL GAINS USING A NEUROPROSTHESIS, Alon Table 3: ADL Tasks and Grasp Release Test Performance Subject Variable Test 1 (baseline), without Handmaster Phone Yes No No No No Yes Yes Fork No No No No No No No Weight No No No No No No No Video No No No No No No No Test 2, with Handmaster Phone Yes Yes Yes Yes No Yes Yes Fork Yes Yes Yes Yes Yes Yes Yes Weight Yes Yes Yes Yes Yes Yes Yes Video Yes Yes Yes Yes Yes Yes Yes Test 3, without Handmaster Phone Yes No No No No Yes Yes Fork No No No No No No No ADL* No No No No No No No Weight No No No No No No No Video No No No No No No No Test 3, with Handmaster Phone Yes Yes Yes Yes Yes Yes Yes Fork Yes Yes Yes Yes Yes Yes Yes ADL Yes Yes Yes Yes Yes Yes Yes Weight Yes Yes Yes Yes Yes Yes Yes Video Yes Yes Yes Yes Yes Yes Yes * See table 4. without stimulation (.57.98N). The final force values (test 3) with the neuroprosthesis were significantly greater than test 2 stimulated scores. There were no changes in subjects grip strength without the stimulation. None of the subjects had any active finger motion without stimulation at baseline or at the final assessment. In contrast to baseline testing, mean stimulated finger motion measurements significantly increased for test 2 ( cm) and test 3 ( cm). No significant difference was observed between test 2 and test 3 stimulated scores. The mean Fugl-Meyer score also improved with the use of the neuroprosthesis. At study commencement, only 1 of the 7 subjects was able to hold the ball (score 1) without the Handmaster system. After 1 week of training (test 2), all subjects held the ball against a firm tug with stimulation (score 2). They were able to repeat this ability in the final testing. Subject Self-Assessment Results of the questionnaire are summarized in table 5. Six subjects rated their overall performance as excellent, and 1 Subject Table 4: Subject-Selected ADLs Activity 1 Pour beverage into glass and drink from it without a straw 2 Grasp bottle, pick it up, and drink from it 3 Grasp full wine glass and drink from it 4 Grasp glass with beverage, lift from table, drink from it, and return it to table 5 Grasp computer disk from disk holder, place into drive, remove disk, and return it to table 6 Grasp a pen from pen holder and write name on paper 7 Grasp a pen from pen holder and write legibly on paper rated his overall performance as good. All 7 subjects reported that their ADL tasks and their grasp and release ability improved with the use of the NESS Handmaster neuroprosthesis and that they required less assistance in performing their routine daily activities. There were no adverse responses or safety issues observed or reported during the study. DISCUSSION The combination of an externally driven FES system with wrist stabilization provided by the Handmaster neuroprosthesis effectively and rapidly improved hand function in all studied persons with C5 and C6 SCI who met the inclusion criteria. Once patients were fitted with the Handmaster orthosis, the stimulation induced consistent activation of the specific forearm musculature to replicate grasp and release patterns, thereby allowing functional use of the stimulated hand. Moreover, improvements in all outcome measures were achieved after just 1 week of use, and 6 of 7 subjects could don and doff the orthosis independently. The success rate in this study far exceeds the results reported by Snoek et al. 10 The discrepancy may be explained in part by our adherence to stringent subject selection criteria that included readily identifiable functional limitations, specific impairments, and a clear understanding on the part of the subject of what the Handmaster system was designed to do. Gorman et al 11 and Snoek 10 have stressed the importance of comprehensive subject screening for successful implementation of an electric stimulation system for subjects with tetraplegia. Our methods provided the strongest evidence yet that, in its present configuration, the Handmaster neuroprosthesis can effectively assist persons with C5 or C6 tetraplegia who have adequate passive mobility of the fingers and excitability of the forearm and finger flexors and extensor muscles but lack the ability to grasp, hold, and release objects. Snoek et al 10 commented that the Handmaster system provided therapeutic benefits to some of their subjects, but they

5 FUNCTIONAL GAINS USING A NEUROPROSTHESIS, Alon 123 Table 5: Subject Self-Assessment Item Response (n) 1. Overall categorization of your performance Excellent (6), good (1) 2. Does the Handmaster improve your performance of selected ADL activity? Yes (7) 3. Does the Handmaster improve your ability to grasp, hold, and release objects? Yes (7) 4. Does the Handmaster reduce the extent of assistance you need in performing any of your daily activities? Yes (7) provided only anecdotal evidence of this. Our data provide direct and statistically significant findings to show that impaired grip strength and finger mobility improved with the use of the neuroprosthesis. The significant improvement in grip force from test 2 to stimulated test 3 may indicate a local increase in muscle contractile capacity, neural adaptation, 15 or both. 16 Because ours was a clinical investigation, elucidating the mechanism that governs the increase in muscle strength was outside its scope. Nevertheless, we noted that 5 of the 7 subjects gradually increased the stimulation amplitude, an indication that the increase of force generation may have been the result of recruiting more motor units. Although the possibility that selected muscle fibers hypertrophy could not be completely ruled out, a visible change in forearm muscle size was not evident after 3 weeks of stimulation. A secondary purpose of our investigation was to determine the safety of using the Handmaster system by the subjects in their home. We were particularly concerned that muscle fatigue may present an adverse response that could hinder the effectiveness of the stimulation protocol. 17 In published investigations, researchers have used various approaches to minimize fatigue, including modulating the pulse frequency (or interpulse intervals) or altering the ratios between stimulation on and off times. 22,23 We elected to use a third approach, known as a gradual conditioning program, in which the length of the stimulation session is initially only few minutes long and is gradually increased every other session until the desired treatment time is reached. 24,25 Because this study was of limited scope and short duration, with an emphasis on functional training after week 1, the duration of exercise was limited to 30 minutes, 2 times a day, after the 10th day. Clinically, this approach turned out to be very effective in these circumstances, because no subject complained of fatigue or a decrease in their ability to use the Handmaster system during the 3-week trial, nor did the stimulation cause any other safety or adverse responses. In fact, all subjects were highly compliant with the program. Much has been written about long-term compliance with hand splinting and other assistive devices used by persons with tetraplegia. Listed determinants of continued use include diversity of functional tasks, cosmesis, and ease of donning and doffing Although not formally included in this study, most subjects successfully performed several additional ADL or specific tasks that they could not do without the Handmaster system. This voluntary activity gave us the impression that if the subjects were permitted to use the Handmaster system after completing the study, they would continue using it. Indeed, we believed that the subjects would attempt to find novel uses for the device. Nevertheless, compliance over prolonged periods and the diversity of useful hand functions that can be performed with the Handmaster system remain unknown and are worthy of further investigation. Additionally, we think that there are compelling reasons to offer a noninvasive neuroprosthesis such as the Handmaster system early in the rehabilitation of subjects with C5 or C6 tetraplegia. It would be useful to investigate how an early intervention might minimize hand impairments and permit faster training of functional and ADL tasks. Compared with invasive methods that may require 6 to 8 months for complete control of the system, 31 our subjects needed only 1 to 2 weeks. Devices such as the Handmaster neuroprosthesis may prove to be a low-cost alternative or an early intervention option that may enhance the decision-making process for persons considering surgical implantation of a neuroprosthesis. 30 We even suggest that if our study subjects were provided with the Handmaster system to both arms, they would have expanded their range of ADL and other functional tasks considerably and would have performed them much faster and more efficiently. CONCLUSION The NESS Handmaster system is an effective and safe noninvasive neuroprosthesis that enhances the performance of specific tasks of the upper limb of selected subjects with C5 or C6 tetraplegia. Its successful use is highly dependent on detailed clinical evaluation of potential candidates and short but skillful training by qualified clinicians. Considering our results and speculating about the advantages and limitations of a noninvasive neuroprosthesis system, we believe that future studies are warranted to investigate early intervention, prolonged use, and the device s usefulness for persons with other neurologic deficits, such as cerebrovascular accident. References 1. Formal CS, Cawley MF, Stiens SA. Spinal cord injury rehabilitation. 3. Functional outcomes. Arch Phys Med Rehabil 1997;78 (3 Suppl):S Kilgore KL, Peckham PH, Thrope GB, Keith MW, Gallaher- Stone, KA. Synthesis of hand grasp using functional neuromuscular stimulation. IEEE Trans Biomed Eng 1989;36: Kilgore KL, Peckham PH, Keith MW, et al. An implanted upperextremity neuroprosthesis. Follow-up of five patients. J Bone Joint Surg Am 1997;79: Carroll S, Cooper C, Brown D, Sormann G, Flood S, Denison M. Australian experience with the Freehand System for restoring grasp in quadriplegia. Aust N Z J Surg 2000;70: Davis SE, Mulcahey MJ, Betz RR, Smith BT, Weiss AA. Outcomes of upper-extremity tendon transfers and functional electrical stimulation in an adolescent with C-5 tetraplegia. Am J Occup Ther 1997;51: Prochazka A, Gauthier M, Wieler M, Kenwell Z. The bionic glove: an electrical stimulator garment that provides controlled grasp and hand opening in quadriplegia. Arch Phys Med Rehabil 1997;78: Popovic D, Stojanovic A, Pjanovic A, et al. Clinical evaluation of the bionic glove. Arch Phys Med Rehabil 1999;80: Ferrari de Castro MC, Cliquet A Jr. Artificial grasping system for the paralyzed hand. Artif Organs 2000;24: Beasley RW. Surgical treatment of hands for C5-C6 tetraplegia. Orthop Clin North Am 1983;14: Snoek GJ, IJzerman MJ, in t Groen FA, Stoffers TS, Zilvold G. Use of the NESS Handmaster to restore hand function in tetraplegia: clinical experiences in ten patients. Spinal Cord 2000;38:

6 124 FUNCTIONAL GAINS USING A NEUROPROSTHESIS, Alon 11. Gorman PH, Wuolle KS, Peckham PH, Heydrick D. Patient selection for an upper extremity neuroprosthesis in tetraplegic individuals. Spinal Cord 1997;35: Andersen JL, Mohr T, Biering-Sorensen F, Galbo H, Kjaer M. Myosin heavy chain isoform transformation in single fibres from m. vastus lateralis in spinal cord injured individuals: effects of long-term functional electrical stimulation (FES). Pflugers Arch 1996;431: Round JM, Barr FM, Moffat B, Jones DA. Fibre areas and histochemical fibre types in the quadriceps muscle of paraplegic subjects. J Neurol Sci 1993;116: Gordon T, Mao J. Muscle atrophy and procedures for training after spinal cord injury. Phys Ther 1994;74: Colson S, Martin A, Van Hoecke J. Re-examination of training effects by electrostimulation in the human elbow musculoskeletal system. Int J Sports Med 2000;21: Duchateau J. Bed rest induces neural and contractile adaptations in triceps surae. Med Sci Sports Exerc 1995;27: Mourselas N, Granat MH. Evaluation of patterned stimulation for use in surface functional electrical stimulation systems. Med Eng Phys 1998;20: Binder-Macleod SA, Lee SC, Russ DW, Kucharski LJ. Effects of activation pattern on human skeletal muscle fatigue. Muscle Nerve 1998;21: Binder-Macleod SA, Lee SC, Fritz AD, Kucharski LJ. New look at force-frequency relationship of human skeletal muscle: effects of fatigue. J Neurophysiol 1998;79: Binder-Macleod SA, Russ DW. Effects of activation frequency and force on low-frequency fatigue in human skeletal muscle. J Appl Physiol 1999;86: Kebaetse MB, Lee SC, Binder-Macleod SA. A novel stimulation pattern improves performance during repetitive dynamic contractions. Muscle Nerve 2001;24: Boom HB, Mulder AJ, Veltink PH. Fatigue during functional neuromuscular stimulation. Prog Brain Res 1993;97: Matheson GO, Dunlop RJ, McKenzie DC, Smith CF, Allen PS. Force output and energy metabolism during neuromuscular electrical stimulation: a 31 P-NMR study. Scand J Rehabil Med 1997; 29: Faghri PD, Rodgers MM, Glaser RM, Bors JG, Ho C, Akuthota P. The effects of functional electrical stimulation on shoulder subluxation, arm function recovery, and shoulder pain in hemiplegic stroke patients. Arch Phys Med Rehabil 1994;75: Alon GD, Dar A, Katz-Behiri D, Weingarden H, Nathan R. Efficacy of a hybrid upper limb neuromuscular electrical stimulation system in lessening selected impairments and dysfunctions consequent to cerebral damage. J Neurol Rehab 1998;12: Caudrey DJ, Seeger BR. Rehabilitation engineering service evaluation: a follow-up study of device effectiveness and patient acceptance. Rehabil Lit 1983;44: Kohn J, Enders S, Preston J Jr, Motloch W. Provision of assistive equipment for handicapped persons. Arch Phys Med Rehabil 1983;64: Nemunaitis GA, Herbison GJ. Cosmetic, functional, independent: self-help aids. Arch Phys Med Rehabil 1991;72: Krajnik SR, Bridle MJ. Hand splinting in quadriplegia: current practice. Am J Occup Ther 1992;46: Triolo R, Nathan R, Handa Y, et al. Challenges to clinical deployment of upper limb neuroprostheses. J Rehabil Res Dev 1996;33: Biering-Sorensen F, Gregersen H, Hagen E, et al. [Improved function of the hand in persons with tetraplegia using electric stimulation via implanted electrodes] [Danish]. Ugeskr Laeger 2000;162: Suppliers a. NESS Ltd, 19 Ha-Haroshet St, PO Box 2500, Ra anana 43654, Israel. b. Poly Software International, PO Box 60, Pearl River, NY