Intramuscular Hand Neuroprosthesis for Chronic Stroke Survivors

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2003 17: 109Neurorehabil Neural RepairJohn Chae and Ronald Hart

Intramuscular Hand Neuroprosthesis for Chronic Stroke Survivors

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Copyright © 2003 The American Society of Neurorehabilitation 109

The purpose of this study was to assess the feasibility of apercutaneous hand neuroprosthesis system for stroke sur-vivors. Case reports of 4 chronic stroke survivors who wereimplanted with percutaneous intramuscular electrodes invarious muscles of the forearm for hand grasp andrelease are presented. A percutaneous hand neuropros-thesis was able to open a spastic hemiparetic hand as longas the upper limb was in a resting position, the wrist andproximal forearm were supported, participants did nottry to assist the stimulation, and an individual other thanthe participant modulated the stimulation. However,when participants tried to assist the stimulation or com-plete a functional task, hand opening was significantlyreduced due to increased finger flexor hypertonia, evenwith increased stimulation intensity. Similarly, electrical-ly stimulated hand opening was significantly reduced fol-lowing voluntary hand closure. Techniques that providereal-time modulation of hypertonia with closed loop con-trol, control strategies that are independent of the con-tralateral limb, and methods to enhance proximal con-trol must be developed to demonstrate the feasibility of ahand neuroprosthesis system for persons with hemiparesis.

Key Words: Neuroprosthesis—Stroke—Hemiparesis.

Functional neuromuscular electrical stimula-tion (NMES) is used to activate paralyzed orparetic muscles in precise sequence and

intensity to assist in the performance of activities ofdaily living. Devices or systems that provide func-tional NMES are also appropriately called neuro-prostheses. An implanted hand neuroprosthesissystem has been shown to enhance the hand func-

tion of persons with cervical spinal cord injury.1 Inview of the success of this system for persons withtetraplegia, it is reasonable to apply this evolvingtechnology to persons with hemiparesis followingstroke.

In 1973, Rebersek and Vodovnik2 demonstratedthat a transcutaneous hand neuroprosthesis systemcould open and close the hemiparetic hand undervolitional control. With training, participantsdemonstrated progressive improvements in thenumber of plugs and baskets they could manipu-late with the device. In 1975, Merletti and associ-ates3 used a similar system to demonstrate thatstroke survivors can use a transcutaneous handneuroprosthesis system to manipulate small plasticbaskets and bottles.

However, since these early studies, there havebeen few additional reports on the development ofhand neuroprosthesis systems for stroke survivors.Cameron and associates4 demonstrated the effec-tiveness of transcutaneous NMES in opening a rest-ing hemiparetic hand. Cyclic transcutaneous NMESwith or without an orthosis has also been shown tofacilitate motor recovery of stroke survivors.5,6

However, the ability of these systems to providedirect hand function has not been demonstrated.Furthermore, earlier work in our laboratorydemonstrated that transcutaneous NMES is noteffective in opening a spastic hemiparetic hand ifthe participant attempts to assist the stimulation orif the stimulation is applied immediately after vol-untary hand closure. Similarly, Lin demonstratedthe varying nature of hypertonia as a function ofmovement of the ipsilateral and contralateral upperlimb and the need for varying the stimulation inten-sity to adequately open the spastic hemiparetichand.7

In view of the recent success of an implantedneuroprosthesis system for persons with tetraplegiaand the inconsistent experience reported in the lit-erature with transcutaneous neuroprosthesis sys-tems among stroke survivors, we elected to furtherexplore the feasibility of a hand neuroprosthesis

Intramuscular Hand Neuroprosthesisfor Chronic Stroke Survivors

John Chae and Ronald Hart

From the Center for Physical Medicine and Rehabilitation andDepartment of Biomedical Engineering (JC), Case WesternReserve University; Departments of Physical Medicine andRehabilitation (JC), MetroHealth Medical Center, ClevelandFunctional Electrical Stimulation Center (JC, RH), Louis StokesCleveland Veterans Affairs Medical Center (RH), Cleveland OH.

Address correspondence to John Chae, MD, ME, AssistantProfessor of Physical Medicine and Rehabilitation, AssistantProfessor of Biomedical Engineering, Case Western ReserveUniversity, MetroHealth Medical Center, 2500 MetroHealthDrive, Cleveland, OH 44109. E-mail: [email protected].

Chae J, Hart R. Intramuscular Hand Neuroprosthesis for ChronicStroke Survivors. Neurorehabil Neural Repair 2003;17:109–117.

DOI: 10.1177/0888439003254402

at CARLETON UNIV on November 30, 2014nnr.sagepub.comDownloaded from


system for persons with hemiparesis. NMES may beable to address the “negative signs” of central nerv-ous system motor dysfunction such as weakness,fatigue, and delay in initiation of muscle contrac-tion. However, it cannot address the “positive”signs such as delay in termination of muscle con-traction, co-contractions of agonist and antagonistmuscles, co-activation of synergistic muscles, andspasticity. These positive signs may be exacerbatedby the cutaneous noxious stimuli of transcutaneousNMES. We elected to evaluate a percutaneouslyplaced intramuscular system to decrease the levelof discomfort associated with transcutaneousNMES.8,9 In addition, intramuscular NMES address-es several inherent limitations of transcutaneoussystems. These include the labor-intensive natureof placing and removing electrodes (especiallywhen multiple electrodes are required), poorreproducibility and muscle selectivity of stimula-tion, and poor access to deeper muscles. Thus,Merletti and associates3 suggested that an implant-ed system would best meet the clinical needs ofpersons with hemiplegia. However, prior to devel-oping and implementing a fully implantable systemin hemiparesis, feasibility should be demonstratedwith a reversible system. A percutaneous systemthat allows intramuscular stimulation meets thiscondition of reversibility. Thus, the specific aims ofthis exploratory study were to 1) demonstrate theadequacy of percutaneous stimulation for openingand closing a hemiparetic hand, 2) identify controlstrategies that reliably open and close the handunder participant control, and 3) demonstrate func-tional efficacy.

METHOD

Four stroke survivors were recruited to participate.Inclusion criteria included age 18 years or older,medical stability, intact cognition, 5 months orgreater from last stroke, and ability to follow 3stage commands. In addition, participants musthave sufficient control of the paretic shoulder andelbow to functionally position the hand. However,active finger extension was absent. The study pro-tocol was reviewed and approved by the studyinstitution’s human subjects committee, and all par-ticipants signed informed consent.

Each participant received multiple percutaneousintramuscular electrodes in the paretic muscles ofthe upper extremity to provide functional handgrasp and release. The specific muscles for implan-tation varied depending on the neurological status

of each participant. The electrode, stimulator, stim-ulation parameters, and implant procedure havebeen described previously.8 One week afterimplantation, each electrode was tested by stimu-lating the implanted muscle. The stimulation of thevarious hand and forearm muscles was than syn-thesized to create a functional grasp andrelease.10,11 Functional grasp or hand closure wasdefined as generation of sufficient grasp strength tohold simple objects such as a utensil or a soda can.Functional release or hand opening was defined assufficient activation of the finger extensors to pro-duce adequate clearance of the finger tips to placea simple object in the hand or to release an objectafter hand closure. In all cases, the stimulation pro-vided hand opening. Hand closing was providedby volitional activation of the finger flexors in 2participants and via electrical stimulation in 2 par-ticipants. The investigator controlled the stimula-tion intensity with a potentiometer or the partici-pant controlled the stimulation via 3 methods,which included shoulder position transducer, wristangle transducer, and EMG controller. The percuta-neous system with these 3 options for control bythe user is shown in Figure 1. Only one of the 3control methods would be used at any one time.Detailed descriptions of these strategies have beenpreviously described.12

Demographic characteristics of each participantare shown in Table 1. The specific musclesimplanted, the number of electrodes, duration ofimplantation, and control strategies used for eachparticipant are shown in Table 2. All participantsreceived electrically stimulated conditioning exer-

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110 Neurorehabilitation and Neural Repair 17(2); 2003

Figure 1. A percutaneous hand neuroprosthesis systemfor hemiplegia. All 3 control options of shoulder trans-ducer, wrist joint angle transducer, and EMG controllerare illustrated. However, only 1 control method is usedat any one time.



cises of the implanted muscles for at least 1 h/dayduring the study period. The upper extremity com-ponent of the Fugl-Meyer Motor Assessment, avalid and reliable measure of poststroke motorimpairment,13,14 was administered to 3 of 4 partici-pants at baseline prior to implantation. Resistanceto passive range of motion (ROM) with extensionof the metacarpophalangeal (MCP) joint was alsoassessed at baseline using the modified AshworthScale (MAS).15 When participants reportedimprovement in arm function without the electricalstimulation, follow-up Fugl-Meyers were adminis-tered.

Case 1

Participant 1 moved his hemiparetic upper extrem-ity in flexor and extensor synergy patterns, pre-dominantly in the proximal limb with minimal dis-tal movement. He scored a 23 out of possible 66 onthe Fugl-Meyer Motor Assessment at baseline. He

exhibited full passive ROM at the MCP, proximalinterphalangeal (PIP) and distal interphalangeal(DIP) joints. However, significant finger flexorshypertonia graded as a 3 on the MAS was noted atthe MCP joint. Clonus was also noted at the MCPjoint.

The stimulator was programmed to provide later-al and palmar grasps. In the open phase of lateralgrasp, the finger and thumb were extended. Thefingers were fully flexed at all joints while thethumb remained extended. The thumb was thenflexed against the lateral aspect of the index fingerto produce a grasp. In the open phase of palmargrasp, the fingers were extended and the thumbwas posted in full abduction. The fingers thenflexed against the thumb, ideally resulting in con-tact between the tip of the thumb and the tips ofthe index and long fingers. Lateral and palmargrasps were achieved through electrical stimulationbut only when the upper limb was in a restingposition, both wrist and proximal forearm weresupported, the participant did not try to assist the

Hand Neuroprosthesis for Hemiparesis

Neurorehabilitation and Neural Repair 17(2); 2003 111

Table 1. Demographic Characteristics of Participants

VolitionalAge Stroke Stroke Onset Fugl- Finger

Participant (years) Gender Type Level Sidea Etiology (mo)b Meyer Flexion

1 54 Male NH Cortical Left Carotid dissection 9.0 23 No2 39 Male NH Cortical Left Thrombotic 6.5 35 Yes3 41 Male NH Cortical and

bilateralcerebellar Right Thrombotic 24.0 23 Yes

4 70 Male NH Cortical Left Thrombotic 5.0 — Yes

NH = nonhemorrhagic. Dash indicates not obtained.a. Side of hemiparesis.b. Stroke onset to study entry.

Table 2. Specific Muscles Implanted, Number of Electrodes Implanted, Duration of Implantation, Control ParadigmsUsed, and Number of Electrodes that Fractured during Removal for Each Participant

Duration of Number ofNumber of Implantation of Electrode

Participant Muscles Implanteda Electrodes Electrodes (months) Control Methods Fractureb

1 EDC, EIP, EPL, APB, 20 17.5 Potentiometer; shoulder 42nd and 3rd DI, FDSc transducer; EMG controller

2 EDC, 2nd and 3rd DI, FDSc 7 17.0 Potentiometer; controller; 7shoulder transducer; wrist

EMG controller3 EPL, EIP, EDC, ECR,c FDSc 10 13.7 Potentiometer; shoulder 8

transducer; EMG controller4 EDC, ECR, EPL, FDS 7 7.0 Potentiometer d

a. EDC = extensor digitorum communis; EIP = extensor indicis propius; EPL = extensor pollicis longus; APB = abductor pollicis brevis;DI = dorsal interosseous; FDS = flexor digitorum superficialis; ECR = extensor carpi radialis.b. Number of electrodes fractured during removal.c. These muscles were implanted to monitor EMG signal for the EMG controller and not for muscle stimulation.d. Participant removed the electrodes himself during a seizure episode and they were discarded prior to examination by the investigators.



stimulation, and the investigator controlled thestimulation. The stimulation opened the hand toreceive a simple utensil and closed the hand usingthe lateral grasp pattern to hold the utensil.Similarly, the stimulation opened the hand toreceive a soda can and closed the hand using thepalmar grasp pattern to hold the can. However,when the participant tried to perform these taskswithout the proximal support, when he tried toassist the stimulation, or when the stimulation wascontrolled by the participant using a shouldertransducer on the contralateral limb, marked clonusof the finger flexors and tremor of the fingers,wrist, and forearm prevented functional use of thesystem. Specifically, the clonus prevented sufficientopening of the hand to receive the utensil, or thecan and the tremor prevented controlled position-ing of the hand. Trials of dantrolene sodium andbaclofen were discontinued due to significant cog-nitive side effects. A temporary motor point blockof the flexor digitorum superficialis (FDS) and pro-fundus (FDP) with lidocaine hydrochloridedecreased resting hypertonia but failed to yield anysignificant reduction in clonus or tremor duringattempts at using the system. Attempts at control-ling hand function by using the EMG signal fromthe FDS were unsuccessful as the participant wasunable to sustain his EMG signal. There was nodetectable EMG signal from the extensor digitorumcommunis (EDC).

The subject participated in the study for a periodof 17.5 months. During the study period, he report-ed significant improvement in the awareness of hishemiparetic arm and its use for gross assist.Increased mobility of the shoulder and elbow werealso reported. Ten months after initial implantation,the Fugl-Meyer score was 35, an increase of 12points relative to baseline. However, all of theimprovements occurred in the proximal portion ofthe measure.

During the study period, there were no episodesof electrode-related skin infections. All electrodeswere removed by gently pulling on the electrodesuntil they loosened from the soft tissue. The distalportion of 4 of 20 electrodes fractured duringremoval. There has been no evidence of infectionor granuloma formation associated with theretained fragments during the 5 years of follow-up.

Case 2

Participant 2 exhibited isolated movements of hisshoulder and elbow with wrist extension and fin-

ger flexion in synergy. There was no volitional fin-ger extension. Although he was able to volitionallyflex and extend his elbow with full ROM, he exhib-ited marked flexor and extensor hypertonia gradedas a 4 on the MAS. He exhibited full passive ROMat MCP, PIP, and DIP joints. However, marked fin-ger flexor hypertonia graded as a 3 on the MAS wasnoted with MCP extension. The patient was beingtreated with baclofen at study entry with marginalsuccess. His upper extremity Fugl-Meyer score was35 out of possible 66 prior to implantation.

Six weeks after implantation, the participantexperienced a grand mal seizure, which was ini-tially treated with phenytoin and subsequentlychanged to carbamazepine. The participant wasnot using the stimulator when the seizure occurred.Baclofen was discontinued and tizanadine wasstarted. However, no significant change in hyperto-nia was noted. The participant subsequently dis-continued the tizanadine due to cognitive sideeffects. The participant continued to have briefepisodes of focal seizures once or twice a year,even after completion of the study.

If investigators controlled the stimulation, theparticipant did not try to assist the electrical stimu-lation, and the wrist was flexed, adequate handopening could be achieved. However, when theparticipant extended his elbow to reach for anobject, increased finger flexion hypertonia signifi-cantly reduced hand opening, even with increasedstimulation intensity. Similarly, stimulation-inducedfunctional hand opening was significantly reducedafter volitional hand closure due to increased fingerflexion hypertonia, which prevented placement ofsimple objects in the hand. When the hand wassufficiently opened, the participant was able topick up small objects with volitional finger flexion.However, attempts at opening the hand with theelectrical stimulation to release the object with ashoulder transducer on the contralateral shoulderwas ineffective due to marked finger flexion toneassociated with effort. Use of a wrist controller,which stimulated EDC and 2nd and 3rd dorsalinterossei with volitional wrist flexion and termi-nated stimulation with volitional wrist extensionwas also ineffective. The participant was able toinitiate hand opening by flexing his wrist.However, as the EDC was activated, the participantwas unable to maintain wrist flexion and fingerextension due to the extensor moment of the EDCon the wrist. After volitional finger closure withwrist extension in synergy, the participant wasunable to flex the wrist adequately to activate fin-ger extension due to wrist extensor hypertonia.

Chae and Hart




Even when the wrist extensor tone was overcome,the residual finger flexor tone severely limited elec-trically stimulated hand opening. A similar phe-nomenon was noted with an EMG controller usingEMG signals from the FDS. Treatment of the hyper-tonia with botulinum toxin A reduced finger flex-ion tone to decrease the clonus. However, the par-ticipant no longer had sufficient control of handclosure to use the system functionally.

The subject participated in the study for a periodof 17 months. He reported improvements in theoverall mobility of shoulder and elbow withincreased use of the hemiparetic upper limb. Hereported initiation of bimanual tasks by placingobjects in his paretic hand and volitionally keepingthe hand closed. Five months into the protocol, theFugl-Meyer score improved to 44, an increase of 9points relative to baseline. Improvements were allseen in the proximal limb.

During the study period, there was 1 superficialinfection at 3 months’ post-implantation. Examina-tion revealed macerated skin surrounding the elec-trode exit sites with purulent discharge. Further-more, the plastic connector was found on top ofthe electrode exit sites instead of away from them.The participant failed to follow instruction and didnot check or clean his electrode site for an entire1-week period. The participant was treated withtopical and oral antibiotics with good resolution.The distal tips of all 7 electrodes fractured duringremoval at the end of the study. There has been noevidence of infection or granuloma formation asso-ciated with the retained fragments during the 3.4years of follow-up.

Case 3

Participant 3 exhibited elbow flexion and extensionin synergy patterns only. There was no volitionalfinger extension. The fingers could be passivelyopened to full range but with significant finger flex-ion tone graded as a 3 on the MAS at the MCP joint.Initial upper-extremity Fugl-Meyer score was 23.Electrically stimulated hand opening was achievedwhen the investigator controlled the stimulation,the upper limb was in a resting position, the par-ticipant did not try to assist the electrical stimula-tion, and the wrist and proximal limb were sup-ported. However, the participant was unable toopen the hand using a shoulder transducer oneither shoulder due to inadequate shoulder controland triggering of finger flexion hypertonia. EMG-controlled hand opening was also ineffective

because the participant could not terminate hisEMG signals from the extensor carpi radialis orFDS. Even with the investigator controlling thestimulation, hand opening following voluntary clo-sure or during attempts at specific tasks was notachieved due to increased finger flexor tone.

The subject participated in the study for 13.7months. He reported no improvements in the useof his paretic upper limb, including the proximalsegments. No additional Fugl-Meyer scores wereobtained. There were no episodes of skin infec-tions during the study period. The distal tips of 8 of10 electrodes fractured during removal at the endof the study period. After 1 year of follow-up, 1granuloma was palpable on examination of themid dorsal forearm. After 2.8 years of follow-up,the same granuloma was noted to have migratedtoward the skin with resultant erythema and ten-derness to palpation. The electrode fragment wasremoved in a minor outpatient procedure underlocal anesthesia without complications. At the timeof the procedure, additional granulomas were pal-pable, but there was no evidence of erythema ortenderness warranting additional interventions.

Case 4

Participant 4 exhibited left upper extremity move-ment in a synergy pattern with proximal movementbeing greater than distal. Weak finger flexion wasin a synergy pattern. There was no finger exten-sion. The participant exhibited full passive ROM ofthe fingers but with significant finger flexion toneat the MCP graded as a 3 on the MAS. The electri-cal stimulation opened the hand fully as long as theinvestigator controlled the stimulus intensity, thelimb was in a resting position, the participant madeno effort to assist the electrical stimulation, and thewrist and proximal forearm were supported. Aswith other participants, electrical stimulation wassignificantly less effective in opening the hand dur-ing attempts at functional tasks and after volitionalhand closure due to increased finger flexion tone.Control methods were not assessed.

There were no episodes of skin infection duringthe study period. The participant reported noimprovements in the use of the hemiparetic limb.No additional Fugl-Meyer scores were obtained.Seven months after implantation, the participantexperienced a grand mal seizure associated with anew right hemisphere infarct. The participant didnot use the stimulator on the day of or on the dayprior to the new stroke and seizure. The participant





removed all the electrodes during the seizureepisode. The electrodes were discarded prior toexamination by the investigators. Thus, it was notpossible to determine whether the distal tips wereintact. The participant experienced marked deteri-oration in cognition and was disenrolled from thestudy. He was subsequently lost to follow-up.

DISCUSSION

These case reports describe the first 4 chronicstroke survivors implanted with a percutaneoushand neuroprosthesis system. Intramuscular stimu-lation was effective in opening and closing thehemiparetic hand as long as the involved limb wasin a resting position, the wrist and proximal fore-arm were supported, the participant did not assistthe stimulation, and an individual other than theparticipant modulated the stimulation intensity.However, when participants attempted to use thesystem in a functional manner or they tried to assistthe stimulation, marked hypertonia with or withoutclonus predominated, which prevented completionof the targeted task. The control strategies evaluat-ed in this report were inadequate. Shoulder trans-ducer control was ineffective due to inadequateproximal control in both shoulders. Wrist positiontransducer control was ineffective due to weakwrist flexion, which could not counter the wristextension moment from the electrically stimulatedEDC. EMG controller was ineffective due to theparticipants’ inability to control their EMG signalsin the paretic muscles. In view of these limitations,functional ability was not formally evaluated.

An earlier report from our laboratory demon-strated that whereas transcutaneous NMES canopen a spastic hemiparetic hand while it was in aresting state, this was not the case if the participanttried to assist the stimulation or if the participantvoluntarily closed the hand just prior to the stimu-lation. These observations were attributed toincreased finger flexor tone associated with effortand the participant’s inability to terminate muscleactivity in a timely manner. We pursued the presentstudy based on the possibility that the discomfortassociated with transcutaneous NMES exacerbatedthe hypertonia and that standard clinical interven-tions would be effective in reducing the hyperto-nia. Specifically, because intramuscular NMES issignificantly less painful than transcutaneousNMES, we hypothesized that intramuscular NMESwould be associated with less finger flexor hyper-tonia. In addition, we hypothesized that standard

oral antispasticity and focal neurolytic techniqueswould be effective in further reducing the fingerflexor hypertonia. However, the persistence of sig-nificant finger flexor hypertonia during intramuscu-lar NMES suggests that noxious stimuli of transcu-taneous NMES is not an important exacerbating fac-tor in the genesis of marked hypertonia duringtranscutaneous NMES. We also found that availableoral antispasticity medication and focal neurolytictechniques are inadequate in reducing finger flexorhypertonia in the present experimental context.

The major barrier to the present investigationwas the dominant role of “positive” signs of centralnervous system injury, which decreased electricallystimulated hand opening. Previous studies havedemonstrated that in addition to the usual “nega-tive” signs of central nervous system, many strokesurvivors exhibit spasticity, delay in termination ofEMG activity,16 abnormal co-contraction of agonistand antagonist muscles,17 and abnormal co-activationof synergistic muscles.18 We previously demonstrat-ed that these abnormalities in the hemipareticupper limb correlate highly with clinical measuresof upper limb motor impairment and physical dis-ability.19,20 Although the presence of these “posi-tive” signs and their clinical implications have beenwell documented, pathophysiologic mechanismsand explanations for their increased prominencewith voluntary activity remain uncertain.Neurophysiologic studies have shown higher Fwave amplitudes, more persistent F waves, andhigher H wave–M wave amplitude ratios in spasticmuscles suggesting increased alpha motoneuronexcitability.21 Some have described positive signs as“release phenomenon” attributed to loss ofsupraspinal inhibitory influences on normalinterneuronal pool.22 Increased and decreasedRenshaw’s inhibition have also been implicated.21

However, a reduction in corticospinal input mayalso result in increased dependence in undamagedvestibulospinal, reticulospinal, and tectospinalpathways.18,23,24 These brainstem pathways exhibitextensive branching, innervating neurons overmany spinal segments, which may induce abnor-mal activation patterns. Cortical reorganization mayalso induce redistribution of cortical pathways tospinal segmental circuits leading to more unfo-cused descending inputs.25 Whether any or all ofthese mechanisms are responsible for the positivesigns observed in this study remains to be eluci-dated.

Two of our participants experienced somemotor-relearning effect during the study period.Motor relearning is defined as the reacquisition of

Chae and Hart




motor skills lost after central nervous system injury.Whether this apparent improvement was a directresult of the electrical stimulation or some otherfactor such as natural recovery cannot be deter-mined from the present study. Nevertheless, previ-ous studies have suggested that NMES-mediatedactive repetitive movement therapy has a signifi-cant motor-relearning effect among stroke sur-vivors.5 We have not observed this phenomenonamong spinal cord patients who use a hand neuro-prosthesis system on a regular basis. Thus, in theimplementation of NMES for stroke survivors, itremains unclear as to when motor relearning endsand when neuroprosthetic needs begin. The appli-cation of NMES for motor relearning will requiretemporary systems such as transcutaneous or per-cutaneous intramuscular systems. The activity willbe in an exercise mode in which muscles are stim-ulated in a cyclic manner. Therefore, because theactivity itself is not functional, the control paradigmdoes not need to be sophisticated. However, neu-roprosthesis systems will be used chronically andwill need to be fully implanted with sophisticatedcontrol systems that allow users to perform func-tional tasks.

Although 2 participants may have experiencedsome motor-relearning effect during the study, allparticipants were too severely impaired to benefitfrom any neuroprosthetic effect. The present sys-tem is likely more appropriate for a small but selectgroup of stroke survivors who have minimal handfunction but have excellent control of the shoulder,elbow, and wrist with minimal hypertonia. A second-generation hand neuroprosthesis,26 which uses animplantable wrist joint angle transducer or an EMGcontroller, may be able to provide grasp-and-release function and basic bimanual functionalcapacity to this population. Experience with such asystem in a limited number of participants may pro-vide insight into the design of future systems thatwill be applicable to the broader stroke population.

The extent to which the scientific, engineering,and medical communities further pursue the devel-opment of a hand neuroprosthesis for hemiparesiswill depend on its functional and technical goals.Although more complex systems are presentlybeing investigated for tetraplegia, the provision ofsimple hand opening and closing is still justifiablein the spinal cord population. However, the systemfor hemiparesis must demonstrate that participantsare able to perform bilateral tasks and are able toperform specific tasks faster and more efficientlycompared to the usual single-handed approach.The system must have sufficient miniaturization

and robustness to allow mobility for ambulatingstroke survivors. The system must provide proxi-mal as well as distal function. In view of the com-plex nature of motor control in hemiplegia, the sys-tem must be able to address the problem of posi-tive signs described earlier. In our experience withspinal cord patients, spasticity is well controlled inmost patients with only oral pharmacologicalagents. Because all our spinal cord participants sus-tained complete injuries, the phenomena of delayin termination, co-contraction, and co-activation,which are likely mediated by cerebral mechanisms,were not relevant issues. Finally, the control para-digm must allow smooth, relatively effortless, voli-tionally controlled functional movement of theimpaired upper extremity without compromisingthe function of the intact or nonparalyzed limbs ormuscles.

To achieve these functional and technical speci-fications, future studies must focus on the follow-ing. Fundamental studies should be carried out tofurther elucidate the motor control issues of hemi-paresis. Dynamic electromyography studies shouldbe carried out to characterize the hypertonia andmotor activation patterns during functional activi-ties. An effective hand neuroprosthesis will be ableto turn off unwanted co-contraction and hypertoniaas well as turn on weak or plegic muscles duringfunctional activities. Clinically available methodsfor treating the positive signs of central nervoussystem injury include oral antispasticity medica-tions; focal neurolytic agents such as phenol,ethanol, and botulinum toxins; and intrathecalbaclofen. However, none of these techniques areable to provide real-time modulation as a functionof specific activity. An alternative strategy is ablocking nerve electrode,27,28 which can undergoreal-time modulation. Blocking electrodes arepresently undergoing development at our centerand could be incorporated into future hand neuro-prosthesis systems. Surgical options such as tendonlengthening should also be considered to decreasethe affects of hypertonia. Closed loop systems thatcorrect the output based on knowledge of the out-put may also improve performance.29 Finally, con-trol paradigms, which use cortical signals, shouldbe developed to provide smooth functional activa-tion of paralyzed muscles without encumbering thefunction of the intact limb.30

This investigation used percutaneous intramuscu-lar electrodes as a proxy for a fully implantable sys-tem. The primary reason for this approach was thereversible nature of the system. A percutaneoussystem was chosen over a transcutaneous system





due to the lower level of discomfort during stimu-lation,8 greater selectivity of muscle activation, andgreater access to deeper muscles. However, percu-taneous electrodes also have limitations. In thisseries, distal tips of 19 of the 37 electrodes availablefor examination fractured during removal. Potentialcomplications from retained fragments include for-mation of granulomas, foreign body response tothe retained fragment, and infection. In this series,1 granuloma developed without infection duringthe follow-up period and was removed. Therewere no other complications associated with theretained fragments over the average follow-up peri-od of 25 months. One episode of skin infection,which was due to poor participant compliance withskin care of the electrode exit sites, required oralantibiotics. Based on 20 years of experience in ourlaboratory with persons with spinal cord injury,stroke, and traumatic brain injury, incidents ofgranuloma formation and electrode infectionoccurred at a rate of 1 per 5½ years of researchsubject participations. Incidents that required out-patient surgical treatment occurred at a rate of 1per 18½ years of research subject participation.

Two of our participants experienced seizures.Participant 2 experienced his seizure 6 weeks afterimplantation and 8 months after his stroke.Participant 4 experienced his seizure 7 months afterinitial implantation and in conjunction with a recur-rent stroke. In both cases, participants were notusing the stimulator when the seizure occurred.Seizures occur in 10% of stroke patients,31 and theincidence is significantly higher among those withcortical strokes.32 Thus, seizures in our participantswere likely due to their strokes rather than theintervention.

In conclusion, the actual clinical implementationof NMES therapy for stroke survivors is unlikely tooccur in isolation from other treatment modalities.If and when an operational hand neuroprosthesissystem becomes available for stroke survivors, itwill likely be implemented in conjunction withnumerous other techniques. One scenario is thatonce all known noninvasive motor-relearning tech-niques have been exhausted, a hand neuropros-thesis may be implemented. An alternative scenariois an early implementation of a NMES system asboth a motor-relearning tool and a neuroprosthesis.Evolving data on motor system neuroplasticityclearly indicate that motor relearning is activitydependent and that the most appropriate activity isboth meaningful and important to the stroke sur-vivor.33 Although cyclic NMES and other exerciseprograms provide repetitive movement therapy,

the activity itself is not functional, which mayexplain why improvements at the level of motorimpairment do not necessarily translate to improve-ments in functional ability.5 A hand neuroprosthe-sis system, which allows stroke survivors to per-form functional activities in a repetitive manner,may be a very effective motor-relearning tool.Such a system may be implemented in conjunctionwith novel motor-relearning strategies such asconstraint-induced therapy34 and robotic therapy35

and also may increase the number of stroke sur-vivors eligible for these techniques.

ACKNOWLEDMENT

This work was supported in part by NIH-NICHDgrant K12 HD01097-01A1.

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Intramuscular Hand Neuroprosthesis for Chronic Stroke Survivors