Functional Neuromuscular Electrical Stimulation

Jayme S. Knutson

Lynne R. Sheffler

John Chae

INTRODUCTION

Neuromuscular electrical stimulation (NMES) refers to the use of low-level electrical current to produce a muscle contraction. In the field of Physical Medicine and Rehabilitation, NMES is used in cases of neurological injury that result in muscle paralysis or paresis. Clinical applications of NMES provide either a therapeutic or functional benefit. Therapeutic NMES applications are intended to reduce specific impairments or to induce or hasten the recovery of volitional motor function and, therefore, are temporary or periodic interventions. Usually, therapeutic NMES applications do not directly provide motor function; provision of motor function is the purpose of functional NMES applications, which are the focus of this chapter. Functional NMES applications produce coordinated contractions of multiple muscles that enable the motor-impaired individual to accomplish functional tasks directly. A functional NMES device is called a neuroprosthesis, because it substitutes for or replaces lost neuromuscular function and is considered to be an ongoing or permanent intervention. Ideally, a neuroprosthesis should be easy to wear all day so that its utility is available whenever needed. This chapter reviews the principles of NMES and neuroprosthetic systems for several functional NMES applications.

PRINCIPLES OF NMES

Electrical Activation of the Neuromuscular System

Action potentials, and therefore muscle contractions, can be generated with electrical current. Electrical current, applied to excitable tissue through a pair of electrodes, creates a localized electric field that depolarizes the axonal membranes of nearby neurons. If the depolarization reaches a critical threshold, an influx of sodium ions from the extracellular space to the intracellular space produces an action potential that propagates from the site of stimulation and has the same effect as a naturally generated action potential. When the action potential reaches the terminals of the axon, neurotransmitter is released and, in the case of motor neurons, muscle fibers contract.

NMES systems generally operate by activating motor neurons rather than the muscle directly, even though NMES is commonly referred to as “muscle stimulation.” It is easier to stimulate a nerve than a muscle. The stimulus threshold for a neural tissue, the lowest level of charge that will generate an action potential, is much less than the threshold for muscle fibers (1). While it is possible to generate action potentials in muscle fibers directly, it is not usually done because of power consumption considerations. This means that for NMES to be applicable in a given patient, their lower motor neurons must be intact from the anterior horns of the spinal cord to the neuromuscular junctions of the target muscles.

Damage to lower motor neurons prevents the successful application of NMES in patients with polio, late-stage amyotrophic lateral sclerosis (ALS), and peripheral nerve injuries (e.g., brachial plexus injury). In addition, patients with disorders at the neuromuscular junction or muscle tissue (e.g., muscular dystrophies) are ineligible for NMES applications. NMES may be used when the lower motor neurons are excitable and the neuromuscular junction and muscle are healthy, as is usually the case in patients with spinal cord injury (SCI), stroke, traumatic brain injury, cerebral palsy, or multiple sclerosis. To date, most motor neuroprostheses have been targeted toward the SCI population.

Large axons are easier to stimulate than small axons. Large-diameter axons, which innervate the larger motor units, have lower stimulus thresholds than small-diameter axons (2). This is because the wider spacing between the nodes of Ranvier in large axons produces larger induced transmembrane voltage changes. The activation of large motor units before small motor units is known as reverse recruitment order and is the opposite of the physiological size principle, where small motor units are initially recruited, followed by larger motor units. In spite of this reverse recruitment order, it is still possible to produce graded muscle contractions with NMES.

Because large-diameter axons have lower stimulus thresholds, type II muscle fibers (fast-fatiguing) are preferentially recruited over type I muscle fibers (fatigue-resistant). Fatigue resistance is highly desirable for most functional NMES applications. Unfortunately, disuse atrophy tends to convert type I to type II fibers (3). However, long-term use of NMES can reverse muscle atrophy and convert type II fast-fatiguing fibers to type I fatigue-resistant fibers (4,5). Therefore, all current neuroprosthetic NMES applications use some form of muscle conditioning regimen to build and maintain fatigue-resistant muscle.

Axons near the stimulus source are easier to stimulate than axons farther away. The electric field diminishes with distance from the stimulus source; as the distance between the electrode and the axonal fiber increases, the stimulus threshold also increases (1). Less current is required to stimulate neurons in the proximity of the stimulating electrode because the transmembrane potentials generated by the electrical current are largest in the axons close to the stimulating electrode. Therefore, to improve the selectivity of stimulation, electrodes are placed as close as possible to target muscles or nerves.

The strength of a muscle contraction produced by NMES can be modulated by manipulating three stimulus parameters that characterize the wave of current pulses: pulse frequency, amplitude, and duration. If the pulse frequency is too low, the muscle responds with a series of twitches. As the pulse frequency is increased, the twitches begin to overlap and build on one another, producing a smooth or “fused” contraction. This cumulative effect of repeated stimulus pulses within a brief period of time is known as temporal summation. Higher stimulus frequencies produce stronger muscle contractions up to a maximum, but also make a muscle fatigue more rapidly than lower-frequency stimulation. Therefore, the ideal stimulus frequency is the lowest frequency that will produce a fused contraction, and depends on the muscle fiber type and the manner in which the stimulation is being delivered (e.g., surface vs. implanted electrode). In upper extremity applications that use implanted electrodes, a stimulus frequency of 12 to 16 Hz has been found to be the minimum required for producing fused contractions if the muscles have been conditioned to have relatively long-duration twitches. The strength of a muscle contraction may also be increased by increasing the pulse amplitude and/or pulse duration, which effectively increases the electric charge per pulse (6). The greater the electric charge, the larger the electric field and broader the region of activation. In this way, more axons and more motor units are activated, an effect known as spatial summation. In most neuroprostheses, the strength of muscle contraction is controlled by modulating the pulse amplitude or pulse duration while keeping the pulse frequency constant and as low as possible to avoid premature fatigue of muscles.

Safe Stimulation of Living Tissue

Safe stimulation waveforms and electrode materials have been experimentally established. For NMES applications using implanted electrodes, a current-regulated stimulator with a balanced biphasic stimulus waveform should be used. With implanted electrodes it is important to use stimulus parameters (pulse amplitudes and durations) that are appropriate for the dimensions and material composition of the electrode so that the charge density per phase remains within the established safe limits, thereby preventing electrode corrosion or dissolution of metal ions (1). With current-regulated stimulation, the current is directly controlled (current is the charge delivered per unit time). Therefore, the quantity of charge delivered per stimulus pulse can be maintained within safe limits. Improper stimulation can also cause tissue damage by producing irreversible electrochemical reactions at the electrode-tissue interface. Irreversible reactions can be avoided with charge-balanced biphasic stimulus waveforms. Biphasic waveforms consist of a repeating current pulse that has a cathodic (negative) phase followed by an anodic (positive) phase. The first, or primary, phase elicits an action potential in nearby axons, and the secondary positive pulse balances the charge of the primary pulse. The purpose of the secondary pulse is to reverse the potentially damaging electrochemical processes that occur at the electrode-tissue interface during the primary pulse, allowing neural stimulation without causing tissue damage (1).

For NMES applications using surface electrodes, other safety factors need to be considered. For example, the electrode-tissue contact area is often not a constant as surface electrodes often pull away from the skin or dry out. If a current-regulated stimulator is used in this circumstance, the reduction in contact area will cause high current densities and can result in burning the skin and underlying tissue. However, with a voltage-regulated stimulator, the magnitude of current delivered to the tissue is dependent on the impedance at the electrode interface (current = voltage/impedance). If the impedance at the electrode-skin interface increases because the electrode dries or loses strong contact with the skin, then the current delivered will decrease, thereby reducing the possibility of skin burns due to high current densities. Although this may be safer, a major disadvantage of voltage-regulated stimulation is that the muscle contraction produced is more variable because the changes in impedance lead to changes in applied current. Regardless of whether current-or voltage-regulated stimulators are used, even with good electrode-skin contact, burning of the tissue can occur if the current densities are too high. Therefore, surface stimulation should be used with caution and with frequent examination of the skin when applied to patients with impaired sensation or cognition. Table 72-1 summarizes the principles of NMES and their practical ramifications when applying NMES systems.

NMES System Configurations and Electrode Types

At least two electrodes are required to produce a current flow in NMES applications. One electrode, often referred to as the active electrode or cathode, is placed near the peripheral nerve or muscle motor point to be stimulated. The other electrode, known as the return electrode or anode, may be placed in a remote area near less excitable tissue (such as tendon or fascia), or it may be positioned close to the active electrode to confine the electric field to a small region of activation and thereby achieve more selective muscle activation. Additional electrodes are needed to achieve coordinated activation of multiple muscles. Multichannel NMES systems stimulate multiple muscles simultaneously and use either a bipolar or monopolar arrangement of electrodes. Bipolar multichannel systems require a return electrode for each active electrode; so for each muscle or nerve to be activated, a pair of electrodes (cathode and anode) is needed. This bipolar arrangement may allow greater selectivity of activation (7), but requires more electrodes and leads. Monopolar electrode systems reduce the number of electrodes and leads by
using only one remote return electrode with an active electrode placed near each motor point or nerve targeted for excitation.

TABLE 72.1 Principles of Safe Electrical Activation of the Neuromuscular System and Practical Ramifications

Principle	Practical Ramification
Action potentials can be produced by NMES.	Paralyzed muscles can be made to contract.
It is easier to stimulate nerve than muscle.	NMES is generally applicable only to patients with intact lower motor neurons.
Large axons are easier to stimulate than small axons.	A muscle conditioning regimen is needed to build and maintain fatigue-resistant muscle.
Axons near the stimulus source are easier to stimulate than axons farther away.	Selectivity of stimulation is improved by placing electrodes close to the target muscles or nerves.
Applying closely spaced stimulus pulses to a muscle produces an overlapping of muscle twitches, resulting in a “fused” contraction—temporal summation.	The strength of a muscle contraction can be modulated by increasing or decreasing the stimulus pulse frequency. However, very high stimulus frequencies cause rapid muscle fatigue.
More axons and motor units of a muscle are activated when the size of the electrical field is increased by increasing the electric charge per stimulus pulse—spatial summation	The strength of a muscle contraction can be modulated by increasing or decreasing the stimulus pulse amplitude and/or duration.
With implanted electrodes, electrode corrosion can be avoided by maintaining the charge density per phase of stimulus pulse within safe levels determined for the particular electrode material composition and dimensions.	Current-regulated stimulators should be used with implanted electrodes.
With implanted electrodes, tissue damage can occur if irreversible electrochemical reactions are produced at the electrode-tissue interface.	Charge-balanced biphasic stimulus waveforms should be used with implanted electrodes.
With surface electrodes, high current densities can cause skin burns.	Surface electrodes that maintain good contact with the skin should be used. Extra caution is needed when applying NMES to patients with reduced sensation or impaired cognition.

Functional NMES systems consist of at least three components: electrodes, a multichannel stimulator, and a controller (Fig. 72-1). The electrodes deliver the electrical current pulses to the excitable tissue, the stimulator generates the current waveforms for multiple cathodes, and the controller regulates the stimulation according to the user’s intent. A controller may be as simple as a switch that the patient hits to turn the stimulation on and off, or may incorporate sensors for recording patient-elicited biopotentials (e.g., EMG or EEG) and use those as signals to regulate the stimulation. Depending on the way these three components are arranged with respect to one another, NMES systems can be categorized as surface, percutaneous, or implanted. In surface systems, the electrodes, the stimulator, and the controller are external to the body. In percutaneous systems, the electrodes are implanted near a muscle or nerve with leads that pass through the skin to an external stimulator with a separate or integrated external controller. In implanted systems, the electrodes and stimulator are implanted and the controller components are either all external or some are implanted and some are external. To date, there is no neuroprosthesis available that has all three components completely implanted, although several research programs are moving in that direction (8,9).

FIGURE 72-1. Block diagram of a basic motor system neuroprosthesis.

Surface NMES systems (sometimes called transcutaneous systems) use electrodes that are placed on the skin and connected with flexible cables to a stimulator, which may be worn around the waist, the arm, or the leg. Usually, a sensor or switch that controls the stimulation is also connected to the stimulator. Surface electrodes are readily available in a variety of sizes from many manufacturers. The electrodes are placed on the skin over the nerves or over the “motor points” of muscles
to be activated. The motor point is the site of stimulation that produces the strongest and most isolated contraction at the lowest level of stimulation. Surface NMES systems offer several distinct advantages: (a) the electrodes are generally easy to apply and remove, (b) the stimulation technique is noninvasive and therefore reversible, (c) the use of surface electrodes can be readily learned and applied in the clinic, and (d) stimulators and surface electrodes are relatively inexpensive and commercially available. Stimulation with surface electrodes is the most widely used technique for therapeutic applications, and has been successfully employed to produce standing, stepping, and grasping motions. However, there are several disadvantages to using surface NMES systems: (a) they cannot produce isolated contractions of small or deep muscles, (b) movement of the target muscle under the skin as the stimulated limb moves can change the proximity of the electrode to the target muscle/nerve, resulting in inconsistent muscle contraction and force production, (c) daily doffing and donning the electrodes can complicate use, especially if electrode positions vary slightly from day to day, (d) in many cases, cutaneous pain receptors are stimulated and patients with preserved or heightened sensation may find it difficult to tolerate, and (e) the system may draw unwanted attention, especially if there are multiple stimulus channels and many cables. These disadvantages have motivated the design of systems with implanted electrodes.

Percutaneous systems use electrodes that are implanted into muscles or near nerves, and have leads that pass through the skin and connect to an external stimulator. Percutaneous electrodes can activate deep muscles, can provide isolated and repeatable muscle contractions, and are less likely to produce pain during stimulation because they bypass the sensory afferents in the skin. Percutaneous electrodes are often formed from a multifilament lead within a single insulator that is wound into a helical configuration to produce maximum flexibility (10,11). Percutaneous intramuscular electrodes are inserted into the target muscle with a hypodermic needle. The needle is withdrawn, leaving the electrode in place and the lead exiting the skin. The exit sites on the skin are protected with a bandage and must be cleaned, dressed, properly inspected, and maintained to reduce the risk of complications (12). A large surface electrode is often used as the return electrode. Percutaneous systems provide a minimally invasive technique for investigating the feasibility of restoring functional muscle contractions without having to prematurely subject research participants to implantable system surgery. Percutaneous systems have served as precursors to fully implanted systems (13) and have provided function in some individuals for periods of years (14). Various studies have reported on the longevity of percutaneous electrodes (11,12,15, 16, 17). Although the failure rate due to breakage is low during the first few months post implantation, the cumulative 1-year failure rate can vary between 56% and 91% (12,17), but this depends on many factors including the type of percutaneous lead, lead-routing technique, and the muscles implanted. Other potential complications of percutaneous electrodes include formation of granulomas from retained electrode fragments and electrode-related infections,

which are treated with oral antibiotics or minor outpatient surgical procedures (12).

Implanted NMES systems are designed for long-term use. Both the electrodes and the stimulator are implanted, but the controller is external for most implanted systems, to date. Communication between the controller and stimulator is through radio-frequency (RF) transmission; therefore, no leads pass through the skin. Because the stimulator both receives RF commands and generates stimulus pulses, it is often called a receiver/stimulator. Implanted electrodes with insulated lead wires are connected directly to the implanted stimulator with inline connectors, which permit the surgical removal and replacement of individual electrodes, if necessary, without removing the stimulator. The electrode leads are larger than percutaneous leads because they need to be more robust and resistant to failure given the intention to make long-term use of them. In most implanted system configurations the circuitry of the stimulator is sealed in a titanium enclosure, which serves as the return electrode. Depending on the application, the stimulator is implanted in the upper chest or abdomen. The stimulator receives power and control instructions through RF telemetry from an external controller. The RF link allows the stimulator to be fully passive with no active battery, thereby eliminating the need for replacement of the implanted stimulator because of battery failure. The telemetry link requires no wires through the skin; rather, a circular coil (antenna) connected to the controller with a cable is taped to the skin over the implanted stimulator. The controller receives information from the user through switches, sensors, an implanted joint angle sensor, or biopotential electrodes to determine the user’s intention and deliver stimulation accordingly. The controller may be worn on the body or carried on a user’s wheelchair. For long-term clinical application, implanted systems provide major advantages over other systems including improved convenience, cosmesis, reliability, and repeatability.

A variety of electrodes may be used with implanted NMES systems (Fig. 72-2). Epimysial electrodes are sutured directly to the epimysium on the muscle surface (18); intramuscular electrodes are inserted directly into a muscle belly (19); epineural electrodes are sutured to the connective tissue surrounding a motor nerve (20); and nerve helix or cuff electrodes are implanted around a nerve (21, 22, 23, 24). Epimysial electrodes have proved to be durable in upper and lower extremity applications (25,26), and are especially useful for activating broad, superficial, or thin muscles. Intramuscular electrodes allow activation of deeper or smaller muscles, such as the intrinsic muscles of the hand. Nerve-based electrodes are used when it is difficult to access the target muscle directly or when more complete muscle recruitment can be obtained by stimulating the nerve (27).

A unique configuration of implanted NMES system is the injectable microstimulator (BION), which is presently undergoing clinical trials for various therapeutic and neuroprosthetic applications (28). The BION (developed at the A.E. Mann Institute at the University of Southern California) is a small cylindrical (2 mm outer diameter × 16 mm length), injectable,
single-channel unit that functions as a receiver/stimulator and electrode (29). BIONs are implanted with a 12-gauge trochar in target muscles or near target nerves; the quantity to be implanted depends on the application. An external RF coil transmits power and control information from an external control unit. Battery-powered BIONs and EMG-sensing micro-injectable units are presently under development.

FIGURE 72-2. Electrodes used with implanted NMES systems. From L to R, epimysial stimulating electrode, intramuscular stimulating electrode, spiral nerve cuff stimulating electrode, epimysial EMG recording electrode. (Courtesy of the Cleveland FES Center, Cleveland, OH.)

These technologies and principles of electrical stimulation form the foundation for clinical applications of NMES. The next section will describe neuroprosthetic systems that have been developed for different upper motor neuron impairments.

CLINICAL APPLICATIONS OF NMES

This section describes the neuroprosthetic systems for four different clinical applications: upper extremity function, lower extremity function, respiratory function, and bladder and bowel function. These four applications are the most developed, have undergone the most clinical testing, and have several different device options available or in development. For each application, the purposes, indications, and specific neuroprosthetic systems will be described. This is not an exhaustive review of every device that has appeared in the research literature, rather only those systems that have undergone clinical trials and are currently commercially available or devices that are currently in the clinical trial phase of development (i.e., may be available through participation in research) will be discussed and are summarized in Table 72-2 at the end of this section. Finally, for each application, new technology developments and future research directions will be outlined.

Upper Extremity Function

The purpose of upper extremity neuroprosthetic systems is to enable individuals to use their paralyzed or paretic arm and hand to perform activities of daily living (ADL) (e.g., eating, personal hygiene, etc.). In particular, these systems provide the ability to grasp and release with the impaired hand and thereby reduce the need of individuals to rely on assistance from others and reduce the time and effort required to perform a task. In addition to hand grasp and release, emerging systems are incorporating elbow extension with shoulder abduction and flexion to provide reaching ability to individuals with proximal and distal upper limb paralysis.

Upper extremity systems may be applicable to people with partial or complete paralysis of the arm and/or hand resulting from cervical SCI or stroke. The hand and forearm muscles targeted for stimulation must not be denervated, that is, the lower motor neurons must be intact. Many persons with C5 and C6 level tetraplegia have preserved lower motor neurons from C7 and C8 neurological segments and may benefit from upper extremity NMES systems that restore grasp and release. Persons with C4 or higher level tetraplegia who have C5 and C6 lower motor neurons preserved may benefit from NMES systems designed to provide shoulder stability and control of elbow flexion and extension, in addition to providing grasp and release. Any joint contractures must be corrected or functional ability will be limited. Spasticity and hypertonia must be under control. The best candidates are individuals with intact cognition, who are motivated, and desire greater independence. In addition, many neuroprosthetic systems require assistance in donning the device, so it may be necessary for the individual to have good attendant support.

The first upper extremity neuroprostheses were developed in the 1960s using surface electrodes, in combination with a flexor hinge splint to open and close the hands of individuals with cervical SCI (30,31). These case studies were followed by work with stroke survivors in the 1970s (32,33). One- and two-channel stimulators activated the finger and thumb extensors and triceps (in some subjects) when the individual elevated their opposite shoulder, a movement that was picked up by a shoulder-mounted transducer. These pioneering efforts have led to the development and clinical testing of several upper extremity neuroprostheses for stroke and spinal cord injured patients (34, 35, 36, 37, 38, 39, 40, 41), some of which have been primarily intended for use as temporary therapeutic devices (see Chapter 71).

The NESS H200 (formerly known as Handmaster) is the only commercially available upper extremity neuroprosthesis (Bioness Inc., Valencia, CA) at the time of this writing. The H200 was originally developed for tetraplegia (42), but is also applicable to stroke survivors (43). The device is a wrist-forearm orthosis (Fig. 72-3), with five embedded surface electrodes that provide patterned stimulation to the finger and thumb flexors and extensors to produce selected hand movements. The
orthosis is connected by a flexible cable to a portable external control unit with push-button controls. The user initiates pre-programmed opening/closing stimulation sequences by pressing buttons on the control unit. The orthosis fixes the wrist in neutral, making it applicable primarily to persons with C5 complete tetraplegia who do not have a tenodesis grasp. In a study of seven subjects with C5 or C6 tetraplegia, the system was used at home to practice three ADL for 3 weeks (44). At the end of the 3 weeks, all seven subjects could use the system successfully to perform ADL that they were unable to perform without the system. Similar results were achieved in a study of H200 with 29 stroke survivors (43). Long-term use of H200 as a neuroprosthesis has not been reported. The H200 has received Food and Drug Administration (FDA) clearance (510(k)) for marketing as providing hand function to stroke survivors or individuals with C5 SCI.

TABLE 72.2 Summary of Available Functional NMES Systems for Four Applications

System Name	Supplier or Research Lab	System Type	FDA Status^a	CE^b Mark
Upper extremity function
NESS H200	Bioness Inc., Valencia, CA	Surface	510(k)	Yes
IST12 hand system	CWRU, Cleveland, OH	Implant	IDE	No
Lower extremity function: footdrop
NESS L300	Bioness Inc., Valencia, CA	Surface	510(k)	Yes
WalkAide	Innovative Neurotronics Inc., Austin, TX	Surface	510(k)	Yes
Odstock dropped-foot stimulator (ODFS)	NDI Medical, Cleveland, OH	Surface	510(k)	Yes
STIMuSTEP	FineTech Medical Ltd, Hertfordshire, UK	Implant	None	Yes
ActiGait	Neurodan A/S, Aalborg, Denmark	Implant	None	Yes
Lower extremity function: stand/transfer
CWRU/VA standing system	CWRU, Cleveland, OH	Implant	IDE	No
Lower extremity function: walk
Parastep system	Sigmedics Inc., Fairborn, OH	Surface	PMA	No
CWRU/VA walking system	CWRU, Cleveland, OH	Implant	IDE	No
Respiratory function
Avery Mark IV	Avery Biomedical Devices, Commack, NY	Implant	PMA	Yes
Atrostim Atrotech Ltd, Tampere, Fineland	Implant	IDE^c	Yes
NeuRx DPS system	Synapse Biomedical Inc., Oberlin, OH	Perc.	PMA	Yes
Bladder/bowel function
FineTech Brindley Bladder control system	FineTech Medical Ltd, Hertfordshire, UK	Implant	PMA	Yes
510(k): Also known as a premarket notification, the applicant has demonstrated that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not subject to PMA, and therefore has been cleared to market the device.
IDE: Investigational device exemption allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a premarket approval (PMA) application or a Premarket Notification (510(k)) submission to FDA.
PMA: Premarket approval, the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. (Class III devices are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.) PMA is the most stringent type of device marketing application required by FDA.
^aFDA: Food and Drug Administration—agency of the United States Department of Health and Human Services that approves medical devices for research and marketing before they are made available to the public. ^bCE Mark: a mandatory European marking for certain product groups to indicate conformity with the essential health and safety requirements set out in European Directives; indicates that the product may be legally placed on the market within the European Free Trade Agreement (EFTA) and European Union (EU) single market (total 28 countries). ^cIDE applied to Version 1.0 of the Atrostim device.

The implanted stimulator-telemeter 12 channel (IST12) system is an implanted upper extremity neuroprosthesis that is presently used in clinical trials conducted by researchers at Case Western Reserve University in Cleveland (45). This group has been developing implanted upper extremity neuroprostheses for SCI patients since 1986, when they implemented the first implanted hand grasp system. The IST12 system is an advanced version of the Freehand system, which underwent extensive assessment of clinical outcomes, received FDA approval (premarket approval, PMA) for use in C5 and C6 tetraplegia, and was commercially available from 1997 to 2002. Like the Freehand system, the IST12 system consists of a receiver/stimulator that is surgically implanted in the upper pectoral region and epimysial, and intramuscular electrodes that are implanted at the motor points of hand and forearm muscles with leads that are routed subcutaneously to the stimulator (Fig. 72-4). The external components include a RF transmitting coil that is taped to the chest over the stimulator and connected to a programmable external control unit. This implanted system approach was shown, in the
multicenter clinical trial of the Freehand system, to be successful in significantly reducing upper extremity impairment and activity limitation (46), and to be well accepted by the recipients (47), with very low rates of infection (<2%) and implant or electrode failure (<1%) (25).

FIGURE 72-4. IST12 system for upper extremity function. (Courtesy of the Cleveland FES Center, Cleveland, OH.)

The IST12 system builds on the clinical success of its predecessor, the Freehand system, by providing additional upper limb function and incorporating implanted EMG control methods. Enhanced function is achieved through additional stimulation channels. The Freehand system had eight stimulus channels (48); the IST12 system has 12. The additional channels are used to activate hand intrinsic muscles, triceps, or pronator quadratus. These additional muscles have resulted in better hand opening, improving object acquisition and release; elbow extension, increasing the user’s workspace; and forearm rotation, improving the user’s ability to optimally orient the hand. In the original Freehand system, the user controlled the opening and closing of their paralyzed hand by moving their opposite shoulder, which required wearing an external shoulder-mounted transducer. With the IST12 system, EMG control strategies are available, where the use of EMG signals are recorded from muscles that the patient still retains the ability to contract and relax. The EMG signals are picked up by implanted EMG-recording electrodes, a strategy that eliminates the need for donning an external sensor and opens the possibility of achieving more natural and intuitive control. Potential control muscles include those that are synergistic to the grasp movement, such as wrist extensors and, to a lesser extent, the brachioradialis, and nonsynergists such as sternocleidomastoid, trapezius, deltoid, platysma, or auricularis. Because the EMG control strategy makes use of muscle signals derived from the ipsilateral side, it allows the neuroprosthesis to be implemented bilaterally, which provides significant additional function to patients with tetraplegia.

The IST12 system is undergoing clinical testing; to date, 15 individuals with tetraplegia have received the system. Four of these participants have two systems implanted, one for each upper limb, in order to enable bimanual task performance. The longest follow-up has been 7 years. The functional results show that the neuroprosthesis provides significantly increased pinch force and grasp function for each subject (45).
All subjects have demonstrated increased independence and improved function in ADL. Thus far, the IST12 system has been implemented mainly in individuals with C5 or C6 SCI; clinical studies have also begun to evaluate the IST12 in patients with higher spinal cord injuries and in stroke survivors with chronic upper extremity hemiplegia and minimal flexor muscle hypertonia.

Future Directions

Current research in upper extremity neuroprostheses focuses on stimulation of additional muscles, evaluation of new control methods, and incorporation of advanced technologies in order to provide additional function, broaden the clinical indications, and facilitate clinical implementation. Patients with C4 and higher levels of SCI need proximal arm control and hand control. Several case studies using percutaneous or surface stimulation of shoulder and elbow, and forearm and hand muscles, have been conducted to test the feasibility of a neuroprosthesis that restores function to the entire upper limb (49, 50, 51). Recently, a patient with high level tetraplegia resulting from a C1 Brown Sequard SCI was implemented with two IST12 implants to produce hand, elbow, and shoulder movements that enable basic daily tasks such as eating and grooming (52). Nerve cuff electrodes are used to stimulate elbow and shoulder muscles, and EMGs from neck and shoulder muscles are recorded with implanted electrodes and used as control signals. The cuff electrodes have exhibited excellent and stable performance for more than 1 year. Extensive functional assessment of this system is underway.

As researchers strive to develop NMES systems that are applicable to individuals with higher SCIs, the need for strategies that allow the user to naturally control the entire upper arm and hand becomes even more important. In addition to further exploring the use of multiple EMG signals and signal processing methods for control (53, 54, 55, 56), alternative control inputs are being studied, including head orientation and movements (57), eye movements, and signals recorded from the brain (58). In the future, cortical signals recorded from electrodes implanted in the brain will be incorporated into neuroprosthetic systems as control sources, which may allow users to control stimulated limbs more naturally (59,60).

Advances are also being made to eliminate the external control unit and RF coil by implanting the control technology and powering the stimulator with a rechargeable battery, similar to cardiac pacemakers. In development at Case Western Reserve University is a networked neuroprosthesis, a totally implantable modular FES system that can be used for all purposes, for example, upper and lower limbs, trunk support, bladder, bowel, and diaphragm function. The networked neuroprosthesis will be upgradeable to provide additional and advanced functions by adding different components, for example, stimulator and sensor modules. The advantage of the system is that multiple applications can be implemented in a single patient without the need for multiple devices that are specially designed for single applications and are difficult to integrate or upgrade (9).

Lower Extremity Function

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